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Wisdom may counter loneliness, burnout in older adults
Wisdom increases with age, and although this personality trait is regarded as nebulous by many, there is evidence that it has biological and neuropsychiatric underpinnings. It could even hold the key to reducing loneliness and burnout among older people.
Those were some of the key messages delivered by Tanya T. Nguyen, PhD, of the department of psychiatry at the University of California, San Diego, who spoke at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
“To many people, wisdom remains a fuzzy concept that’s difficult to operationalize and measure. It’s analogous to the concepts of consciousness, emotions, and cognitions, which at one point were considered nonscientific, but today we accept them as biological and scientific entities,” Dr. Nguyen said during her talk at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.
Interest in quantifying and studying wisdom has picked up in recent years, and Dr. Nguyen gave a definition with six elements that includes prosocial behaviors such as empathy and compassion, as well as emotional regulation, self-reflection, decisiveness, and social decision-making. She also included a spirituality component, though she conceded that this is controversial.
She noted that there are cultural variations in the definition of wisdom, but it has changed little over time, suggesting that it may be biological rather than cultural in nature, and therefore may have a neuropsychiatric underpinning.
Loss of some or all characteristics of wisdom occurs in some behaviors and disorders, including most markedly in the neurodegenerative disorder frontotemporal dementia (FTD), which is characterized by damage only in the prefrontal cortex and anterior temporal lobes. It usually occurs before age 60, and patients exhibit poor social awareness, impulsivity, antisocial behavior, and a lack of insight and empathy.
This and other lines of evidence have led to the suggestion that wisdom may be governed by processes in the prefrontal cortex and the limbic striatum. The prefrontal cortex controls executive functions such as planning, predicting, and anticipating events, as well as managing emotional reactions and impulses. “Thus, wisdom involves parts of the brain that balance cold, hard analytical reasoning with primitive desires and drives, which ultimately leads to self-regulation, social insight, theory of mind, and empathy,” said Dr. Nguyen.
Wisdom has long been associated with age, but age is also linked to cognitive decline. A recent discovery that the brain does not stop evolving at older age may help explain this contradiction. Brains develop in a back to front order, so that the prefrontal cortex is the last to mature. As we age, neural activity shifts from the occipital lobes to the prefrontal cortex and its executive decision-making power.
“The brain may recruit higher-order networks to the prefrontal cortex that are associated with wisdom development,” said Dr. Nguyen. She also pointed out that asymmetry between the left and right hemisphere is reduced with age, as tasks that relied on circuits from one hemisphere or another more often call upon both. “In order to make up for lost synapses and neurons with aging, active older adults use more neuronal networks from both hemispheres to perform the same mental activity,” Dr. Nguyen said.
Some interventions can improve scores in traits associated with wisdom in older adults, and could be an important contributor to improvements in health and longevity, said Dr. Nguyen. Randomized, controlled trials have demonstrated that psychosocial or behavioral interventions can improve elements of wisdom such as prosocial behaviors and emotional regulation, both in people with mental illness and in the general population, with moderate to large effect sizes. But such studies don’t prove an effect on overall wisdom.
The intervention achieved positive results in 89 participants in senior housing communities, though the effect sizes were small, possibly because of high baseline resilience. A subanalysis suggested that reduction in loneliness was mediated by an increase in compassion.
“One of the most striking findings from our research on wisdom is this consistent and very strongly negative correlation between wisdom and loneliness,” Dr. Nguyen said. She highlighted other U.S. nationwide and cross-cultural studies that showed inverse relationships between loneliness and wisdom.
Loneliness is an important topic because it can contribute to burnout and suicide rates.
“Loneliness has a profound effect on how we show up in the workplace, in school, and in our communities. And that leads to anxiety, depression, depersonalization, and emotional fatigue. All are key features of burnout. And together loneliness and burnout have contributed to increased rates of suicide by 30%, and opioid-related deaths almost sixfold since the late 1990s,” Dr. Nguyen said.
Loneliness also is associated with worse physical health, and it may be linked to wisdom. “Loneliness can be conceptualized as being caused and maintained by objective circumstances, such as physical or social distancing, and by thoughts, behaviors, and feelings surrounding those experiences, including biased perceptions of social relations, and a negative assessment of one’s social skills, which then results in a discrepancy between one’s desired and perceived social relationships, which then can contribute to social withdrawal,” Dr. Nguyen said.
Dr. Nguyen highlighted the AARP Foundation’s Experience Corps program, which recruits older adults to act as mentors and tutors for children in kindergarten through third grade. It involves 15 hours per week over an entire school year, with a focus on child literacy, development, and behavioral management skills. A study revealed a significant impact. “It showed improvements in children’s grades and happiness, as well as seniors’ mental and physical health,” Dr. Nguyen said.
Dr. Nguyen concluded that wisdom “may be a vaccine against compassion fatigue and burnout that drive today’s behavioral epidemics of loneliness, opioid abuse, and suicide. It’s a tool for our times. It’s nuanced, flexible, pragmatic, compassionate, and it presents a reasonable framework for getting along in the often messy world that we all share.”
Implications for psychiatrists
Henry A. Nasrallah, MD, who organized the conference, suggested that the benefits of wisdom may not be limited to patients. He pointed out that surgeons often retire at age 60 or 65 because of declining physical skills, while psychiatrists continue to practice.
“We develop more wisdom and better skills, and we can practice into our 60s and 70s. I know psychiatrists who practice sometimes into their 80s. It’s really a wonderful thing to know that what you do in life develops or enhances the neuroplasticity of certain brain regions. In our case, in psychiatry, it is the brain regions involved in wisdom,” commented Dr. Nasrallah, who is a professor of psychiatry, neurology, and neuroscience at the University of Cincinnati.
Dr. Nguyen has no financial disclosures. Dr. Nasrallah has received grants from Abbott, AstraZeneca, Forest, Janssen, Lilly, Pfizer, and Shire, and advises Abbott, AstraZeneca, and Shire.
Wisdom increases with age, and although this personality trait is regarded as nebulous by many, there is evidence that it has biological and neuropsychiatric underpinnings. It could even hold the key to reducing loneliness and burnout among older people.
Those were some of the key messages delivered by Tanya T. Nguyen, PhD, of the department of psychiatry at the University of California, San Diego, who spoke at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
“To many people, wisdom remains a fuzzy concept that’s difficult to operationalize and measure. It’s analogous to the concepts of consciousness, emotions, and cognitions, which at one point were considered nonscientific, but today we accept them as biological and scientific entities,” Dr. Nguyen said during her talk at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.
Interest in quantifying and studying wisdom has picked up in recent years, and Dr. Nguyen gave a definition with six elements that includes prosocial behaviors such as empathy and compassion, as well as emotional regulation, self-reflection, decisiveness, and social decision-making. She also included a spirituality component, though she conceded that this is controversial.
She noted that there are cultural variations in the definition of wisdom, but it has changed little over time, suggesting that it may be biological rather than cultural in nature, and therefore may have a neuropsychiatric underpinning.
Loss of some or all characteristics of wisdom occurs in some behaviors and disorders, including most markedly in the neurodegenerative disorder frontotemporal dementia (FTD), which is characterized by damage only in the prefrontal cortex and anterior temporal lobes. It usually occurs before age 60, and patients exhibit poor social awareness, impulsivity, antisocial behavior, and a lack of insight and empathy.
This and other lines of evidence have led to the suggestion that wisdom may be governed by processes in the prefrontal cortex and the limbic striatum. The prefrontal cortex controls executive functions such as planning, predicting, and anticipating events, as well as managing emotional reactions and impulses. “Thus, wisdom involves parts of the brain that balance cold, hard analytical reasoning with primitive desires and drives, which ultimately leads to self-regulation, social insight, theory of mind, and empathy,” said Dr. Nguyen.
Wisdom has long been associated with age, but age is also linked to cognitive decline. A recent discovery that the brain does not stop evolving at older age may help explain this contradiction. Brains develop in a back to front order, so that the prefrontal cortex is the last to mature. As we age, neural activity shifts from the occipital lobes to the prefrontal cortex and its executive decision-making power.
“The brain may recruit higher-order networks to the prefrontal cortex that are associated with wisdom development,” said Dr. Nguyen. She also pointed out that asymmetry between the left and right hemisphere is reduced with age, as tasks that relied on circuits from one hemisphere or another more often call upon both. “In order to make up for lost synapses and neurons with aging, active older adults use more neuronal networks from both hemispheres to perform the same mental activity,” Dr. Nguyen said.
Some interventions can improve scores in traits associated with wisdom in older adults, and could be an important contributor to improvements in health and longevity, said Dr. Nguyen. Randomized, controlled trials have demonstrated that psychosocial or behavioral interventions can improve elements of wisdom such as prosocial behaviors and emotional regulation, both in people with mental illness and in the general population, with moderate to large effect sizes. But such studies don’t prove an effect on overall wisdom.
The intervention achieved positive results in 89 participants in senior housing communities, though the effect sizes were small, possibly because of high baseline resilience. A subanalysis suggested that reduction in loneliness was mediated by an increase in compassion.
“One of the most striking findings from our research on wisdom is this consistent and very strongly negative correlation between wisdom and loneliness,” Dr. Nguyen said. She highlighted other U.S. nationwide and cross-cultural studies that showed inverse relationships between loneliness and wisdom.
Loneliness is an important topic because it can contribute to burnout and suicide rates.
“Loneliness has a profound effect on how we show up in the workplace, in school, and in our communities. And that leads to anxiety, depression, depersonalization, and emotional fatigue. All are key features of burnout. And together loneliness and burnout have contributed to increased rates of suicide by 30%, and opioid-related deaths almost sixfold since the late 1990s,” Dr. Nguyen said.
Loneliness also is associated with worse physical health, and it may be linked to wisdom. “Loneliness can be conceptualized as being caused and maintained by objective circumstances, such as physical or social distancing, and by thoughts, behaviors, and feelings surrounding those experiences, including biased perceptions of social relations, and a negative assessment of one’s social skills, which then results in a discrepancy between one’s desired and perceived social relationships, which then can contribute to social withdrawal,” Dr. Nguyen said.
Dr. Nguyen highlighted the AARP Foundation’s Experience Corps program, which recruits older adults to act as mentors and tutors for children in kindergarten through third grade. It involves 15 hours per week over an entire school year, with a focus on child literacy, development, and behavioral management skills. A study revealed a significant impact. “It showed improvements in children’s grades and happiness, as well as seniors’ mental and physical health,” Dr. Nguyen said.
Dr. Nguyen concluded that wisdom “may be a vaccine against compassion fatigue and burnout that drive today’s behavioral epidemics of loneliness, opioid abuse, and suicide. It’s a tool for our times. It’s nuanced, flexible, pragmatic, compassionate, and it presents a reasonable framework for getting along in the often messy world that we all share.”
Implications for psychiatrists
Henry A. Nasrallah, MD, who organized the conference, suggested that the benefits of wisdom may not be limited to patients. He pointed out that surgeons often retire at age 60 or 65 because of declining physical skills, while psychiatrists continue to practice.
“We develop more wisdom and better skills, and we can practice into our 60s and 70s. I know psychiatrists who practice sometimes into their 80s. It’s really a wonderful thing to know that what you do in life develops or enhances the neuroplasticity of certain brain regions. In our case, in psychiatry, it is the brain regions involved in wisdom,” commented Dr. Nasrallah, who is a professor of psychiatry, neurology, and neuroscience at the University of Cincinnati.
Dr. Nguyen has no financial disclosures. Dr. Nasrallah has received grants from Abbott, AstraZeneca, Forest, Janssen, Lilly, Pfizer, and Shire, and advises Abbott, AstraZeneca, and Shire.
Wisdom increases with age, and although this personality trait is regarded as nebulous by many, there is evidence that it has biological and neuropsychiatric underpinnings. It could even hold the key to reducing loneliness and burnout among older people.
Those were some of the key messages delivered by Tanya T. Nguyen, PhD, of the department of psychiatry at the University of California, San Diego, who spoke at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
“To many people, wisdom remains a fuzzy concept that’s difficult to operationalize and measure. It’s analogous to the concepts of consciousness, emotions, and cognitions, which at one point were considered nonscientific, but today we accept them as biological and scientific entities,” Dr. Nguyen said during her talk at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.
Interest in quantifying and studying wisdom has picked up in recent years, and Dr. Nguyen gave a definition with six elements that includes prosocial behaviors such as empathy and compassion, as well as emotional regulation, self-reflection, decisiveness, and social decision-making. She also included a spirituality component, though she conceded that this is controversial.
She noted that there are cultural variations in the definition of wisdom, but it has changed little over time, suggesting that it may be biological rather than cultural in nature, and therefore may have a neuropsychiatric underpinning.
Loss of some or all characteristics of wisdom occurs in some behaviors and disorders, including most markedly in the neurodegenerative disorder frontotemporal dementia (FTD), which is characterized by damage only in the prefrontal cortex and anterior temporal lobes. It usually occurs before age 60, and patients exhibit poor social awareness, impulsivity, antisocial behavior, and a lack of insight and empathy.
This and other lines of evidence have led to the suggestion that wisdom may be governed by processes in the prefrontal cortex and the limbic striatum. The prefrontal cortex controls executive functions such as planning, predicting, and anticipating events, as well as managing emotional reactions and impulses. “Thus, wisdom involves parts of the brain that balance cold, hard analytical reasoning with primitive desires and drives, which ultimately leads to self-regulation, social insight, theory of mind, and empathy,” said Dr. Nguyen.
Wisdom has long been associated with age, but age is also linked to cognitive decline. A recent discovery that the brain does not stop evolving at older age may help explain this contradiction. Brains develop in a back to front order, so that the prefrontal cortex is the last to mature. As we age, neural activity shifts from the occipital lobes to the prefrontal cortex and its executive decision-making power.
“The brain may recruit higher-order networks to the prefrontal cortex that are associated with wisdom development,” said Dr. Nguyen. She also pointed out that asymmetry between the left and right hemisphere is reduced with age, as tasks that relied on circuits from one hemisphere or another more often call upon both. “In order to make up for lost synapses and neurons with aging, active older adults use more neuronal networks from both hemispheres to perform the same mental activity,” Dr. Nguyen said.
Some interventions can improve scores in traits associated with wisdom in older adults, and could be an important contributor to improvements in health and longevity, said Dr. Nguyen. Randomized, controlled trials have demonstrated that psychosocial or behavioral interventions can improve elements of wisdom such as prosocial behaviors and emotional regulation, both in people with mental illness and in the general population, with moderate to large effect sizes. But such studies don’t prove an effect on overall wisdom.
The intervention achieved positive results in 89 participants in senior housing communities, though the effect sizes were small, possibly because of high baseline resilience. A subanalysis suggested that reduction in loneliness was mediated by an increase in compassion.
“One of the most striking findings from our research on wisdom is this consistent and very strongly negative correlation between wisdom and loneliness,” Dr. Nguyen said. She highlighted other U.S. nationwide and cross-cultural studies that showed inverse relationships between loneliness and wisdom.
Loneliness is an important topic because it can contribute to burnout and suicide rates.
“Loneliness has a profound effect on how we show up in the workplace, in school, and in our communities. And that leads to anxiety, depression, depersonalization, and emotional fatigue. All are key features of burnout. And together loneliness and burnout have contributed to increased rates of suicide by 30%, and opioid-related deaths almost sixfold since the late 1990s,” Dr. Nguyen said.
Loneliness also is associated with worse physical health, and it may be linked to wisdom. “Loneliness can be conceptualized as being caused and maintained by objective circumstances, such as physical or social distancing, and by thoughts, behaviors, and feelings surrounding those experiences, including biased perceptions of social relations, and a negative assessment of one’s social skills, which then results in a discrepancy between one’s desired and perceived social relationships, which then can contribute to social withdrawal,” Dr. Nguyen said.
Dr. Nguyen highlighted the AARP Foundation’s Experience Corps program, which recruits older adults to act as mentors and tutors for children in kindergarten through third grade. It involves 15 hours per week over an entire school year, with a focus on child literacy, development, and behavioral management skills. A study revealed a significant impact. “It showed improvements in children’s grades and happiness, as well as seniors’ mental and physical health,” Dr. Nguyen said.
Dr. Nguyen concluded that wisdom “may be a vaccine against compassion fatigue and burnout that drive today’s behavioral epidemics of loneliness, opioid abuse, and suicide. It’s a tool for our times. It’s nuanced, flexible, pragmatic, compassionate, and it presents a reasonable framework for getting along in the often messy world that we all share.”
Implications for psychiatrists
Henry A. Nasrallah, MD, who organized the conference, suggested that the benefits of wisdom may not be limited to patients. He pointed out that surgeons often retire at age 60 or 65 because of declining physical skills, while psychiatrists continue to practice.
“We develop more wisdom and better skills, and we can practice into our 60s and 70s. I know psychiatrists who practice sometimes into their 80s. It’s really a wonderful thing to know that what you do in life develops or enhances the neuroplasticity of certain brain regions. In our case, in psychiatry, it is the brain regions involved in wisdom,” commented Dr. Nasrallah, who is a professor of psychiatry, neurology, and neuroscience at the University of Cincinnati.
Dr. Nguyen has no financial disclosures. Dr. Nasrallah has received grants from Abbott, AstraZeneca, Forest, Janssen, Lilly, Pfizer, and Shire, and advises Abbott, AstraZeneca, and Shire.
REPORTING FROM FOCUS ON NEUROPSYCHIATRY 2021
Procedureless intragastric balloon may cut costs as well as weight
Using a procedureless intragastric balloon (PIGB) as a first-line treatment for obesity is cost effective as either a standalone intervention or a bridge to bariatric surgery, according to a new simulation model study published in PLOS One.
PIGB boasts a noninvasive delivery mechanism in the form of a swallowable capsule. Upon reaching the stomach, the capsule is filled with fluid via a catheter. The clinician uses x-ray or fluoroscopy to confirm correct positioning of the balloon. After 4 months, the balloon’s release valve opens to drain the fluid, and the balloon is excreted naturally. If presented with a major complication, clinicians can typically remove PIGB endoscopically. This not only translates into much lower costs than bariatric surgery but also fewer adverse events.
The available evidence surrounding PIGB’s relative efficacy is less clear. Prior studies have shown that PIGB produces an average weight loss of 14.2% after a single, 4-month treatment episode, compared with 32% after bariatric surgery. When compared against other intragastric balloon devices, however, PIGB has been shown to lead to comparable or superior levels of weight loss. There is also limited evidence about PIGB’s long-term efficacy, but some data suggest that weight lost is generally regained after removal of the balloon.
To date, though, there had been no analysis of whether PIBG’s proposed advantages would make it more cost effective when measured against the superior outcomes of commonly performed bariatric surgeries.
Assessing the cost of PIGB
Researchers compared the cost-effectiveness of six regimens: PIGB; standalone gastric bypass or sleeve gastrectomy; PIGB as a bridge to gastric bypass or sleeve gastrectomy; and no treatment. The specific PIGB device the investigators assessed was the Elipse balloon (Allurion Technologies), which is approved in Europe, Asia, and Latin America, and is in the premarket approval process in the United States.
They then applied an individual patient-level Markov microsimulation model to compare these separate regimens in terms of costs and quality-adjusted life years (QALYs). The simulation incorporated data from 10,000 adults aged 18-64 with body mass index (BMI) ≥ 35, of which 44% had a BMI ≥ 40. The model assumed patients initially underwent treatment with PIGB, gastric bypass, or sleeve gastrectomy. Based on the predicted weight loss resulting from that intervention, the model then estimated how PIGB-only, gastric bypass–only, and sleeve gastrectomy–only patients transitioned to a new health state, ranging from no obesity to death. It also incorporated a hybrid strategy in which patients underwent bariatric surgery if their BMI was still ≥ 35. The researchers modeled complications in all groups as chance events, with a probability of occurrence based on BMI state.
The model determined that the most cost-effective approach was using PIGB as a bridge to sleeve gastrectomy, which had an incremental cost-effectiveness ratio (ICER) of $3,781 per QALY. PIGB alone was not cost effective versus bariatric surgery, but it did outperform no treatment (ICER, $21,711 per QALY).
The study investigators noted that there was a counterintuitive aspect to finding that PIGB was most cost effective when used as a bridge to surgery.
“Contrary to expectations that an add-on treatment to already expensive bariatric surgery would further increase health care costs, our results show that using PIGB as an add-on treatment reduces total costs and improves health outcomes, compared with bariatric surgery alone,” they wrote. “Consequently, as decision-makers look for ways to curb rising health care costs, it will be worthwhile to consider incorporating PIGB prior to bariatric surgery within the clinical care pathway.”
They also noted that initial PIGB may help patients achieve a lower BMI following surgery.
An appealing option
“This technique is very appealing to a lot of patients because you don’t need sedation, you can do it fairly quickly, and the risks and complications of endoscopy or surgery aren’t there with the procedureless balloon, at least on implantation,” said Reem Sharaiha, MD, associate professor of medicine and director of Bariatric & Metabolic Endoscopy at Weill Cornell Medicine, when asked to comment on the study’s results. “I believe that you need to offer a lot of options to tackle obesity as an epidemic and to give patients multiple treatment options, because it’s not going to be a one and done. It’s going to be multiple procedures in their lifetime.”
Dr. Sharaiha added that PIGB’s noninvasive qualities may make it a viable option for addressing a notable gap in obesity treatment; only about 2% of individuals who would qualify for surgery actually do so each year.
“A lot of people are reluctant to undergo it because of the fear of complications or the fear of invasiveness. They do not want to be off work for many weeks,” she said. “Many people come to see me and say, ‘I don’t want to tell anyone that I’ve had it done.’ Or, ‘I don’t want any scars.’ So, a lot of these [factors] come into play as well.”
Dr. Sharaiha is a consultant for Boston Scientific and has participated in trials conducted to seek Food and Drug Administration approval for the Elipse device.
Using a procedureless intragastric balloon (PIGB) as a first-line treatment for obesity is cost effective as either a standalone intervention or a bridge to bariatric surgery, according to a new simulation model study published in PLOS One.
PIGB boasts a noninvasive delivery mechanism in the form of a swallowable capsule. Upon reaching the stomach, the capsule is filled with fluid via a catheter. The clinician uses x-ray or fluoroscopy to confirm correct positioning of the balloon. After 4 months, the balloon’s release valve opens to drain the fluid, and the balloon is excreted naturally. If presented with a major complication, clinicians can typically remove PIGB endoscopically. This not only translates into much lower costs than bariatric surgery but also fewer adverse events.
The available evidence surrounding PIGB’s relative efficacy is less clear. Prior studies have shown that PIGB produces an average weight loss of 14.2% after a single, 4-month treatment episode, compared with 32% after bariatric surgery. When compared against other intragastric balloon devices, however, PIGB has been shown to lead to comparable or superior levels of weight loss. There is also limited evidence about PIGB’s long-term efficacy, but some data suggest that weight lost is generally regained after removal of the balloon.
To date, though, there had been no analysis of whether PIBG’s proposed advantages would make it more cost effective when measured against the superior outcomes of commonly performed bariatric surgeries.
Assessing the cost of PIGB
Researchers compared the cost-effectiveness of six regimens: PIGB; standalone gastric bypass or sleeve gastrectomy; PIGB as a bridge to gastric bypass or sleeve gastrectomy; and no treatment. The specific PIGB device the investigators assessed was the Elipse balloon (Allurion Technologies), which is approved in Europe, Asia, and Latin America, and is in the premarket approval process in the United States.
They then applied an individual patient-level Markov microsimulation model to compare these separate regimens in terms of costs and quality-adjusted life years (QALYs). The simulation incorporated data from 10,000 adults aged 18-64 with body mass index (BMI) ≥ 35, of which 44% had a BMI ≥ 40. The model assumed patients initially underwent treatment with PIGB, gastric bypass, or sleeve gastrectomy. Based on the predicted weight loss resulting from that intervention, the model then estimated how PIGB-only, gastric bypass–only, and sleeve gastrectomy–only patients transitioned to a new health state, ranging from no obesity to death. It also incorporated a hybrid strategy in which patients underwent bariatric surgery if their BMI was still ≥ 35. The researchers modeled complications in all groups as chance events, with a probability of occurrence based on BMI state.
The model determined that the most cost-effective approach was using PIGB as a bridge to sleeve gastrectomy, which had an incremental cost-effectiveness ratio (ICER) of $3,781 per QALY. PIGB alone was not cost effective versus bariatric surgery, but it did outperform no treatment (ICER, $21,711 per QALY).
The study investigators noted that there was a counterintuitive aspect to finding that PIGB was most cost effective when used as a bridge to surgery.
“Contrary to expectations that an add-on treatment to already expensive bariatric surgery would further increase health care costs, our results show that using PIGB as an add-on treatment reduces total costs and improves health outcomes, compared with bariatric surgery alone,” they wrote. “Consequently, as decision-makers look for ways to curb rising health care costs, it will be worthwhile to consider incorporating PIGB prior to bariatric surgery within the clinical care pathway.”
They also noted that initial PIGB may help patients achieve a lower BMI following surgery.
An appealing option
“This technique is very appealing to a lot of patients because you don’t need sedation, you can do it fairly quickly, and the risks and complications of endoscopy or surgery aren’t there with the procedureless balloon, at least on implantation,” said Reem Sharaiha, MD, associate professor of medicine and director of Bariatric & Metabolic Endoscopy at Weill Cornell Medicine, when asked to comment on the study’s results. “I believe that you need to offer a lot of options to tackle obesity as an epidemic and to give patients multiple treatment options, because it’s not going to be a one and done. It’s going to be multiple procedures in their lifetime.”
Dr. Sharaiha added that PIGB’s noninvasive qualities may make it a viable option for addressing a notable gap in obesity treatment; only about 2% of individuals who would qualify for surgery actually do so each year.
“A lot of people are reluctant to undergo it because of the fear of complications or the fear of invasiveness. They do not want to be off work for many weeks,” she said. “Many people come to see me and say, ‘I don’t want to tell anyone that I’ve had it done.’ Or, ‘I don’t want any scars.’ So, a lot of these [factors] come into play as well.”
Dr. Sharaiha is a consultant for Boston Scientific and has participated in trials conducted to seek Food and Drug Administration approval for the Elipse device.
Using a procedureless intragastric balloon (PIGB) as a first-line treatment for obesity is cost effective as either a standalone intervention or a bridge to bariatric surgery, according to a new simulation model study published in PLOS One.
PIGB boasts a noninvasive delivery mechanism in the form of a swallowable capsule. Upon reaching the stomach, the capsule is filled with fluid via a catheter. The clinician uses x-ray or fluoroscopy to confirm correct positioning of the balloon. After 4 months, the balloon’s release valve opens to drain the fluid, and the balloon is excreted naturally. If presented with a major complication, clinicians can typically remove PIGB endoscopically. This not only translates into much lower costs than bariatric surgery but also fewer adverse events.
The available evidence surrounding PIGB’s relative efficacy is less clear. Prior studies have shown that PIGB produces an average weight loss of 14.2% after a single, 4-month treatment episode, compared with 32% after bariatric surgery. When compared against other intragastric balloon devices, however, PIGB has been shown to lead to comparable or superior levels of weight loss. There is also limited evidence about PIGB’s long-term efficacy, but some data suggest that weight lost is generally regained after removal of the balloon.
To date, though, there had been no analysis of whether PIBG’s proposed advantages would make it more cost effective when measured against the superior outcomes of commonly performed bariatric surgeries.
Assessing the cost of PIGB
Researchers compared the cost-effectiveness of six regimens: PIGB; standalone gastric bypass or sleeve gastrectomy; PIGB as a bridge to gastric bypass or sleeve gastrectomy; and no treatment. The specific PIGB device the investigators assessed was the Elipse balloon (Allurion Technologies), which is approved in Europe, Asia, and Latin America, and is in the premarket approval process in the United States.
They then applied an individual patient-level Markov microsimulation model to compare these separate regimens in terms of costs and quality-adjusted life years (QALYs). The simulation incorporated data from 10,000 adults aged 18-64 with body mass index (BMI) ≥ 35, of which 44% had a BMI ≥ 40. The model assumed patients initially underwent treatment with PIGB, gastric bypass, or sleeve gastrectomy. Based on the predicted weight loss resulting from that intervention, the model then estimated how PIGB-only, gastric bypass–only, and sleeve gastrectomy–only patients transitioned to a new health state, ranging from no obesity to death. It also incorporated a hybrid strategy in which patients underwent bariatric surgery if their BMI was still ≥ 35. The researchers modeled complications in all groups as chance events, with a probability of occurrence based on BMI state.
The model determined that the most cost-effective approach was using PIGB as a bridge to sleeve gastrectomy, which had an incremental cost-effectiveness ratio (ICER) of $3,781 per QALY. PIGB alone was not cost effective versus bariatric surgery, but it did outperform no treatment (ICER, $21,711 per QALY).
The study investigators noted that there was a counterintuitive aspect to finding that PIGB was most cost effective when used as a bridge to surgery.
“Contrary to expectations that an add-on treatment to already expensive bariatric surgery would further increase health care costs, our results show that using PIGB as an add-on treatment reduces total costs and improves health outcomes, compared with bariatric surgery alone,” they wrote. “Consequently, as decision-makers look for ways to curb rising health care costs, it will be worthwhile to consider incorporating PIGB prior to bariatric surgery within the clinical care pathway.”
They also noted that initial PIGB may help patients achieve a lower BMI following surgery.
An appealing option
“This technique is very appealing to a lot of patients because you don’t need sedation, you can do it fairly quickly, and the risks and complications of endoscopy or surgery aren’t there with the procedureless balloon, at least on implantation,” said Reem Sharaiha, MD, associate professor of medicine and director of Bariatric & Metabolic Endoscopy at Weill Cornell Medicine, when asked to comment on the study’s results. “I believe that you need to offer a lot of options to tackle obesity as an epidemic and to give patients multiple treatment options, because it’s not going to be a one and done. It’s going to be multiple procedures in their lifetime.”
Dr. Sharaiha added that PIGB’s noninvasive qualities may make it a viable option for addressing a notable gap in obesity treatment; only about 2% of individuals who would qualify for surgery actually do so each year.
“A lot of people are reluctant to undergo it because of the fear of complications or the fear of invasiveness. They do not want to be off work for many weeks,” she said. “Many people come to see me and say, ‘I don’t want to tell anyone that I’ve had it done.’ Or, ‘I don’t want any scars.’ So, a lot of these [factors] come into play as well.”
Dr. Sharaiha is a consultant for Boston Scientific and has participated in trials conducted to seek Food and Drug Administration approval for the Elipse device.
FROM PLOS ONE
Low-dose aspirin linked to lower dementia risk in some
, according to a retrospective analysis of two large cohorts. The association with all-cause dementia was weak, but much more pronounced in subjects with coronary heart disease.
The results underscore that individuals with cardiovascular disease risk factors should be prescribed LDASA, and they should be encouraged to be compliant. The study differed from previous observational and randomized, controlled trials, which yielded mixed results. Many looked at individuals older than age 65. The pathological changes associated with dementia may occur up to 2 decades before symptom onset, and it appears that LDASA cannot counter cognitive decline after a diagnosis is made. “The use of LDASA at this age may be already too late,” said Thi Ngoc Mai Nguyen, a PhD student at Network Aging Research, Heidelberg University, Germany. She presented the results at the 2021 Alzheimer’s Association International Conference.
Previous studies also included individuals using LDASA to prevent cardiovascular disease, and they didn’t always adjust for these risk factors. The current work used two large databases, UK Biobank and ESTHER, with a follow-up time of over 10 years for both. “We were able to balance out the distribution of measured baseline covariates (to be) similar between LDASA users and nonusers, and thus, we were able to adjust for confounders more comprehensively,” said Ms. Nguyen.
Not yet a definitive answer
Although the findings are promising, Ms. Nguyen noted that the study is not the final word. “Residual confounding is possible, and causation cannot be tested. The only way to answer this is to have clinical trials with at least 10 years of follow-up,” said Ms. Nguyen. She plans to conduct similar studies in non-White populations, and also to examine whether LDASA can help preserve cognitive function in middle-age adults.
The study is interesting, said Claire Sexton, DPhil, who was asked to comment, but she suggested that it is not practice changing. “There is not evidence from the dementia science perspective that should go against whatever the recommendations are for cardiovascular risk,” said Dr. Sexton, director of scientific programs and outreach at the Alzheimer’s Association. “I don’t think this study alone can provide a definitive answer on low-dose aspirin and its association with dementia and Alzheimer’s disease, but it’s an important addition to the literature,” she added.
Meta-analysis data
The researchers examined two prospective cohort studies, and combined them into a meta-analysis. It included the ESTHER cohort from Saarland, Germany, with 5,258 individuals and 14.3 years of follow-up, and the UK Biobank cohort, with 305,394 individuals and 11.6 years of follow-up. Subjects selected for analysis were 55 years old or older.
The meta-analysis showed no significant association between LDASA use and reduced risk of Alzheimer’s disease, but there was an association between LDASA use and all-cause dementia (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.93-0.99).
There were no sex differences with respect to Alzheimer’s dementia, but in males, LDASA was associated with lower risk of vascular dementia (HR, 0.85; 95% CI, 0.79-0.93) and all-cause dementia (HR, 0.87; 95% CI, 0.83-0.92). However, in females, LDASA was tied to greater risk of both vascular dementia (HR, 1.13; 95% CI, 1.02-1.24) and all-cause dementia (HR, 1.07; 95% CI, 1.02-1.13).
The strongest association between LDASA and reduced dementia risk was found in subjects with coronary heart disease (HR, 0.69; 95% CI, 0.59-0.80).
The researchers also used UK Biobank primary care data to analyze associations between longer use of LDASA and reduced dementia risk. Those who used LDASA for 0-5 years were at a higher than average risk of all-cause dementia (HR, 2.80; 95% CI, 2.48-3.16), Alzheimer’s disease (HR, 2.26; 95% CI, 1.84-2.77), and vascular dementia (HR, 3.79; 95% CI, 3.17-4.53). Long-term LDASA users, defined as 10 years or longer, had a lower risk of all-cause dementia (HR, 0.51; 95% CI, 0.47-0.56), Alzheimer’s disease (HR, 0.58; 95% CI, 0.51-0.68), and vascular dementia (HR, 0.48; 95% CI, 0.42-0.56).
Dr. Nguyen and Dr. Sexton have no relevant financial disclosures.
, according to a retrospective analysis of two large cohorts. The association with all-cause dementia was weak, but much more pronounced in subjects with coronary heart disease.
The results underscore that individuals with cardiovascular disease risk factors should be prescribed LDASA, and they should be encouraged to be compliant. The study differed from previous observational and randomized, controlled trials, which yielded mixed results. Many looked at individuals older than age 65. The pathological changes associated with dementia may occur up to 2 decades before symptom onset, and it appears that LDASA cannot counter cognitive decline after a diagnosis is made. “The use of LDASA at this age may be already too late,” said Thi Ngoc Mai Nguyen, a PhD student at Network Aging Research, Heidelberg University, Germany. She presented the results at the 2021 Alzheimer’s Association International Conference.
Previous studies also included individuals using LDASA to prevent cardiovascular disease, and they didn’t always adjust for these risk factors. The current work used two large databases, UK Biobank and ESTHER, with a follow-up time of over 10 years for both. “We were able to balance out the distribution of measured baseline covariates (to be) similar between LDASA users and nonusers, and thus, we were able to adjust for confounders more comprehensively,” said Ms. Nguyen.
Not yet a definitive answer
Although the findings are promising, Ms. Nguyen noted that the study is not the final word. “Residual confounding is possible, and causation cannot be tested. The only way to answer this is to have clinical trials with at least 10 years of follow-up,” said Ms. Nguyen. She plans to conduct similar studies in non-White populations, and also to examine whether LDASA can help preserve cognitive function in middle-age adults.
The study is interesting, said Claire Sexton, DPhil, who was asked to comment, but she suggested that it is not practice changing. “There is not evidence from the dementia science perspective that should go against whatever the recommendations are for cardiovascular risk,” said Dr. Sexton, director of scientific programs and outreach at the Alzheimer’s Association. “I don’t think this study alone can provide a definitive answer on low-dose aspirin and its association with dementia and Alzheimer’s disease, but it’s an important addition to the literature,” she added.
Meta-analysis data
The researchers examined two prospective cohort studies, and combined them into a meta-analysis. It included the ESTHER cohort from Saarland, Germany, with 5,258 individuals and 14.3 years of follow-up, and the UK Biobank cohort, with 305,394 individuals and 11.6 years of follow-up. Subjects selected for analysis were 55 years old or older.
The meta-analysis showed no significant association between LDASA use and reduced risk of Alzheimer’s disease, but there was an association between LDASA use and all-cause dementia (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.93-0.99).
There were no sex differences with respect to Alzheimer’s dementia, but in males, LDASA was associated with lower risk of vascular dementia (HR, 0.85; 95% CI, 0.79-0.93) and all-cause dementia (HR, 0.87; 95% CI, 0.83-0.92). However, in females, LDASA was tied to greater risk of both vascular dementia (HR, 1.13; 95% CI, 1.02-1.24) and all-cause dementia (HR, 1.07; 95% CI, 1.02-1.13).
The strongest association between LDASA and reduced dementia risk was found in subjects with coronary heart disease (HR, 0.69; 95% CI, 0.59-0.80).
The researchers also used UK Biobank primary care data to analyze associations between longer use of LDASA and reduced dementia risk. Those who used LDASA for 0-5 years were at a higher than average risk of all-cause dementia (HR, 2.80; 95% CI, 2.48-3.16), Alzheimer’s disease (HR, 2.26; 95% CI, 1.84-2.77), and vascular dementia (HR, 3.79; 95% CI, 3.17-4.53). Long-term LDASA users, defined as 10 years or longer, had a lower risk of all-cause dementia (HR, 0.51; 95% CI, 0.47-0.56), Alzheimer’s disease (HR, 0.58; 95% CI, 0.51-0.68), and vascular dementia (HR, 0.48; 95% CI, 0.42-0.56).
Dr. Nguyen and Dr. Sexton have no relevant financial disclosures.
, according to a retrospective analysis of two large cohorts. The association with all-cause dementia was weak, but much more pronounced in subjects with coronary heart disease.
The results underscore that individuals with cardiovascular disease risk factors should be prescribed LDASA, and they should be encouraged to be compliant. The study differed from previous observational and randomized, controlled trials, which yielded mixed results. Many looked at individuals older than age 65. The pathological changes associated with dementia may occur up to 2 decades before symptom onset, and it appears that LDASA cannot counter cognitive decline after a diagnosis is made. “The use of LDASA at this age may be already too late,” said Thi Ngoc Mai Nguyen, a PhD student at Network Aging Research, Heidelberg University, Germany. She presented the results at the 2021 Alzheimer’s Association International Conference.
Previous studies also included individuals using LDASA to prevent cardiovascular disease, and they didn’t always adjust for these risk factors. The current work used two large databases, UK Biobank and ESTHER, with a follow-up time of over 10 years for both. “We were able to balance out the distribution of measured baseline covariates (to be) similar between LDASA users and nonusers, and thus, we were able to adjust for confounders more comprehensively,” said Ms. Nguyen.
Not yet a definitive answer
Although the findings are promising, Ms. Nguyen noted that the study is not the final word. “Residual confounding is possible, and causation cannot be tested. The only way to answer this is to have clinical trials with at least 10 years of follow-up,” said Ms. Nguyen. She plans to conduct similar studies in non-White populations, and also to examine whether LDASA can help preserve cognitive function in middle-age adults.
The study is interesting, said Claire Sexton, DPhil, who was asked to comment, but she suggested that it is not practice changing. “There is not evidence from the dementia science perspective that should go against whatever the recommendations are for cardiovascular risk,” said Dr. Sexton, director of scientific programs and outreach at the Alzheimer’s Association. “I don’t think this study alone can provide a definitive answer on low-dose aspirin and its association with dementia and Alzheimer’s disease, but it’s an important addition to the literature,” she added.
Meta-analysis data
The researchers examined two prospective cohort studies, and combined them into a meta-analysis. It included the ESTHER cohort from Saarland, Germany, with 5,258 individuals and 14.3 years of follow-up, and the UK Biobank cohort, with 305,394 individuals and 11.6 years of follow-up. Subjects selected for analysis were 55 years old or older.
The meta-analysis showed no significant association between LDASA use and reduced risk of Alzheimer’s disease, but there was an association between LDASA use and all-cause dementia (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.93-0.99).
There were no sex differences with respect to Alzheimer’s dementia, but in males, LDASA was associated with lower risk of vascular dementia (HR, 0.85; 95% CI, 0.79-0.93) and all-cause dementia (HR, 0.87; 95% CI, 0.83-0.92). However, in females, LDASA was tied to greater risk of both vascular dementia (HR, 1.13; 95% CI, 1.02-1.24) and all-cause dementia (HR, 1.07; 95% CI, 1.02-1.13).
The strongest association between LDASA and reduced dementia risk was found in subjects with coronary heart disease (HR, 0.69; 95% CI, 0.59-0.80).
The researchers also used UK Biobank primary care data to analyze associations between longer use of LDASA and reduced dementia risk. Those who used LDASA for 0-5 years were at a higher than average risk of all-cause dementia (HR, 2.80; 95% CI, 2.48-3.16), Alzheimer’s disease (HR, 2.26; 95% CI, 1.84-2.77), and vascular dementia (HR, 3.79; 95% CI, 3.17-4.53). Long-term LDASA users, defined as 10 years or longer, had a lower risk of all-cause dementia (HR, 0.51; 95% CI, 0.47-0.56), Alzheimer’s disease (HR, 0.58; 95% CI, 0.51-0.68), and vascular dementia (HR, 0.48; 95% CI, 0.42-0.56).
Dr. Nguyen and Dr. Sexton have no relevant financial disclosures.
FROM AAIC 2021
Short sleep is linked to future dementia
, according to a new analysis of data from the Whitehall II cohort study.
Previous work had identified links between short sleep duration and dementia risk, but few studies examined sleep habits long before onset of dementia. Those that did produced inconsistent results, according to Séverine Sabia, PhD, who is a research associate at Inserm (France) and the University College London.
“One potential reason for these inconstancies is the large range of ages of the study populations, and the small number of participants within each sleep duration group. The novelty of our study is to examine this association among almost 8,000 participants with a follow-up of 30 years, using repeated measures of sleep duration starting in midlife to consider sleep duration at specific ages,” Dr. Sabia said in an interview. She presented the research at the 2021 Alzheimer’s Association International Conference.
Those previous studies found a U-shaped association between sleep duration and dementia risk, with lowest risk associated with 7-8 hours of sleep, but greater risk for shorter and longer durations. However, because the studies had follow-up periods shorter than 10 years, they are at greater risk of reverse causation bias. Longer follow-up studies tended to have small sample sizes or to focus on older adults.
The longer follow-up in the current study makes for a more compelling case, said Claire Sexton, DPhil, director of Scientific Programs & Outreach for the Alzheimer’s Association. Observations of short or long sleep closer to the onset of symptoms could just be a warning sign of dementia. “But looking at age 50, age 60 ... if you’re seeing those relationships, then it’s less likely that it is just purely prodromal,” said Dr. Sexton. But it still doesn’t necessarily confirm causation. “It could also be a risk factor,” Dr. Sexton added.
Multifactorial risk
Dr. Sabia also noted that the magnitude of risk was similar to that seen with smoking or obesity, and many factors play a role in dementia risk. “Even if the risk of dementia was 30% higher in those with persistent short sleep duration, in absolute terms, the percentage of those with persistent short duration who developed dementia was 8%, and 6% in those with persistent sleep duration of 7 hours. Dementia is a multifactorial disease, which means that several factors are likely to influence its onset. Sleep duration is one of them, but if a person has poor sleep and does not manage to increase it, there are other important prevention measures. It is important to keep a healthy lifestyle and cardiometabolic measures in the normal range. All together it is likely to be beneficial for brain health in later life,” she said.
Dr. Sexton agreed. “With sleep we’re still trying to tease apart what aspect of sleep is important. Is it the sleep duration? Is it the quality of sleep? Is it certain sleep stages?” she said.
Regardless of sleep’s potential influence on dementia risk, both Dr. Sexton and Dr. Sabia noted the importance of sleep for general health. “These types of problems are very prevalent, so it’s good for people to be aware of them. And then if they notice any problems with their sleep, or any changes, to go and see their health care provider, and to be discussing them, and then to be investigating the cause, and to see whether changes in sleep hygiene and treatments for insomnia could address these sleep problems,” said Dr. Sexton.
Decades of data
During the Whitehall II study, researchers assessed average sleep duration (“How many hours of sleep do you have on an average weeknight?”) six times over 30 years of follow-up. Dr. Sabia’s group extracted self-reported sleep duration data at ages 50, 60, and 70. Short sleep duration was defined as fewer than 5 hours, or 6 hours. Normal sleep duration was defined as 7 hours. Long duration was defined as 8 hours or more.
A questioner during the Q&A period noted that this grouping is a little unusual. Many studies define 7-8 hours as normal. Dr. Sabia answered that they were unable to examine periods of 9 hours or more due to the nature of the data, and the lowest associated risk was found at 7 hours.
The researchers analyzed data from 7,959 participants (33.0% women). At age 50, compared with 7 hours of sleep, 6 or few hours of sleep was associated with a higher risk of dementia over the ensuing 25 years of follow-up (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.01-1.48). The same was true at age 60 (15 years of follow-up HR, 1.37; 95% CI, 1.10-1.72). There was a trend at age 70 (8 years follow-up; HR, 1.24; 95% CI, 0.98-1.57). For 8 or more hours of sleep, there were trends toward increased risk at age 50 (HR, 1.25; 95% CI, 0.98-1.60). Long sleep at age 60 and 70 was associated with heightened risk, but the confidence intervals were well outside statistical significance.
Twenty percent of participants had persistent short sleep over the course of follow-up, 37% had persistent normal sleep, and 7% had persistent long sleep. Seven percent of participants experienced a change from normal sleep to short sleep, 16% had a change from short sleep to normal sleep, and 13% had a change from normal sleep to long sleep.
Persistent short sleep between age 50 and 70 was associated with a 30% increased risk of dementia (HR, 1.30; 95% CI, 1.00-1.69). There were no statistically significant associations between dementia risk and any of the changing sleep pattern groups.
Dr. Sabia and Dr. Sexton have no relevant financial disclosures.
, according to a new analysis of data from the Whitehall II cohort study.
Previous work had identified links between short sleep duration and dementia risk, but few studies examined sleep habits long before onset of dementia. Those that did produced inconsistent results, according to Séverine Sabia, PhD, who is a research associate at Inserm (France) and the University College London.
“One potential reason for these inconstancies is the large range of ages of the study populations, and the small number of participants within each sleep duration group. The novelty of our study is to examine this association among almost 8,000 participants with a follow-up of 30 years, using repeated measures of sleep duration starting in midlife to consider sleep duration at specific ages,” Dr. Sabia said in an interview. She presented the research at the 2021 Alzheimer’s Association International Conference.
Those previous studies found a U-shaped association between sleep duration and dementia risk, with lowest risk associated with 7-8 hours of sleep, but greater risk for shorter and longer durations. However, because the studies had follow-up periods shorter than 10 years, they are at greater risk of reverse causation bias. Longer follow-up studies tended to have small sample sizes or to focus on older adults.
The longer follow-up in the current study makes for a more compelling case, said Claire Sexton, DPhil, director of Scientific Programs & Outreach for the Alzheimer’s Association. Observations of short or long sleep closer to the onset of symptoms could just be a warning sign of dementia. “But looking at age 50, age 60 ... if you’re seeing those relationships, then it’s less likely that it is just purely prodromal,” said Dr. Sexton. But it still doesn’t necessarily confirm causation. “It could also be a risk factor,” Dr. Sexton added.
Multifactorial risk
Dr. Sabia also noted that the magnitude of risk was similar to that seen with smoking or obesity, and many factors play a role in dementia risk. “Even if the risk of dementia was 30% higher in those with persistent short sleep duration, in absolute terms, the percentage of those with persistent short duration who developed dementia was 8%, and 6% in those with persistent sleep duration of 7 hours. Dementia is a multifactorial disease, which means that several factors are likely to influence its onset. Sleep duration is one of them, but if a person has poor sleep and does not manage to increase it, there are other important prevention measures. It is important to keep a healthy lifestyle and cardiometabolic measures in the normal range. All together it is likely to be beneficial for brain health in later life,” she said.
Dr. Sexton agreed. “With sleep we’re still trying to tease apart what aspect of sleep is important. Is it the sleep duration? Is it the quality of sleep? Is it certain sleep stages?” she said.
Regardless of sleep’s potential influence on dementia risk, both Dr. Sexton and Dr. Sabia noted the importance of sleep for general health. “These types of problems are very prevalent, so it’s good for people to be aware of them. And then if they notice any problems with their sleep, or any changes, to go and see their health care provider, and to be discussing them, and then to be investigating the cause, and to see whether changes in sleep hygiene and treatments for insomnia could address these sleep problems,” said Dr. Sexton.
Decades of data
During the Whitehall II study, researchers assessed average sleep duration (“How many hours of sleep do you have on an average weeknight?”) six times over 30 years of follow-up. Dr. Sabia’s group extracted self-reported sleep duration data at ages 50, 60, and 70. Short sleep duration was defined as fewer than 5 hours, or 6 hours. Normal sleep duration was defined as 7 hours. Long duration was defined as 8 hours or more.
A questioner during the Q&A period noted that this grouping is a little unusual. Many studies define 7-8 hours as normal. Dr. Sabia answered that they were unable to examine periods of 9 hours or more due to the nature of the data, and the lowest associated risk was found at 7 hours.
The researchers analyzed data from 7,959 participants (33.0% women). At age 50, compared with 7 hours of sleep, 6 or few hours of sleep was associated with a higher risk of dementia over the ensuing 25 years of follow-up (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.01-1.48). The same was true at age 60 (15 years of follow-up HR, 1.37; 95% CI, 1.10-1.72). There was a trend at age 70 (8 years follow-up; HR, 1.24; 95% CI, 0.98-1.57). For 8 or more hours of sleep, there were trends toward increased risk at age 50 (HR, 1.25; 95% CI, 0.98-1.60). Long sleep at age 60 and 70 was associated with heightened risk, but the confidence intervals were well outside statistical significance.
Twenty percent of participants had persistent short sleep over the course of follow-up, 37% had persistent normal sleep, and 7% had persistent long sleep. Seven percent of participants experienced a change from normal sleep to short sleep, 16% had a change from short sleep to normal sleep, and 13% had a change from normal sleep to long sleep.
Persistent short sleep between age 50 and 70 was associated with a 30% increased risk of dementia (HR, 1.30; 95% CI, 1.00-1.69). There were no statistically significant associations between dementia risk and any of the changing sleep pattern groups.
Dr. Sabia and Dr. Sexton have no relevant financial disclosures.
, according to a new analysis of data from the Whitehall II cohort study.
Previous work had identified links between short sleep duration and dementia risk, but few studies examined sleep habits long before onset of dementia. Those that did produced inconsistent results, according to Séverine Sabia, PhD, who is a research associate at Inserm (France) and the University College London.
“One potential reason for these inconstancies is the large range of ages of the study populations, and the small number of participants within each sleep duration group. The novelty of our study is to examine this association among almost 8,000 participants with a follow-up of 30 years, using repeated measures of sleep duration starting in midlife to consider sleep duration at specific ages,” Dr. Sabia said in an interview. She presented the research at the 2021 Alzheimer’s Association International Conference.
Those previous studies found a U-shaped association between sleep duration and dementia risk, with lowest risk associated with 7-8 hours of sleep, but greater risk for shorter and longer durations. However, because the studies had follow-up periods shorter than 10 years, they are at greater risk of reverse causation bias. Longer follow-up studies tended to have small sample sizes or to focus on older adults.
The longer follow-up in the current study makes for a more compelling case, said Claire Sexton, DPhil, director of Scientific Programs & Outreach for the Alzheimer’s Association. Observations of short or long sleep closer to the onset of symptoms could just be a warning sign of dementia. “But looking at age 50, age 60 ... if you’re seeing those relationships, then it’s less likely that it is just purely prodromal,” said Dr. Sexton. But it still doesn’t necessarily confirm causation. “It could also be a risk factor,” Dr. Sexton added.
Multifactorial risk
Dr. Sabia also noted that the magnitude of risk was similar to that seen with smoking or obesity, and many factors play a role in dementia risk. “Even if the risk of dementia was 30% higher in those with persistent short sleep duration, in absolute terms, the percentage of those with persistent short duration who developed dementia was 8%, and 6% in those with persistent sleep duration of 7 hours. Dementia is a multifactorial disease, which means that several factors are likely to influence its onset. Sleep duration is one of them, but if a person has poor sleep and does not manage to increase it, there are other important prevention measures. It is important to keep a healthy lifestyle and cardiometabolic measures in the normal range. All together it is likely to be beneficial for brain health in later life,” she said.
Dr. Sexton agreed. “With sleep we’re still trying to tease apart what aspect of sleep is important. Is it the sleep duration? Is it the quality of sleep? Is it certain sleep stages?” she said.
Regardless of sleep’s potential influence on dementia risk, both Dr. Sexton and Dr. Sabia noted the importance of sleep for general health. “These types of problems are very prevalent, so it’s good for people to be aware of them. And then if they notice any problems with their sleep, or any changes, to go and see their health care provider, and to be discussing them, and then to be investigating the cause, and to see whether changes in sleep hygiene and treatments for insomnia could address these sleep problems,” said Dr. Sexton.
Decades of data
During the Whitehall II study, researchers assessed average sleep duration (“How many hours of sleep do you have on an average weeknight?”) six times over 30 years of follow-up. Dr. Sabia’s group extracted self-reported sleep duration data at ages 50, 60, and 70. Short sleep duration was defined as fewer than 5 hours, or 6 hours. Normal sleep duration was defined as 7 hours. Long duration was defined as 8 hours or more.
A questioner during the Q&A period noted that this grouping is a little unusual. Many studies define 7-8 hours as normal. Dr. Sabia answered that they were unable to examine periods of 9 hours or more due to the nature of the data, and the lowest associated risk was found at 7 hours.
The researchers analyzed data from 7,959 participants (33.0% women). At age 50, compared with 7 hours of sleep, 6 or few hours of sleep was associated with a higher risk of dementia over the ensuing 25 years of follow-up (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.01-1.48). The same was true at age 60 (15 years of follow-up HR, 1.37; 95% CI, 1.10-1.72). There was a trend at age 70 (8 years follow-up; HR, 1.24; 95% CI, 0.98-1.57). For 8 or more hours of sleep, there were trends toward increased risk at age 50 (HR, 1.25; 95% CI, 0.98-1.60). Long sleep at age 60 and 70 was associated with heightened risk, but the confidence intervals were well outside statistical significance.
Twenty percent of participants had persistent short sleep over the course of follow-up, 37% had persistent normal sleep, and 7% had persistent long sleep. Seven percent of participants experienced a change from normal sleep to short sleep, 16% had a change from short sleep to normal sleep, and 13% had a change from normal sleep to long sleep.
Persistent short sleep between age 50 and 70 was associated with a 30% increased risk of dementia (HR, 1.30; 95% CI, 1.00-1.69). There were no statistically significant associations between dementia risk and any of the changing sleep pattern groups.
Dr. Sabia and Dr. Sexton have no relevant financial disclosures.
FROM AAIC 2021
Inflammatory diet is linked to dementia
according to a new analysis of longitudinal data from the Framingham Heart Study Offspring Cohort.
The lack of an association with Alzheimer’s disease was a surprise because amyloid-beta prompts microglia and astrocytes to release markers of systemic inflammation, according to Debora Melo van Lent, PhD, who is a postdoctoral fellow at the University of Texas Health San Antonio – Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases. “We expected to see a relationship between higher DII scores and an increased risk for incident Alzheimer’s disease,” said Dr. Melo van Lent, who presented the findings at the 2021 Alzheimer’s Association International Conference.
Dr. Melo van Lent added that the most likely explanation is that the study was underpowered to produce a positive association, and the team is conducting further study in a larger population.
A modifiable risk factor
The study is the first to look at all-cause dementia and Alzheimer’s disease dementia and their association with DII, Dr. Melo van Lent said.
“As diet is a modifiable risk factor, we can actually do something about it. If we take a closer look at five components of the DII which are most anti-inflammatory, these components are present in green leafy vegetables, vegetables, fruit, soy, whole grains, and green and black tea. Most of these components are included in the Mediterranean diet. When we look at the three most proinflammatory components, they are present in high caloric products; such as butter or margarine, pastries and sweets, fried snacks, and red or processed meat. These components are present in ‘Western diets,’ which are discouraged,” said Dr. Melo van Lent.
The researchers analyzed data from 1,486 participants who were free of dementia, stroke, or other neurologic diseases at baseline. They analyzed DII scores both in a continuous range and divided into quartiles, using the first quartile as a reference.
The mean age of participants was 69 years, and 53% were women. During follow-up, 11.3% developed AD dementia, and 14.8% developed non-AD dementia.
In the continuous model, DII was associated with increased risk of all-cause dementia after adjusting for age, sex, APOE E4 status, body mass index, smoking, physical activity index score, total energy intake, lipid-lowering medications, and total cholesterol to HDL cholesterol ratio (hazard ratio, 1.18; P =.001). In the quartile analysis, after adjustments, compared with quartile 1, there was an increased risk of all-cause dementia for those in quartile 3 (HR, 1.69; P =.020) and quartile 4 (HR, 1.84; P =.013).
In the continuous analysis, after adjustments, there was an association between DII score and Alzheimer’s dementia (HR, 1.15; P =.020). In the quartile analysis, no associations were significant, though there was a trend of quartile 4 versus quartile 1 (HR, 1.65; P =.077).
The researchers found no significant interactions between higher DII scores and sex, the APOE E4 allele, or physical activity with respect to all-cause dementia or Alzheimer’s dementia.
Intertwined variables
The results were interesting, but cause and effect relationships can be difficult to tease out from such a study, according to Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, who was asked to comment on the study. Dr. Sexton noted that individuals who eat well are more likely to have energy to exercise, which could in turn help them to sleep better, and all of those factors could be involved in reducing dementia risk. “They’re all kind of intertwined. So in this study, they were taking into account physical activity, but they can’t take into account every single variable. It’s important for them to be followed up by randomized control trials.”
Dr. Sexton also referenced the U.S. Pointer study being conducted by the Alzheimer’s Association, which is examining various interventions related to diet, physical activity, and cognitive stimulation. “Whether intervening and improving people’s health behaviors then goes on to reduce their risk for dementia is a key question. We still need more results from studies to be reporting out before we get definitive answers,” she said.
The study was funded by the ASPEN Rhoads Research Foundation. Dr. Melo van Lent and Dr. Sexton have no relevant financial disclosures.
according to a new analysis of longitudinal data from the Framingham Heart Study Offspring Cohort.
The lack of an association with Alzheimer’s disease was a surprise because amyloid-beta prompts microglia and astrocytes to release markers of systemic inflammation, according to Debora Melo van Lent, PhD, who is a postdoctoral fellow at the University of Texas Health San Antonio – Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases. “We expected to see a relationship between higher DII scores and an increased risk for incident Alzheimer’s disease,” said Dr. Melo van Lent, who presented the findings at the 2021 Alzheimer’s Association International Conference.
Dr. Melo van Lent added that the most likely explanation is that the study was underpowered to produce a positive association, and the team is conducting further study in a larger population.
A modifiable risk factor
The study is the first to look at all-cause dementia and Alzheimer’s disease dementia and their association with DII, Dr. Melo van Lent said.
“As diet is a modifiable risk factor, we can actually do something about it. If we take a closer look at five components of the DII which are most anti-inflammatory, these components are present in green leafy vegetables, vegetables, fruit, soy, whole grains, and green and black tea. Most of these components are included in the Mediterranean diet. When we look at the three most proinflammatory components, they are present in high caloric products; such as butter or margarine, pastries and sweets, fried snacks, and red or processed meat. These components are present in ‘Western diets,’ which are discouraged,” said Dr. Melo van Lent.
The researchers analyzed data from 1,486 participants who were free of dementia, stroke, or other neurologic diseases at baseline. They analyzed DII scores both in a continuous range and divided into quartiles, using the first quartile as a reference.
The mean age of participants was 69 years, and 53% were women. During follow-up, 11.3% developed AD dementia, and 14.8% developed non-AD dementia.
In the continuous model, DII was associated with increased risk of all-cause dementia after adjusting for age, sex, APOE E4 status, body mass index, smoking, physical activity index score, total energy intake, lipid-lowering medications, and total cholesterol to HDL cholesterol ratio (hazard ratio, 1.18; P =.001). In the quartile analysis, after adjustments, compared with quartile 1, there was an increased risk of all-cause dementia for those in quartile 3 (HR, 1.69; P =.020) and quartile 4 (HR, 1.84; P =.013).
In the continuous analysis, after adjustments, there was an association between DII score and Alzheimer’s dementia (HR, 1.15; P =.020). In the quartile analysis, no associations were significant, though there was a trend of quartile 4 versus quartile 1 (HR, 1.65; P =.077).
The researchers found no significant interactions between higher DII scores and sex, the APOE E4 allele, or physical activity with respect to all-cause dementia or Alzheimer’s dementia.
Intertwined variables
The results were interesting, but cause and effect relationships can be difficult to tease out from such a study, according to Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, who was asked to comment on the study. Dr. Sexton noted that individuals who eat well are more likely to have energy to exercise, which could in turn help them to sleep better, and all of those factors could be involved in reducing dementia risk. “They’re all kind of intertwined. So in this study, they were taking into account physical activity, but they can’t take into account every single variable. It’s important for them to be followed up by randomized control trials.”
Dr. Sexton also referenced the U.S. Pointer study being conducted by the Alzheimer’s Association, which is examining various interventions related to diet, physical activity, and cognitive stimulation. “Whether intervening and improving people’s health behaviors then goes on to reduce their risk for dementia is a key question. We still need more results from studies to be reporting out before we get definitive answers,” she said.
The study was funded by the ASPEN Rhoads Research Foundation. Dr. Melo van Lent and Dr. Sexton have no relevant financial disclosures.
according to a new analysis of longitudinal data from the Framingham Heart Study Offspring Cohort.
The lack of an association with Alzheimer’s disease was a surprise because amyloid-beta prompts microglia and astrocytes to release markers of systemic inflammation, according to Debora Melo van Lent, PhD, who is a postdoctoral fellow at the University of Texas Health San Antonio – Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases. “We expected to see a relationship between higher DII scores and an increased risk for incident Alzheimer’s disease,” said Dr. Melo van Lent, who presented the findings at the 2021 Alzheimer’s Association International Conference.
Dr. Melo van Lent added that the most likely explanation is that the study was underpowered to produce a positive association, and the team is conducting further study in a larger population.
A modifiable risk factor
The study is the first to look at all-cause dementia and Alzheimer’s disease dementia and their association with DII, Dr. Melo van Lent said.
“As diet is a modifiable risk factor, we can actually do something about it. If we take a closer look at five components of the DII which are most anti-inflammatory, these components are present in green leafy vegetables, vegetables, fruit, soy, whole grains, and green and black tea. Most of these components are included in the Mediterranean diet. When we look at the three most proinflammatory components, they are present in high caloric products; such as butter or margarine, pastries and sweets, fried snacks, and red or processed meat. These components are present in ‘Western diets,’ which are discouraged,” said Dr. Melo van Lent.
The researchers analyzed data from 1,486 participants who were free of dementia, stroke, or other neurologic diseases at baseline. They analyzed DII scores both in a continuous range and divided into quartiles, using the first quartile as a reference.
The mean age of participants was 69 years, and 53% were women. During follow-up, 11.3% developed AD dementia, and 14.8% developed non-AD dementia.
In the continuous model, DII was associated with increased risk of all-cause dementia after adjusting for age, sex, APOE E4 status, body mass index, smoking, physical activity index score, total energy intake, lipid-lowering medications, and total cholesterol to HDL cholesterol ratio (hazard ratio, 1.18; P =.001). In the quartile analysis, after adjustments, compared with quartile 1, there was an increased risk of all-cause dementia for those in quartile 3 (HR, 1.69; P =.020) and quartile 4 (HR, 1.84; P =.013).
In the continuous analysis, after adjustments, there was an association between DII score and Alzheimer’s dementia (HR, 1.15; P =.020). In the quartile analysis, no associations were significant, though there was a trend of quartile 4 versus quartile 1 (HR, 1.65; P =.077).
The researchers found no significant interactions between higher DII scores and sex, the APOE E4 allele, or physical activity with respect to all-cause dementia or Alzheimer’s dementia.
Intertwined variables
The results were interesting, but cause and effect relationships can be difficult to tease out from such a study, according to Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, who was asked to comment on the study. Dr. Sexton noted that individuals who eat well are more likely to have energy to exercise, which could in turn help them to sleep better, and all of those factors could be involved in reducing dementia risk. “They’re all kind of intertwined. So in this study, they were taking into account physical activity, but they can’t take into account every single variable. It’s important for them to be followed up by randomized control trials.”
Dr. Sexton also referenced the U.S. Pointer study being conducted by the Alzheimer’s Association, which is examining various interventions related to diet, physical activity, and cognitive stimulation. “Whether intervening and improving people’s health behaviors then goes on to reduce their risk for dementia is a key question. We still need more results from studies to be reporting out before we get definitive answers,” she said.
The study was funded by the ASPEN Rhoads Research Foundation. Dr. Melo van Lent and Dr. Sexton have no relevant financial disclosures.
FROM AAIC 2021
Alzheimer’s disease plasma biomarkers may be nuanced
Such tests are likely to be widely available in the near future.
But work remains to be done to translate findings from academic studies to the more general population. A key consideration is that plasma levels of these biomarkers could be affected by other conditions, which could in turn skew test results, according to Michelle Mielke, PhD, who spoke on the topic at the 2021 Alzheimer’s Association International Conference.
“The markers, which we’ve published on as well, look really promising. But they have primarily been looked at in more specialty clinics or memory clinics, and have not been examined in the general community. The goal of this presentation was really just to take a look at this in the community, in older individuals that have multiple comorbidities, and to understand what factors might affect the levels of these markers. Because as we do go forward and develop cut points, we are going to have to consider these aspects,” said Dr. Mielke in an interview. She is a professor of epidemiology and neurology at the Mayo Clinic in Rochester, Minn.
Case in point
To illustrate the point, Dr. Mielke presented data from her group, which analyzed P-tau 181 and P-tau 217 data from 1,329 Mayo clinic patients. Of that total, 1,161 were cognitively unimpaired (CU), 153 had mild cognitive impairment (MCI), and 15 had dementia. The median age was 67, 55% were male, and 26% had the APOE e4 allele.
After adjustment for age and sex, there were statistically significantly elevated levels of both biomarkers among patients who had tested positive for amyloid and patients who had had a stroke or myocardial infarction, and in the presence of chronic kidney disease (CKD). There also was a trend towards an increase of biomarker levels with increasing body mass index. The differences remained even after the analysis was restricted to individuals who were amyloid negative.
The researchers then looked more closely at the impact of CKD, stroke, and MI on P-tau cut points and the ability to predict abnormal amyloid positron emission tomography (PET) scans. They defined an abnormal range as 1.96 standard deviation units beyond the mean among amyloid-negative individuals who are cognitively impaired. They excluded subjects with those risk factors and then established new cut points in the absence of the factors. The approach led to a significant change for the cutoff of P-tau 181 values, from 1.57 pg/mL or greater for individuals without stroke, MI, or CKD, and 1.75 pg/mL or greater for individuals with one such factor. There was little difference in the cutoff value for P-tau 217, from 0.25 pg/mL to 0.26 pg/mL.
Among people without a history of stroke, MI, or CKD, a P-tau 181 cutoff of 1.57 pg/mL or greater had an area under the receiving operating characteristic (AUROC) value of 0.717 (95% confidence interval, 0.691-0.744), compared with an AUROC of 0.687 (95% CI, 0.662-0.712) at a cutoff of 1.75 pg/mL or greater among people with those conditions. For P-tau 217, the values were 0.737 pg/mL (95% CI, 0.712-0.762) and 0.724 pg/mL (95% CI, 0.699-0.748), respectively.
“The sensitivity was better when they excluded those individuals with these conditions. Specificity was slightly, but not significantly, lower,” said Dr. Mielke during her talk.
Other considerations
Dr. Mielke added that it will be important to account for these and other factors when applying biomarkers in community settings, but they should also be considered in the context of health care disparities. Stroke, MI, and CKD are more common in African Americans, for example, suggesting that there could be racial differences in biomarker levels, though she said the difference in biomarker levels would be more likely attributable to the underlying comorbidities than race per se. “As shown, these factors can affect the consideration of an accuracy of cut points for clinical use. So I think future discussions will be needed as to how best to determine the cut points, and how to base them off of (different) populations,” said Dr. Mielke.
These sorts of refinements are important, according to Christopher Weber, PhD, who was asked for comment. “We have learned the importance of an early and accurate diagnosis. The blood test is a biomarker that does detect the hallmarks of Alzheimer’s disease sometimes up to decades before symptoms even appear,” said Dr. Weber, who is director of Global Science Initiatives at the Alzheimer’s Association.
But “there’s a lot more that we need to learn regarding when exactly to use them, who they’re appropriate for. And I think validation is the key to these blood biomarkers,” Dr. Weber added.
Dr. Mielke has been a consultant with the Brain Protection Company and Biogen. Dr. Weber has no relevant financial disclosures.
Such tests are likely to be widely available in the near future.
But work remains to be done to translate findings from academic studies to the more general population. A key consideration is that plasma levels of these biomarkers could be affected by other conditions, which could in turn skew test results, according to Michelle Mielke, PhD, who spoke on the topic at the 2021 Alzheimer’s Association International Conference.
“The markers, which we’ve published on as well, look really promising. But they have primarily been looked at in more specialty clinics or memory clinics, and have not been examined in the general community. The goal of this presentation was really just to take a look at this in the community, in older individuals that have multiple comorbidities, and to understand what factors might affect the levels of these markers. Because as we do go forward and develop cut points, we are going to have to consider these aspects,” said Dr. Mielke in an interview. She is a professor of epidemiology and neurology at the Mayo Clinic in Rochester, Minn.
Case in point
To illustrate the point, Dr. Mielke presented data from her group, which analyzed P-tau 181 and P-tau 217 data from 1,329 Mayo clinic patients. Of that total, 1,161 were cognitively unimpaired (CU), 153 had mild cognitive impairment (MCI), and 15 had dementia. The median age was 67, 55% were male, and 26% had the APOE e4 allele.
After adjustment for age and sex, there were statistically significantly elevated levels of both biomarkers among patients who had tested positive for amyloid and patients who had had a stroke or myocardial infarction, and in the presence of chronic kidney disease (CKD). There also was a trend towards an increase of biomarker levels with increasing body mass index. The differences remained even after the analysis was restricted to individuals who were amyloid negative.
The researchers then looked more closely at the impact of CKD, stroke, and MI on P-tau cut points and the ability to predict abnormal amyloid positron emission tomography (PET) scans. They defined an abnormal range as 1.96 standard deviation units beyond the mean among amyloid-negative individuals who are cognitively impaired. They excluded subjects with those risk factors and then established new cut points in the absence of the factors. The approach led to a significant change for the cutoff of P-tau 181 values, from 1.57 pg/mL or greater for individuals without stroke, MI, or CKD, and 1.75 pg/mL or greater for individuals with one such factor. There was little difference in the cutoff value for P-tau 217, from 0.25 pg/mL to 0.26 pg/mL.
Among people without a history of stroke, MI, or CKD, a P-tau 181 cutoff of 1.57 pg/mL or greater had an area under the receiving operating characteristic (AUROC) value of 0.717 (95% confidence interval, 0.691-0.744), compared with an AUROC of 0.687 (95% CI, 0.662-0.712) at a cutoff of 1.75 pg/mL or greater among people with those conditions. For P-tau 217, the values were 0.737 pg/mL (95% CI, 0.712-0.762) and 0.724 pg/mL (95% CI, 0.699-0.748), respectively.
“The sensitivity was better when they excluded those individuals with these conditions. Specificity was slightly, but not significantly, lower,” said Dr. Mielke during her talk.
Other considerations
Dr. Mielke added that it will be important to account for these and other factors when applying biomarkers in community settings, but they should also be considered in the context of health care disparities. Stroke, MI, and CKD are more common in African Americans, for example, suggesting that there could be racial differences in biomarker levels, though she said the difference in biomarker levels would be more likely attributable to the underlying comorbidities than race per se. “As shown, these factors can affect the consideration of an accuracy of cut points for clinical use. So I think future discussions will be needed as to how best to determine the cut points, and how to base them off of (different) populations,” said Dr. Mielke.
These sorts of refinements are important, according to Christopher Weber, PhD, who was asked for comment. “We have learned the importance of an early and accurate diagnosis. The blood test is a biomarker that does detect the hallmarks of Alzheimer’s disease sometimes up to decades before symptoms even appear,” said Dr. Weber, who is director of Global Science Initiatives at the Alzheimer’s Association.
But “there’s a lot more that we need to learn regarding when exactly to use them, who they’re appropriate for. And I think validation is the key to these blood biomarkers,” Dr. Weber added.
Dr. Mielke has been a consultant with the Brain Protection Company and Biogen. Dr. Weber has no relevant financial disclosures.
Such tests are likely to be widely available in the near future.
But work remains to be done to translate findings from academic studies to the more general population. A key consideration is that plasma levels of these biomarkers could be affected by other conditions, which could in turn skew test results, according to Michelle Mielke, PhD, who spoke on the topic at the 2021 Alzheimer’s Association International Conference.
“The markers, which we’ve published on as well, look really promising. But they have primarily been looked at in more specialty clinics or memory clinics, and have not been examined in the general community. The goal of this presentation was really just to take a look at this in the community, in older individuals that have multiple comorbidities, and to understand what factors might affect the levels of these markers. Because as we do go forward and develop cut points, we are going to have to consider these aspects,” said Dr. Mielke in an interview. She is a professor of epidemiology and neurology at the Mayo Clinic in Rochester, Minn.
Case in point
To illustrate the point, Dr. Mielke presented data from her group, which analyzed P-tau 181 and P-tau 217 data from 1,329 Mayo clinic patients. Of that total, 1,161 were cognitively unimpaired (CU), 153 had mild cognitive impairment (MCI), and 15 had dementia. The median age was 67, 55% were male, and 26% had the APOE e4 allele.
After adjustment for age and sex, there were statistically significantly elevated levels of both biomarkers among patients who had tested positive for amyloid and patients who had had a stroke or myocardial infarction, and in the presence of chronic kidney disease (CKD). There also was a trend towards an increase of biomarker levels with increasing body mass index. The differences remained even after the analysis was restricted to individuals who were amyloid negative.
The researchers then looked more closely at the impact of CKD, stroke, and MI on P-tau cut points and the ability to predict abnormal amyloid positron emission tomography (PET) scans. They defined an abnormal range as 1.96 standard deviation units beyond the mean among amyloid-negative individuals who are cognitively impaired. They excluded subjects with those risk factors and then established new cut points in the absence of the factors. The approach led to a significant change for the cutoff of P-tau 181 values, from 1.57 pg/mL or greater for individuals without stroke, MI, or CKD, and 1.75 pg/mL or greater for individuals with one such factor. There was little difference in the cutoff value for P-tau 217, from 0.25 pg/mL to 0.26 pg/mL.
Among people without a history of stroke, MI, or CKD, a P-tau 181 cutoff of 1.57 pg/mL or greater had an area under the receiving operating characteristic (AUROC) value of 0.717 (95% confidence interval, 0.691-0.744), compared with an AUROC of 0.687 (95% CI, 0.662-0.712) at a cutoff of 1.75 pg/mL or greater among people with those conditions. For P-tau 217, the values were 0.737 pg/mL (95% CI, 0.712-0.762) and 0.724 pg/mL (95% CI, 0.699-0.748), respectively.
“The sensitivity was better when they excluded those individuals with these conditions. Specificity was slightly, but not significantly, lower,” said Dr. Mielke during her talk.
Other considerations
Dr. Mielke added that it will be important to account for these and other factors when applying biomarkers in community settings, but they should also be considered in the context of health care disparities. Stroke, MI, and CKD are more common in African Americans, for example, suggesting that there could be racial differences in biomarker levels, though she said the difference in biomarker levels would be more likely attributable to the underlying comorbidities than race per se. “As shown, these factors can affect the consideration of an accuracy of cut points for clinical use. So I think future discussions will be needed as to how best to determine the cut points, and how to base them off of (different) populations,” said Dr. Mielke.
These sorts of refinements are important, according to Christopher Weber, PhD, who was asked for comment. “We have learned the importance of an early and accurate diagnosis. The blood test is a biomarker that does detect the hallmarks of Alzheimer’s disease sometimes up to decades before symptoms even appear,” said Dr. Weber, who is director of Global Science Initiatives at the Alzheimer’s Association.
But “there’s a lot more that we need to learn regarding when exactly to use them, who they’re appropriate for. And I think validation is the key to these blood biomarkers,” Dr. Weber added.
Dr. Mielke has been a consultant with the Brain Protection Company and Biogen. Dr. Weber has no relevant financial disclosures.
FROM AAIC 2021
Remote cognitive assessments get positive mark
That is the message behind numerous publications in recent years, and the COVID-19 pandemic has accelerated that trend.
“The publications have just skyrocketed since 2018, but I think there are still some additional tests that we need to validate using this medium of assessment. Also, I think we need to kind of put on our thinking caps as a field and think outside the box. What novel tests can we develop that will capitalize upon the telehealth environment – interactive tests that are monitoring [the individuals’] performance in real time and giving the examiner feedback, things like that,” said Munro Cullum, PhD, in an interview. Dr. Cullum spoke on the topic at the 2021 Alzheimer’s Association International Conference.
Still, challenges remain, especially factors in the home environment that can adversely affect testing. “Some of our tests are a question-answer, pencil-paper sort of tests that can be well suited to a telemedicine environment, [but] other tests don’t translate as well. So we still have a ways to go to kind of get our test to the next generation when being administered during this type of assessment. But a lot of the verbal tests work extremely well,” said Dr. Cullum, who is a professor of psychiatry at the University of Texas Southwestern Medical Center, Dallas.
Preliminary evidence of equivalence
Some years ago, Dr. Cullum was interested in getting a better understanding of what existing tests could best be performed remotely, and what populations could most benefit from remote assessments. Existing studies were generally supportive of remote testing, but varied significantly in their methodology and design. He went on to publish a study in 2014 showing equivalency of existing tests in the in-person and remote environment, and that helped pave the way for a wave of more recent studies that seem to confirm equivalence of in-person methods.
“If you look at the literature overall, there is a nice, growing body of evidence suggesting support for a host of neuropsychological test instruments. For the most part, almost all have shown good reliability across test conditions,” Dr. Cullum said during the talk.
He said that he is often asked if different test norms will be required for remote tests, but that doesn’t seem to be a concern. “It looks like the regular old neuropsych test norms should serve as well in this remote assessment environment. Although as within hospital testing of patients, conservative use of norms is always an order. They are interpretive guidelines,” he added.
One concern is potential threats to validity within the home environment. He posted an image of a woman at home, taking a remote cognitive test. The desk she sat at overlooked a wooded scene, and had a sewing machine on it. A small dog lay in her lap. “So assessing the home environment, ensuring that it is as close to a clinical standard setting as possible, is certainly advised,” said Dr. Cullum.
Although much progress has been made in studying existing tests in a telemedicine environment, many commonly used tests still haven’t been studied. The risk of intrusions and distractions, and even connectivity issues, can be limiting factors. Some tests may be ineligible for remote use due to copyright issues that might prevent required materials from being displayed online. For those reasons and others, not all individuals are suited for a remote test.
Finally, remote tests should be viewed with healthy skepticism. “In doing clinical evaluations this way, we have to be extra careful to not mis- or overinterpret the findings in case there were any distractions or glitches in the examination that came up during the test,” said Dr. Cullum.
Looking toward the future
Moving forward, Dr. Cullum called for more research to design new tests to exploit the telehealth format. “I think this is a really important opportunity for new test development in neuropsychology with increasing incorporation of computerized measures and integration with more cognitive neuroscience and clinical neuropsychology principles.”
He also suggested that remote testing could be combined with neuroimaging, neuromodulation, and even portable magnetoencephalography. “These opportunities for research can enhance compliance, enhance large-scale studies to allow for the inclusion of brief cognitive outcome metrics that might not have other otherwise been [possible],” said Dr. Cullum.
During the question-and-answer session, someone asked if the momentum towards telehealth will continue once the COVID-19 pandemic recedes. “We believe telehealth is here to stay, or at least I do,” said session moderator Allison Lindauer, PhD, who was asked to comment. Dr. Lindauer is an associate professor at the Layton Aging and Alzheimer’s Disease Center in Portland, Ore.
Dr. Lindauer has also conducted studies on telehealth-delivered assessments and also found encouraging results. “Work like this says, we have confidence in our work, we can believe that what we’re assessing and what we’re doing – if we did it face to face, we would get similar results,” Dr. Lindauer said in an interview.
Plenty of challenges remain, and the most important is widely available broadband internet, said Dr. Lindauer. “We need a huge push to get broadband everywhere. Granted, you’re going to have people that don’t want to use the computer, or they’re nervous about doing it online. But in my experience, most people with enough coaching can do it and are fine with it.”
Dr. Cullum and Dr. Lindauer have no relevant financial disclosures.
That is the message behind numerous publications in recent years, and the COVID-19 pandemic has accelerated that trend.
“The publications have just skyrocketed since 2018, but I think there are still some additional tests that we need to validate using this medium of assessment. Also, I think we need to kind of put on our thinking caps as a field and think outside the box. What novel tests can we develop that will capitalize upon the telehealth environment – interactive tests that are monitoring [the individuals’] performance in real time and giving the examiner feedback, things like that,” said Munro Cullum, PhD, in an interview. Dr. Cullum spoke on the topic at the 2021 Alzheimer’s Association International Conference.
Still, challenges remain, especially factors in the home environment that can adversely affect testing. “Some of our tests are a question-answer, pencil-paper sort of tests that can be well suited to a telemedicine environment, [but] other tests don’t translate as well. So we still have a ways to go to kind of get our test to the next generation when being administered during this type of assessment. But a lot of the verbal tests work extremely well,” said Dr. Cullum, who is a professor of psychiatry at the University of Texas Southwestern Medical Center, Dallas.
Preliminary evidence of equivalence
Some years ago, Dr. Cullum was interested in getting a better understanding of what existing tests could best be performed remotely, and what populations could most benefit from remote assessments. Existing studies were generally supportive of remote testing, but varied significantly in their methodology and design. He went on to publish a study in 2014 showing equivalency of existing tests in the in-person and remote environment, and that helped pave the way for a wave of more recent studies that seem to confirm equivalence of in-person methods.
“If you look at the literature overall, there is a nice, growing body of evidence suggesting support for a host of neuropsychological test instruments. For the most part, almost all have shown good reliability across test conditions,” Dr. Cullum said during the talk.
He said that he is often asked if different test norms will be required for remote tests, but that doesn’t seem to be a concern. “It looks like the regular old neuropsych test norms should serve as well in this remote assessment environment. Although as within hospital testing of patients, conservative use of norms is always an order. They are interpretive guidelines,” he added.
One concern is potential threats to validity within the home environment. He posted an image of a woman at home, taking a remote cognitive test. The desk she sat at overlooked a wooded scene, and had a sewing machine on it. A small dog lay in her lap. “So assessing the home environment, ensuring that it is as close to a clinical standard setting as possible, is certainly advised,” said Dr. Cullum.
Although much progress has been made in studying existing tests in a telemedicine environment, many commonly used tests still haven’t been studied. The risk of intrusions and distractions, and even connectivity issues, can be limiting factors. Some tests may be ineligible for remote use due to copyright issues that might prevent required materials from being displayed online. For those reasons and others, not all individuals are suited for a remote test.
Finally, remote tests should be viewed with healthy skepticism. “In doing clinical evaluations this way, we have to be extra careful to not mis- or overinterpret the findings in case there were any distractions or glitches in the examination that came up during the test,” said Dr. Cullum.
Looking toward the future
Moving forward, Dr. Cullum called for more research to design new tests to exploit the telehealth format. “I think this is a really important opportunity for new test development in neuropsychology with increasing incorporation of computerized measures and integration with more cognitive neuroscience and clinical neuropsychology principles.”
He also suggested that remote testing could be combined with neuroimaging, neuromodulation, and even portable magnetoencephalography. “These opportunities for research can enhance compliance, enhance large-scale studies to allow for the inclusion of brief cognitive outcome metrics that might not have other otherwise been [possible],” said Dr. Cullum.
During the question-and-answer session, someone asked if the momentum towards telehealth will continue once the COVID-19 pandemic recedes. “We believe telehealth is here to stay, or at least I do,” said session moderator Allison Lindauer, PhD, who was asked to comment. Dr. Lindauer is an associate professor at the Layton Aging and Alzheimer’s Disease Center in Portland, Ore.
Dr. Lindauer has also conducted studies on telehealth-delivered assessments and also found encouraging results. “Work like this says, we have confidence in our work, we can believe that what we’re assessing and what we’re doing – if we did it face to face, we would get similar results,” Dr. Lindauer said in an interview.
Plenty of challenges remain, and the most important is widely available broadband internet, said Dr. Lindauer. “We need a huge push to get broadband everywhere. Granted, you’re going to have people that don’t want to use the computer, or they’re nervous about doing it online. But in my experience, most people with enough coaching can do it and are fine with it.”
Dr. Cullum and Dr. Lindauer have no relevant financial disclosures.
That is the message behind numerous publications in recent years, and the COVID-19 pandemic has accelerated that trend.
“The publications have just skyrocketed since 2018, but I think there are still some additional tests that we need to validate using this medium of assessment. Also, I think we need to kind of put on our thinking caps as a field and think outside the box. What novel tests can we develop that will capitalize upon the telehealth environment – interactive tests that are monitoring [the individuals’] performance in real time and giving the examiner feedback, things like that,” said Munro Cullum, PhD, in an interview. Dr. Cullum spoke on the topic at the 2021 Alzheimer’s Association International Conference.
Still, challenges remain, especially factors in the home environment that can adversely affect testing. “Some of our tests are a question-answer, pencil-paper sort of tests that can be well suited to a telemedicine environment, [but] other tests don’t translate as well. So we still have a ways to go to kind of get our test to the next generation when being administered during this type of assessment. But a lot of the verbal tests work extremely well,” said Dr. Cullum, who is a professor of psychiatry at the University of Texas Southwestern Medical Center, Dallas.
Preliminary evidence of equivalence
Some years ago, Dr. Cullum was interested in getting a better understanding of what existing tests could best be performed remotely, and what populations could most benefit from remote assessments. Existing studies were generally supportive of remote testing, but varied significantly in their methodology and design. He went on to publish a study in 2014 showing equivalency of existing tests in the in-person and remote environment, and that helped pave the way for a wave of more recent studies that seem to confirm equivalence of in-person methods.
“If you look at the literature overall, there is a nice, growing body of evidence suggesting support for a host of neuropsychological test instruments. For the most part, almost all have shown good reliability across test conditions,” Dr. Cullum said during the talk.
He said that he is often asked if different test norms will be required for remote tests, but that doesn’t seem to be a concern. “It looks like the regular old neuropsych test norms should serve as well in this remote assessment environment. Although as within hospital testing of patients, conservative use of norms is always an order. They are interpretive guidelines,” he added.
One concern is potential threats to validity within the home environment. He posted an image of a woman at home, taking a remote cognitive test. The desk she sat at overlooked a wooded scene, and had a sewing machine on it. A small dog lay in her lap. “So assessing the home environment, ensuring that it is as close to a clinical standard setting as possible, is certainly advised,” said Dr. Cullum.
Although much progress has been made in studying existing tests in a telemedicine environment, many commonly used tests still haven’t been studied. The risk of intrusions and distractions, and even connectivity issues, can be limiting factors. Some tests may be ineligible for remote use due to copyright issues that might prevent required materials from being displayed online. For those reasons and others, not all individuals are suited for a remote test.
Finally, remote tests should be viewed with healthy skepticism. “In doing clinical evaluations this way, we have to be extra careful to not mis- or overinterpret the findings in case there were any distractions or glitches in the examination that came up during the test,” said Dr. Cullum.
Looking toward the future
Moving forward, Dr. Cullum called for more research to design new tests to exploit the telehealth format. “I think this is a really important opportunity for new test development in neuropsychology with increasing incorporation of computerized measures and integration with more cognitive neuroscience and clinical neuropsychology principles.”
He also suggested that remote testing could be combined with neuroimaging, neuromodulation, and even portable magnetoencephalography. “These opportunities for research can enhance compliance, enhance large-scale studies to allow for the inclusion of brief cognitive outcome metrics that might not have other otherwise been [possible],” said Dr. Cullum.
During the question-and-answer session, someone asked if the momentum towards telehealth will continue once the COVID-19 pandemic recedes. “We believe telehealth is here to stay, or at least I do,” said session moderator Allison Lindauer, PhD, who was asked to comment. Dr. Lindauer is an associate professor at the Layton Aging and Alzheimer’s Disease Center in Portland, Ore.
Dr. Lindauer has also conducted studies on telehealth-delivered assessments and also found encouraging results. “Work like this says, we have confidence in our work, we can believe that what we’re assessing and what we’re doing – if we did it face to face, we would get similar results,” Dr. Lindauer said in an interview.
Plenty of challenges remain, and the most important is widely available broadband internet, said Dr. Lindauer. “We need a huge push to get broadband everywhere. Granted, you’re going to have people that don’t want to use the computer, or they’re nervous about doing it online. But in my experience, most people with enough coaching can do it and are fine with it.”
Dr. Cullum and Dr. Lindauer have no relevant financial disclosures.
FROM AAIC 2021
Dementia caregivers benefit from telehealth support
The program combines information, education, and skills training to help participants overcome specific challenges.
“It focuses on individualized problem solving and is tailored to the needs of the person. The focus is not just on educating caregivers, but working on strategies to maintain independence in the person with dementia and support them to remain active and engaged,” said Kate Laver, PhD, who presented the study at the annual meeting of the Alzheimer’s Association International Conference. Dr. Laver is an associate professor in the College of Medicine and Public Health at Flinders University in Adelaide, South Australia.
The program is called Care of Persons with Dementia in Their Environments (COPE), and has previously been demonstrated to improve outcomes when conducted through in-person home visits. Over a maximum of ten sessions in 4 months, COPE employs occupational therapists and individuals with nursing skills to identify environmental stressors that can be modified to reduce sensory, physical, and cognitive demands. It also looks for comorbidities in the person with dementia that could be contributing to poor functioning. The goal of COPE is to encourage the person with dementia to reengage in daily activities, and to reduce caregiver burden as a result.
In a 2020 study, Dr. Laver and colleagues showed that COPE is noninferior when delivered by telehealth compared with in-person delivery. They randomized 63 caregiver-patient dyads to telehealth or home visit delivery of the COPE program. Sixty percent of the persons with dementia were male, and the mean caregiver time was 32 months.
Similar improvements in outcomes were seen in both groups, with no statistically significant differences for the primary outcome of change in Caregiver Mastery Index score at 4 months (mean difference, 0.09; 95% confidence interval, –1.26 to 1.45). Similar changes were also seen in the Perceived Change Scale, which is a 13-item caregiver questionnaire that covers day-to-day care challenges, including feeling overwhelmed or upset, sleeping patterns, and availability of personal time.
Not surprisingly, telehealth implementation led to reduced mean travel time (77.2 minutes vs. 255.9 minutes; P < .0001). The face-to-face time was shorter in the telehealth group (308 vs. 337 minutes), though the difference was not statistically significant. Dr. Laver noted that the consent rate was high at 75%, but there were some missed sessions.
Lessons learned
During the presentation, Dr. Laver emphasized some lessons learned from conversion to a telehealth model. These included providing a tablet and stand on loan, a user guide with pictures, and an initial on-site training session. The first two sessions were conducted on site to do an in-person demonstration and to assess the participants and the home environment.
She noted that it was important to have an IT support person on call to help participants use the provided tablet if needed, though this was rarely used.
“Although few people (at the time) had their own devices, they were able to quickly master videoconferencing. We felt that it was important to ensure that the first couple of consultations were in person – this enabled the therapist to develop rapport, practice use of videoconferencing, and get a good idea of the person’s environment and relationship with the person with dementia,” said Dr. Laver.
She noted that telehealth can be more efficient, and even preferred, during times like the COVID-19 pandemic, as well as in rural settings. But home visits will always be needed. “They are important for developing rapport and enabling a comprehensive assessment of the person with dementia, relationships, and environment. They are also preferred by some caregivers,” said Dr. Laver.
The demonstration of equivalence to in-person delivery was welcome, said Ingo Kilimann, MD, who comoderated the session where Dr. Laver presented. “We have to bring help to the families where they are, and not just tell them where they can get the help, because some people are just not able to actually come to some specialists’ centers. So it’s very important information that it does work,” said Dr. Kilimann, who is a dementia neurologist and head of the memory clinic at the The German Center for Neurodegenerative Diseases in Bonn.
He added that mixing of on-site and remote sessions is a good model. “I think that is the way to be most effective – to have someone in person at the person with dementia’s house, and then have online support for the rest of the time, and then it can be as successful as a total in-person intervention,” said Dr. Kilimann.
Dr. Laver had no relevant financial disclosures.
The program combines information, education, and skills training to help participants overcome specific challenges.
“It focuses on individualized problem solving and is tailored to the needs of the person. The focus is not just on educating caregivers, but working on strategies to maintain independence in the person with dementia and support them to remain active and engaged,” said Kate Laver, PhD, who presented the study at the annual meeting of the Alzheimer’s Association International Conference. Dr. Laver is an associate professor in the College of Medicine and Public Health at Flinders University in Adelaide, South Australia.
The program is called Care of Persons with Dementia in Their Environments (COPE), and has previously been demonstrated to improve outcomes when conducted through in-person home visits. Over a maximum of ten sessions in 4 months, COPE employs occupational therapists and individuals with nursing skills to identify environmental stressors that can be modified to reduce sensory, physical, and cognitive demands. It also looks for comorbidities in the person with dementia that could be contributing to poor functioning. The goal of COPE is to encourage the person with dementia to reengage in daily activities, and to reduce caregiver burden as a result.
In a 2020 study, Dr. Laver and colleagues showed that COPE is noninferior when delivered by telehealth compared with in-person delivery. They randomized 63 caregiver-patient dyads to telehealth or home visit delivery of the COPE program. Sixty percent of the persons with dementia were male, and the mean caregiver time was 32 months.
Similar improvements in outcomes were seen in both groups, with no statistically significant differences for the primary outcome of change in Caregiver Mastery Index score at 4 months (mean difference, 0.09; 95% confidence interval, –1.26 to 1.45). Similar changes were also seen in the Perceived Change Scale, which is a 13-item caregiver questionnaire that covers day-to-day care challenges, including feeling overwhelmed or upset, sleeping patterns, and availability of personal time.
Not surprisingly, telehealth implementation led to reduced mean travel time (77.2 minutes vs. 255.9 minutes; P < .0001). The face-to-face time was shorter in the telehealth group (308 vs. 337 minutes), though the difference was not statistically significant. Dr. Laver noted that the consent rate was high at 75%, but there were some missed sessions.
Lessons learned
During the presentation, Dr. Laver emphasized some lessons learned from conversion to a telehealth model. These included providing a tablet and stand on loan, a user guide with pictures, and an initial on-site training session. The first two sessions were conducted on site to do an in-person demonstration and to assess the participants and the home environment.
She noted that it was important to have an IT support person on call to help participants use the provided tablet if needed, though this was rarely used.
“Although few people (at the time) had their own devices, they were able to quickly master videoconferencing. We felt that it was important to ensure that the first couple of consultations were in person – this enabled the therapist to develop rapport, practice use of videoconferencing, and get a good idea of the person’s environment and relationship with the person with dementia,” said Dr. Laver.
She noted that telehealth can be more efficient, and even preferred, during times like the COVID-19 pandemic, as well as in rural settings. But home visits will always be needed. “They are important for developing rapport and enabling a comprehensive assessment of the person with dementia, relationships, and environment. They are also preferred by some caregivers,” said Dr. Laver.
The demonstration of equivalence to in-person delivery was welcome, said Ingo Kilimann, MD, who comoderated the session where Dr. Laver presented. “We have to bring help to the families where they are, and not just tell them where they can get the help, because some people are just not able to actually come to some specialists’ centers. So it’s very important information that it does work,” said Dr. Kilimann, who is a dementia neurologist and head of the memory clinic at the The German Center for Neurodegenerative Diseases in Bonn.
He added that mixing of on-site and remote sessions is a good model. “I think that is the way to be most effective – to have someone in person at the person with dementia’s house, and then have online support for the rest of the time, and then it can be as successful as a total in-person intervention,” said Dr. Kilimann.
Dr. Laver had no relevant financial disclosures.
The program combines information, education, and skills training to help participants overcome specific challenges.
“It focuses on individualized problem solving and is tailored to the needs of the person. The focus is not just on educating caregivers, but working on strategies to maintain independence in the person with dementia and support them to remain active and engaged,” said Kate Laver, PhD, who presented the study at the annual meeting of the Alzheimer’s Association International Conference. Dr. Laver is an associate professor in the College of Medicine and Public Health at Flinders University in Adelaide, South Australia.
The program is called Care of Persons with Dementia in Their Environments (COPE), and has previously been demonstrated to improve outcomes when conducted through in-person home visits. Over a maximum of ten sessions in 4 months, COPE employs occupational therapists and individuals with nursing skills to identify environmental stressors that can be modified to reduce sensory, physical, and cognitive demands. It also looks for comorbidities in the person with dementia that could be contributing to poor functioning. The goal of COPE is to encourage the person with dementia to reengage in daily activities, and to reduce caregiver burden as a result.
In a 2020 study, Dr. Laver and colleagues showed that COPE is noninferior when delivered by telehealth compared with in-person delivery. They randomized 63 caregiver-patient dyads to telehealth or home visit delivery of the COPE program. Sixty percent of the persons with dementia were male, and the mean caregiver time was 32 months.
Similar improvements in outcomes were seen in both groups, with no statistically significant differences for the primary outcome of change in Caregiver Mastery Index score at 4 months (mean difference, 0.09; 95% confidence interval, –1.26 to 1.45). Similar changes were also seen in the Perceived Change Scale, which is a 13-item caregiver questionnaire that covers day-to-day care challenges, including feeling overwhelmed or upset, sleeping patterns, and availability of personal time.
Not surprisingly, telehealth implementation led to reduced mean travel time (77.2 minutes vs. 255.9 minutes; P < .0001). The face-to-face time was shorter in the telehealth group (308 vs. 337 minutes), though the difference was not statistically significant. Dr. Laver noted that the consent rate was high at 75%, but there were some missed sessions.
Lessons learned
During the presentation, Dr. Laver emphasized some lessons learned from conversion to a telehealth model. These included providing a tablet and stand on loan, a user guide with pictures, and an initial on-site training session. The first two sessions were conducted on site to do an in-person demonstration and to assess the participants and the home environment.
She noted that it was important to have an IT support person on call to help participants use the provided tablet if needed, though this was rarely used.
“Although few people (at the time) had their own devices, they were able to quickly master videoconferencing. We felt that it was important to ensure that the first couple of consultations were in person – this enabled the therapist to develop rapport, practice use of videoconferencing, and get a good idea of the person’s environment and relationship with the person with dementia,” said Dr. Laver.
She noted that telehealth can be more efficient, and even preferred, during times like the COVID-19 pandemic, as well as in rural settings. But home visits will always be needed. “They are important for developing rapport and enabling a comprehensive assessment of the person with dementia, relationships, and environment. They are also preferred by some caregivers,” said Dr. Laver.
The demonstration of equivalence to in-person delivery was welcome, said Ingo Kilimann, MD, who comoderated the session where Dr. Laver presented. “We have to bring help to the families where they are, and not just tell them where they can get the help, because some people are just not able to actually come to some specialists’ centers. So it’s very important information that it does work,” said Dr. Kilimann, who is a dementia neurologist and head of the memory clinic at the The German Center for Neurodegenerative Diseases in Bonn.
He added that mixing of on-site and remote sessions is a good model. “I think that is the way to be most effective – to have someone in person at the person with dementia’s house, and then have online support for the rest of the time, and then it can be as successful as a total in-person intervention,” said Dr. Kilimann.
Dr. Laver had no relevant financial disclosures.
FROM AAIC 2021
Tofacitinib in UC: Watch out for herpes zoster reactivation, thrombosis
In a real-world test, tofacitinib had a similar safety profile to what was seen in clinical trials. The majority of adverse events seen were infections, and few were serious; however, the study did find evidence of rare venous thromboembolism (VTE) in patients with preexisting risk factors, which suggests that precaution is warranted in this group.
Tofacitinib, a Janus kinase inhibitor, was approved by the Food and Drug Administration in 2018 for adults with moderate to severe ulcerative colitis (UC). Three phase 3 clinical trials and an open-label, long-term extension trial found that the drug was associated with increased infection rates and higher lipid levels.
In rheumatoid arthritis patients, an interim analysis of a safety clinical trial of twice-daily doses of 10 mg tofacitinib showed increased rates of pulmonary embolism and all-cause mortality, compared to treatment with a dose of 5 mg or a tumor necrosis factor antagonist. That finding led to a black box label warning against thrombosis.
The current study, led by Parakkal Deepak, MBBS, MS, and colleagues and published in Clinical Gastroenterology and Hepatology, included patients from six centers in the United States.
The findings suggest that patients should be counseled about the potential risk for herpes zoster (HZ) reactivation, especially older patients taking corticosteroids. The authors also recommended vaccination with an inactivated HZ vaccine. “Our data suggest a careful risk-benefit discussion before starting tofacitinib, especially in patients with preexisting risk factors for VTE, dose deescalation to the lowest clinically feasible dose, and monitoring for clinical signs of VTE, especially among those who continue on a dose of 10 mg twice a day,” the authors wrote.
The researchers followed 260 patients over a median of 6 months (median age, 38 years; 58.1% male; 71.9% non-Hispanic). Overall, 88.5% had previously received treatment with a biologic, most often an anti–TNF-alpha agent (76.5%). During follow-up, 15.7% experienced adverse events, most commonly infections (5.0%) and rash (3.5%). Joint pain (1.5%) and anemia (1.5%) also occurred. The incidence rate for any adverse event was 27.2 per 100 person-years. Adverse events occurred more often in older patients (mean age, 42 vs. 37 years; P = .02) and those who had not undergone previous anti-TNF therapy (63.4% vs 79.8%; P = .03). There was no association between concomitant steroid use and adverse events on univariate analysis. Of the overall cohort, 5.8% experienced a severe adverse event, with the most common being herpes zoster rash (26.7% of severe adverse events). Therapy was discontinued by 4.6%.
Five patients developed herpes zoster (3.29 per 100 person-years; 95% CI, 1.37-7.90). Risk factors for VTE were seen in 31.2% of the cohort, and two cases of VTE occurred during follow-up (1.32 per 100 person-years; 95% CI, 0.33-5.28), both in patients with extensive UC. There was no increased risk of complications following abdominal surgery.
At baseline, 38.4% had an abnormal lipid profile, and this increased to 48.3% following 8 weeks of treatment.
Overall, 45% of patients were anemic at baseline. Females experienced a significant improvement by week 26 (median hemoglobin level, 13.0 g/dL; interquartile range, 12.5-13.8), while a similar improvement occurred by week 52 in males (median hemoglobin level, 13.6 g/dL; IQR, 12.57-14.0). At 52 weeks, the mean increase in hemoglobin was 5% (IQR, 0%-11.1%). The increase was greater in females (7.7%; IQR, 4.2%-11.7%) than in males (2.1%; IQR, –0.5% to 11.3%).
Limitations of the study include its retrospective nature and that the tools by which data were collected could have missed some adverse events because they were not adequately captured in the treating clinician’s notes. However, the data trend similarly to a prospective study.
“In summary, we report safety signals on a real-world cohort of patients with UC initiated on tofacitinib in whom increasing age is a risk factor for AEs and consistent with recent reports of a dose-dependent risk of HZ reactivation and VTE events in patients with a risk factor for VTE on the 10-mg twice-daily dosing,” the authors concluded.
The study was funded by the American College of Gastroenterology, the Crohn’s and Colitis Foundation, the Givin’ it all for Guts Foundation, and the Lawrence C. Pakula, MD, Inflammatory Bowel Disease Research Innovation and Education Fund. The authors have financial ties with various pharmaceutical companies.
This article was updated July 19, 2021.
Tofacitinib is an oral small molecule that received approval by the Food and Drug Administration in December 2019. To date, most safety data have been derived from clinical trials or past marketing registries. In this study, Deepak and colleagues report real-world data from a multicenter cohort.
The second adverse event of interest was VTE. The risk of VTE with tofacitinib first came to light in 2019 during an interim analysis of a safety trial in rheumatoid arthritis. The data prompted the FDA to issue a safety communication. In this study two patients developed VTE. Both were males on the 10-mg twice-daily dose. This number is a higher than expected for a cohort of this size and highlights the need for careful patient selection, risk-benefit discussion, close monitoring for signs of VTE and early dose tapering when feasible.
In summary, most adverse effects related to tofacitinib can be mitigated with careful patient selection, pretreatment zoster vaccination, and timely dose taper.
Manreet Kaur, MD, medical director of Inflammatory Bowel Disease Center at Baylor College of Medicine, Houston. She has no conflicts of interest.
Tofacitinib is an oral small molecule that received approval by the Food and Drug Administration in December 2019. To date, most safety data have been derived from clinical trials or past marketing registries. In this study, Deepak and colleagues report real-world data from a multicenter cohort.
The second adverse event of interest was VTE. The risk of VTE with tofacitinib first came to light in 2019 during an interim analysis of a safety trial in rheumatoid arthritis. The data prompted the FDA to issue a safety communication. In this study two patients developed VTE. Both were males on the 10-mg twice-daily dose. This number is a higher than expected for a cohort of this size and highlights the need for careful patient selection, risk-benefit discussion, close monitoring for signs of VTE and early dose tapering when feasible.
In summary, most adverse effects related to tofacitinib can be mitigated with careful patient selection, pretreatment zoster vaccination, and timely dose taper.
Manreet Kaur, MD, medical director of Inflammatory Bowel Disease Center at Baylor College of Medicine, Houston. She has no conflicts of interest.
Tofacitinib is an oral small molecule that received approval by the Food and Drug Administration in December 2019. To date, most safety data have been derived from clinical trials or past marketing registries. In this study, Deepak and colleagues report real-world data from a multicenter cohort.
The second adverse event of interest was VTE. The risk of VTE with tofacitinib first came to light in 2019 during an interim analysis of a safety trial in rheumatoid arthritis. The data prompted the FDA to issue a safety communication. In this study two patients developed VTE. Both were males on the 10-mg twice-daily dose. This number is a higher than expected for a cohort of this size and highlights the need for careful patient selection, risk-benefit discussion, close monitoring for signs of VTE and early dose tapering when feasible.
In summary, most adverse effects related to tofacitinib can be mitigated with careful patient selection, pretreatment zoster vaccination, and timely dose taper.
Manreet Kaur, MD, medical director of Inflammatory Bowel Disease Center at Baylor College of Medicine, Houston. She has no conflicts of interest.
In a real-world test, tofacitinib had a similar safety profile to what was seen in clinical trials. The majority of adverse events seen were infections, and few were serious; however, the study did find evidence of rare venous thromboembolism (VTE) in patients with preexisting risk factors, which suggests that precaution is warranted in this group.
Tofacitinib, a Janus kinase inhibitor, was approved by the Food and Drug Administration in 2018 for adults with moderate to severe ulcerative colitis (UC). Three phase 3 clinical trials and an open-label, long-term extension trial found that the drug was associated with increased infection rates and higher lipid levels.
In rheumatoid arthritis patients, an interim analysis of a safety clinical trial of twice-daily doses of 10 mg tofacitinib showed increased rates of pulmonary embolism and all-cause mortality, compared to treatment with a dose of 5 mg or a tumor necrosis factor antagonist. That finding led to a black box label warning against thrombosis.
The current study, led by Parakkal Deepak, MBBS, MS, and colleagues and published in Clinical Gastroenterology and Hepatology, included patients from six centers in the United States.
The findings suggest that patients should be counseled about the potential risk for herpes zoster (HZ) reactivation, especially older patients taking corticosteroids. The authors also recommended vaccination with an inactivated HZ vaccine. “Our data suggest a careful risk-benefit discussion before starting tofacitinib, especially in patients with preexisting risk factors for VTE, dose deescalation to the lowest clinically feasible dose, and monitoring for clinical signs of VTE, especially among those who continue on a dose of 10 mg twice a day,” the authors wrote.
The researchers followed 260 patients over a median of 6 months (median age, 38 years; 58.1% male; 71.9% non-Hispanic). Overall, 88.5% had previously received treatment with a biologic, most often an anti–TNF-alpha agent (76.5%). During follow-up, 15.7% experienced adverse events, most commonly infections (5.0%) and rash (3.5%). Joint pain (1.5%) and anemia (1.5%) also occurred. The incidence rate for any adverse event was 27.2 per 100 person-years. Adverse events occurred more often in older patients (mean age, 42 vs. 37 years; P = .02) and those who had not undergone previous anti-TNF therapy (63.4% vs 79.8%; P = .03). There was no association between concomitant steroid use and adverse events on univariate analysis. Of the overall cohort, 5.8% experienced a severe adverse event, with the most common being herpes zoster rash (26.7% of severe adverse events). Therapy was discontinued by 4.6%.
Five patients developed herpes zoster (3.29 per 100 person-years; 95% CI, 1.37-7.90). Risk factors for VTE were seen in 31.2% of the cohort, and two cases of VTE occurred during follow-up (1.32 per 100 person-years; 95% CI, 0.33-5.28), both in patients with extensive UC. There was no increased risk of complications following abdominal surgery.
At baseline, 38.4% had an abnormal lipid profile, and this increased to 48.3% following 8 weeks of treatment.
Overall, 45% of patients were anemic at baseline. Females experienced a significant improvement by week 26 (median hemoglobin level, 13.0 g/dL; interquartile range, 12.5-13.8), while a similar improvement occurred by week 52 in males (median hemoglobin level, 13.6 g/dL; IQR, 12.57-14.0). At 52 weeks, the mean increase in hemoglobin was 5% (IQR, 0%-11.1%). The increase was greater in females (7.7%; IQR, 4.2%-11.7%) than in males (2.1%; IQR, –0.5% to 11.3%).
Limitations of the study include its retrospective nature and that the tools by which data were collected could have missed some adverse events because they were not adequately captured in the treating clinician’s notes. However, the data trend similarly to a prospective study.
“In summary, we report safety signals on a real-world cohort of patients with UC initiated on tofacitinib in whom increasing age is a risk factor for AEs and consistent with recent reports of a dose-dependent risk of HZ reactivation and VTE events in patients with a risk factor for VTE on the 10-mg twice-daily dosing,” the authors concluded.
The study was funded by the American College of Gastroenterology, the Crohn’s and Colitis Foundation, the Givin’ it all for Guts Foundation, and the Lawrence C. Pakula, MD, Inflammatory Bowel Disease Research Innovation and Education Fund. The authors have financial ties with various pharmaceutical companies.
This article was updated July 19, 2021.
In a real-world test, tofacitinib had a similar safety profile to what was seen in clinical trials. The majority of adverse events seen were infections, and few were serious; however, the study did find evidence of rare venous thromboembolism (VTE) in patients with preexisting risk factors, which suggests that precaution is warranted in this group.
Tofacitinib, a Janus kinase inhibitor, was approved by the Food and Drug Administration in 2018 for adults with moderate to severe ulcerative colitis (UC). Three phase 3 clinical trials and an open-label, long-term extension trial found that the drug was associated with increased infection rates and higher lipid levels.
In rheumatoid arthritis patients, an interim analysis of a safety clinical trial of twice-daily doses of 10 mg tofacitinib showed increased rates of pulmonary embolism and all-cause mortality, compared to treatment with a dose of 5 mg or a tumor necrosis factor antagonist. That finding led to a black box label warning against thrombosis.
The current study, led by Parakkal Deepak, MBBS, MS, and colleagues and published in Clinical Gastroenterology and Hepatology, included patients from six centers in the United States.
The findings suggest that patients should be counseled about the potential risk for herpes zoster (HZ) reactivation, especially older patients taking corticosteroids. The authors also recommended vaccination with an inactivated HZ vaccine. “Our data suggest a careful risk-benefit discussion before starting tofacitinib, especially in patients with preexisting risk factors for VTE, dose deescalation to the lowest clinically feasible dose, and monitoring for clinical signs of VTE, especially among those who continue on a dose of 10 mg twice a day,” the authors wrote.
The researchers followed 260 patients over a median of 6 months (median age, 38 years; 58.1% male; 71.9% non-Hispanic). Overall, 88.5% had previously received treatment with a biologic, most often an anti–TNF-alpha agent (76.5%). During follow-up, 15.7% experienced adverse events, most commonly infections (5.0%) and rash (3.5%). Joint pain (1.5%) and anemia (1.5%) also occurred. The incidence rate for any adverse event was 27.2 per 100 person-years. Adverse events occurred more often in older patients (mean age, 42 vs. 37 years; P = .02) and those who had not undergone previous anti-TNF therapy (63.4% vs 79.8%; P = .03). There was no association between concomitant steroid use and adverse events on univariate analysis. Of the overall cohort, 5.8% experienced a severe adverse event, with the most common being herpes zoster rash (26.7% of severe adverse events). Therapy was discontinued by 4.6%.
Five patients developed herpes zoster (3.29 per 100 person-years; 95% CI, 1.37-7.90). Risk factors for VTE were seen in 31.2% of the cohort, and two cases of VTE occurred during follow-up (1.32 per 100 person-years; 95% CI, 0.33-5.28), both in patients with extensive UC. There was no increased risk of complications following abdominal surgery.
At baseline, 38.4% had an abnormal lipid profile, and this increased to 48.3% following 8 weeks of treatment.
Overall, 45% of patients were anemic at baseline. Females experienced a significant improvement by week 26 (median hemoglobin level, 13.0 g/dL; interquartile range, 12.5-13.8), while a similar improvement occurred by week 52 in males (median hemoglobin level, 13.6 g/dL; IQR, 12.57-14.0). At 52 weeks, the mean increase in hemoglobin was 5% (IQR, 0%-11.1%). The increase was greater in females (7.7%; IQR, 4.2%-11.7%) than in males (2.1%; IQR, –0.5% to 11.3%).
Limitations of the study include its retrospective nature and that the tools by which data were collected could have missed some adverse events because they were not adequately captured in the treating clinician’s notes. However, the data trend similarly to a prospective study.
“In summary, we report safety signals on a real-world cohort of patients with UC initiated on tofacitinib in whom increasing age is a risk factor for AEs and consistent with recent reports of a dose-dependent risk of HZ reactivation and VTE events in patients with a risk factor for VTE on the 10-mg twice-daily dosing,” the authors concluded.
The study was funded by the American College of Gastroenterology, the Crohn’s and Colitis Foundation, the Givin’ it all for Guts Foundation, and the Lawrence C. Pakula, MD, Inflammatory Bowel Disease Research Innovation and Education Fund. The authors have financial ties with various pharmaceutical companies.
This article was updated July 19, 2021.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Network meta-analysis ranks first-line H. pylori regimens
A network meta-analysis of current first-line dual, triple, and quadruple therapies for Helicobacter pylori infection found that vonoprazan triple therapy was most effective, while standard triple therapy of a proton pump inhibitor (PPI), amoxicillin, and clarithromycin was least effective. Levofloxacin-containing triple therapy performed best in Western countries and West Asia, while reverse hybrid therapy was most effective in East Asia.
The results “[suggest that] a new approach concerning H. pylori treatment is now needed and that the time for transitioning from trial and error to antimicrobial stewardship [of H. pylori infection] has arrived,” wrote Theodore Rokkas, PhD, MD, of the European University of Cyprus in Engomi, and colleagues. Their study was published online April 8 in Gastroenterology.
H. pylori infection is the primary cause of gastritis, peptic ulcer disease, gastric mucosa–associated lymphoid tissue lymphoma, and gastric cancer.
Since H. pylori infection was first recognized, physicians have employed a range of drugs in double, triple, and quadruple combinations to combat it.
Despite those efforts, treatment success is lower than with many other infectious diseases. A newcomer is the potassium-competing acid blocker vonoprazan, which increases efficacy of amoxicillin combination therapies and has, thereby, generated renewed interest in all combination therapies, according to the study authors. Vonoprazan is currently available in some Asian countries, but not the United States or Europe.
Current guidelines for H. pylori treatment relied on randomized controlled trials and relevant pair-wise meta-analyses, but no previous pairwise analysis has included all currently available medications, the authors noted. Network meta-analyses can help fill this evidence gap: They incorporate both direct and indirect evidence from a collection of randomized controlled trials to estimate the comparative effectiveness of three or more regimens.
The researchers conducted a network meta-analysis that included 68 randomized, controlled trials totaling 22,975 patients. The following regimens were included in the analysis: Concomitant quadruple bismuth treatment (bismuth quadruple therapy), concomitant quadruple nonbismuth treatment (nonbismuth quadruple therapy), high-dose amoxicillin double treatment (Amox-dual therapy), levofloxacin-containing treatment (Levo-therapy), reverse hybrid therapy (R-hybrid therapy), sequential quadruple treatment (sequential therapy), standard triple treatment (triple therapy), and vonoprazan-containing therapy (Vono-triple therapy).
Statistically significant results were found with Vono-triple therapy versus triple therapy (odds ratio, 3.80; 95% confidence interval, 1.62-8.94), sequential therapy versus triple therapy (OR, 1.79; 95% CI, 1.26-2.53), nonbismuth quadruple therapy versus triple therapy (OR, 2.08; 95% CI, 1.45-2.98), bismuth quadruple therapy versus triple therapy (OR, 1.47; 95% CI, 1.02-2.11), and Levo-therapy versus triple therapy (OR, 1.79; 95% CI, 1.26-2.53).
In the overall data, mean cure rates greater than 90% were seen only in Vono-triple therapy (91.4%; 95% CI, 88.5-93.5%) and R-hybrid therapy (93.6%; 95% CI, 90.4-96.8%). Cure rates were lower for Nonbismuth quadruple therapy (84.3%; 95% CI, 82.7-85.8%), Levo-therapy (83.8%; 95% CI, 82.1-85.4%), Sequential therapy (83.7%; 95% CI, 82.7-84.7%), bismuth quadruple therapy (81.3%; 95% CI, 79.5-83.1%), Amox-dual therapy (80.2%; 75.3%-84.4%), and triple therapy (75.7%; 95% CI, 74.9-76.4%). Levo-therapy performed best in Western countries (88.5%; 95% CI, 86.5-90.5%) and West Asia (88.4%; 95% CI, 84.6-91.1%). R-hybrid therapy performed best in East Asia (93.6%; 95% CI, 90.4-96.8%).
A surface under the cumulative ranking (SUCRA) value, which represents the efficacy of the intervention compared to an ideal intervention, was 92.4% for Vono-triple therapy. The second highest SUCRA value was for 68.8% for nonbismuth quadruple therapy. The SUCRA value of standard triple therapy was 4.7%.
A key limitation to the study is that Vono-triple therapy was tested only in Japan, and requires additional study in other geographic regions.
The study received support from the Department of Veteran Affairs. The authors have consulted for and received research funding from various pharmaceutical companies.
In this perspective, the network meta-analysis by Rokkas and colleagues is very important: The purpose of this study is not only to identify those regimens with the highest treatment success in comparison but also stratifies for world regions and time-shift aspects. The key value of the network approach, however, is the ability for indirect comparisons, as presented here. Using the surface under the cumulative ranking values, vonoprazan-based triple therapy may be the most promising candidate for the future, non–bismuth quadruple and R-hybrid therapies are also suitable.
In this perspective, with currently sparse vonoprazan data limited to Japan, I still prefer to go primarily for the non–bismuth quadruple therapy (56 pills to be taken in 1 week), and from my own published data, this regimen will still work if only taken for 5 days. Vice versa, in the presence of macrolide resistance, amoxicillin allergy, previous treatment failures, I go for the bismuth quadruple therapy – if I can expect good treatment compliance because proton pump inhibitor plus potassium, metronidazole, and tetracycline for 10 days can mean 140 pills. Gerhard G. Treiber, MD, AGAF, is with the department of internal medicine at Saarland University Hospital, Homburg, Germany. He has no conflicts of interest.
In this perspective, the network meta-analysis by Rokkas and colleagues is very important: The purpose of this study is not only to identify those regimens with the highest treatment success in comparison but also stratifies for world regions and time-shift aspects. The key value of the network approach, however, is the ability for indirect comparisons, as presented here. Using the surface under the cumulative ranking values, vonoprazan-based triple therapy may be the most promising candidate for the future, non–bismuth quadruple and R-hybrid therapies are also suitable.
In this perspective, with currently sparse vonoprazan data limited to Japan, I still prefer to go primarily for the non–bismuth quadruple therapy (56 pills to be taken in 1 week), and from my own published data, this regimen will still work if only taken for 5 days. Vice versa, in the presence of macrolide resistance, amoxicillin allergy, previous treatment failures, I go for the bismuth quadruple therapy – if I can expect good treatment compliance because proton pump inhibitor plus potassium, metronidazole, and tetracycline for 10 days can mean 140 pills. Gerhard G. Treiber, MD, AGAF, is with the department of internal medicine at Saarland University Hospital, Homburg, Germany. He has no conflicts of interest.
In this perspective, the network meta-analysis by Rokkas and colleagues is very important: The purpose of this study is not only to identify those regimens with the highest treatment success in comparison but also stratifies for world regions and time-shift aspects. The key value of the network approach, however, is the ability for indirect comparisons, as presented here. Using the surface under the cumulative ranking values, vonoprazan-based triple therapy may be the most promising candidate for the future, non–bismuth quadruple and R-hybrid therapies are also suitable.
In this perspective, with currently sparse vonoprazan data limited to Japan, I still prefer to go primarily for the non–bismuth quadruple therapy (56 pills to be taken in 1 week), and from my own published data, this regimen will still work if only taken for 5 days. Vice versa, in the presence of macrolide resistance, amoxicillin allergy, previous treatment failures, I go for the bismuth quadruple therapy – if I can expect good treatment compliance because proton pump inhibitor plus potassium, metronidazole, and tetracycline for 10 days can mean 140 pills. Gerhard G. Treiber, MD, AGAF, is with the department of internal medicine at Saarland University Hospital, Homburg, Germany. He has no conflicts of interest.
A network meta-analysis of current first-line dual, triple, and quadruple therapies for Helicobacter pylori infection found that vonoprazan triple therapy was most effective, while standard triple therapy of a proton pump inhibitor (PPI), amoxicillin, and clarithromycin was least effective. Levofloxacin-containing triple therapy performed best in Western countries and West Asia, while reverse hybrid therapy was most effective in East Asia.
The results “[suggest that] a new approach concerning H. pylori treatment is now needed and that the time for transitioning from trial and error to antimicrobial stewardship [of H. pylori infection] has arrived,” wrote Theodore Rokkas, PhD, MD, of the European University of Cyprus in Engomi, and colleagues. Their study was published online April 8 in Gastroenterology.
H. pylori infection is the primary cause of gastritis, peptic ulcer disease, gastric mucosa–associated lymphoid tissue lymphoma, and gastric cancer.
Since H. pylori infection was first recognized, physicians have employed a range of drugs in double, triple, and quadruple combinations to combat it.
Despite those efforts, treatment success is lower than with many other infectious diseases. A newcomer is the potassium-competing acid blocker vonoprazan, which increases efficacy of amoxicillin combination therapies and has, thereby, generated renewed interest in all combination therapies, according to the study authors. Vonoprazan is currently available in some Asian countries, but not the United States or Europe.
Current guidelines for H. pylori treatment relied on randomized controlled trials and relevant pair-wise meta-analyses, but no previous pairwise analysis has included all currently available medications, the authors noted. Network meta-analyses can help fill this evidence gap: They incorporate both direct and indirect evidence from a collection of randomized controlled trials to estimate the comparative effectiveness of three or more regimens.
The researchers conducted a network meta-analysis that included 68 randomized, controlled trials totaling 22,975 patients. The following regimens were included in the analysis: Concomitant quadruple bismuth treatment (bismuth quadruple therapy), concomitant quadruple nonbismuth treatment (nonbismuth quadruple therapy), high-dose amoxicillin double treatment (Amox-dual therapy), levofloxacin-containing treatment (Levo-therapy), reverse hybrid therapy (R-hybrid therapy), sequential quadruple treatment (sequential therapy), standard triple treatment (triple therapy), and vonoprazan-containing therapy (Vono-triple therapy).
Statistically significant results were found with Vono-triple therapy versus triple therapy (odds ratio, 3.80; 95% confidence interval, 1.62-8.94), sequential therapy versus triple therapy (OR, 1.79; 95% CI, 1.26-2.53), nonbismuth quadruple therapy versus triple therapy (OR, 2.08; 95% CI, 1.45-2.98), bismuth quadruple therapy versus triple therapy (OR, 1.47; 95% CI, 1.02-2.11), and Levo-therapy versus triple therapy (OR, 1.79; 95% CI, 1.26-2.53).
In the overall data, mean cure rates greater than 90% were seen only in Vono-triple therapy (91.4%; 95% CI, 88.5-93.5%) and R-hybrid therapy (93.6%; 95% CI, 90.4-96.8%). Cure rates were lower for Nonbismuth quadruple therapy (84.3%; 95% CI, 82.7-85.8%), Levo-therapy (83.8%; 95% CI, 82.1-85.4%), Sequential therapy (83.7%; 95% CI, 82.7-84.7%), bismuth quadruple therapy (81.3%; 95% CI, 79.5-83.1%), Amox-dual therapy (80.2%; 75.3%-84.4%), and triple therapy (75.7%; 95% CI, 74.9-76.4%). Levo-therapy performed best in Western countries (88.5%; 95% CI, 86.5-90.5%) and West Asia (88.4%; 95% CI, 84.6-91.1%). R-hybrid therapy performed best in East Asia (93.6%; 95% CI, 90.4-96.8%).
A surface under the cumulative ranking (SUCRA) value, which represents the efficacy of the intervention compared to an ideal intervention, was 92.4% for Vono-triple therapy. The second highest SUCRA value was for 68.8% for nonbismuth quadruple therapy. The SUCRA value of standard triple therapy was 4.7%.
A key limitation to the study is that Vono-triple therapy was tested only in Japan, and requires additional study in other geographic regions.
The study received support from the Department of Veteran Affairs. The authors have consulted for and received research funding from various pharmaceutical companies.
A network meta-analysis of current first-line dual, triple, and quadruple therapies for Helicobacter pylori infection found that vonoprazan triple therapy was most effective, while standard triple therapy of a proton pump inhibitor (PPI), amoxicillin, and clarithromycin was least effective. Levofloxacin-containing triple therapy performed best in Western countries and West Asia, while reverse hybrid therapy was most effective in East Asia.
The results “[suggest that] a new approach concerning H. pylori treatment is now needed and that the time for transitioning from trial and error to antimicrobial stewardship [of H. pylori infection] has arrived,” wrote Theodore Rokkas, PhD, MD, of the European University of Cyprus in Engomi, and colleagues. Their study was published online April 8 in Gastroenterology.
H. pylori infection is the primary cause of gastritis, peptic ulcer disease, gastric mucosa–associated lymphoid tissue lymphoma, and gastric cancer.
Since H. pylori infection was first recognized, physicians have employed a range of drugs in double, triple, and quadruple combinations to combat it.
Despite those efforts, treatment success is lower than with many other infectious diseases. A newcomer is the potassium-competing acid blocker vonoprazan, which increases efficacy of amoxicillin combination therapies and has, thereby, generated renewed interest in all combination therapies, according to the study authors. Vonoprazan is currently available in some Asian countries, but not the United States or Europe.
Current guidelines for H. pylori treatment relied on randomized controlled trials and relevant pair-wise meta-analyses, but no previous pairwise analysis has included all currently available medications, the authors noted. Network meta-analyses can help fill this evidence gap: They incorporate both direct and indirect evidence from a collection of randomized controlled trials to estimate the comparative effectiveness of three or more regimens.
The researchers conducted a network meta-analysis that included 68 randomized, controlled trials totaling 22,975 patients. The following regimens were included in the analysis: Concomitant quadruple bismuth treatment (bismuth quadruple therapy), concomitant quadruple nonbismuth treatment (nonbismuth quadruple therapy), high-dose amoxicillin double treatment (Amox-dual therapy), levofloxacin-containing treatment (Levo-therapy), reverse hybrid therapy (R-hybrid therapy), sequential quadruple treatment (sequential therapy), standard triple treatment (triple therapy), and vonoprazan-containing therapy (Vono-triple therapy).
Statistically significant results were found with Vono-triple therapy versus triple therapy (odds ratio, 3.80; 95% confidence interval, 1.62-8.94), sequential therapy versus triple therapy (OR, 1.79; 95% CI, 1.26-2.53), nonbismuth quadruple therapy versus triple therapy (OR, 2.08; 95% CI, 1.45-2.98), bismuth quadruple therapy versus triple therapy (OR, 1.47; 95% CI, 1.02-2.11), and Levo-therapy versus triple therapy (OR, 1.79; 95% CI, 1.26-2.53).
In the overall data, mean cure rates greater than 90% were seen only in Vono-triple therapy (91.4%; 95% CI, 88.5-93.5%) and R-hybrid therapy (93.6%; 95% CI, 90.4-96.8%). Cure rates were lower for Nonbismuth quadruple therapy (84.3%; 95% CI, 82.7-85.8%), Levo-therapy (83.8%; 95% CI, 82.1-85.4%), Sequential therapy (83.7%; 95% CI, 82.7-84.7%), bismuth quadruple therapy (81.3%; 95% CI, 79.5-83.1%), Amox-dual therapy (80.2%; 75.3%-84.4%), and triple therapy (75.7%; 95% CI, 74.9-76.4%). Levo-therapy performed best in Western countries (88.5%; 95% CI, 86.5-90.5%) and West Asia (88.4%; 95% CI, 84.6-91.1%). R-hybrid therapy performed best in East Asia (93.6%; 95% CI, 90.4-96.8%).
A surface under the cumulative ranking (SUCRA) value, which represents the efficacy of the intervention compared to an ideal intervention, was 92.4% for Vono-triple therapy. The second highest SUCRA value was for 68.8% for nonbismuth quadruple therapy. The SUCRA value of standard triple therapy was 4.7%.
A key limitation to the study is that Vono-triple therapy was tested only in Japan, and requires additional study in other geographic regions.
The study received support from the Department of Veteran Affairs. The authors have consulted for and received research funding from various pharmaceutical companies.
FROM GASTROENTEROLOGY