Vaccinating older adults against shingles in Canada is likely cost-effective, according to a study in CMAJ (Canadian Medical Association Journal), and the Shingrix vaccine appears to provide better protection than the Zostavax vaccine.
26 aug 2019--Herpes zoster, or shingles, affects about 1 in every 3 adults, causing a painful rash that can result in long-term pain in 8% to 27% of people.
The study used a model to compare the effectiveness and cost-effectiveness of the recombinant subunit (RZV, Shingrix) and live attenuated zoster (LZV, Zostavax) vaccines in adults aged 50 years and older in Canada. The LZV vaccine has been available in Canada since 2008, and RZV was approved in 2017.
The number of people needed to be vaccinated to prevent one case of shingles was lower for RZV (Shingrix) than for LZV (Zostavax) for all ages. For example, in people aged 60 years, the number needed to vaccinate was 18 for RZV and 78 for LZV.
"Our model predicted that the recombinant subunit zoster vaccine is likely cost-effective in Canada for adults 60 years or older and that it provides greater health benefits than the live attenuated zoster vaccine for all age groups," writes Dr. Marc Brisson, Centre de research du Centre hospitalier de l'Université de Québec and the Université Laval, Québec, Quebec, with coauthors.
The study results are consistent with other economic evaluations in the United States and the Netherlands.
Researchers from Boston University School of Medicine (BUSM), National Center for PTSD at VA Boston Healthcare System and Harvard T.H. Chan School of Public Health, have found that individuals with greater optimism are more likely to live longer and to achieve "exceptional longevity," that is, living to age 85 or older.
26 aug 2019--Optimism refers to a general expectation that good things will happen, or believing that the future will be favorable because we can control important outcomes. Whereas research has identified manyrisk factorsthat increase the likelihood of diseases and premature death, much less is known about positive psychosocial factors that can promotehealthy aging.
The study was based on 69,744 women and 1,429 men. Both groups completed survey measures to assess their level of optimism, as well as their overall health and health habits such as diet, smoking and alcohol use. Women were followed for 10 years, while the men were followed for 30 years. When individuals were compared based on their initial levels of optimism, the researchers found that the most optimistic men and women demonstrated, on average, an 11 to 15 percent longer lifespan, and had 50-70 percent greater odds of reaching 85 years old compared to the least optimistic groups. The results were maintained after accounting for age, demographic factors such as educational attainment, chronic diseases, depression and also health behaviors, such as alcohol use, exercise, diet and primary care visits.
"While research has identified many risk factors for diseases and premature death, we know relatively less about positive psychosocial factors that can promote healthy aging," explained corresponding author Lewina Lee, Ph.D., clinical research psychologist at the National Center for PTSD at VA Boston and assistant professor of psychiatry at BUSM. "This study has strong public health relevance because it suggests that optimism is one such psychosocial asset that has the potential to extend the human lifespan. Interestingly, optimism may be modifiable using relatively simple techniques or therapies."
It is unclear how exactly optimism helps people attain longer life. "Other research suggests that more optimistic people may be able to regulate emotions and behavior as well as bounce back from stressors and difficulties more effectively," said senior author Laura Kubzansky, Ph.D., MPH, Lee Kum Kee Professor of Social and Behavioral Sciences and co-director, Lee Kum Sheung Center for Health and Happiness at the Harvard T.H. Chan School of Public Health. The researchers also consider that more optimistic people tend to have healthier habits, such as being more likely to engage in more exercise and less likely to smoke, which could extend lifespan. "Research on the reason why optimism matters so much remains to be done, but the link between optimism and health is becoming more evident," noted senior author Fran Grodstein, ScD, professor of epidemiology at the Harvard T.H. Chan School of Public Health and professor of medicine at the Channing Division of Network Medicine at Brigham and Women's Hospital and Harvard Medical School.
"Our study contributes to scientific knowledge on health assets that may protect against mortality risk and promote resilient aging. We hope that our findings will inspire further research on interventions to enhance positive health assets that may improve the public's health with aging," added Lee.
These findings appear in the journal Proceedings of the National Academy of Sciences.
More information: Lewina O. Lee el al., "Optimism is associated with exceptional longevity in 2 epidemiologic cohorts of men and women," PNAS (2019). www.pnas.org/cgi/doi/10.1073/pnas.1900712116
Journal information: Proceedings of the National Academy of Sciences
Provided by Boston University School of Medicine
Sunday, August 25, 2019
Positive effect of music and dance on dementia proven in study
Stereotypically viewed as passive and immobile, a University of Otago pilot study has shown the powerful influence music and dance can have on older adults with dementia.
25 aug 2019--Researchers from the Department of Dance and Department of Psychological Medicine used familiar, reminiscentmusicand the natural gestures of a group of 22 participants to create an original series ofdanceexercises.
Lead author Ting Choo, Dance Studies Masters graduate, says the aim was to promote a better quality of life for people with dementia by providing memory stimulation, mood moderation and social interaction.
Performed over 10 weekly sessions, the intuitive movement re-embodiment (IMR) programme provided humour, imagination, and intuition which motivated the participants to dance and interact with joy.
The study results, published in the American Journal of Alzheimer's Disease & Other Dementias, show participants reported significant improvements in their quality of life after session six.
"They responded to the music greatly and showed enthusiasm in moving to the music regardless of their physical limitation. Positive responses such as memory recalling, spontaneous dancing and joking with each other were observed in every session.
"These observations have certainly reversed the stereotypical understanding of this group of people being passive and immobile. The music stimulates their responses much better than verbal instructions," Ms Choo says.
The researchers now intend to expand the pilot study, refining and enlarging the IMR programme to better cater to the needs and conditions of the participants.
Ms Choo hopes further research will gain the programme support and recognition from the medical community.
"There is scope for future exploration of creativity and dementia."
She believes the use of arts, including painting, music, drama and dance, has been undervalued in the clinical field, due to a lack of standardized conduct and consistent study results.
"As a former dancer and current dance educator, I understand the 'less important role' of arts in the society, as well as the insignificant therapeutic effects of music and dance for dementia, when compared to clinical research of much larger scale," she says.
More information: Ting Choo et al. The Effects of Intuitive Movement Reembodiment on the Quality of Life of Older Adults With Dementia: A Pilot Study, American Journal of Alzheimer's Disease & Other Dementias® (2019). DOI: 10.1177/1533317519860331
Journal information: American Journal of Alzheimer\'s Disease and Other Dementias
Provided by University of Otago
Apples, tea and moderation—the 3 ingredients for a long life
Consuming flavonoid-rich items such as apples and tea protects against cancer and heart disease, particularly for smokers and heavy drinkers, according to new research from Edith Cowan University (ECU).
25 aug 2019--Researchers from ECU's School of Medical and Health Sciences analysed data from the Danish Diet, Cancer and Health cohort that assessed the diets of 53,048 Danes over 23 years.
They found that people who habitually consumed moderate to high amounts of foods rich in flavonoids, compounds found in plant-based foods and drinks, were less likely to die from cancer or heart disease.
No quick fix for poor habits
Lead researcher Dr. Nicola Bondonno said while the study found a lower risk of death in those who ate flavonoid-rich foods, the protective effect appeared to be strongest for those at high risk of chronic diseases due to cigarette smoking and those who drank more than two standard alcoholic drinks a day.
"These findings are important as they highlight the potential to prevent cancer and heart disease by encouraging the consumption of flavonoid-rich foods, particularly in people at high risk of these chronic diseases," she said.
"But it's also important to note that flavonoid consumption does not counteract all of the increased risk of death caused by smoking and high alcohol consumption. By far the best thing to do for your health is to quit smoking and cut down on alcohol.
"We know these kind of lifestyle changes can be very challenging, so encouraging flavonoid consumption might be a novel way to alleviate the increased risk, while also encouraging people to quit smoking and reduce their alcohol intake."
How much is enough?
Participants consuming about 500mg of total flavonoids each day had the lowest risk of a cancer or heart disease-related death.
"It's important to consume a variety of different flavonoid compounds found in different plant based food and drink. This is easily achievable through the diet: one cup of tea, one apple, one orange, 100g of blueberries, and 100g of broccoli would provide a wide range of flavonoid compounds and over 500mg of total flavonoids".
Dr. Bondonno said while the research had established an association between flavonoid consumption and lower risk of death, the exact nature of the protective effect was unclear but likely to be multifaceted.
"Alcohol consumption and smoking both increase inflammation and damage blood vessels, which can increase the risk of a range of diseases," she said.
"Flavonoids have been shown to be anti-inflammatory and improve blood vessel function, which may explain why they are associated with a lower risk of death from heart disease and cancer.".
Dr. Bondonno said the next step for the research was to look more closely at which types of heart disease cancers were most protected by flavonoids.
More information: 'Flavonoid intake is associated with lower mortality in the Danish Diet Cancer and Health Cohort,' Nature Communications (2019). DOI: 10.1038/s41467-019-11622-x
Provided by Edith Cowan University
'Silent' strokes common after surgery, researchers find
Dr. PJ Devereaux is a senior scientist at the Population Health Research Institute of McMaster University and Hamilton Health Sciences. Credit: McMaster University/Hamilton Health Sciences.
Canadian researchers have discovered that covert—or 'silent' - strokes are common in seniors after they have elective, non-cardiac surgery and double their risk of cognitive decline one year later.
25 aug 2019--While an overt stroke causes obvious symptoms, such as weakness in one arm or speech problems that last more than a day, a covert stroke is not obvious except on brain scans, such as MRI. Each year, approximately 0.5 per cent of the 50 million people age 65 years or greater worldwide who have major, non-cardiac surgerywill suffer an overt stroke, but until now little was known about the incidence or impacts of silent stroke aftersurgery.
The results of the NeuroVISION study were published today in The Lancet.
"We've found that 'silent' covert strokes are actually more common than overt strokes in people aged 65 or older who have surgery," said Dr. PJ Devereaux, co-principal investigator of the NeuroVISION study. Dr. Devereaux is a cardiologist at Hamilton Health Sciences (HHS), professor in the departments of health research methods, evidence, and impact, and medicine at McMaster University, and a senior scientist at the Population Health Research Institute of McMaster University and HHS.
Dr. Devereaux and his team found that one in 14 people over age 65 who had elective, non-cardiac surgery had a silent stroke, suggesting that as many as three million people in this age category globally suffer a covert stroke after surgery each year.
NeuroVISION involved 1,114 patients aged 65 years and older from 12 centres in North and South America, Asia, New Zealand, and Europe. All patients received an MRI within nine days of their surgery to look for imaging evidence of silent stroke. The research team followed patients for one year after their surgery to assess their cognitive capabilities. They found that people who had a silent stroke after surgery were more likely to experience cognitive decline, perioperative delirium, overt stroke or transient ischaemic attack within one year, compared to patients who did not have a silent stroke.
"Over the last century, surgery has greatly improved the health and the quality of life of patients around the world," said Dr. Marko Mrkobrada, an associate professor of medicine at University of Western Ontario and co-principal investigator for the NeuroVISION study. "Surgeons are now able to operate on older and sicker patients thanks to improvements in surgical and anesthetic techniques. Despite the benefits of surgery, we also need to understand the risks."
"Vascular brain injuries, both overt and covert, are more frequently being detected, recognized and prevented through research funded by our Institute and CIHR," says Dr. Brian Rowe, scientific director of the Institute of Circulatory and Respiratory Health, Canadian Institutes of Health Research (CIHR). "The NeuroVISION Study provides important insights into the development of vascular brain injury after surgery, and adds to the mounting evidence of the importance of vascular health on cognitive decline. The results of NeuroVISION are important and represent a meaningful discovery that will facilitate tackling the issue of cognitive decline after surgery."
Certain dietary supplements tied to dysphagia, choking in seniors
Most reports of swallowing problems caused by dietary supplements involve seniors taking multivitamins or calcium supplements, according to a research letter published online Aug. 20 in the Annals of Internal Medicine.
25 aug 2019--Cecile Punzalan, M.D., from the U.S. Food and Drug Administration in College Park, Maryland, and colleagues used data from the FDA Center for Food Safety and Applied Nutrition Adverse Event Reporting System (2006 through 2015) to understanddietary supplement-associated adverse events caused by pill size.
The researchers found that of the 20,791 reported adverse events, in 19.1 percent of the cases, the patients indicated swallowing problems. Woman predominately filed these adverse swallowing reports (85.6 percent), which represented one-quarter of all adverse reports made by women. Of the roughly two-thirds of reports of swallowing problems that included age data, more than three-quarters (76.8 percent) involved adults aged 65 years or older. One in seven reports of swallowing problems cited serious adverse events, including three deaths due to supplement-induced airway obstruction or aspiration. Most reports of swallowing difficulty involved multivitamins (72.9 percent), followed by calcium supplements (17.3 percent). Ten dietary supplements were tied to more than three-quarters (76.4 percent) of swallowing problems and had a weighted mean pill length, width, and height of 19.3 mm, 9.8 mm, and 7.8 mm, respectively. Four in 10 reports of swallowing problems involved a single multivitamin product marketed to older women.
"These data identify a specific harm—choking—that may be preventable, particularly in older adults who regularly consume dietary supplements," the authors write.
Mean 24-hour diastolic blood pressure (DBP) in Parkinson disease (PD) participants with and without fatigue. The presence of fatigue was assessed using the Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part 1. Investigators compared blood pressure measurements in fatigued versus non-fatigued PD individuals assessed overnight, morning, midday and evening. Credit: IOS Press
Fatigue is a common debilitating symptom in Parkinson's disease (PD). A novel research study has found that fatigue symptoms in PD are associated with small but persistent reductions in diastolic blood pressure (DBP) throughout the day, report scientists in the Journal of Parkinson's Disease.
25 aug 2019--PD is a slowly progressive disorder that affects movement, muscle control and balance. It is the second most common age-related neurodegenerative disorder affecting about 3 percent of the population by the age of 65 and up to 5 percent of individuals over 85 years of age. Fatigue is a disabling non-motorsymptomthat affects about half of all individuals with PD. A 2015systematic reviewon this topic confirmed the absence of high quality evidence supporting any particular PD fatigue treatment.
"The majority of people with PD consider fatigue, defined as diminished energy levels or increased perception of effort that is disproportionate to attempted activities, to be one of their three biggest symptomatic concerns. But despite its high prevalence and disabling nature, we know relatively little about its underlying causes," explained lead investigator Vikas Kotagal, MD, MS, Department of Neurology, University of Michigan and Veterans Affairs Ann Arbor Health System (VAAAHS) and GRECC, Ann Arbor, MI, U.S.. "Understanding the biological basis for fatigue in PD is a key step towards designing effective treatments. This is an important goal for the field of PD clinical research."
Investigators conducted a cross-sectional study research assessment of 35 people with PD recruited from the Ann Arbor Veterans Affairs Health System, all of whom wore a 24-hour blood pressure monitor to track their blood pressure hourly while they were at home. Researchers asked participants about the presence of fatigue symptoms and grouped them into two categories: those with fatigue and those without.
The data demonstrate study participants with fatigue symptoms had lower mean DBP compared to those without fatigue. The differences were most notable in the morning.
"This is a novel finding that we hope may open the door for new, currently untapped ways to treat fatigue symptoms in PD," commented Dr. Kotagal. "We hope these results will help move us towards better treatments for PD fatigue. If we can design and test treatments that increase DBP without worsening the harmful cardiovascular effects of high systolic blood pressure (SBP), we may be able improve fatigue symptoms in PD. Our data may also have implications on the off-target side effects of some classes of antihypertensive medications when used by patients with PD and fatigue."
SBP, the top number typically given when blood pressure values are presented, is commonly used to describe people's blood pressure because it is a good marker for atherosclerosis and cardiovascular disease. It often gets more attention than DBP, which is typically presented at the bottom. DBP gets comparatively less attention but may better reflect the type of autonomic dysfunction that is common in PD.
More information: Vikas Kotagal et al. Fatigue in Parkinson's Disease Associates with Lower Ambulatory Diastolic Blood Pressure, Journal of Parkinson's Disease (2019). DOI: 10.3233/JPD-191579
Journal information: Journal of Parkinson's Disease
Provided by IOS Press
Low grip strength linked to impaired cognition, memory loss in older Americans
For older Americans, poor handgrip may be a sign of impaired cognition and memory, a new study suggests.
25 aug 2019--Researchers from the University of Michigan and North Dakota State University followed nearly 14,000 participants from the 2006 Health and Retirement Study, age 50 and older, for eight years.
They found that every 5-kg reduction in handgrip strength was associated with 10% greater odds for any cognitive impairment 18% greater odds for severe cognitive impairment.
They assessed handgrip with a hand-held dynamometer, and cognitive function with a modified Mini-Mental State Examination, a widely used test among the elderly that includes tests of orientation, attention, memory, language and visual-spatial skills.
Study co-author Sheria Robinson-Lane, assistant professor at the U-M School of Nursing, said the findings are important for providers and individuals seeking ways to retain physical and mental function.
The findings, published in the Journal of Alzheimer's Disease, contribute to mounting evidence that providers should include grip strength––not currently used––in routine health assessments for older adults, said first author Ryan McGrath, assistant professor at North Dakota State University.
More importantly, the researchers interpreted the findings to mean that a reduction in grip strength is associated with neural degeneration, which underscores the importance of muscle-building exercise.
"These findings suggest that this is another instance where you're seeing that staying physically active affects your overall health and your cognitive health," Robinson-Lane said.
More information: Ryan McGrath et al. Handgrip Strength Is Associated with Poorer Cognitive Functioning in Aging Americans, Journal of Alzheimer's Disease (2019). DOI: 10.3233/JAD-190042
Journal information: Journal of Alzheimer's Disease
Provided by University of Michigan
Tuesday, August 06, 2019
Amyloid is a less accurate marker for measuring severity, progression of Alzheimer's
PET imaging using the radiotracers FDG and florbetapir to quantify cognitive decline in patients with Alzheimer’s disease (AD), mild cognitive impairment (MCI), and healthy controls. Credit: Penn Medicine
While the presence of beta-amyloid plaques in the brain may be a hallmark of Alzheimer's disease, giving patients an amyloid PET scan is not an effective method for measuring their cognitive function, according to a new study from researchers in the Perelman School of Medicine at the University of Pennsylvania and Thomas Jefferson University. The researchers concluded that fluorodeoxyglucose (FDG) PET, which measures the brain's glucose consumption as a marker of neural activity, is a stronger approach for assessing the progression and severity of Alzheimer's and mild cognitive impairment (MCI) as compared to florbetapir-PET scans, which reveal amyloid protein deposits in the brain.
06 aug 2019--This suggests that FDG-PET is also a better means for determining the effectiveness of Alzheimer's therapies, as well as tracking patients' disease advancement, in both clinical and research settings. Results of this study are detailed in the August issue of the Journal of Alzheimer's Disease.
"Both florbetapir-PET and FDG-PET are approved diagnostic methods for Alzheimer's disease, and both appear to be effective in indicating some sort of cognitive impairment. However, we have now shown that FDG-PET is significantly more precise inclinical studies, and it is also available for routine use with modest costs," said the study's co-principal investigator Abass Alavi, MD, Ph.D., a professor of Radiology at Penn. "Our results support the notion that amyloid imaging does not reflect levels ofbrainfunction, and therefore it may be of limited value for assessing patients with cognitive decline."
Alzheimer's disease, the most common cause of dementia, is the sixth leading cause of death in the United States, affecting up to 5.8 million Americans currently. As clinicians aim to spot and treat the symptoms of dementia in its earliest stages, PET plays an increasingly pivotal role in diagnosing and monitoring Alzheimer's disease, as well as MCI, a condition that often precedes dementia.
Two of the most significant biomarkers found in Alzheimer's are decreased glucose uptake and the accumulation of amyloid plaques in the brain. PET scans use different radioactive drugs, called radiotracers, to measure these biomarkers within the brain tissue of patients with cognitive impairment. FDG-PET is one of the most commonly used imaging techniques to diagnose Alzheimer's. However, in recent years, several other radiotracers, such as florbetapir, have been developed to detect the deposition of amyloid plaques.
Recently, the effectiveness of amyloid imaging as a strategy for monitoring dementia symptoms has been called into question. While the presence of amyloid plaques in the brain is considered as being characteristic of Alzheimer's, some studies have shown that large amounts of amyloid plaques were present in healthy, non-demented individuals. Conversely, recent clinical trials have shown that the intended removal of amyloid from the brains of patients with Alzheimer's disease led to no change in, or even worsened, cognitive performance.
In this study, the researchers evaluated 63 individuals, including 19 with clinically diagnosed Alzheimer's disease, 23 with MCI, and 21 healthy individuals. The study participants underwent both FDG- and florbetapir-PET imaging. They were then assessed with a Mini Mental Status Examination (MMSE), a widely used diagnostic test for detecting and assessing the severity of cognitive impairment. The researchers used a novel "global quantification approach" to generate data from five different regions of the brain, which were correlated with the results from the MMSE scores.
The study revealed that both FDG- and florbetapir-PET scans are able to effectively discriminate the individuals with dementia from the healthy control group. However, when compared with the MMSE scores, the correlation between low cognitive performance and high levels of amyloid was significantly weaker than the correlation between FDG and low cognitive performance for all groups included in the study. This suggests that FDG-PET is a more sensitive indicator of cognitive decline.
"Amyloid imaging has a value in diagnosing or ruling out Alzheimer's disease, but it's a bit like all or nothing. Our study shows that it can reveal disease, but you wouldn't be able to differentiate between someone who had very mild or very severe symptoms," said co-principal investigator Andrew Newberg, MD, a professor of Radiology at Thomas Jefferson University, who added that these findings have important implications for clinical research.
"In a clinical drug trial, for example, it may be more relevant to do an FDG-PET scan, rather than using amyloid as a marker, to find out whether the therapy is working," Newberg said.
While FDG-PET may not be a perfect diagnostic tool, the study confirms that currently it is the best available method for monitoring symptoms of dementia, according to Alavi.
"Right now, FDG is king when it comes to looking at brain function, not only in Alzheimer's disease, but also diseases like vascular dementia and cancer," Alavi said.
More information: Mohsen Khosravi et al, 18F-FDG Is a Superior Indicator of Cognitive Performance Compared to 18F-Florbetapir in Alzheimer's Disease and Mild Cognitive Impairment Evaluation: A Global Quantitative Analysis, Journal of Alzheimer's Disease (2019). DOI: 10.3233/JAD-190220
Journal information: Journal of Alzheimer's Disease
Provided by Perelman School of Medicine at the University of Pennsylvania
Saturday, August 03, 2019
Frailty is a medical condition, not an inevitable result of aging
Frailty is not simply an adjective associated with old age, it is a medical condition all on its own. And it has significant medical, social and economic implications.
03 aug 2019--A landmark study published today (August 2) in theJournal of the American Medical Association (JAMA) Network Open, led by researchers at Monash University in Australia, explored the incidence of frailty in 120,000 people over the age of 60 in 28 countries.
It is the first global study to estimate the likelihood of community-dwelling older adultsdeveloping frailty.
The study, led by Dr. Richard Ofori-Asenso and Professor Danny Liew from the Monash School of Public Health and Preventive Medicine, looked at 46 studies of more than 120,000 people across 28 countries to reveal that, in over 60s, 4.3 per cent will develop frailty per year.
According to Dr. Ofori-Asenso, this is the first time that a global estimate of the incidence of frailty in the population has been quantified. The results also showed that women were more likely than men to develop frailty.
As yet, there is, no 'gold standard' definition of frailty, but researchers and clinicians tend to regard it as a condition that meets three out of the following five criteria:
low physical activity
weak grip strength
low energy
slow walking speed
non-deliberate weight loss
Frailty is associated with a lower quality of life and a higher risk of death, hospitalisation, and institutionalisation. The condition tends to occur among older adults, but even young people can be frail if they have one or more disabling chronic diseases.
As more than 20 per cent of the world's population will be aged over 60 years by 2050, the number of people diagnosed with frailty is projected to increase.
According to Dr. Ofori-Asenso: "our results suggest that the risk of developing frailty in older people is high. This is a worldwide problem and highlights a major challenge facing countries with ageing populations."
However, the news is not all bad. Interventions such as muscle strength training and protein supplementation may help to prevent or delay the progression of frailty.
Thus, the study authors advocate for "regular screening to assess older people's vulnerability to developing frailty so that appropriate interventions can be implemented in a timely manner".
Furthermore, in a previous study, the authors found that frailty may even be reversed, suggesting that the condition is a dynamic one.
More information: Richard Ofori-Asenso et al, Global Incidence of Frailty and Prefrailty Among Community-Dwelling Older Adults, JAMA Network Open (2019). DOI: 10.1001/jamanetworkopen.2019.8398
Journal information: JAMA Network Open
Provided by Monash University
Thursday, August 01, 2019
Blood test is 94% accurate at identifying early Alzheimer's disease
Diagram of the brain of a person with Alzheimer's Disease. Credit: Wikipedia/public domain.
Up to two decades before people develop the characteristic memory loss and confusion of Alzheimer's disease, damaging clumps of protein start to build up in their brains. Now, a blood test to detect such early brain changes has moved one step closer to clinical use.
01 aug 2019--Researchers from Washington University School of Medicine in St. Louis report that they can measure levels of the Alzheimer's proteinamyloidbeta in thebloodand use such levels to predict whether the protein has accumulated in thebrain. When blood amyloid levels are combined with two other major Alzheimer'srisk factors—age and the presence of the genetic variant APOE4—people with early Alzheimer's brain changes can be identified with 94% accuracy, the study found.
The findings, published Aug. 1 in the journal Neurology, represent another step toward a blood test to identify people on track to develop Alzheimer's before symptoms arise. Surprisingly, the test may be even more sensitive than the gold standard—a PET brain scan—at detecting the beginnings of amyloid deposition in the brain.
Such a test may become available at doctors' offices within a few years, but its benefits will be much greater once there are treatments to halt the disease process and forestall dementia. Clinical trials of preventive drug candidates have been hampered by the difficulty of identifying participants who have Alzheimer's brain changes but no cognitive problems. The blood test could provide a way to efficiently screen for people with early signs of disease so they can participate in clinical trialsevaluating whether drugs can prevent Alzheimer's dementia.
"Right now we screen people for clinical trials with brain scans, which is time-consuming and expensive, and enrolling participants takes years," said senior author Randall J. Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor of Neurology. "But with a blood test, we could potentially screen thousands of people a month. That means we can more efficiently enroll participants in clinical trials, which will help us find treatments faster, and could have an enormous impact on the cost of the disease as well as the human suffering that goes with it."
The test, an earlier version of which first was reported two years ago, uses a technique called mass spectrometry to precisely measure the amounts of two forms of amyloid beta in the blood: amyloid beta 42 and amyloid beta 40. The ratio of the two forms goes down as the amount of amyloid beta deposits in the brain goes up.
The current study involved 158 adults over age 50. All but 10 of the participants in the new study were cognitively normal, and each provided at least one blood sample and underwent one PET brain scan. The researchers classified each blood sample and PET scan as amyloid positive or negative, and found that the blood test from each participant agreed with his or her PET scan 88 percent of the time, which is promising but not accurate enough for a clinical diagnostic test.
In an effort to improve the test's accuracy, the researchers incorporated several major risk factors for Alzheimer's. Age is the largest known risk factor; after age 65, the chance of developing the disease doubles every five years. A genetic variant called APOE4 raises the risk of developing Alzheimer's three- to fivefold. And gender also plays a role: Two out of three Alzheimer's patients are women.
When the researchers included these risk factors in the analysis, they found that age and APOE4 status raised the accuracy of the blood test to 94%. Sex did not significantly affected the analysis.
"Sex did affect the amyloid beta ratio, but not enough to change whether people were classified as amyloid positive or amyloid negative, so including it didn't improve the accuracy of the analysis," said first author Suzanne Schindler, MD, Ph.D., an assistant professor of neurology.
Further, the results of some people's blood tests initially were considered false positives because the blood test was positive for amyloid beta but the brain scan came back negative. But some people with mismatched results tested positive on subsequent brain scans taken an average of four years later. The finding suggests that, far from being wrong, the initial blood tests had flagged early signs of disease missed by the gold-standard brain scan.
There is growing consensus among neurologists that Alzheimer's treatment needs to begin as early as possible, ideally before any cognitive symptoms arise. By the time people become forgetful, their brains are so severely damaged no therapy is likely to fully heal them. But testing preventive treatments requires screening thousands of healthy people to find a study population of people with amyloid build-up and no cognitive problems, a slow and expensive process.
As part of the study, the researchers analyzed the enrollment process for a prominent Alzheimer's prevention trial called the A4 study that used PET scans to confirm the presence of early Alzheimer's brain changes in potential participants. They concluded that prescreening with a blood test followed by a PET scan for confirmation would have reduced the number of PET scans needed by two thirds. Unlike blood tests, which cost a few hundred dollars, each PET scan costs upward of $4,000. A single site can only run a few dozen PET brain scans a month, because PET scanners are primarily reserved for patient care, not research studies.
"If you want to screen an asymptomatic population for a prevention trial, you would have to screen, say, 10,000 people just to get 1,500 or 2,000 that would qualify," Bateman said. "Reducing the number of PET scans could enable us to conduct twice as many clinical trials for the same amount of time and money. It's not the $4,000 per PET scan that we're worried about. It's the millions of patients that are suffering while we don't have a treatment. If we can run these trials faster, that will get us closer to ending this disease."
