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FDA OKs First-Line Lazertinib With Amivantamab for NSCLC
This marks the first approval for lazertinib. Amivantamab was initially approved by the FDA in 2021 and carries a few indications for locally advanced or metastatic NSCLC. Both drugs are manufactured by Janssen Biotech Inc.
“Patients will now have the option of a potential new first-line standard of care with significant clinical benefits over osimertinib,” study investigator Alexander Spira, MD, PhD, director, Virginia Cancer Specialists Research Institute, said in a news release from Johnson & Johnson .
Lazertinib is an oral, highly selective, third-generation EGFR tyrosine kinase inhibitor that can penetrate the brain and amivantamab is a bispecific antibody targeting EGFR and MET.
The approval was based on results from the phase 3 MARIPOSA trial, which showed that the combination reduced the risk of disease progression or death by 30% compared with osimertinib.
The MARIPOSA trial randomly allocated 1074 patients with exon 19 deletion or exon 21 L858R substitution mutation-positive locally advanced or metastatic NSCLC and no prior systemic therapy for advanced disease to amivantamab plus lazertinib, osimertinib alone, or lazertinib alone.
Lazertinib plus amivantamab demonstrated a statistically significant improvement in progression-free survival compared with osimertinib (hazard ratio, 0.70; P < .001). Median progression-free survival was 23.7 months with the combination vs 16.6 months osimertinib alone and 18.5 months with lazertinib alone.
The median duration of response was 9 months longer with the combination compared with osimertinib (25.8 months vs 16.7 months).
The most common adverse reactions (≥ 20%) were rash, nail toxicity, infusion-related reactions (amivantamab), musculoskeletal pain, edema, stomatitis, venous thromboembolism, paresthesia, fatigue, diarrhea, constipation, COVID-19, hemorrhage, dry skin, decreased appetite, pruritus, nausea, and ocular toxicity.
“A serious safety signal of venous thromboembolic events was observed with lazertinib in combination with amivantamab and prophylactic anticoagulation should be administered for the first four months of therapy,” the FDA noted in a statement announcing the approval.
Results from MARIPOSA were first presented at the European Society for Medical Oncology 2023 Congress and published in The New England Journal of Medicine in June. Longer-term follow-up data from MARIPOSA will be presented at the International Association for the Study of Lung Cancer 2024 World Congress on Lung Cancer in September.
A version of this article appeared on Medscape.com.
This marks the first approval for lazertinib. Amivantamab was initially approved by the FDA in 2021 and carries a few indications for locally advanced or metastatic NSCLC. Both drugs are manufactured by Janssen Biotech Inc.
“Patients will now have the option of a potential new first-line standard of care with significant clinical benefits over osimertinib,” study investigator Alexander Spira, MD, PhD, director, Virginia Cancer Specialists Research Institute, said in a news release from Johnson & Johnson .
Lazertinib is an oral, highly selective, third-generation EGFR tyrosine kinase inhibitor that can penetrate the brain and amivantamab is a bispecific antibody targeting EGFR and MET.
The approval was based on results from the phase 3 MARIPOSA trial, which showed that the combination reduced the risk of disease progression or death by 30% compared with osimertinib.
The MARIPOSA trial randomly allocated 1074 patients with exon 19 deletion or exon 21 L858R substitution mutation-positive locally advanced or metastatic NSCLC and no prior systemic therapy for advanced disease to amivantamab plus lazertinib, osimertinib alone, or lazertinib alone.
Lazertinib plus amivantamab demonstrated a statistically significant improvement in progression-free survival compared with osimertinib (hazard ratio, 0.70; P < .001). Median progression-free survival was 23.7 months with the combination vs 16.6 months osimertinib alone and 18.5 months with lazertinib alone.
The median duration of response was 9 months longer with the combination compared with osimertinib (25.8 months vs 16.7 months).
The most common adverse reactions (≥ 20%) were rash, nail toxicity, infusion-related reactions (amivantamab), musculoskeletal pain, edema, stomatitis, venous thromboembolism, paresthesia, fatigue, diarrhea, constipation, COVID-19, hemorrhage, dry skin, decreased appetite, pruritus, nausea, and ocular toxicity.
“A serious safety signal of venous thromboembolic events was observed with lazertinib in combination with amivantamab and prophylactic anticoagulation should be administered for the first four months of therapy,” the FDA noted in a statement announcing the approval.
Results from MARIPOSA were first presented at the European Society for Medical Oncology 2023 Congress and published in The New England Journal of Medicine in June. Longer-term follow-up data from MARIPOSA will be presented at the International Association for the Study of Lung Cancer 2024 World Congress on Lung Cancer in September.
A version of this article appeared on Medscape.com.
This marks the first approval for lazertinib. Amivantamab was initially approved by the FDA in 2021 and carries a few indications for locally advanced or metastatic NSCLC. Both drugs are manufactured by Janssen Biotech Inc.
“Patients will now have the option of a potential new first-line standard of care with significant clinical benefits over osimertinib,” study investigator Alexander Spira, MD, PhD, director, Virginia Cancer Specialists Research Institute, said in a news release from Johnson & Johnson .
Lazertinib is an oral, highly selective, third-generation EGFR tyrosine kinase inhibitor that can penetrate the brain and amivantamab is a bispecific antibody targeting EGFR and MET.
The approval was based on results from the phase 3 MARIPOSA trial, which showed that the combination reduced the risk of disease progression or death by 30% compared with osimertinib.
The MARIPOSA trial randomly allocated 1074 patients with exon 19 deletion or exon 21 L858R substitution mutation-positive locally advanced or metastatic NSCLC and no prior systemic therapy for advanced disease to amivantamab plus lazertinib, osimertinib alone, or lazertinib alone.
Lazertinib plus amivantamab demonstrated a statistically significant improvement in progression-free survival compared with osimertinib (hazard ratio, 0.70; P < .001). Median progression-free survival was 23.7 months with the combination vs 16.6 months osimertinib alone and 18.5 months with lazertinib alone.
The median duration of response was 9 months longer with the combination compared with osimertinib (25.8 months vs 16.7 months).
The most common adverse reactions (≥ 20%) were rash, nail toxicity, infusion-related reactions (amivantamab), musculoskeletal pain, edema, stomatitis, venous thromboembolism, paresthesia, fatigue, diarrhea, constipation, COVID-19, hemorrhage, dry skin, decreased appetite, pruritus, nausea, and ocular toxicity.
“A serious safety signal of venous thromboembolic events was observed with lazertinib in combination with amivantamab and prophylactic anticoagulation should be administered for the first four months of therapy,” the FDA noted in a statement announcing the approval.
Results from MARIPOSA were first presented at the European Society for Medical Oncology 2023 Congress and published in The New England Journal of Medicine in June. Longer-term follow-up data from MARIPOSA will be presented at the International Association for the Study of Lung Cancer 2024 World Congress on Lung Cancer in September.
A version of this article appeared on Medscape.com.
Is Vision Loss a New Dementia Risk Factor? What Do the Data Say?
In 2019, 57 million people worldwide were living with dementia, a figure expected to soar to 153 million by 2050. A recent Lancet Commission report suggests that nearly half of dementia cases could be prevented or delayed by addressing 14 modifiable risk factors, including impaired vision.
The report’s authors recommend that vision-loss screening and treatment be universally available. But are these recommendations warranted? What is the evidence? What is the potential mechanism? And what are the potential implications for clinical practice?
Worldwide, the prevalence of avoidable vision loss and blindness in adults aged 50 years or older is estimated to hover around 13%.
“There is now overwhelming evidence that vision impairment in later life is associated with more rapid cognitive decline and an increased risk of dementia,” said Joshua Ehrlich, MD, MPH, associate professor in ophthalmology and visual sciences, the Institute for Social Research at the University of Michigan, Ann Arbor.
The evidence includes a meta-analysis of 14 prospective cohort studies with roughly 6.2 million older adults who were cognitively intact at baseline. Over the course of up to 14 years, 171,888 developed dementia. Vision loss was associated with a pooled relative risk (RR) for dementia of 1.47.
A separate meta-analysis also identified an increased risk for dementia (RR, 1.38) with visual loss. When broken down into different eye conditions, an increased dementia risk was associated with cataracts and diabetic retinopathy but not with glaucoma or age-related macular degeneration.
A US study that followed roughly 3000 older adults with cataracts and normal cognition at baseline for more than 20 years found that those who had cataract extraction had significantly reduced risk for dementia compared with those who did not have cataract extraction (hazard ratio, 0.71), after controlling for age, race, APOE genotype, education, smoking, and an extensive list of comorbidities.
Causation or Coincidence?
The mechanisms behind these associations might be related to underlying illness, such as diabetes, which is a risk factor for dementia; vision loss itself, as might be suggested by a possible effect of cataract surgery; or shared neuropathologic processes in the retina and the brain.
A longitudinal study from Korea that included roughly 6 million adults showed that dementia risk increased with severity of visual loss, which supports the hypothesis that vision loss in itself might be causal or that there is a dose-response effect to a shared causal factor.
“Work is still needed to sort out” exactly how visual deficits may raise dementia risk, although several hypotheses exist, Dr. Ehrlich said.
For example, “decreased input to the brain via the visual pathways may directly induce brain changes. Also, consequences of vision loss, like social isolation, physical inactivity, and depression, are themselves risk factors for dementia and may explain the pathways through which vision impairment increases risk,” he said.
Is the link causal? “We’ll never know definitively because we can’t randomize people to not get cataract surgery versus getting cataract surgery, because we know that improving vision improves quality of life, so we’d never want to do that. But the new evidence that’s come in over the last 5 years or so is pretty promising,” said Esme Fuller-Thomson, PhD, director of the Institute for Life Course and Aging and professor, Department of Family and Community Medicine and Faculty of Nursing, at the University of Toronto, Ontario, Canada.
She noted that results of two studies that have looked at this “seem to indicate that those who have cataract surgery are not nearly at as high risk of dementia as those who have cataracts but don’t have the surgery. That’s leaning towards causality.”
A study published in July suggests that cataracts increase dementia risk through vascular and non–Alzheimer’s disease mechanisms.
Clear Clinical Implications
Dr. Ehrlich said that evidence for an association between untreated vision loss and dementia risk and potential modification by treatment has clear implications for care.
“Loss of vision impacts so many aspects of people’s lives beyond just how they see the world and losing vision in later life is not a normal part of aging. Thus, when older adults experience vision loss, this should be a cause for concern and prompt an immediate referral to an eye care professional,” he noted.
Dr. Fuller-Thomson agrees. “Addressing vision loss will certainly help people see better and function at a higher level and improve quality of life, and it seems probable that it might decrease dementia risk so it’s a win-win,” she said.
In her own research, Dr. Fuller-Thomson has found that the combination of hearing loss and vision loss is linked to an eightfold increased risk for cognitive impairment.
“The idea is that vision and/or hearing loss makes it harder for you to be physically active, to be socially engaged, to be mentally stimulated. They are equally important in terms of social isolation, which could lead to loneliness, and we know that loneliness is not good for dementia,” she said.
“With dual sensory impairment, you don’t have as much information coming in — your brain is not engaged as much — and having an engaged brain, doing hobbies, having intellectually stimulating conversation, all of those are factors are associated with lowering risk of dementia,” Dr. Fuller-Thomson said.
The latest Lancet Commission report noted that treatment for visual loss is “effective and cost-effective” for an estimated 90% of people. However, across the world, particularly in low- and middle-income countries, visual loss often goes untreated.
the report concluded.
Dr. Ehrlich and Dr. Fuller-Thomson have no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
In 2019, 57 million people worldwide were living with dementia, a figure expected to soar to 153 million by 2050. A recent Lancet Commission report suggests that nearly half of dementia cases could be prevented or delayed by addressing 14 modifiable risk factors, including impaired vision.
The report’s authors recommend that vision-loss screening and treatment be universally available. But are these recommendations warranted? What is the evidence? What is the potential mechanism? And what are the potential implications for clinical practice?
Worldwide, the prevalence of avoidable vision loss and blindness in adults aged 50 years or older is estimated to hover around 13%.
“There is now overwhelming evidence that vision impairment in later life is associated with more rapid cognitive decline and an increased risk of dementia,” said Joshua Ehrlich, MD, MPH, associate professor in ophthalmology and visual sciences, the Institute for Social Research at the University of Michigan, Ann Arbor.
The evidence includes a meta-analysis of 14 prospective cohort studies with roughly 6.2 million older adults who were cognitively intact at baseline. Over the course of up to 14 years, 171,888 developed dementia. Vision loss was associated with a pooled relative risk (RR) for dementia of 1.47.
A separate meta-analysis also identified an increased risk for dementia (RR, 1.38) with visual loss. When broken down into different eye conditions, an increased dementia risk was associated with cataracts and diabetic retinopathy but not with glaucoma or age-related macular degeneration.
A US study that followed roughly 3000 older adults with cataracts and normal cognition at baseline for more than 20 years found that those who had cataract extraction had significantly reduced risk for dementia compared with those who did not have cataract extraction (hazard ratio, 0.71), after controlling for age, race, APOE genotype, education, smoking, and an extensive list of comorbidities.
Causation or Coincidence?
The mechanisms behind these associations might be related to underlying illness, such as diabetes, which is a risk factor for dementia; vision loss itself, as might be suggested by a possible effect of cataract surgery; or shared neuropathologic processes in the retina and the brain.
A longitudinal study from Korea that included roughly 6 million adults showed that dementia risk increased with severity of visual loss, which supports the hypothesis that vision loss in itself might be causal or that there is a dose-response effect to a shared causal factor.
“Work is still needed to sort out” exactly how visual deficits may raise dementia risk, although several hypotheses exist, Dr. Ehrlich said.
For example, “decreased input to the brain via the visual pathways may directly induce brain changes. Also, consequences of vision loss, like social isolation, physical inactivity, and depression, are themselves risk factors for dementia and may explain the pathways through which vision impairment increases risk,” he said.
Is the link causal? “We’ll never know definitively because we can’t randomize people to not get cataract surgery versus getting cataract surgery, because we know that improving vision improves quality of life, so we’d never want to do that. But the new evidence that’s come in over the last 5 years or so is pretty promising,” said Esme Fuller-Thomson, PhD, director of the Institute for Life Course and Aging and professor, Department of Family and Community Medicine and Faculty of Nursing, at the University of Toronto, Ontario, Canada.
She noted that results of two studies that have looked at this “seem to indicate that those who have cataract surgery are not nearly at as high risk of dementia as those who have cataracts but don’t have the surgery. That’s leaning towards causality.”
A study published in July suggests that cataracts increase dementia risk through vascular and non–Alzheimer’s disease mechanisms.
Clear Clinical Implications
Dr. Ehrlich said that evidence for an association between untreated vision loss and dementia risk and potential modification by treatment has clear implications for care.
“Loss of vision impacts so many aspects of people’s lives beyond just how they see the world and losing vision in later life is not a normal part of aging. Thus, when older adults experience vision loss, this should be a cause for concern and prompt an immediate referral to an eye care professional,” he noted.
Dr. Fuller-Thomson agrees. “Addressing vision loss will certainly help people see better and function at a higher level and improve quality of life, and it seems probable that it might decrease dementia risk so it’s a win-win,” she said.
In her own research, Dr. Fuller-Thomson has found that the combination of hearing loss and vision loss is linked to an eightfold increased risk for cognitive impairment.
“The idea is that vision and/or hearing loss makes it harder for you to be physically active, to be socially engaged, to be mentally stimulated. They are equally important in terms of social isolation, which could lead to loneliness, and we know that loneliness is not good for dementia,” she said.
“With dual sensory impairment, you don’t have as much information coming in — your brain is not engaged as much — and having an engaged brain, doing hobbies, having intellectually stimulating conversation, all of those are factors are associated with lowering risk of dementia,” Dr. Fuller-Thomson said.
The latest Lancet Commission report noted that treatment for visual loss is “effective and cost-effective” for an estimated 90% of people. However, across the world, particularly in low- and middle-income countries, visual loss often goes untreated.
the report concluded.
Dr. Ehrlich and Dr. Fuller-Thomson have no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
In 2019, 57 million people worldwide were living with dementia, a figure expected to soar to 153 million by 2050. A recent Lancet Commission report suggests that nearly half of dementia cases could be prevented or delayed by addressing 14 modifiable risk factors, including impaired vision.
The report’s authors recommend that vision-loss screening and treatment be universally available. But are these recommendations warranted? What is the evidence? What is the potential mechanism? And what are the potential implications for clinical practice?
Worldwide, the prevalence of avoidable vision loss and blindness in adults aged 50 years or older is estimated to hover around 13%.
“There is now overwhelming evidence that vision impairment in later life is associated with more rapid cognitive decline and an increased risk of dementia,” said Joshua Ehrlich, MD, MPH, associate professor in ophthalmology and visual sciences, the Institute for Social Research at the University of Michigan, Ann Arbor.
The evidence includes a meta-analysis of 14 prospective cohort studies with roughly 6.2 million older adults who were cognitively intact at baseline. Over the course of up to 14 years, 171,888 developed dementia. Vision loss was associated with a pooled relative risk (RR) for dementia of 1.47.
A separate meta-analysis also identified an increased risk for dementia (RR, 1.38) with visual loss. When broken down into different eye conditions, an increased dementia risk was associated with cataracts and diabetic retinopathy but not with glaucoma or age-related macular degeneration.
A US study that followed roughly 3000 older adults with cataracts and normal cognition at baseline for more than 20 years found that those who had cataract extraction had significantly reduced risk for dementia compared with those who did not have cataract extraction (hazard ratio, 0.71), after controlling for age, race, APOE genotype, education, smoking, and an extensive list of comorbidities.
Causation or Coincidence?
The mechanisms behind these associations might be related to underlying illness, such as diabetes, which is a risk factor for dementia; vision loss itself, as might be suggested by a possible effect of cataract surgery; or shared neuropathologic processes in the retina and the brain.
A longitudinal study from Korea that included roughly 6 million adults showed that dementia risk increased with severity of visual loss, which supports the hypothesis that vision loss in itself might be causal or that there is a dose-response effect to a shared causal factor.
“Work is still needed to sort out” exactly how visual deficits may raise dementia risk, although several hypotheses exist, Dr. Ehrlich said.
For example, “decreased input to the brain via the visual pathways may directly induce brain changes. Also, consequences of vision loss, like social isolation, physical inactivity, and depression, are themselves risk factors for dementia and may explain the pathways through which vision impairment increases risk,” he said.
Is the link causal? “We’ll never know definitively because we can’t randomize people to not get cataract surgery versus getting cataract surgery, because we know that improving vision improves quality of life, so we’d never want to do that. But the new evidence that’s come in over the last 5 years or so is pretty promising,” said Esme Fuller-Thomson, PhD, director of the Institute for Life Course and Aging and professor, Department of Family and Community Medicine and Faculty of Nursing, at the University of Toronto, Ontario, Canada.
She noted that results of two studies that have looked at this “seem to indicate that those who have cataract surgery are not nearly at as high risk of dementia as those who have cataracts but don’t have the surgery. That’s leaning towards causality.”
A study published in July suggests that cataracts increase dementia risk through vascular and non–Alzheimer’s disease mechanisms.
Clear Clinical Implications
Dr. Ehrlich said that evidence for an association between untreated vision loss and dementia risk and potential modification by treatment has clear implications for care.
“Loss of vision impacts so many aspects of people’s lives beyond just how they see the world and losing vision in later life is not a normal part of aging. Thus, when older adults experience vision loss, this should be a cause for concern and prompt an immediate referral to an eye care professional,” he noted.
Dr. Fuller-Thomson agrees. “Addressing vision loss will certainly help people see better and function at a higher level and improve quality of life, and it seems probable that it might decrease dementia risk so it’s a win-win,” she said.
In her own research, Dr. Fuller-Thomson has found that the combination of hearing loss and vision loss is linked to an eightfold increased risk for cognitive impairment.
“The idea is that vision and/or hearing loss makes it harder for you to be physically active, to be socially engaged, to be mentally stimulated. They are equally important in terms of social isolation, which could lead to loneliness, and we know that loneliness is not good for dementia,” she said.
“With dual sensory impairment, you don’t have as much information coming in — your brain is not engaged as much — and having an engaged brain, doing hobbies, having intellectually stimulating conversation, all of those are factors are associated with lowering risk of dementia,” Dr. Fuller-Thomson said.
The latest Lancet Commission report noted that treatment for visual loss is “effective and cost-effective” for an estimated 90% of people. However, across the world, particularly in low- and middle-income countries, visual loss often goes untreated.
the report concluded.
Dr. Ehrlich and Dr. Fuller-Thomson have no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
BRCA Mutations in Men: Important but Often Overlooked
BRCA1 and BRCA2 pathogenic variants carry well-known associations with breast and ovarian cancers in women, which has led to robust clinical guidelines for early genetic testing and risk-reduction strategies.
Male carriers of BRCA1/2 pathogenic variants also face an increased risk for cancer, particularly of the prostate, pancreas, and breast.
However, men often fly under the radar.
“Most people (including their clinicians) are unaware of their carrier status,” Heather Cheng, MD, PhD, with University of Washington, Seattle, and colleagues explained in a comprehensive review on the subject, published in JAMA Oncology. Most are also unaware of “the associated cancer risks, and management recommendations” for BRCA carriers.
The testing gap in males may exist, in part, because of a “general lack of awareness” that BRCA gene mutations can be passed down to children from both the mother and father, Elisa Port, MD, chief of breast surgery for the Mount Sinai Health System in New York City, told this news organization.
A daughter can inherit a mutated BRCA gene that puts her at risk for breast or ovarian cancer from her mother’s or father’s family and, similarly, a son can inherit a mutated BRCA gene from either side of the family that puts him at an increased risk for developing prostate and other cancers, explained Dr. Port, director of the Center of Excellence for Breast Cancer at The Tisch Cancer Institute at Mount Sinai.
Considering family history and genetics on both sides of the family is important when assessing cancer risk in men and women, Dr. Port said.
BRCA Mutations in Men: What’s the Risk?
Although fewer than 1% of all breast cancers occur in men, when men do carry a BRCA mutation, their risk for breast cancer can increase considerably. The lifetime risk for breast cancer can be as high as 9% in male BRCA2 carriers and up to 1.2% in BRCA1 carriers.
BRCA1/2 mutations also put men at increased risk for pancreatic and prostate cancers.
For pancreatic cancer, male BRCA1 carriers have a nearly twofold increased risk compared with the general population, with a lifetime risk of 3%. BRCA2 carriers have a three- to nearly eightfold increased risk, with a lifetime risk up to 7%.
Male BRCA1 carriers face a nearly fourfold increased risk of developing prostate cancer and an absolute lifetime risk of 15%-45%. Male BRCA2 carriers have a five- to ninefold increased risk for prostate cancer, with an absolute lifetime risk between 27% and 60%.
When to Test, When to Screen?
Despite the increased risk for several cancers associated with BRCA mutations, many men are not offered genetic testing.
BRCA1/2 genetic testing in men is “ultra-important but underutilized and is an evolving unmet need that the field needs to address,” Kai Tsao, MD MS, medical director of the Medical Oncology Prostate Cancer Program at Mount Sinai in New York City, told this news organization.
For men considering genetic testing, in Dr. Tsao’s experience, barriers may include fear that insurance may not cover the test and that a positive test may increase insurance premiums, as well as concerns about what the test result may mean for them and their family.
Even for confirmed BRCA carriers, cancer screening guidelines for men vary.
For breast screening in men, there’s limited data to inform guidelines. The National Cancer Center Network currently recommends breast awareness and teaching self-examination starting at age 35 and recommends men with BRCA variants consider yearly mammograms starting at age 50, or 10 years before the earliest male breast cancer diagnosis in the family.
Data show that screening mammography in men at high-risk for breast cancer yields similar cancer detection rates in men and women, “suggesting mammography screening may be valuable in male BRCA carriers,” the review authors noted. And, in a recent study of men with BRCA1/2 pathogenic variants, most (71%) recommended for screening mammography completed their screening.
The European Society for Medical Oncology (ESMO) has similar screening recommendations but focuses only on men with BRCA2 mutations and suggests breast ultrasonography as well as mammography as a screening option.
The larger “issue is the general population doesn’t think of breast cancer when they think of men, which may delay seeking medical attention,” said Melissa Fana, MD, of NYU Grossman Long Island School of Medicine and NYU Langone Health, who wasn’t involved in the review.
For pancreatic cancer, guidelines suggest BRCA1/2 carriers be screened for pancreatic cancer starting at age 50, or 10 years before the earliest known pancreatic cancer in the family, although the guidelines vary on the role family history should play.
And for prostate cancer, current guidelines recommend male BRCA carriers begin prostate-specific antigen screening between age 40 and 45 years, although recommendations on screening intervals and start age vary. ESMO recommendations are similar but only apply to BRCA2 carriers.
A male patient with a BRCA1/2 variant is typically referred for genetic counseling as well, Dr. Tsao explained. But “the challenge is that we don’t have a very good healthcare infrastructure right now” to follow through with that, he added. “Oftentimes a patient will wait many months or even more than a year for a genetic counseling appointment.”
To help improve these issues, Mount Sinai recently launched a comprehensive BRCA program for men and women that offers genetic testing and counseling for patients and family members.
Overall, identifying more male BRCA1/2 carriers will “maximize opportunities for cancer early detection, targeted risk management, and cancer treatment for males, along with facilitating opportunities for risk reduction and prevention in their family members, thereby decreasing the burden of hereditary cancer,” Dr. Cheng and colleagues concluded.
Support for the review was provided in part by BRCA Research and Cure Alliance and the Men & BRCA Program at the Basser Center for BRCA. Cheng reported grants from Promontory Pharmaceutics, Medivation, Sanofi, Janssen, royalties from UpToDate, nonfinancial support from Color Health, personal fees from AstraZeneca, BRCA Research and Cure Alliance (CureBRCA) outside the submitted work. Dr. Port, Dr. Tsao, and Dr. Fana had no conflicts of interest.
A version of this article first appeared on Medscape.com.
BRCA1 and BRCA2 pathogenic variants carry well-known associations with breast and ovarian cancers in women, which has led to robust clinical guidelines for early genetic testing and risk-reduction strategies.
Male carriers of BRCA1/2 pathogenic variants also face an increased risk for cancer, particularly of the prostate, pancreas, and breast.
However, men often fly under the radar.
“Most people (including their clinicians) are unaware of their carrier status,” Heather Cheng, MD, PhD, with University of Washington, Seattle, and colleagues explained in a comprehensive review on the subject, published in JAMA Oncology. Most are also unaware of “the associated cancer risks, and management recommendations” for BRCA carriers.
The testing gap in males may exist, in part, because of a “general lack of awareness” that BRCA gene mutations can be passed down to children from both the mother and father, Elisa Port, MD, chief of breast surgery for the Mount Sinai Health System in New York City, told this news organization.
A daughter can inherit a mutated BRCA gene that puts her at risk for breast or ovarian cancer from her mother’s or father’s family and, similarly, a son can inherit a mutated BRCA gene from either side of the family that puts him at an increased risk for developing prostate and other cancers, explained Dr. Port, director of the Center of Excellence for Breast Cancer at The Tisch Cancer Institute at Mount Sinai.
Considering family history and genetics on both sides of the family is important when assessing cancer risk in men and women, Dr. Port said.
BRCA Mutations in Men: What’s the Risk?
Although fewer than 1% of all breast cancers occur in men, when men do carry a BRCA mutation, their risk for breast cancer can increase considerably. The lifetime risk for breast cancer can be as high as 9% in male BRCA2 carriers and up to 1.2% in BRCA1 carriers.
BRCA1/2 mutations also put men at increased risk for pancreatic and prostate cancers.
For pancreatic cancer, male BRCA1 carriers have a nearly twofold increased risk compared with the general population, with a lifetime risk of 3%. BRCA2 carriers have a three- to nearly eightfold increased risk, with a lifetime risk up to 7%.
Male BRCA1 carriers face a nearly fourfold increased risk of developing prostate cancer and an absolute lifetime risk of 15%-45%. Male BRCA2 carriers have a five- to ninefold increased risk for prostate cancer, with an absolute lifetime risk between 27% and 60%.
When to Test, When to Screen?
Despite the increased risk for several cancers associated with BRCA mutations, many men are not offered genetic testing.
BRCA1/2 genetic testing in men is “ultra-important but underutilized and is an evolving unmet need that the field needs to address,” Kai Tsao, MD MS, medical director of the Medical Oncology Prostate Cancer Program at Mount Sinai in New York City, told this news organization.
For men considering genetic testing, in Dr. Tsao’s experience, barriers may include fear that insurance may not cover the test and that a positive test may increase insurance premiums, as well as concerns about what the test result may mean for them and their family.
Even for confirmed BRCA carriers, cancer screening guidelines for men vary.
For breast screening in men, there’s limited data to inform guidelines. The National Cancer Center Network currently recommends breast awareness and teaching self-examination starting at age 35 and recommends men with BRCA variants consider yearly mammograms starting at age 50, or 10 years before the earliest male breast cancer diagnosis in the family.
Data show that screening mammography in men at high-risk for breast cancer yields similar cancer detection rates in men and women, “suggesting mammography screening may be valuable in male BRCA carriers,” the review authors noted. And, in a recent study of men with BRCA1/2 pathogenic variants, most (71%) recommended for screening mammography completed their screening.
The European Society for Medical Oncology (ESMO) has similar screening recommendations but focuses only on men with BRCA2 mutations and suggests breast ultrasonography as well as mammography as a screening option.
The larger “issue is the general population doesn’t think of breast cancer when they think of men, which may delay seeking medical attention,” said Melissa Fana, MD, of NYU Grossman Long Island School of Medicine and NYU Langone Health, who wasn’t involved in the review.
For pancreatic cancer, guidelines suggest BRCA1/2 carriers be screened for pancreatic cancer starting at age 50, or 10 years before the earliest known pancreatic cancer in the family, although the guidelines vary on the role family history should play.
And for prostate cancer, current guidelines recommend male BRCA carriers begin prostate-specific antigen screening between age 40 and 45 years, although recommendations on screening intervals and start age vary. ESMO recommendations are similar but only apply to BRCA2 carriers.
A male patient with a BRCA1/2 variant is typically referred for genetic counseling as well, Dr. Tsao explained. But “the challenge is that we don’t have a very good healthcare infrastructure right now” to follow through with that, he added. “Oftentimes a patient will wait many months or even more than a year for a genetic counseling appointment.”
To help improve these issues, Mount Sinai recently launched a comprehensive BRCA program for men and women that offers genetic testing and counseling for patients and family members.
Overall, identifying more male BRCA1/2 carriers will “maximize opportunities for cancer early detection, targeted risk management, and cancer treatment for males, along with facilitating opportunities for risk reduction and prevention in their family members, thereby decreasing the burden of hereditary cancer,” Dr. Cheng and colleagues concluded.
Support for the review was provided in part by BRCA Research and Cure Alliance and the Men & BRCA Program at the Basser Center for BRCA. Cheng reported grants from Promontory Pharmaceutics, Medivation, Sanofi, Janssen, royalties from UpToDate, nonfinancial support from Color Health, personal fees from AstraZeneca, BRCA Research and Cure Alliance (CureBRCA) outside the submitted work. Dr. Port, Dr. Tsao, and Dr. Fana had no conflicts of interest.
A version of this article first appeared on Medscape.com.
BRCA1 and BRCA2 pathogenic variants carry well-known associations with breast and ovarian cancers in women, which has led to robust clinical guidelines for early genetic testing and risk-reduction strategies.
Male carriers of BRCA1/2 pathogenic variants also face an increased risk for cancer, particularly of the prostate, pancreas, and breast.
However, men often fly under the radar.
“Most people (including their clinicians) are unaware of their carrier status,” Heather Cheng, MD, PhD, with University of Washington, Seattle, and colleagues explained in a comprehensive review on the subject, published in JAMA Oncology. Most are also unaware of “the associated cancer risks, and management recommendations” for BRCA carriers.
The testing gap in males may exist, in part, because of a “general lack of awareness” that BRCA gene mutations can be passed down to children from both the mother and father, Elisa Port, MD, chief of breast surgery for the Mount Sinai Health System in New York City, told this news organization.
A daughter can inherit a mutated BRCA gene that puts her at risk for breast or ovarian cancer from her mother’s or father’s family and, similarly, a son can inherit a mutated BRCA gene from either side of the family that puts him at an increased risk for developing prostate and other cancers, explained Dr. Port, director of the Center of Excellence for Breast Cancer at The Tisch Cancer Institute at Mount Sinai.
Considering family history and genetics on both sides of the family is important when assessing cancer risk in men and women, Dr. Port said.
BRCA Mutations in Men: What’s the Risk?
Although fewer than 1% of all breast cancers occur in men, when men do carry a BRCA mutation, their risk for breast cancer can increase considerably. The lifetime risk for breast cancer can be as high as 9% in male BRCA2 carriers and up to 1.2% in BRCA1 carriers.
BRCA1/2 mutations also put men at increased risk for pancreatic and prostate cancers.
For pancreatic cancer, male BRCA1 carriers have a nearly twofold increased risk compared with the general population, with a lifetime risk of 3%. BRCA2 carriers have a three- to nearly eightfold increased risk, with a lifetime risk up to 7%.
Male BRCA1 carriers face a nearly fourfold increased risk of developing prostate cancer and an absolute lifetime risk of 15%-45%. Male BRCA2 carriers have a five- to ninefold increased risk for prostate cancer, with an absolute lifetime risk between 27% and 60%.
When to Test, When to Screen?
Despite the increased risk for several cancers associated with BRCA mutations, many men are not offered genetic testing.
BRCA1/2 genetic testing in men is “ultra-important but underutilized and is an evolving unmet need that the field needs to address,” Kai Tsao, MD MS, medical director of the Medical Oncology Prostate Cancer Program at Mount Sinai in New York City, told this news organization.
For men considering genetic testing, in Dr. Tsao’s experience, barriers may include fear that insurance may not cover the test and that a positive test may increase insurance premiums, as well as concerns about what the test result may mean for them and their family.
Even for confirmed BRCA carriers, cancer screening guidelines for men vary.
For breast screening in men, there’s limited data to inform guidelines. The National Cancer Center Network currently recommends breast awareness and teaching self-examination starting at age 35 and recommends men with BRCA variants consider yearly mammograms starting at age 50, or 10 years before the earliest male breast cancer diagnosis in the family.
Data show that screening mammography in men at high-risk for breast cancer yields similar cancer detection rates in men and women, “suggesting mammography screening may be valuable in male BRCA carriers,” the review authors noted. And, in a recent study of men with BRCA1/2 pathogenic variants, most (71%) recommended for screening mammography completed their screening.
The European Society for Medical Oncology (ESMO) has similar screening recommendations but focuses only on men with BRCA2 mutations and suggests breast ultrasonography as well as mammography as a screening option.
The larger “issue is the general population doesn’t think of breast cancer when they think of men, which may delay seeking medical attention,” said Melissa Fana, MD, of NYU Grossman Long Island School of Medicine and NYU Langone Health, who wasn’t involved in the review.
For pancreatic cancer, guidelines suggest BRCA1/2 carriers be screened for pancreatic cancer starting at age 50, or 10 years before the earliest known pancreatic cancer in the family, although the guidelines vary on the role family history should play.
And for prostate cancer, current guidelines recommend male BRCA carriers begin prostate-specific antigen screening between age 40 and 45 years, although recommendations on screening intervals and start age vary. ESMO recommendations are similar but only apply to BRCA2 carriers.
A male patient with a BRCA1/2 variant is typically referred for genetic counseling as well, Dr. Tsao explained. But “the challenge is that we don’t have a very good healthcare infrastructure right now” to follow through with that, he added. “Oftentimes a patient will wait many months or even more than a year for a genetic counseling appointment.”
To help improve these issues, Mount Sinai recently launched a comprehensive BRCA program for men and women that offers genetic testing and counseling for patients and family members.
Overall, identifying more male BRCA1/2 carriers will “maximize opportunities for cancer early detection, targeted risk management, and cancer treatment for males, along with facilitating opportunities for risk reduction and prevention in their family members, thereby decreasing the burden of hereditary cancer,” Dr. Cheng and colleagues concluded.
Support for the review was provided in part by BRCA Research and Cure Alliance and the Men & BRCA Program at the Basser Center for BRCA. Cheng reported grants from Promontory Pharmaceutics, Medivation, Sanofi, Janssen, royalties from UpToDate, nonfinancial support from Color Health, personal fees from AstraZeneca, BRCA Research and Cure Alliance (CureBRCA) outside the submitted work. Dr. Port, Dr. Tsao, and Dr. Fana had no conflicts of interest.
A version of this article first appeared on Medscape.com.
FDA Grants Livdelzi Accelerated Approval for Primary Biliary Cholangitis
, or as monotherapy in those who can’t tolerate UDCA.
Livdelzi, a selective agonist of peroxisome proliferator–activated receptor delta, is not recommended in adults who have or develop decompensated cirrhosis.
PBC is a rare, chronic, autoimmune disease of the bile ducts that affects roughly 130,000 Americans, primarily women, and can cause liver damage and possible liver failure if untreated. The disease currently has no cure.
The FDA approved Livdelzi based largely on results of the phase 3 RESPONSE study, in which the drug significantly improved liver biomarkers of disease activity and bothersome symptoms of pruritus in adults with PBC.
The primary endpoint of the trial was a biochemical response, defined as an alkaline phosphatase (ALP) level < 1.67 times the upper limit of the normal range, with a decrease of 15% or more from baseline, and a normal total bilirubin level, at 12 months.
After 12 months, 62% of patients taking Livdelzi met the primary endpoint vs 20% of patients taking placebo.
In addition, significantly more patients taking Livdelzi than placebo had normalization of the ALP level (25% vs 0%). The average decrease in ALP from baseline was 42.4% in the Livdelzi group vs 4.3% in the placebo group.
At 12 months, alanine aminotransferase and gamma-glutamyl transferase levels were reduced by 23.5% and 39.1%, respectively, in the Livdelzi group compared with 6.5% and 11.4%, respectively, in the placebo group.
A key secondary endpoint was change in patient-reported pruritus.
At baseline, 38.3% of patients in the Livdelzi group and 35.4% of those in the placebo group had moderate to severe pruritus, with a daily numerical rating scale (NRS) score ≥ 4 out of 10.
Among these patients, the reduction from baseline in the pruritus NRS score at month 6 was significantly greater with Livdelzi than with placebo (change from baseline, -3.2 vs -1.7 points). These improvements were sustained through 12 months.
Improvements on the 5-D Itch Scale in both the moderate- to severe-pruritis population and the overall population also favored Livdelzi over placebo for itch relief, which had a positive impact on sleep.
“The availability of a new treatment option that can help reduce [the] intense itching while also improving biomarkers of active liver disease is a milestone for our community,” Carol Roberts, president, The PBCers Organization, said in a news release announcing the approval.
The most common adverse reactions with Livdelzi were headache, abdominal pain, nausea, abdominal distension, and dizziness.
The company noted that the FDA granted accelerated approval for Livdelzi based on a reduction of ALP. Improvement in survival or prevention of liver decompensation events have not been demonstrated. Continued approval of Livdelzi for PBC may be contingent on verification and description of clinical benefit in confirmatory trial(s).
A version of this article appeared on Medscape.com.
, or as monotherapy in those who can’t tolerate UDCA.
Livdelzi, a selective agonist of peroxisome proliferator–activated receptor delta, is not recommended in adults who have or develop decompensated cirrhosis.
PBC is a rare, chronic, autoimmune disease of the bile ducts that affects roughly 130,000 Americans, primarily women, and can cause liver damage and possible liver failure if untreated. The disease currently has no cure.
The FDA approved Livdelzi based largely on results of the phase 3 RESPONSE study, in which the drug significantly improved liver biomarkers of disease activity and bothersome symptoms of pruritus in adults with PBC.
The primary endpoint of the trial was a biochemical response, defined as an alkaline phosphatase (ALP) level < 1.67 times the upper limit of the normal range, with a decrease of 15% or more from baseline, and a normal total bilirubin level, at 12 months.
After 12 months, 62% of patients taking Livdelzi met the primary endpoint vs 20% of patients taking placebo.
In addition, significantly more patients taking Livdelzi than placebo had normalization of the ALP level (25% vs 0%). The average decrease in ALP from baseline was 42.4% in the Livdelzi group vs 4.3% in the placebo group.
At 12 months, alanine aminotransferase and gamma-glutamyl transferase levels were reduced by 23.5% and 39.1%, respectively, in the Livdelzi group compared with 6.5% and 11.4%, respectively, in the placebo group.
A key secondary endpoint was change in patient-reported pruritus.
At baseline, 38.3% of patients in the Livdelzi group and 35.4% of those in the placebo group had moderate to severe pruritus, with a daily numerical rating scale (NRS) score ≥ 4 out of 10.
Among these patients, the reduction from baseline in the pruritus NRS score at month 6 was significantly greater with Livdelzi than with placebo (change from baseline, -3.2 vs -1.7 points). These improvements were sustained through 12 months.
Improvements on the 5-D Itch Scale in both the moderate- to severe-pruritis population and the overall population also favored Livdelzi over placebo for itch relief, which had a positive impact on sleep.
“The availability of a new treatment option that can help reduce [the] intense itching while also improving biomarkers of active liver disease is a milestone for our community,” Carol Roberts, president, The PBCers Organization, said in a news release announcing the approval.
The most common adverse reactions with Livdelzi were headache, abdominal pain, nausea, abdominal distension, and dizziness.
The company noted that the FDA granted accelerated approval for Livdelzi based on a reduction of ALP. Improvement in survival or prevention of liver decompensation events have not been demonstrated. Continued approval of Livdelzi for PBC may be contingent on verification and description of clinical benefit in confirmatory trial(s).
A version of this article appeared on Medscape.com.
, or as monotherapy in those who can’t tolerate UDCA.
Livdelzi, a selective agonist of peroxisome proliferator–activated receptor delta, is not recommended in adults who have or develop decompensated cirrhosis.
PBC is a rare, chronic, autoimmune disease of the bile ducts that affects roughly 130,000 Americans, primarily women, and can cause liver damage and possible liver failure if untreated. The disease currently has no cure.
The FDA approved Livdelzi based largely on results of the phase 3 RESPONSE study, in which the drug significantly improved liver biomarkers of disease activity and bothersome symptoms of pruritus in adults with PBC.
The primary endpoint of the trial was a biochemical response, defined as an alkaline phosphatase (ALP) level < 1.67 times the upper limit of the normal range, with a decrease of 15% or more from baseline, and a normal total bilirubin level, at 12 months.
After 12 months, 62% of patients taking Livdelzi met the primary endpoint vs 20% of patients taking placebo.
In addition, significantly more patients taking Livdelzi than placebo had normalization of the ALP level (25% vs 0%). The average decrease in ALP from baseline was 42.4% in the Livdelzi group vs 4.3% in the placebo group.
At 12 months, alanine aminotransferase and gamma-glutamyl transferase levels were reduced by 23.5% and 39.1%, respectively, in the Livdelzi group compared with 6.5% and 11.4%, respectively, in the placebo group.
A key secondary endpoint was change in patient-reported pruritus.
At baseline, 38.3% of patients in the Livdelzi group and 35.4% of those in the placebo group had moderate to severe pruritus, with a daily numerical rating scale (NRS) score ≥ 4 out of 10.
Among these patients, the reduction from baseline in the pruritus NRS score at month 6 was significantly greater with Livdelzi than with placebo (change from baseline, -3.2 vs -1.7 points). These improvements were sustained through 12 months.
Improvements on the 5-D Itch Scale in both the moderate- to severe-pruritis population and the overall population also favored Livdelzi over placebo for itch relief, which had a positive impact on sleep.
“The availability of a new treatment option that can help reduce [the] intense itching while also improving biomarkers of active liver disease is a milestone for our community,” Carol Roberts, president, The PBCers Organization, said in a news release announcing the approval.
The most common adverse reactions with Livdelzi were headache, abdominal pain, nausea, abdominal distension, and dizziness.
The company noted that the FDA granted accelerated approval for Livdelzi based on a reduction of ALP. Improvement in survival or prevention of liver decompensation events have not been demonstrated. Continued approval of Livdelzi for PBC may be contingent on verification and description of clinical benefit in confirmatory trial(s).
A version of this article appeared on Medscape.com.
FIT Screening Cuts Colorectal Cancer Mortality by One Third
TOPLINE:
METHODOLOGY:
- In the United States, annual FIT screening is recommended among average-risk adults to reduce the risk for death from CRC, but evidence on its effectiveness is limited.
- Researchers performed a nested case-control study within two large, demographically diverse health systems with long-standing programs of mailing FITs to promote CRC screening efforts.
- They compared 1103 adults who had died of CRC between 2011 and 2017 (cases) with 9608 matched, randomly selected people who were alive and free of CRC (controls).
- Analyses focused on FIT screening completed within 5 years before CRC diagnosis for cases or the corresponding date for controls.
- The primary outcome measured was CRC death overall and by tumor location; secondary analyses assessed CRC death by race and ethnicity.
TAKEAWAY:
- In regression analysis, completing one or more FIT screenings was associated with a 33% lower risk for CRC death overall.
- There was a 42% lower risk for death from left colon and rectum cancers but no significant reduction in mortality from right colon cancers.
- The benefits of FIT screening were observed across racial and ethnic groups, with significant mortality reductions of 63% in non-Hispanic Asian, 42% in non-Hispanic Black, and 29% in non-Hispanic White individuals.
IN PRACTICE:
“The findings support the use of strategies for coordinated and equitable large-scale population-based delivery of FIT screening with follow-up of abnormal screening results to help avert preventable premature CRC deaths,” the authors wrote.
SOURCE:
The study, with first author Chyke A. Doubeni, MD, MPH, Center for Health Equity, The Ohio State University Wexner Medical Center, Columbus, Ohio, was published online in JAMA Network Open.
LIMITATIONS:
Almost one half of study subjects had completed two or more FITs, but the case-control design was not suitable for assessing the impact of repeated screening. The study was conducted prior to the US Preventive Services Task Force recommendation to start screening at age 45 years, so the findings may not directly apply to adults aged 45-49 years.
DISCLOSURES:
The study was funded by the National Cancer Institute. Dr. Doubeni reported receiving royalties from UpToDate, and additional authors reported receiving grants outside the submitted work. No other disclosures were reported.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- In the United States, annual FIT screening is recommended among average-risk adults to reduce the risk for death from CRC, but evidence on its effectiveness is limited.
- Researchers performed a nested case-control study within two large, demographically diverse health systems with long-standing programs of mailing FITs to promote CRC screening efforts.
- They compared 1103 adults who had died of CRC between 2011 and 2017 (cases) with 9608 matched, randomly selected people who were alive and free of CRC (controls).
- Analyses focused on FIT screening completed within 5 years before CRC diagnosis for cases or the corresponding date for controls.
- The primary outcome measured was CRC death overall and by tumor location; secondary analyses assessed CRC death by race and ethnicity.
TAKEAWAY:
- In regression analysis, completing one or more FIT screenings was associated with a 33% lower risk for CRC death overall.
- There was a 42% lower risk for death from left colon and rectum cancers but no significant reduction in mortality from right colon cancers.
- The benefits of FIT screening were observed across racial and ethnic groups, with significant mortality reductions of 63% in non-Hispanic Asian, 42% in non-Hispanic Black, and 29% in non-Hispanic White individuals.
IN PRACTICE:
“The findings support the use of strategies for coordinated and equitable large-scale population-based delivery of FIT screening with follow-up of abnormal screening results to help avert preventable premature CRC deaths,” the authors wrote.
SOURCE:
The study, with first author Chyke A. Doubeni, MD, MPH, Center for Health Equity, The Ohio State University Wexner Medical Center, Columbus, Ohio, was published online in JAMA Network Open.
LIMITATIONS:
Almost one half of study subjects had completed two or more FITs, but the case-control design was not suitable for assessing the impact of repeated screening. The study was conducted prior to the US Preventive Services Task Force recommendation to start screening at age 45 years, so the findings may not directly apply to adults aged 45-49 years.
DISCLOSURES:
The study was funded by the National Cancer Institute. Dr. Doubeni reported receiving royalties from UpToDate, and additional authors reported receiving grants outside the submitted work. No other disclosures were reported.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- In the United States, annual FIT screening is recommended among average-risk adults to reduce the risk for death from CRC, but evidence on its effectiveness is limited.
- Researchers performed a nested case-control study within two large, demographically diverse health systems with long-standing programs of mailing FITs to promote CRC screening efforts.
- They compared 1103 adults who had died of CRC between 2011 and 2017 (cases) with 9608 matched, randomly selected people who were alive and free of CRC (controls).
- Analyses focused on FIT screening completed within 5 years before CRC diagnosis for cases or the corresponding date for controls.
- The primary outcome measured was CRC death overall and by tumor location; secondary analyses assessed CRC death by race and ethnicity.
TAKEAWAY:
- In regression analysis, completing one or more FIT screenings was associated with a 33% lower risk for CRC death overall.
- There was a 42% lower risk for death from left colon and rectum cancers but no significant reduction in mortality from right colon cancers.
- The benefits of FIT screening were observed across racial and ethnic groups, with significant mortality reductions of 63% in non-Hispanic Asian, 42% in non-Hispanic Black, and 29% in non-Hispanic White individuals.
IN PRACTICE:
“The findings support the use of strategies for coordinated and equitable large-scale population-based delivery of FIT screening with follow-up of abnormal screening results to help avert preventable premature CRC deaths,” the authors wrote.
SOURCE:
The study, with first author Chyke A. Doubeni, MD, MPH, Center for Health Equity, The Ohio State University Wexner Medical Center, Columbus, Ohio, was published online in JAMA Network Open.
LIMITATIONS:
Almost one half of study subjects had completed two or more FITs, but the case-control design was not suitable for assessing the impact of repeated screening. The study was conducted prior to the US Preventive Services Task Force recommendation to start screening at age 45 years, so the findings may not directly apply to adults aged 45-49 years.
DISCLOSURES:
The study was funded by the National Cancer Institute. Dr. Doubeni reported receiving royalties from UpToDate, and additional authors reported receiving grants outside the submitted work. No other disclosures were reported.
A version of this article first appeared on Medscape.com.
Almost 50% of Global Dementia Cases May Be Preventable
PHILADELPHIA – a report from the Lancet Commission on dementia prevention, intervention, and care.
The report adds two new modifiable risk factors for dementia — high cholesterol and vision loss — to the 12 risk factors identified in the 2020 Lancet Commission report, which were linked to about 40% of all dementia cases.
The original Lancet Commission report, published in 2017, identified nine modifiable risk factors that were estimated to be responsible for one third of dementia cases.
“Our new report reveals that there is much more that can and should be done to reduce the risk of dementia. It’s never too early or too late to act, with opportunities to make an impact at any stage of life,” lead author Gill Livingston, MD, from University College London in England, said in a statement.
The 57-page report was published online in The Lancet Neurology (to coincide with its presentation at the 2024 Alzheimer’s Association International Conference (AAIC).
‘Compelling’ New Evidence
The 12 risk factors cited in the 2020 report are lower levels of education, hearing loss, hypertension, smoking, obesity, depression, physical inactivity, diabetes, excessive alcohol consumption, traumatic brain injury (TBI), air pollution, and social isolation.
According to the authors of the current report, there is “new compelling evidence” that untreated vision loss and elevated low-density lipoprotein (LDL) cholesterol are also risk factors for dementia.
These two added risk factors are associated with 9% of all dementia cases — with an estimated 7% of cases caused by high LDL cholesterol from about age 40 years, and 2% of cases caused by untreated vision loss in later life, the authors said.
Out of all 14 risk factors, those tied to the greatest proportion of dementia in the global population are hearing impairment and high LDL cholesterol (7% each), along with less education in early life, and social isolation in later life (5% each), the report estimates.
The new report also outlines 13 recommendations aimed at individuals and governments to help guard against dementia. They include preventing and treating hearing loss, vision loss, and depression; being cognitively active throughout life; using head protection in contact sports; reducing vascular risk factors (high cholesterol, diabetes, obesity, hypertension); improving air quality; and providing supportive community environments to increase social contact.
Tara Spires-Jones, PhD, president of the British Neuroscience Association, emphasized that, while this research doesn’t directly link specific factors to dementia, it supports evidence that a healthy lifestyle — encompassing education, social activities, exercise, cognitive engagement, and avoiding head injuries and harmful factors for heart and lung health — can enhance brain resilience and prevent dementia.
In an interview, Heather M. Snyder, PhD, senior vice president of medical and scientific relations, Alzheimer’s Association, said: “Our brains are complex and what happens throughout our lives may increase or decrease our risk for dementia as we age. Protecting brain health as we age requires a comprehensive approach that includes discussions on diet, exercise, heart health, hearing, and vision.”
Also weighing in on the new report, Shaheen Lakhan, MD, PhD, neurologist and researcher based in Miami, Florida, said the addition of high cholesterol is “particularly noteworthy as it reinforces the intricate connection between vascular health and brain health — a link we’ve long suspected but can now target more effectively.”
As for vision loss, “it’s not just a matter of seeing clearly; it’s a matter of thinking clearly. Untreated vision loss can lead to social isolation, reduced physical activity, and cognitive decline,” said Dr. Lakhan.
Dementia Is Not Inevitable
In his view, “the potential to prevent or delay nearly half of dementia cases by addressing these risk factors is nothing short of revolutionary. It shifts our perspective from viewing dementia as an inevitable part of aging to seeing it as a condition we can actively work to prevent,” Dr. Lakhan added.
He said the report’s emphasis on health equity is also important.
“Dementia risk factors disproportionately affect socioeconomically disadvantaged groups and low- and middle-income countries. Addressing these disparities isn’t just a matter of fairness in the fight against dementia, equality in prevention is as important as equality in treatment,” Dr. Lakhan commented.
While the report offers hope, it also presents a challenge, he said.
Implementing the recommended preventive measures requires a “coordinated effort from individuals, healthcare systems, and policymakers. The potential benefits, both in terms of quality of life and economic savings, make this effort not just worthwhile but imperative. Preventing dementia is not just a medical imperative — it’s an economic and humanitarian one,” Dr. Lakhan said.
Masud Husain, PhD, with the University of Oxford in England, agreed.
The conclusions in this report are “very important for all of us, but particularly for health policy makers and government,” he said.
“If we did simple things well such as screening for some of the factors identified in this report, with adequate resources to perform this, we have the potential to prevent dementia on a national scale. This would be far more cost effective than developing high-tech treatments, which so far have been disappointing in their impacts on people with established dementia,” Dr. Husain said.
The Lancet Commission was funded by University College London, Alzheimer’s Society, Alzheimer’s Research UK, and the Economic and Social Research Council. A complete list of author disclosures is available with the original article. Dr. Snyder, Dr. Lakhan, Dr. Husain and Dr. Spires-Jones have no relevant disclosures.
A version of this article appeared on Medscape.com.
PHILADELPHIA – a report from the Lancet Commission on dementia prevention, intervention, and care.
The report adds two new modifiable risk factors for dementia — high cholesterol and vision loss — to the 12 risk factors identified in the 2020 Lancet Commission report, which were linked to about 40% of all dementia cases.
The original Lancet Commission report, published in 2017, identified nine modifiable risk factors that were estimated to be responsible for one third of dementia cases.
“Our new report reveals that there is much more that can and should be done to reduce the risk of dementia. It’s never too early or too late to act, with opportunities to make an impact at any stage of life,” lead author Gill Livingston, MD, from University College London in England, said in a statement.
The 57-page report was published online in The Lancet Neurology (to coincide with its presentation at the 2024 Alzheimer’s Association International Conference (AAIC).
‘Compelling’ New Evidence
The 12 risk factors cited in the 2020 report are lower levels of education, hearing loss, hypertension, smoking, obesity, depression, physical inactivity, diabetes, excessive alcohol consumption, traumatic brain injury (TBI), air pollution, and social isolation.
According to the authors of the current report, there is “new compelling evidence” that untreated vision loss and elevated low-density lipoprotein (LDL) cholesterol are also risk factors for dementia.
These two added risk factors are associated with 9% of all dementia cases — with an estimated 7% of cases caused by high LDL cholesterol from about age 40 years, and 2% of cases caused by untreated vision loss in later life, the authors said.
Out of all 14 risk factors, those tied to the greatest proportion of dementia in the global population are hearing impairment and high LDL cholesterol (7% each), along with less education in early life, and social isolation in later life (5% each), the report estimates.
The new report also outlines 13 recommendations aimed at individuals and governments to help guard against dementia. They include preventing and treating hearing loss, vision loss, and depression; being cognitively active throughout life; using head protection in contact sports; reducing vascular risk factors (high cholesterol, diabetes, obesity, hypertension); improving air quality; and providing supportive community environments to increase social contact.
Tara Spires-Jones, PhD, president of the British Neuroscience Association, emphasized that, while this research doesn’t directly link specific factors to dementia, it supports evidence that a healthy lifestyle — encompassing education, social activities, exercise, cognitive engagement, and avoiding head injuries and harmful factors for heart and lung health — can enhance brain resilience and prevent dementia.
In an interview, Heather M. Snyder, PhD, senior vice president of medical and scientific relations, Alzheimer’s Association, said: “Our brains are complex and what happens throughout our lives may increase or decrease our risk for dementia as we age. Protecting brain health as we age requires a comprehensive approach that includes discussions on diet, exercise, heart health, hearing, and vision.”
Also weighing in on the new report, Shaheen Lakhan, MD, PhD, neurologist and researcher based in Miami, Florida, said the addition of high cholesterol is “particularly noteworthy as it reinforces the intricate connection between vascular health and brain health — a link we’ve long suspected but can now target more effectively.”
As for vision loss, “it’s not just a matter of seeing clearly; it’s a matter of thinking clearly. Untreated vision loss can lead to social isolation, reduced physical activity, and cognitive decline,” said Dr. Lakhan.
Dementia Is Not Inevitable
In his view, “the potential to prevent or delay nearly half of dementia cases by addressing these risk factors is nothing short of revolutionary. It shifts our perspective from viewing dementia as an inevitable part of aging to seeing it as a condition we can actively work to prevent,” Dr. Lakhan added.
He said the report’s emphasis on health equity is also important.
“Dementia risk factors disproportionately affect socioeconomically disadvantaged groups and low- and middle-income countries. Addressing these disparities isn’t just a matter of fairness in the fight against dementia, equality in prevention is as important as equality in treatment,” Dr. Lakhan commented.
While the report offers hope, it also presents a challenge, he said.
Implementing the recommended preventive measures requires a “coordinated effort from individuals, healthcare systems, and policymakers. The potential benefits, both in terms of quality of life and economic savings, make this effort not just worthwhile but imperative. Preventing dementia is not just a medical imperative — it’s an economic and humanitarian one,” Dr. Lakhan said.
Masud Husain, PhD, with the University of Oxford in England, agreed.
The conclusions in this report are “very important for all of us, but particularly for health policy makers and government,” he said.
“If we did simple things well such as screening for some of the factors identified in this report, with adequate resources to perform this, we have the potential to prevent dementia on a national scale. This would be far more cost effective than developing high-tech treatments, which so far have been disappointing in their impacts on people with established dementia,” Dr. Husain said.
The Lancet Commission was funded by University College London, Alzheimer’s Society, Alzheimer’s Research UK, and the Economic and Social Research Council. A complete list of author disclosures is available with the original article. Dr. Snyder, Dr. Lakhan, Dr. Husain and Dr. Spires-Jones have no relevant disclosures.
A version of this article appeared on Medscape.com.
PHILADELPHIA – a report from the Lancet Commission on dementia prevention, intervention, and care.
The report adds two new modifiable risk factors for dementia — high cholesterol and vision loss — to the 12 risk factors identified in the 2020 Lancet Commission report, which were linked to about 40% of all dementia cases.
The original Lancet Commission report, published in 2017, identified nine modifiable risk factors that were estimated to be responsible for one third of dementia cases.
“Our new report reveals that there is much more that can and should be done to reduce the risk of dementia. It’s never too early or too late to act, with opportunities to make an impact at any stage of life,” lead author Gill Livingston, MD, from University College London in England, said in a statement.
The 57-page report was published online in The Lancet Neurology (to coincide with its presentation at the 2024 Alzheimer’s Association International Conference (AAIC).
‘Compelling’ New Evidence
The 12 risk factors cited in the 2020 report are lower levels of education, hearing loss, hypertension, smoking, obesity, depression, physical inactivity, diabetes, excessive alcohol consumption, traumatic brain injury (TBI), air pollution, and social isolation.
According to the authors of the current report, there is “new compelling evidence” that untreated vision loss and elevated low-density lipoprotein (LDL) cholesterol are also risk factors for dementia.
These two added risk factors are associated with 9% of all dementia cases — with an estimated 7% of cases caused by high LDL cholesterol from about age 40 years, and 2% of cases caused by untreated vision loss in later life, the authors said.
Out of all 14 risk factors, those tied to the greatest proportion of dementia in the global population are hearing impairment and high LDL cholesterol (7% each), along with less education in early life, and social isolation in later life (5% each), the report estimates.
The new report also outlines 13 recommendations aimed at individuals and governments to help guard against dementia. They include preventing and treating hearing loss, vision loss, and depression; being cognitively active throughout life; using head protection in contact sports; reducing vascular risk factors (high cholesterol, diabetes, obesity, hypertension); improving air quality; and providing supportive community environments to increase social contact.
Tara Spires-Jones, PhD, president of the British Neuroscience Association, emphasized that, while this research doesn’t directly link specific factors to dementia, it supports evidence that a healthy lifestyle — encompassing education, social activities, exercise, cognitive engagement, and avoiding head injuries and harmful factors for heart and lung health — can enhance brain resilience and prevent dementia.
In an interview, Heather M. Snyder, PhD, senior vice president of medical and scientific relations, Alzheimer’s Association, said: “Our brains are complex and what happens throughout our lives may increase or decrease our risk for dementia as we age. Protecting brain health as we age requires a comprehensive approach that includes discussions on diet, exercise, heart health, hearing, and vision.”
Also weighing in on the new report, Shaheen Lakhan, MD, PhD, neurologist and researcher based in Miami, Florida, said the addition of high cholesterol is “particularly noteworthy as it reinforces the intricate connection between vascular health and brain health — a link we’ve long suspected but can now target more effectively.”
As for vision loss, “it’s not just a matter of seeing clearly; it’s a matter of thinking clearly. Untreated vision loss can lead to social isolation, reduced physical activity, and cognitive decline,” said Dr. Lakhan.
Dementia Is Not Inevitable
In his view, “the potential to prevent or delay nearly half of dementia cases by addressing these risk factors is nothing short of revolutionary. It shifts our perspective from viewing dementia as an inevitable part of aging to seeing it as a condition we can actively work to prevent,” Dr. Lakhan added.
He said the report’s emphasis on health equity is also important.
“Dementia risk factors disproportionately affect socioeconomically disadvantaged groups and low- and middle-income countries. Addressing these disparities isn’t just a matter of fairness in the fight against dementia, equality in prevention is as important as equality in treatment,” Dr. Lakhan commented.
While the report offers hope, it also presents a challenge, he said.
Implementing the recommended preventive measures requires a “coordinated effort from individuals, healthcare systems, and policymakers. The potential benefits, both in terms of quality of life and economic savings, make this effort not just worthwhile but imperative. Preventing dementia is not just a medical imperative — it’s an economic and humanitarian one,” Dr. Lakhan said.
Masud Husain, PhD, with the University of Oxford in England, agreed.
The conclusions in this report are “very important for all of us, but particularly for health policy makers and government,” he said.
“If we did simple things well such as screening for some of the factors identified in this report, with adequate resources to perform this, we have the potential to prevent dementia on a national scale. This would be far more cost effective than developing high-tech treatments, which so far have been disappointing in their impacts on people with established dementia,” Dr. Husain said.
The Lancet Commission was funded by University College London, Alzheimer’s Society, Alzheimer’s Research UK, and the Economic and Social Research Council. A complete list of author disclosures is available with the original article. Dr. Snyder, Dr. Lakhan, Dr. Husain and Dr. Spires-Jones have no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM AAIC 2024
Promising New Data Support GLP-1s for Dementia Prevention
PHILADELPHIA –
In the phase 2b ELAD clinical trial, adults with early-stage Alzheimer’s disease taking the GLP-1 receptor agonist liraglutide exhibited slower decline in memory and thinking and experienced less brain atrophy over 12 months, compared with placebo.
“The slower loss of brain volume suggests liraglutide protects the brain, much like statins protect the heart,” study chief Paul Edison, MD, PhD, with Imperial College London, London, England, said in a statement.
“While further research is needed, liraglutide may work through various mechanisms, such as reducing inflammation in the brain, lowering insulin resistance and the toxic effects of Alzheimer’s biomarkers amyloid beta and tau, and improving how the brain’s nerve cells communicate,” Dr. Edison said.
He presented the study results at the 2024 Alzheimer’s Association International Conference (AAIC).
Brain Benefits
Liraglutide has previously demonstrated promising neuroprotective effects in animal models of Alzheimer’s disease and epidemiologic studies.
In ELAD, 204 patients with mild to moderate Alzheimer’s disease were randomly allocated (1:1) to a daily subcutaneous injection of up to 1.8 mg of liraglutide or placebo for 12 months; 80 patients in the liraglutide group and 89 in the placebo group completed the study.
Brain MRI was performed at baseline and at 12 months, along with neuropsychometric evaluation and 18F-fludeoxyglucose PET.
The study’s primary endpoint — change in the cerebral glucose metabolic rate in the cortical regions of the brain (hippocampus, medial temporal lobe, and posterior cingulate) — was not met.
However, patients taking liraglutide experienced a significant slowing of cognitive decline, compared with placebo group (P = .01), which was a key secondary outcome, calculated as a composite score of 18 different tests of memory, comprehension, language, and spatial orientation.
Although the study was not powered to assess cognitive changes, adults taking liraglutide had an 18% slower decline in cognitive function over 12 months, compared with those on placebo, Dr. Edison reported.
In addition, patients treated with liraglutide had nearly 50% less volume loss in several areas of the brain involved in memory, language, and decision-making, including frontal, temporal, parietal, and total gray matter, as measured by MRI.
Liraglutide daily subcutaneous injections were safe and well tolerated in patients with Alzheimer’s disease, Dr. Edison reported. There were 25 serious side effects — 18 in the placebo group and 7 in the liraglutide group — and most were considered unlikely to be related to the study treatment. There were no deaths.
Promising, Preliminary
This study shows a positive effect of liraglutide on the brain in terms of “slowing down of brain atrophy and slowing down the rate of cognitive decline,” said Howard Fillit, MD, founding executive director of the Alzheimer’s Drug Discovery Foundation, who wasn’t involved in the study.
Heather Snyder, PhD, vice-president of medical and scientific relations at the Alzheimer’s Association, said it’s “interesting” to see slowing of brain volume loss and some cognitive benefit “especially as the study was not powered necessarily to see some of those changes. The fact that they did see these changes in this small study provides a window into what may happen, but we certainly need larger phase 3 studies.”
In a statement from the UK nonprofit Science Media Centre, Tara Spires-Jones, PhD, president of the British Neuroscience Association and group leader at the UK Dementia Research Institute, called the data “promising.”
“There are clear links from strong data in the field between vascular risk factors including diabetes and obesity being associated with increased risk of dementia. The GLP-1 drug should help reduce these risk factors as well as potentially directly protecting brain cells,” Dr. Spires-Jones said.
However, she said “more research in bigger trials is needed to confirm whether this type of treatment will be effective in people with Alzheimer’s disease.”
Stephen Evans, MSc, emeritus professor, London School of Hygiene and Tropical Medicine, noted that the repurposing of drugs is “an important avenue of research but there is a lot of uncertainty here.”
He cautioned that the “50% brain volume change may not translate to important cognitive effects, and reporting only on those who completed the full 52 weeks of treatment could bring bias into the results. It sounds like it is worth pursuing a larger trial, but these results cannot demonstrate that liraglutide can protect against dementia.”
The ongoing phase 3 EVOKE trial is investigating the effects of the GLP-1 receptor agonist semaglutide in early Alzheimer’s disease.
Funding for the study was provided by Alzheimer’s Society UK, Alzheimer’s Drug Discovery Foundation, Novo Nordisk, John and Lucille Van Geest Foundation, and the National Institute for Health and Care Research Biomedical Research Centre. Dr. Edison, Dr. Fillit, Dr. Snyder, Mr. Evans, and Dr. Spires-Jones had no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
PHILADELPHIA –
In the phase 2b ELAD clinical trial, adults with early-stage Alzheimer’s disease taking the GLP-1 receptor agonist liraglutide exhibited slower decline in memory and thinking and experienced less brain atrophy over 12 months, compared with placebo.
“The slower loss of brain volume suggests liraglutide protects the brain, much like statins protect the heart,” study chief Paul Edison, MD, PhD, with Imperial College London, London, England, said in a statement.
“While further research is needed, liraglutide may work through various mechanisms, such as reducing inflammation in the brain, lowering insulin resistance and the toxic effects of Alzheimer’s biomarkers amyloid beta and tau, and improving how the brain’s nerve cells communicate,” Dr. Edison said.
He presented the study results at the 2024 Alzheimer’s Association International Conference (AAIC).
Brain Benefits
Liraglutide has previously demonstrated promising neuroprotective effects in animal models of Alzheimer’s disease and epidemiologic studies.
In ELAD, 204 patients with mild to moderate Alzheimer’s disease were randomly allocated (1:1) to a daily subcutaneous injection of up to 1.8 mg of liraglutide or placebo for 12 months; 80 patients in the liraglutide group and 89 in the placebo group completed the study.
Brain MRI was performed at baseline and at 12 months, along with neuropsychometric evaluation and 18F-fludeoxyglucose PET.
The study’s primary endpoint — change in the cerebral glucose metabolic rate in the cortical regions of the brain (hippocampus, medial temporal lobe, and posterior cingulate) — was not met.
However, patients taking liraglutide experienced a significant slowing of cognitive decline, compared with placebo group (P = .01), which was a key secondary outcome, calculated as a composite score of 18 different tests of memory, comprehension, language, and spatial orientation.
Although the study was not powered to assess cognitive changes, adults taking liraglutide had an 18% slower decline in cognitive function over 12 months, compared with those on placebo, Dr. Edison reported.
In addition, patients treated with liraglutide had nearly 50% less volume loss in several areas of the brain involved in memory, language, and decision-making, including frontal, temporal, parietal, and total gray matter, as measured by MRI.
Liraglutide daily subcutaneous injections were safe and well tolerated in patients with Alzheimer’s disease, Dr. Edison reported. There were 25 serious side effects — 18 in the placebo group and 7 in the liraglutide group — and most were considered unlikely to be related to the study treatment. There were no deaths.
Promising, Preliminary
This study shows a positive effect of liraglutide on the brain in terms of “slowing down of brain atrophy and slowing down the rate of cognitive decline,” said Howard Fillit, MD, founding executive director of the Alzheimer’s Drug Discovery Foundation, who wasn’t involved in the study.
Heather Snyder, PhD, vice-president of medical and scientific relations at the Alzheimer’s Association, said it’s “interesting” to see slowing of brain volume loss and some cognitive benefit “especially as the study was not powered necessarily to see some of those changes. The fact that they did see these changes in this small study provides a window into what may happen, but we certainly need larger phase 3 studies.”
In a statement from the UK nonprofit Science Media Centre, Tara Spires-Jones, PhD, president of the British Neuroscience Association and group leader at the UK Dementia Research Institute, called the data “promising.”
“There are clear links from strong data in the field between vascular risk factors including diabetes and obesity being associated with increased risk of dementia. The GLP-1 drug should help reduce these risk factors as well as potentially directly protecting brain cells,” Dr. Spires-Jones said.
However, she said “more research in bigger trials is needed to confirm whether this type of treatment will be effective in people with Alzheimer’s disease.”
Stephen Evans, MSc, emeritus professor, London School of Hygiene and Tropical Medicine, noted that the repurposing of drugs is “an important avenue of research but there is a lot of uncertainty here.”
He cautioned that the “50% brain volume change may not translate to important cognitive effects, and reporting only on those who completed the full 52 weeks of treatment could bring bias into the results. It sounds like it is worth pursuing a larger trial, but these results cannot demonstrate that liraglutide can protect against dementia.”
The ongoing phase 3 EVOKE trial is investigating the effects of the GLP-1 receptor agonist semaglutide in early Alzheimer’s disease.
Funding for the study was provided by Alzheimer’s Society UK, Alzheimer’s Drug Discovery Foundation, Novo Nordisk, John and Lucille Van Geest Foundation, and the National Institute for Health and Care Research Biomedical Research Centre. Dr. Edison, Dr. Fillit, Dr. Snyder, Mr. Evans, and Dr. Spires-Jones had no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
PHILADELPHIA –
In the phase 2b ELAD clinical trial, adults with early-stage Alzheimer’s disease taking the GLP-1 receptor agonist liraglutide exhibited slower decline in memory and thinking and experienced less brain atrophy over 12 months, compared with placebo.
“The slower loss of brain volume suggests liraglutide protects the brain, much like statins protect the heart,” study chief Paul Edison, MD, PhD, with Imperial College London, London, England, said in a statement.
“While further research is needed, liraglutide may work through various mechanisms, such as reducing inflammation in the brain, lowering insulin resistance and the toxic effects of Alzheimer’s biomarkers amyloid beta and tau, and improving how the brain’s nerve cells communicate,” Dr. Edison said.
He presented the study results at the 2024 Alzheimer’s Association International Conference (AAIC).
Brain Benefits
Liraglutide has previously demonstrated promising neuroprotective effects in animal models of Alzheimer’s disease and epidemiologic studies.
In ELAD, 204 patients with mild to moderate Alzheimer’s disease were randomly allocated (1:1) to a daily subcutaneous injection of up to 1.8 mg of liraglutide or placebo for 12 months; 80 patients in the liraglutide group and 89 in the placebo group completed the study.
Brain MRI was performed at baseline and at 12 months, along with neuropsychometric evaluation and 18F-fludeoxyglucose PET.
The study’s primary endpoint — change in the cerebral glucose metabolic rate in the cortical regions of the brain (hippocampus, medial temporal lobe, and posterior cingulate) — was not met.
However, patients taking liraglutide experienced a significant slowing of cognitive decline, compared with placebo group (P = .01), which was a key secondary outcome, calculated as a composite score of 18 different tests of memory, comprehension, language, and spatial orientation.
Although the study was not powered to assess cognitive changes, adults taking liraglutide had an 18% slower decline in cognitive function over 12 months, compared with those on placebo, Dr. Edison reported.
In addition, patients treated with liraglutide had nearly 50% less volume loss in several areas of the brain involved in memory, language, and decision-making, including frontal, temporal, parietal, and total gray matter, as measured by MRI.
Liraglutide daily subcutaneous injections were safe and well tolerated in patients with Alzheimer’s disease, Dr. Edison reported. There were 25 serious side effects — 18 in the placebo group and 7 in the liraglutide group — and most were considered unlikely to be related to the study treatment. There were no deaths.
Promising, Preliminary
This study shows a positive effect of liraglutide on the brain in terms of “slowing down of brain atrophy and slowing down the rate of cognitive decline,” said Howard Fillit, MD, founding executive director of the Alzheimer’s Drug Discovery Foundation, who wasn’t involved in the study.
Heather Snyder, PhD, vice-president of medical and scientific relations at the Alzheimer’s Association, said it’s “interesting” to see slowing of brain volume loss and some cognitive benefit “especially as the study was not powered necessarily to see some of those changes. The fact that they did see these changes in this small study provides a window into what may happen, but we certainly need larger phase 3 studies.”
In a statement from the UK nonprofit Science Media Centre, Tara Spires-Jones, PhD, president of the British Neuroscience Association and group leader at the UK Dementia Research Institute, called the data “promising.”
“There are clear links from strong data in the field between vascular risk factors including diabetes and obesity being associated with increased risk of dementia. The GLP-1 drug should help reduce these risk factors as well as potentially directly protecting brain cells,” Dr. Spires-Jones said.
However, she said “more research in bigger trials is needed to confirm whether this type of treatment will be effective in people with Alzheimer’s disease.”
Stephen Evans, MSc, emeritus professor, London School of Hygiene and Tropical Medicine, noted that the repurposing of drugs is “an important avenue of research but there is a lot of uncertainty here.”
He cautioned that the “50% brain volume change may not translate to important cognitive effects, and reporting only on those who completed the full 52 weeks of treatment could bring bias into the results. It sounds like it is worth pursuing a larger trial, but these results cannot demonstrate that liraglutide can protect against dementia.”
The ongoing phase 3 EVOKE trial is investigating the effects of the GLP-1 receptor agonist semaglutide in early Alzheimer’s disease.
Funding for the study was provided by Alzheimer’s Society UK, Alzheimer’s Drug Discovery Foundation, Novo Nordisk, John and Lucille Van Geest Foundation, and the National Institute for Health and Care Research Biomedical Research Centre. Dr. Edison, Dr. Fillit, Dr. Snyder, Mr. Evans, and Dr. Spires-Jones had no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM AAIC 2024
Tau Blood Test Flags Preclinical Alzheimer’s Disease
Recruiting preclinical Alzheimer’s disease participants for clinical research is challenging, owing to a lack of symptoms and the high cost and invasiveness of cerebrospinal fluid (CSF) tests and brain amyloid PET imaging.
Plasma p-tau217 has consistently shown high performance in detecting Alzheimer’s disease pathology in patients with mild cognitive impairment and dementia, but there has been concern that it may have lower accuracy in cognitively unimpaired adults, said lead investigator Gemma Salvadó, PhD, with the Clinical Memory Research Unit, Lund University, Lund, Sweden.
However, “our study shows that plasma p-tau217, alone or in combination with invasive tests, can be used accurately to assess amyloid positivity in cognitively unimpaired participants, to streamline the inclusion of these participants in preventive clinical trials,” she said.
The findings were presented at the 2024 Alzheimer’s Association International Conference (AAIC).
Correlation to CSF, PET Amyloid Status
The investigators assessed the clinical accuracy of plasma p-tau217 as a prescreening method in 2917 cognitively unimpaired adults (mean age, 67 years; 57% women) across 12 independent cohorts who had available plasma p-tau217 and amyloid beta PET imaging or CSF samples.
They found that plasma p-tau217 levels correlated with amyloid beta CSF status and PET load.
As a standalone test, plasma p-tau217 identified amyloid beta PET–positive cognitively normal adults with a positive predictive value of 80% or greater.
The positive predictive value increased to 95% or greater when amyloid beta CSF or PET was used to confirm a positive plasma p-tau217 result.
As a first step, plasma p-tau217 could significantly reduce the number of invasive tests performed because only individuals with a positive p-tau217 test would go on to PET imaging or CSF sampling, Dr. Salvadó told conference attendees. This may reduce trial recruitment costs and get more patients enrolled.
Although the study had a large sample size, “these results should be replicated in independent studies, [in] more heterogeneous participants, and coming from the clinical setting instead of observational studies to avoid possible bias,” Dr. Salvadó added.
A New Diagnostic Era
Commenting on the research, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said what’s particularly interesting about this study is that the researchers examined multiple cohorts of cognitively unimpaired individuals and “consistently” found that plasma p-tau217 could identify individuals with amyloid-positive PET and CSF with high accuracy.
“This may reduce the need for more expensive and more invasive scans or lumbar punctures to confirm if an individual has the biology,” Dr. Snyder said.
“Blood tests are revolutionizing Alzheimer’s detection, diagnosis and ultimately treatment,” added Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation.
He predicted that blood tests will “soon replace more invasive and costly PET scans as the standard of care and serve as the first line of defense in diagnosing the disease.”
“After many years of research, the field is in a place where we have novel biomarkers and diagnostics to support a diagnosis,” the way cholesterol is used to help detect heart disease, said Dr. Fillit.
“The diagnostic framework for Alzheimer’s — an incredibly complex disease — is constantly evolving. As we usher in the new era of care, we are moving closer to the day when blood tests will be complemented by digital tools to provide precise and timely diagnoses and risk assessments backed by numerous data points, complementing existing cognitive tests,” he added.
Funding for the study was provided by the Alzheimer’s Association, the European Union’s Horizon 2020 Research and Innovation Program, Alzheimerfonden, and Strategic Research Area MultiPark. Dr. Salvadó, Dr. Snyder, and Dr. Fillit have no relevant disclosures.
A version of this article appeared on Medscape.com.
Recruiting preclinical Alzheimer’s disease participants for clinical research is challenging, owing to a lack of symptoms and the high cost and invasiveness of cerebrospinal fluid (CSF) tests and brain amyloid PET imaging.
Plasma p-tau217 has consistently shown high performance in detecting Alzheimer’s disease pathology in patients with mild cognitive impairment and dementia, but there has been concern that it may have lower accuracy in cognitively unimpaired adults, said lead investigator Gemma Salvadó, PhD, with the Clinical Memory Research Unit, Lund University, Lund, Sweden.
However, “our study shows that plasma p-tau217, alone or in combination with invasive tests, can be used accurately to assess amyloid positivity in cognitively unimpaired participants, to streamline the inclusion of these participants in preventive clinical trials,” she said.
The findings were presented at the 2024 Alzheimer’s Association International Conference (AAIC).
Correlation to CSF, PET Amyloid Status
The investigators assessed the clinical accuracy of plasma p-tau217 as a prescreening method in 2917 cognitively unimpaired adults (mean age, 67 years; 57% women) across 12 independent cohorts who had available plasma p-tau217 and amyloid beta PET imaging or CSF samples.
They found that plasma p-tau217 levels correlated with amyloid beta CSF status and PET load.
As a standalone test, plasma p-tau217 identified amyloid beta PET–positive cognitively normal adults with a positive predictive value of 80% or greater.
The positive predictive value increased to 95% or greater when amyloid beta CSF or PET was used to confirm a positive plasma p-tau217 result.
As a first step, plasma p-tau217 could significantly reduce the number of invasive tests performed because only individuals with a positive p-tau217 test would go on to PET imaging or CSF sampling, Dr. Salvadó told conference attendees. This may reduce trial recruitment costs and get more patients enrolled.
Although the study had a large sample size, “these results should be replicated in independent studies, [in] more heterogeneous participants, and coming from the clinical setting instead of observational studies to avoid possible bias,” Dr. Salvadó added.
A New Diagnostic Era
Commenting on the research, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said what’s particularly interesting about this study is that the researchers examined multiple cohorts of cognitively unimpaired individuals and “consistently” found that plasma p-tau217 could identify individuals with amyloid-positive PET and CSF with high accuracy.
“This may reduce the need for more expensive and more invasive scans or lumbar punctures to confirm if an individual has the biology,” Dr. Snyder said.
“Blood tests are revolutionizing Alzheimer’s detection, diagnosis and ultimately treatment,” added Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation.
He predicted that blood tests will “soon replace more invasive and costly PET scans as the standard of care and serve as the first line of defense in diagnosing the disease.”
“After many years of research, the field is in a place where we have novel biomarkers and diagnostics to support a diagnosis,” the way cholesterol is used to help detect heart disease, said Dr. Fillit.
“The diagnostic framework for Alzheimer’s — an incredibly complex disease — is constantly evolving. As we usher in the new era of care, we are moving closer to the day when blood tests will be complemented by digital tools to provide precise and timely diagnoses and risk assessments backed by numerous data points, complementing existing cognitive tests,” he added.
Funding for the study was provided by the Alzheimer’s Association, the European Union’s Horizon 2020 Research and Innovation Program, Alzheimerfonden, and Strategic Research Area MultiPark. Dr. Salvadó, Dr. Snyder, and Dr. Fillit have no relevant disclosures.
A version of this article appeared on Medscape.com.
Recruiting preclinical Alzheimer’s disease participants for clinical research is challenging, owing to a lack of symptoms and the high cost and invasiveness of cerebrospinal fluid (CSF) tests and brain amyloid PET imaging.
Plasma p-tau217 has consistently shown high performance in detecting Alzheimer’s disease pathology in patients with mild cognitive impairment and dementia, but there has been concern that it may have lower accuracy in cognitively unimpaired adults, said lead investigator Gemma Salvadó, PhD, with the Clinical Memory Research Unit, Lund University, Lund, Sweden.
However, “our study shows that plasma p-tau217, alone or in combination with invasive tests, can be used accurately to assess amyloid positivity in cognitively unimpaired participants, to streamline the inclusion of these participants in preventive clinical trials,” she said.
The findings were presented at the 2024 Alzheimer’s Association International Conference (AAIC).
Correlation to CSF, PET Amyloid Status
The investigators assessed the clinical accuracy of plasma p-tau217 as a prescreening method in 2917 cognitively unimpaired adults (mean age, 67 years; 57% women) across 12 independent cohorts who had available plasma p-tau217 and amyloid beta PET imaging or CSF samples.
They found that plasma p-tau217 levels correlated with amyloid beta CSF status and PET load.
As a standalone test, plasma p-tau217 identified amyloid beta PET–positive cognitively normal adults with a positive predictive value of 80% or greater.
The positive predictive value increased to 95% or greater when amyloid beta CSF or PET was used to confirm a positive plasma p-tau217 result.
As a first step, plasma p-tau217 could significantly reduce the number of invasive tests performed because only individuals with a positive p-tau217 test would go on to PET imaging or CSF sampling, Dr. Salvadó told conference attendees. This may reduce trial recruitment costs and get more patients enrolled.
Although the study had a large sample size, “these results should be replicated in independent studies, [in] more heterogeneous participants, and coming from the clinical setting instead of observational studies to avoid possible bias,” Dr. Salvadó added.
A New Diagnostic Era
Commenting on the research, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said what’s particularly interesting about this study is that the researchers examined multiple cohorts of cognitively unimpaired individuals and “consistently” found that plasma p-tau217 could identify individuals with amyloid-positive PET and CSF with high accuracy.
“This may reduce the need for more expensive and more invasive scans or lumbar punctures to confirm if an individual has the biology,” Dr. Snyder said.
“Blood tests are revolutionizing Alzheimer’s detection, diagnosis and ultimately treatment,” added Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation.
He predicted that blood tests will “soon replace more invasive and costly PET scans as the standard of care and serve as the first line of defense in diagnosing the disease.”
“After many years of research, the field is in a place where we have novel biomarkers and diagnostics to support a diagnosis,” the way cholesterol is used to help detect heart disease, said Dr. Fillit.
“The diagnostic framework for Alzheimer’s — an incredibly complex disease — is constantly evolving. As we usher in the new era of care, we are moving closer to the day when blood tests will be complemented by digital tools to provide precise and timely diagnoses and risk assessments backed by numerous data points, complementing existing cognitive tests,” he added.
Funding for the study was provided by the Alzheimer’s Association, the European Union’s Horizon 2020 Research and Innovation Program, Alzheimerfonden, and Strategic Research Area MultiPark. Dr. Salvadó, Dr. Snyder, and Dr. Fillit have no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM AAIC 2024
Alzheimer’s Blood Test in Primary Care Could Slash Diagnostic, Treatment Wait Times
As disease-modifying treatments for Alzheimer’s disease (AD) become available, . Currently, the patient diagnostic journey is often prolonged owing to the limited number of AD specialists, causing concern among healthcare providers and patients alike. Now, a new study suggests that use of high-performing blood tests in primary care could identify potential patients with AD much earlier, possibly reducing wait times for specialist care and receipt of treatment.
“We need to triage in primary care and send preferentially the ones that actually could be eligible for treatment, and not those who are just worried because their grandmother reported that she has Alzheimer’s,” lead researcher Soeren Mattke, MD, DSc, told this news organization.
“By combining a brief cognitive test with an accurate blood test of Alzheimer’s pathology in primary care, we can reduce unnecessary referrals, and shorten appointment wait times,” said Dr. Mattke, director of the Brain Health Observatory at the University of Southern California in Los Angeles.
The findings were presented at the Alzheimer’s Association International Conference (AAIC) 2024.
Projected Wait Times 100 Months by 2033
The investigators used a Markov model to estimate wait times for patients eligible for AD treatment, taking into account constrained capacity for specialist visits.
The model included the projected US population of people aged 55 years or older from 2023 to 2032. It assumed that individuals would undergo a brief cognitive assessment in primary care and, if suggestive of early-stage cognitive impairment, be referred to a AD specialist under three scenarios: no blood test, blood test to rule out AD pathology, and blood test to confirm AD pathology.
According to the model, without an accurate blood test for AD pathology, projected wait times to see a specialist are about 12 months in 2024 and will increase to more than 100 months in 2033, largely owing to a lack of specialist appointments.
In contrast, with the availability of an accurate blood test to rule out AD, average wait times would be just 3 months in 2024 and increase to only about 13 months in 2033, because far fewer patients would need to see a specialist.
Availability of a blood test to rule in AD pathology in primary care would have a limited effect on wait times because 50% of patients would still undergo confirmatory testing based on expert assumptions, the model suggests.
Prioritizing Resources
“Millions of people have mild memory complaints, and if they all start coming to neurologists, it could completely flood the system and create long wait times for everybody,” Dr. Mattke told this news organization.
The problem, he said, is that brief cognitive tests performed in primary care are not particularly specific for mild cognitive impairment.
“They work pretty well for manifest advanced dementia but for mild cognitive impairment, which is a very subtle, symptomatic disease, they are only about 75% accurate. One quarter are false-positives. That’s a lot of people,” Dr. Mattke said.
He also noted that although earlier blood tests were about 75% accurate, they are now about 90% accurate, “so we are getting to a level where we can pretty much say with confidence that this is likely Alzheimer’s,” Dr. Mattke said.
Commenting on this research for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said it is clear that blood tests, “once confirmed, could have a significant impact on the wait times” for dementia assessment.
“After an initial blood test, we might be able to rule out or rule in individuals who should go to a specialist for further follow-up and testing. This allows us to really ensure that we’re prioritizing resources accordingly,” said Dr. Snyder, who was not involved in the study.
This project was supported by a research contract from C2N Diagnostics LLC to USC. Dr. Mattke serves on the board of directors of Senscio Systems Inc. and the scientific advisory board of ALZPath and Boston Millennia Partners and has received consulting fees from Biogen, C2N, Eisai, Eli Lilly, Novartis, and Roche/Genentech. Dr. Snyder has no relevant disclosures.
A version of this article first appeared on Medscape.com.
As disease-modifying treatments for Alzheimer’s disease (AD) become available, . Currently, the patient diagnostic journey is often prolonged owing to the limited number of AD specialists, causing concern among healthcare providers and patients alike. Now, a new study suggests that use of high-performing blood tests in primary care could identify potential patients with AD much earlier, possibly reducing wait times for specialist care and receipt of treatment.
“We need to triage in primary care and send preferentially the ones that actually could be eligible for treatment, and not those who are just worried because their grandmother reported that she has Alzheimer’s,” lead researcher Soeren Mattke, MD, DSc, told this news organization.
“By combining a brief cognitive test with an accurate blood test of Alzheimer’s pathology in primary care, we can reduce unnecessary referrals, and shorten appointment wait times,” said Dr. Mattke, director of the Brain Health Observatory at the University of Southern California in Los Angeles.
The findings were presented at the Alzheimer’s Association International Conference (AAIC) 2024.
Projected Wait Times 100 Months by 2033
The investigators used a Markov model to estimate wait times for patients eligible for AD treatment, taking into account constrained capacity for specialist visits.
The model included the projected US population of people aged 55 years or older from 2023 to 2032. It assumed that individuals would undergo a brief cognitive assessment in primary care and, if suggestive of early-stage cognitive impairment, be referred to a AD specialist under three scenarios: no blood test, blood test to rule out AD pathology, and blood test to confirm AD pathology.
According to the model, without an accurate blood test for AD pathology, projected wait times to see a specialist are about 12 months in 2024 and will increase to more than 100 months in 2033, largely owing to a lack of specialist appointments.
In contrast, with the availability of an accurate blood test to rule out AD, average wait times would be just 3 months in 2024 and increase to only about 13 months in 2033, because far fewer patients would need to see a specialist.
Availability of a blood test to rule in AD pathology in primary care would have a limited effect on wait times because 50% of patients would still undergo confirmatory testing based on expert assumptions, the model suggests.
Prioritizing Resources
“Millions of people have mild memory complaints, and if they all start coming to neurologists, it could completely flood the system and create long wait times for everybody,” Dr. Mattke told this news organization.
The problem, he said, is that brief cognitive tests performed in primary care are not particularly specific for mild cognitive impairment.
“They work pretty well for manifest advanced dementia but for mild cognitive impairment, which is a very subtle, symptomatic disease, they are only about 75% accurate. One quarter are false-positives. That’s a lot of people,” Dr. Mattke said.
He also noted that although earlier blood tests were about 75% accurate, they are now about 90% accurate, “so we are getting to a level where we can pretty much say with confidence that this is likely Alzheimer’s,” Dr. Mattke said.
Commenting on this research for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said it is clear that blood tests, “once confirmed, could have a significant impact on the wait times” for dementia assessment.
“After an initial blood test, we might be able to rule out or rule in individuals who should go to a specialist for further follow-up and testing. This allows us to really ensure that we’re prioritizing resources accordingly,” said Dr. Snyder, who was not involved in the study.
This project was supported by a research contract from C2N Diagnostics LLC to USC. Dr. Mattke serves on the board of directors of Senscio Systems Inc. and the scientific advisory board of ALZPath and Boston Millennia Partners and has received consulting fees from Biogen, C2N, Eisai, Eli Lilly, Novartis, and Roche/Genentech. Dr. Snyder has no relevant disclosures.
A version of this article first appeared on Medscape.com.
As disease-modifying treatments for Alzheimer’s disease (AD) become available, . Currently, the patient diagnostic journey is often prolonged owing to the limited number of AD specialists, causing concern among healthcare providers and patients alike. Now, a new study suggests that use of high-performing blood tests in primary care could identify potential patients with AD much earlier, possibly reducing wait times for specialist care and receipt of treatment.
“We need to triage in primary care and send preferentially the ones that actually could be eligible for treatment, and not those who are just worried because their grandmother reported that she has Alzheimer’s,” lead researcher Soeren Mattke, MD, DSc, told this news organization.
“By combining a brief cognitive test with an accurate blood test of Alzheimer’s pathology in primary care, we can reduce unnecessary referrals, and shorten appointment wait times,” said Dr. Mattke, director of the Brain Health Observatory at the University of Southern California in Los Angeles.
The findings were presented at the Alzheimer’s Association International Conference (AAIC) 2024.
Projected Wait Times 100 Months by 2033
The investigators used a Markov model to estimate wait times for patients eligible for AD treatment, taking into account constrained capacity for specialist visits.
The model included the projected US population of people aged 55 years or older from 2023 to 2032. It assumed that individuals would undergo a brief cognitive assessment in primary care and, if suggestive of early-stage cognitive impairment, be referred to a AD specialist under three scenarios: no blood test, blood test to rule out AD pathology, and blood test to confirm AD pathology.
According to the model, without an accurate blood test for AD pathology, projected wait times to see a specialist are about 12 months in 2024 and will increase to more than 100 months in 2033, largely owing to a lack of specialist appointments.
In contrast, with the availability of an accurate blood test to rule out AD, average wait times would be just 3 months in 2024 and increase to only about 13 months in 2033, because far fewer patients would need to see a specialist.
Availability of a blood test to rule in AD pathology in primary care would have a limited effect on wait times because 50% of patients would still undergo confirmatory testing based on expert assumptions, the model suggests.
Prioritizing Resources
“Millions of people have mild memory complaints, and if they all start coming to neurologists, it could completely flood the system and create long wait times for everybody,” Dr. Mattke told this news organization.
The problem, he said, is that brief cognitive tests performed in primary care are not particularly specific for mild cognitive impairment.
“They work pretty well for manifest advanced dementia but for mild cognitive impairment, which is a very subtle, symptomatic disease, they are only about 75% accurate. One quarter are false-positives. That’s a lot of people,” Dr. Mattke said.
He also noted that although earlier blood tests were about 75% accurate, they are now about 90% accurate, “so we are getting to a level where we can pretty much say with confidence that this is likely Alzheimer’s,” Dr. Mattke said.
Commenting on this research for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said it is clear that blood tests, “once confirmed, could have a significant impact on the wait times” for dementia assessment.
“After an initial blood test, we might be able to rule out or rule in individuals who should go to a specialist for further follow-up and testing. This allows us to really ensure that we’re prioritizing resources accordingly,” said Dr. Snyder, who was not involved in the study.
This project was supported by a research contract from C2N Diagnostics LLC to USC. Dr. Mattke serves on the board of directors of Senscio Systems Inc. and the scientific advisory board of ALZPath and Boston Millennia Partners and has received consulting fees from Biogen, C2N, Eisai, Eli Lilly, Novartis, and Roche/Genentech. Dr. Snyder has no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM AAIC 2024
New Criteria Distinguish Memory Disorder Often Misdiagnosed as Alzheimer’s
Proposed clinical criteria for a memory loss disorder that is often misdiagnosed as Alzheimer’s disease (AD) have been published.
The new criteria for limbic-predominant amnestic neurodegenerative syndrome (LANS) provide a framework for neurologists and other experts to classify the condition and offer a more precise diagnosis and potential treatments.
“In our clinical work, we see patients whose memory symptoms appear to mimic Alzheimer’s disease, but when you look at their brain imaging or biomarkers, it’s clear they don’t have Alzheimer’s. Until now, there has not been a specific medical diagnosis to point to, but now we can offer them some answers,” senior investigator David T. Jones, MD, said in a release.
The proposed criteria and the research behind it were published online in Brain Communications and will be presented at the Alzheimer›s Association International Conference in Philadelphia.
Already in Use
Predominant limbic degeneration has been linked to various underlying etiologies, older age, predominant impairment of episodic memory, and slow clinical progression, the investigators noted. However, they added, the neurologic syndrome associated with predominant limbic degeneration is undefined.
Developing clinical criteria and validating them “is critical to distinguish such a syndrome from those originating from neocortical degeneration, which may differ in underlying etiology, disease course, and therapeutic needs,” the investigators wrote.
The newly proposed clinical criteria apply to LANS, which is “highly associated with limbic-predominant age-related TDP-43 encephalopathy but also other pathologic entities.”
The criteria incorporate core, standard, and advanced features including older age at evaluation, mild clinical syndrome, disproportionate hippocampal atrophy, impaired semantic memory, limbic hypometabolism, absence of endocortical degeneration, and low likelihood of neocortical tau with highest, high, moderate, and low degrees of certainty.
“A detailed history of the clinical symptoms, which may be supported by neuropsychological testing, with the observation of disproportionate hippocampal atrophy and limbic degeneration on MRI/FDG yields a high confidence in a diagnosis of LANS, where the most likely symptom-driving proteinopathy is TDP-43 and not Alzheimer’s associated proteins,” the first author, Nick Corriveau-Lecavalier, PhD, assistant professor of neurology and psychology at Mayo Clinic, Rochester, Minnesota, told this news organization.
To validate the criteria, the investigators screened autopsied patients from Mayo Clinic and Alzheimer’s Disease Neuroimaging Initiative cohorts and applied the criteria to those with a predominant amnestic syndrome and those who had AD neuropathologic change, limbic-predominant age-related TDP-43 encephalopathy, or both pathologies at autopsy.
“The criteria effectively categorized these cases, with Alzheimer’s disease having the lowest likelihoods, limbic-predominant age-related TDP-43 encephalopathy patients having the highest likelihoods, and patients with both pathologies having intermediate likelihoods,” the investigators reported.
“Patients with high likelihoods had a milder and slower clinical course and more severe temporo-limbic degeneration compared to those with low likelihoods,” they added.
Dr. Corriveau-Lecavalier said the team is currently analyzing longitudinal cognitive and imaging trajectories in LANS over several years. “This will help us better understand how LANS and Alzheimer’s differ in their sequence of symptoms over time.”
It is important to understand that memory symptoms in old age are not “unequivocally” driven by Alzheimer’s and that LANS progresses more slowly and has a better prognosis than AD, he noted.
In addition, in vivo markers of TDP-43 are “on the horizon and can hopefully make their way to human research settings soon. This will help better understand the underlying molecular etiologies causing LANS and associated symptoms,” he said.
Dr. Corriveau-Lecavalier said the LANS criteria are ready for clinical use by experts in neurologic care. These criteria can be used to inform not only diagnosis but also prognosis, where this syndrome is associated with slow and mild progression and a memory-dominant profile.
He added that “the new criteria are also routinely used in our practice to make decisions about anti-amyloid treatment eligibility.”
Commenting on the research for this news organization, Rebecca M. Edelmayer, PhD, Alzheimer’s Association senior director of scientific engagement, said the research “exemplifies the great need to develop objective criteria for diagnosis and staging of Alzheimer’s and all other types of dementia and to create an integrated biological and clinical staging scheme that can be used effectively by physicians.”
“Advances in biomarkers will help to differentiate all types of dementia when incorporated into the diagnostic workup, but until those tools are available, a more succinct clinical criteria for diagnosis can be used to support a more personalized medicine approach to treatment, care, and enrollment into clinical studies,” said Dr. Edelmayer, who wasn’t involved in the research.
The research was funded in part by the National Institutes of Health and by the Robert Wood Johnson Foundation, the Elsie & Marvin Dekelboum Family Foundation, the Liston Family Foundation, the Edson Family, the Gerald A. and Henrietta Rauenhorst Foundation, and the Foundation Dr Corinne Schuler. Dr. Corriveau-Lecavalier and Dr. Edelmayer had no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Proposed clinical criteria for a memory loss disorder that is often misdiagnosed as Alzheimer’s disease (AD) have been published.
The new criteria for limbic-predominant amnestic neurodegenerative syndrome (LANS) provide a framework for neurologists and other experts to classify the condition and offer a more precise diagnosis and potential treatments.
“In our clinical work, we see patients whose memory symptoms appear to mimic Alzheimer’s disease, but when you look at their brain imaging or biomarkers, it’s clear they don’t have Alzheimer’s. Until now, there has not been a specific medical diagnosis to point to, but now we can offer them some answers,” senior investigator David T. Jones, MD, said in a release.
The proposed criteria and the research behind it were published online in Brain Communications and will be presented at the Alzheimer›s Association International Conference in Philadelphia.
Already in Use
Predominant limbic degeneration has been linked to various underlying etiologies, older age, predominant impairment of episodic memory, and slow clinical progression, the investigators noted. However, they added, the neurologic syndrome associated with predominant limbic degeneration is undefined.
Developing clinical criteria and validating them “is critical to distinguish such a syndrome from those originating from neocortical degeneration, which may differ in underlying etiology, disease course, and therapeutic needs,” the investigators wrote.
The newly proposed clinical criteria apply to LANS, which is “highly associated with limbic-predominant age-related TDP-43 encephalopathy but also other pathologic entities.”
The criteria incorporate core, standard, and advanced features including older age at evaluation, mild clinical syndrome, disproportionate hippocampal atrophy, impaired semantic memory, limbic hypometabolism, absence of endocortical degeneration, and low likelihood of neocortical tau with highest, high, moderate, and low degrees of certainty.
“A detailed history of the clinical symptoms, which may be supported by neuropsychological testing, with the observation of disproportionate hippocampal atrophy and limbic degeneration on MRI/FDG yields a high confidence in a diagnosis of LANS, where the most likely symptom-driving proteinopathy is TDP-43 and not Alzheimer’s associated proteins,” the first author, Nick Corriveau-Lecavalier, PhD, assistant professor of neurology and psychology at Mayo Clinic, Rochester, Minnesota, told this news organization.
To validate the criteria, the investigators screened autopsied patients from Mayo Clinic and Alzheimer’s Disease Neuroimaging Initiative cohorts and applied the criteria to those with a predominant amnestic syndrome and those who had AD neuropathologic change, limbic-predominant age-related TDP-43 encephalopathy, or both pathologies at autopsy.
“The criteria effectively categorized these cases, with Alzheimer’s disease having the lowest likelihoods, limbic-predominant age-related TDP-43 encephalopathy patients having the highest likelihoods, and patients with both pathologies having intermediate likelihoods,” the investigators reported.
“Patients with high likelihoods had a milder and slower clinical course and more severe temporo-limbic degeneration compared to those with low likelihoods,” they added.
Dr. Corriveau-Lecavalier said the team is currently analyzing longitudinal cognitive and imaging trajectories in LANS over several years. “This will help us better understand how LANS and Alzheimer’s differ in their sequence of symptoms over time.”
It is important to understand that memory symptoms in old age are not “unequivocally” driven by Alzheimer’s and that LANS progresses more slowly and has a better prognosis than AD, he noted.
In addition, in vivo markers of TDP-43 are “on the horizon and can hopefully make their way to human research settings soon. This will help better understand the underlying molecular etiologies causing LANS and associated symptoms,” he said.
Dr. Corriveau-Lecavalier said the LANS criteria are ready for clinical use by experts in neurologic care. These criteria can be used to inform not only diagnosis but also prognosis, where this syndrome is associated with slow and mild progression and a memory-dominant profile.
He added that “the new criteria are also routinely used in our practice to make decisions about anti-amyloid treatment eligibility.”
Commenting on the research for this news organization, Rebecca M. Edelmayer, PhD, Alzheimer’s Association senior director of scientific engagement, said the research “exemplifies the great need to develop objective criteria for diagnosis and staging of Alzheimer’s and all other types of dementia and to create an integrated biological and clinical staging scheme that can be used effectively by physicians.”
“Advances in biomarkers will help to differentiate all types of dementia when incorporated into the diagnostic workup, but until those tools are available, a more succinct clinical criteria for diagnosis can be used to support a more personalized medicine approach to treatment, care, and enrollment into clinical studies,” said Dr. Edelmayer, who wasn’t involved in the research.
The research was funded in part by the National Institutes of Health and by the Robert Wood Johnson Foundation, the Elsie & Marvin Dekelboum Family Foundation, the Liston Family Foundation, the Edson Family, the Gerald A. and Henrietta Rauenhorst Foundation, and the Foundation Dr Corinne Schuler. Dr. Corriveau-Lecavalier and Dr. Edelmayer had no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Proposed clinical criteria for a memory loss disorder that is often misdiagnosed as Alzheimer’s disease (AD) have been published.
The new criteria for limbic-predominant amnestic neurodegenerative syndrome (LANS) provide a framework for neurologists and other experts to classify the condition and offer a more precise diagnosis and potential treatments.
“In our clinical work, we see patients whose memory symptoms appear to mimic Alzheimer’s disease, but when you look at their brain imaging or biomarkers, it’s clear they don’t have Alzheimer’s. Until now, there has not been a specific medical diagnosis to point to, but now we can offer them some answers,” senior investigator David T. Jones, MD, said in a release.
The proposed criteria and the research behind it were published online in Brain Communications and will be presented at the Alzheimer›s Association International Conference in Philadelphia.
Already in Use
Predominant limbic degeneration has been linked to various underlying etiologies, older age, predominant impairment of episodic memory, and slow clinical progression, the investigators noted. However, they added, the neurologic syndrome associated with predominant limbic degeneration is undefined.
Developing clinical criteria and validating them “is critical to distinguish such a syndrome from those originating from neocortical degeneration, which may differ in underlying etiology, disease course, and therapeutic needs,” the investigators wrote.
The newly proposed clinical criteria apply to LANS, which is “highly associated with limbic-predominant age-related TDP-43 encephalopathy but also other pathologic entities.”
The criteria incorporate core, standard, and advanced features including older age at evaluation, mild clinical syndrome, disproportionate hippocampal atrophy, impaired semantic memory, limbic hypometabolism, absence of endocortical degeneration, and low likelihood of neocortical tau with highest, high, moderate, and low degrees of certainty.
“A detailed history of the clinical symptoms, which may be supported by neuropsychological testing, with the observation of disproportionate hippocampal atrophy and limbic degeneration on MRI/FDG yields a high confidence in a diagnosis of LANS, where the most likely symptom-driving proteinopathy is TDP-43 and not Alzheimer’s associated proteins,” the first author, Nick Corriveau-Lecavalier, PhD, assistant professor of neurology and psychology at Mayo Clinic, Rochester, Minnesota, told this news organization.
To validate the criteria, the investigators screened autopsied patients from Mayo Clinic and Alzheimer’s Disease Neuroimaging Initiative cohorts and applied the criteria to those with a predominant amnestic syndrome and those who had AD neuropathologic change, limbic-predominant age-related TDP-43 encephalopathy, or both pathologies at autopsy.
“The criteria effectively categorized these cases, with Alzheimer’s disease having the lowest likelihoods, limbic-predominant age-related TDP-43 encephalopathy patients having the highest likelihoods, and patients with both pathologies having intermediate likelihoods,” the investigators reported.
“Patients with high likelihoods had a milder and slower clinical course and more severe temporo-limbic degeneration compared to those with low likelihoods,” they added.
Dr. Corriveau-Lecavalier said the team is currently analyzing longitudinal cognitive and imaging trajectories in LANS over several years. “This will help us better understand how LANS and Alzheimer’s differ in their sequence of symptoms over time.”
It is important to understand that memory symptoms in old age are not “unequivocally” driven by Alzheimer’s and that LANS progresses more slowly and has a better prognosis than AD, he noted.
In addition, in vivo markers of TDP-43 are “on the horizon and can hopefully make their way to human research settings soon. This will help better understand the underlying molecular etiologies causing LANS and associated symptoms,” he said.
Dr. Corriveau-Lecavalier said the LANS criteria are ready for clinical use by experts in neurologic care. These criteria can be used to inform not only diagnosis but also prognosis, where this syndrome is associated with slow and mild progression and a memory-dominant profile.
He added that “the new criteria are also routinely used in our practice to make decisions about anti-amyloid treatment eligibility.”
Commenting on the research for this news organization, Rebecca M. Edelmayer, PhD, Alzheimer’s Association senior director of scientific engagement, said the research “exemplifies the great need to develop objective criteria for diagnosis and staging of Alzheimer’s and all other types of dementia and to create an integrated biological and clinical staging scheme that can be used effectively by physicians.”
“Advances in biomarkers will help to differentiate all types of dementia when incorporated into the diagnostic workup, but until those tools are available, a more succinct clinical criteria for diagnosis can be used to support a more personalized medicine approach to treatment, care, and enrollment into clinical studies,” said Dr. Edelmayer, who wasn’t involved in the research.
The research was funded in part by the National Institutes of Health and by the Robert Wood Johnson Foundation, the Elsie & Marvin Dekelboum Family Foundation, the Liston Family Foundation, the Edson Family, the Gerald A. and Henrietta Rauenhorst Foundation, and the Foundation Dr Corinne Schuler. Dr. Corriveau-Lecavalier and Dr. Edelmayer had no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.