Psychosis Linked to Higher Misdiagnosis Rates in Dementia Patients

(St. Michael’s Hospital) People with Alzheimer’s disease who experience psychosis — including delusions and hallucinations — are five times more likely to be misdiagnosed with dementia with Lewy bodies compared to patients who do not, new research suggests.

Alzheimer’s disease is a type of dementia characterized by protein deposits in the brain including twisted fibers found inside brain cells. Dementia with Lewy bodies is believed to be caused by the buildup of a different abnormal protein aggregate found in nerve cells in the brain. Effective treatments for these conditions are still under development, but will almost certainly be different, according to the authors.

Researchers also found that Alzheimer’s disease was misdiagnosed in 24 per cent of all cases, with false positive and false negative rates both being 12 per cent. Previous research suggested that the rate of misdiagnosis in Alzheimer’s disease ranged from 12-23 per cent.

The findings, published online in Alzheimer’s & Dementia: Translational Research & Clinical Interventions, raise concern that there may be an under appreciation of how common psychotic symptoms are in Alzheimer’s disease, said Dr. Corinne Fischer, director of the Memory Disorders Clinic at St. Michael’s Hospital in Toronto and lead author of the study.

“Psychosis can be a symptom of Alzheimer’s disease, but it is a defining clinical feature in other types of dementia, including Parkinson’s disease related dementia and dementia with Lewy bodies,” she said.

“Consequently, clinicians are more reluctant to diagnose a patient with Alzheimer’s disease when they present with delusions or hallucinations.”

About 36 per cent of people with Alzheimer’s are thought to have delusions and 18 per cent have hallucinations. Psychotic symptoms are significant in Alzheimer’s patients because they have been shown to be associated with increased burden on caregivers, increased functional decline and more rapid progression of the disease.

Researchers examined 961 people using data from the National Alzheimer’s Coordinating Centre database, collected from 29 Alzheimer’s disease centres in the United States between 2005 and 2012. They included participants who had been clinically diagnosed with Alzheimer’s while they were alive, as well as those whose autopsies showed they the signature physical signs of Alzheimer’s in their brains.

Patients who experienced psychosis had a higher rate of false negative diagnosis and a lower rate of false positive diagnosis of Alzheimer’s disease compared to those who did not. Whether patients experienced delusions, hallucinations, or a combination of both did not affect the rate of misdiagnosis, according to the authors.

The Alzheimer’s Society of Canada estimates there are 564,000 people living with dementia in Canada, and that number is expected to almost double over the next 15 years, thus reinforcing the relevance of the study’s findings according to Winnie Qian, a Master’s student in the Neuroscience Research Program at St. Michael’s and an author on the study.

“An advantage of our study is that we used the final clinical diagnosis after years of follow-up, so the rate of misdiagnosis we described is the rate under ideal conditions,” she said.

“This means that it should be considered a minimum. If you extrapolate that and apply it to the general population, the magnitude of the problem could be much greater.”

Dr. Fischer said when patients do not present with psychosis, clinicians should be more careful when considering alternative diagnoses to Alzheimer’s disease.

“Many dementia patients never receive a definitive clinical diagnosis while they’re alive, so the hope is that by understanding what factors can lead to a misdiagnosis, we can be more accurate and provide patients with the best possible care,” she said.

Citation

http://www.stmichaelshospital.com/media/detail.php?source=hospital_news/2017/0630

Journal Reference:

Corinne E. Fischer, Winnie Qian, Tom A. Schweizer, Zahinoor Ismail, Eric E. Smith, Colleen P. Millikin, David G. Munoz. Determining the impact of psychosis on rates of false-positive and false-negative diagnosis in Alzheimer’s disease. Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 2017; 3 (3): 385 DOI: 10.1016/j.trci.2017.06.001

Copyright © 2017 St. Michael’s Hospital. All rights reserved.

 

Age and Obesity Conspire to Damage Blood Vessels that Feed Heart, Causing Heart Failure

(Medical College of Georgia at Augusta University) Age and obesity appear to create a perfect storm that can reduce blood flow through the tiny blood vessels that directly feed our heart muscle and put us at risk for heart failure, scientists report.

They call it “aged fat” and scientists now have evidence that the inflammation created by both age and fat have an additive effect that can thicken the walls of our coronary microvasculature without any  evidence of  the classic atherosclerotic plaque that many of us associate with heart disease.

“Older obese patients and sometimes women who suffer heart failure go to the cardiac catheterization lab and the cardiologist finds nothing that would explain their heart failure,” said Dr. Zsolt Bagi, vascular biologist in the Vascular Biology Center at the Medical College of Georgia at Augusta University.

“They have normal large blood vessels in the heart still the heart failure has developed.”

What isn’t readily seen with these routine exams is the thickened walls that can hinder dilation of the small capillaries fed by these bigger vessels, a condition called coronary microvascular dysfunction, or cardiac syndrome X, says Bagi, corresponding author of the study in the journal Arteriosclerosis, Thrombosis, and Vascular Biology.

In patients and animal models, who are both older and obese, Bagi has found a key dynamic in the dysfunction is an enzyme called ADAM17, which is involved in a huge variety of functions like releasing growth factors as we develop, but also implicated in diseases from Alzheimer’s to arthritis.

ADAM17 levels increase in obesity while levels of its natural inhibitor, the protein caveolin-1, decrease with age, enabling the perfect storm.

ADAM17 was discovered 20 years ago for its ability to cut and release previously inactive tumor necrosis factor, or TNF, from the cell membrane. TNF is a multifunctional protein, or cytokine, that gets its name from its skill at killing tumors and is a major promoter of inflammation that also directly impacts the function of the endothelial cells that line blood vessels.

The MCG scientist found that ADAM17 cleaves TNF from fat, releasing it into the bloodstream where it preferentially targets the heart.

The bottom line: the walls of the hair-sized microvasculature become thicker, less elastic, less able to dilate and to properly sustain the heart.

His research team found ADAM17 highly expressed in fat and even higher in the blood vessels of aged human fat. The protein level was increased in younger mice on a high-fat diet, but the significant increase in its activity came with age and fat.

In humans, they looked at small pieces of heart tissue as well as fat from around the heart removed during surgery by MCG cardiothoracic surgeons Drs. Vijay Patel and M. Vinayak Kamath. They also studied a combination of mice that included young and obese, old and obese, and just obese or just old.

“We tried to examine every possible scenario,” Bagi says.

“We were able to show that exactly the same thing happens with the small blood vessels in a mouse and man when they are both older and obese,” he says.

In humans, they saw the ability of the tiny vessels to dilate in response to bradykinin – a peptide used to lower blood pressure because of its ability to dilate blood vessels – significantly reduced in those ages 69 and older and further reduced in older individuals – males and females – who also were obese.

They found ADAM17 present in the fat of young and old mice on high-fat diets compared to normals, but it was only significantly active in the older mice on a high-fat diet. When they looked at younger and older obese patients, again much like the mice, they found high levels of expression of ADAM17 in the lining of blood vessel walls.

When they transplanted fat from aged obese mice to younger mice, it increased circulating levels of proinflammatory factors and impaired dilation of the coronary microvasculature.

“It basically mimicked the old vascular phenotype in the young animals,” he says.

One of the future studies they want to do is transplant younger fat to old, obese animals to also measure its impact. Others have evidence that transfusing young blood to older animals, can slow aging, Bagi notes.

Bagi and his colleagues’ previous studies have shown that mice missing the ADAM17 inhibitor, caveolin1, also have impaired ability to dilate the larger coronary arteries as well as hypertension when fed a high-fat diet. Related human studies have shown that the reactive oxygen species generated in diabetes disrupt caveolae, or “little caves” in the lining of the blood vessels. Caveonlin-1 is the main component of caveolae.

Being female, a family history of heart failure, diabetes and high blood pressure all are associated with coronary microvascular dysfunction. Its potential result, heart failure, is an impaired ability of the heart muscle to pump. Symptoms can include fatigue, shortness of breath that make everyday activities difficult as well as coughing.

Rather than having trouble with the heart contracting so it can pump blood out to the body, older, obese individuals in heart failure tend to have issues with the heart muscle being able to relax and fill efficiently, called diastolic heart failure, Bagi says.

Relaxation actually requires more energy than contracting, and the scientist hopes his studies will help this patient population, for which currently there are no good, targeted treatment options.  He has begun looking at antibodies that would directly target and ideally reduce levels of ADAM17 in the face of aged fat and at least delay development of small vessel disease.

Bagi thinks a similar process may happen in the brains of older obese individuals, so also has ongoing studies of how microvascular disease can lead to Alzheimer’s in these individuals.

He notes that young, obese individuals could help themselves avoid this and likely other diseases like diabetes, by losing weight while they are young. Activities like walking can also help even the tiniest blood vessels become more accustomed to handling more blood flow.

In the nearly 70-year-old Framingham Heart Study, a higher risk of heart failure was identified in 732 older subjects with inflammatory mediators like TNF and interleukin-6 who never even had a heart attack. Others have shown that elevated levels of TNF in the blood and fat strongly correlate with the severity of coronary artery disease in the elderly.

Bagi’s research was supported by the National Institutes of Health and the American Heart Association.

Citation

http://jagwire.augusta.edu/archives/ 45733

by Toni Baker

Copyright © 2017. Augusta University

Drug Discovery: Alzheimer’s and Parkinson’s Spurred by Same Enzyme

(MedicalXpress) Alzheimer’s disease and Parkinson’s disease are not the same. They affect different regions of the brain and have distinct genetic and environmental risk factors.

But at the biochemical level, these two neurodegenerative diseases start to look similar. That’s how Emory scientists led by Keqiang Ye, PhD, landed on a potential drug target for Parkinson’s.

In both Alzheimer’s (AD) and Parkinson’s (PD), a sticky protein forms toxic clumps in . In AD, the troublemaker inside cells is called tau, making up neurofibrillary tangles. In PD, the sticky protein is alpha-synuclein, forming Lewy bodies.

Ye and his colleagues had previously identified an enzyme (asparagine endopeptidase or AEP) that trims tau in a way that makes it more sticky and toxic. Drugs that inhibit AEP have beneficial effects in Alzheimer’s animal models.

In a new Nature Structural and Molecular Biology paper, Emory researchers show that AEP acts in the same way toward .

“In Parkinson’s, alpha-synuclein behaves much like Tau in Alzheimer’s,” Ye says.

“We reasoned that if AEP cuts Tau, it’s very likely that it will cut alpha-synuclein too.”

A particular chunk of alpha-synuclein produced by AEP’s scissors can be found in samples of brain tissue from patients with PD, but not in control samples, Ye’s team found.

In control brain samples AEP was confined to lysosomes, parts of the cell with a garbage disposal function. But in PD samples, AEP was leaking out of the lysosomes to the rest of the cell.

The researchers also observed that the chunk of alpha-synuclein generated by AEP is more likely to aggregate into clumps than the full length protein, and is more toxic when introduced into cells or mouse brains. In addition, alpha-synuclein mutated so that AEP can’t cut it is less toxic.

Ye cautions that AEP is not the only enzyme that cuts alpha-synuclein into various toxic pieces, and the full-length alpha-synuclein protein is still able to aggregate and cause harm. Nevertheless, he says his team is moving on to testing drugs that inhibit AEP in Parkinson’s animal models.

Citation

https://medicalxpress.com/news/2017-07-drug-discovery-alzheimer-parkinson-spurred.html#jCp

More information: Asparagine endopeptidase cleaves α-synuclein and mediates pathologic activities in Parkinson’s disease, Nature Structural and Molecular Biology, DOI: 10.1038/nsmb.3433

Journal reference: Nature Structural and Molecular Biology search and more info website

Provided by: Emory University search and more info

© Medical Xpress 2011 – 2017, Science X network

 

Cocoa and Chocolate are Not Just Treats — They are Good for your Cognition

(Frontiers) A balanced diet is chocolate in both hands — a phrase commonly used to justify ones chocolate snacking behavior. A phrase now shown to actually harbor some truth, as the cocoa bean is a rich source of flavanols: a class of natural compounds that has neuroprotective effects.

In their recent review published in Frontiers in Nutrition, Italian researchers examined the available literature for the effects of acute and chronic administration of cocoa flavanols on different cognitive domains. In other words: what happens to your brain up to a few hours after you eat cocoa flavanols, and what happens when you sustain such a cocoa flavanol enriched diet for a prolonged period of time?

Although randomized controlled trials investigating the acute effect of cocoa flavanols are sparse, most of them point towards a beneficial effect on cognitive performance. Participants showed, among others, enhancements in working memory performance and improved visual information processing after having had cocoa flavanols.

And for women, eating cocoa after a night of total sleep deprivation actually counteracted the cognitive impairment (i.e. less accuracy in performing tasks) that such a night brings about. Promising results for people that suffer from chronic sleep deprivation or work shifts.

It has to be noted though, that the effects depended on the length and mental load of the used cognitive tests to measure the effect of acute cocoa consumption. In young and healthy adults, for example, a high demanding cognitive test was required to uncover the subtle immediate behavioral effects that cocoa flavanols have on this group.

The effects of relatively long-term ingestion of cocoa flavanols (ranging from 5 days up to 3 months) has generally been investigated in elderly individuals. It turns out that for them cognitive performance was improved by a daily intake of cocoa flavanols. Factors such as attention, processing speed, working memory, and verbal fluency were greatly affected. These effects were, however, most pronounced in older adults with a starting memory decline or other mild cognitive impairments.

And this was exactly the most unexpected and promising result according to authors Valentina Socci and Michele Ferrara from the University of L’Aquila in Italy.

“This result suggests the potential of cocoa flavanols to protect cognition in vulnerable populations over time by improving cognitive performance. If you look at the underlying mechanism, the cocoa flavanols have beneficial effects for cardiovascular health and can increase cerebral blood volume in the dentate gyrus of the hippocampus. This structure is particularly affected by aging and therefore the potential source of age-related memory decline in humans.”

So should cocoa become a dietary supplement to improve our cognition?

“Regular intake of cocoa and chocolate could indeed provide beneficial effects on cognitive functioning over time. There are, however, potential side effects of eating cocoa and chocolate. Those are generally linked to the caloric value of chocolate, some inherent chemical compounds of the cocoa plant such as caffeine and theobromine, and a variety of additives we add to chocolate such as sugar or milk.”

Nonetheless, the scientists are the first to put their results into practice:

“Dark chocolate is a rich source of flavanols. So we always eat some dark chocolate. Every day.”

Citation

https://www.sciencedaily.com/releases/2017/06/170629101648.htm

Journal Reference:

Valentina Socci, Daniela Tempesta, Giovambattista Desideri, Luigi De Gennaro, Michele Ferrara. Enhancing Human Cognition with Cocoa Flavonoids. Frontiers in Nutrition, 2017; 4 DOI: 10.3389/fnut.2017.00019

Copyright 2017 ScienceDaily or by third parties, where indicated.

 

 

Evidence Supporting Three Interventions That Might Slow Cognitive Decline and the Onset of Dementia is Encouraging but Insufficient to Justify Public Health Campaign on Their Adoption

(National Academies of Sciences, Engineering, and Medicine) Cognitive training, blood pressure management for people with hypertension, and increased physical activity all show modest but inconclusive evidence that they can help prevent cognitive decline and dementia, but there is insufficient evidence to support a public health campaign encouraging their adoption, says a new report from the National Academies of Sciences, Engineering, and Medicine.  Additional research is needed to further understand and gain confidence in their effectiveness, said the committee that conducted the study and wrote the report.

“There is good cause for hope that in the next several years much more will be known about how to prevent cognitive decline and dementia, as more clinical trial results become available and more evidence emerges,” said Alan I. Leshner, chair of the committee and CEO emeritus, American Association for the Advancement of Science.

“Even though clinical trials have not conclusively supported the three interventions discussed in our report, the evidence is strong enough to suggest the public should at least have access to these results to help inform their decisions about how they can invest their time and resources to maintain brain health with aging.”

An earlier systematic review published in 2010 by the Agency for Healthcare Research and Quality (AHRQ) and an associated “state of the science” conference at the National Institutes of Health had concluded that there was insufficient evidence to make recommendations about any interventions to prevent cognitive decline and dementia.

Since then, understanding of the pathological processes that result in dementia has advanced significantly, and a number of clinical trials of potential preventive interventions have been completed and published.  In 2015, the National Institute on Aging (NIA) contracted with AHRQ to conduct another systematic review of the current evidence.  NIA also asked the National Academies to convene an expert committee to help inform the design of the AHRQ review and then use the results to make recommendations to inform the development of public health messaging, as well as recommendations for future research.

This report examines the most recent evidence on steps that can be taken to prevent, slow, or delay the onset of mild cognitive impairment and clinical Alzheimer’s-type dementia as well as steps that can delay or slow age-related cognitive decline.

Overall, the committee determined that despite an array of advances in understanding cognitive decline and dementia, the available evidence on interventions derived from randomized controlled trials – considered the gold standard of evidence – remains relatively limited and has significant shortcomings.

Based on the totality of available evidence, however, the committee concluded that three classes of interventions can be described as supported by encouraging but inconclusive evidence.  These interventions are:

  • cognitive training – which includes programs aimed at enhancing reasoning and problem solving, memory, and speed of processing – to delay or slow age-related cognitive decline.  Such structured training exercises may or may not be computer-based.
  • blood pressure management for people with hypertension – to prevent, delay, or slow clinical Alzheimer’s-type dementia.
  • increased physical activity – to delay or slow age-related cognitive decline.

Cognitive training has been the object of considerable interest and debate in both the academic and commercial sectors, particularly within the last 15 years.  Good evidence shows that cognitive training can improve performance on a trained task, at least in the short term.  However, debate has centered on evidence for long-term benefits and whether training in one domain, such as processing speed, yields benefits in others, such as in memory and reasoning, and if this can translate to maintaining independence in instrumental activities of daily living, such as driving and remembering to take medications.

Evidence from one randomized controlled trial suggests that cognitive training delivered over time and in an interactive context can improve long-term cognitive function as well as help maintain independence in instrumental activities of daily living for adults with normal cognition.  However, results from other randomized controlled trials that tested cognitive training were mixed.

Managing blood pressure for people with hypertension, particularly during midlife – generally ages 35 to 65 years – is supported by encouraging but inconclusive evidence for preventing, delaying, and slowing clinical Alzheimer’s-type dementia, the committee said.

The available evidence, together with the strong evidence for blood pressure management in preventing stroke and cardiovascular disease and the relative benefit/risk ratio of antihypertensive medications and lifestyle interventions, is sufficient to justify communication with the public regarding the use of blood pressure management, particularly during midlife, for preventing, delaying, and slowing clinical Alzheimer’s-type dementia, the report says.

It is well-documented that physical activity has many health benefits, and some of these benefits – such as stroke prevention – are causally related to brain health.  The AHRQ systematic review found that the pattern of randomized controlled trials results across different types of physical activity interventions provides an indication of the effectiveness of increased physical activity in delaying or slowing age-related cognitive decline, although these results were not consistently positive.

However, several other considerations led the committee to conclude that the evidence is sufficient to justify communicating to the public that increased physical activity for delaying or slowing age-related cognitive decline is supported by encouraging but inconclusive evidence.

None of the interventions evaluated in the AHRQ systematic review met the criteria for being supported by high-strength evidence, based on the quality of randomized controlled trials and the lack of consistently positive results across independent studies.  This limitation suggests the need for additional research as well as methodological improvements in the future research.

The National Institutes of Health and other interested organizations should support further research to strengthen the evidence base on cognitive training, blood pressure management, and increased physical activity, the committee said.  Examples of research priorities for these three classes of interventions include evaluating the comparative effectiveness of different forms of cognitive training interventions; determining whether there are optimal blood pressure targets and approaches across different age ranges; and comparing the effects of different forms of physical activity.

When funding research on preventing cognitive decline and dementia, the National Institutes of Health and other interested organizations should identify individuals who are at higher risk of cognitive decline and dementia; increase participation of underrepresented populations; begin more interventions at younger ages and have longer follow-up periods; use consistent cognitive outcome measures across trials to enable pooling; integrate robust cognitive outcome measures into trials with other primary purposes; include biomarkers as intermediate outcomes; and conduct large trials designed to test the effectiveness of an intervention in broad, routine clinical practices or community settings.

The study was sponsored by the National Institute on Aging.  The National Academies of Sciences, Engineering, and Medicine are private, nonprofit institutions that provide independent, objective analysis and advice to the nation to solve complex problems and inform public policy decisions related to science, technology, and medicine.  The National Academies operate under an 1863 congressional charter to the National Academy of Sciences, signed by President Lincoln.  For more information, visit http://national-academies.org.

Citation

http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=24782

Copyright © 2017 National Academy of Sciences. All rights reserved.

 

Leisure Activities Lower Blood Pressure in Alzheimer’s Caregivers

(Wolters Kluwer Health: Lippincott Williams and Wilkins) Going for a walk outside, reading, listening to music — these and other enjoyable activities can reduce blood pressure for elderly caregivers of spouses with Alzheimer’s disease, suggests a study in Psychosomatic Medicine: Journal of Biobehavioral Medicine, the official journal of the American Psychosomatic Society. The journal is published by Wolters Kluwer.

“Greater engagement in pleasant leisure activities was associated with lowered caregivers’ blood pressure over time,” according to the report by Brent T. Mausbach, PhD, of University of California San Diego and colleagues.

“Participation in pleasant leisure activities may have cardiovascular benefits for Alzheimer’s caregivers.”

The study included 126 caregivers enrolled in the UCSD Alzheimer’s Caregiver Study, a follow-up study evaluating associations between stress, coping, and cardiovascular risk in Alzheimer’s caregivers. The caregivers were 89 women and 37 men, average age 74 years, providing in-home care for a spouse with Alzheimer’s disease.

As part of annual interviews over five years, the caregivers provided information on how often they engaged in various pleasant leisure activities. These ratings were analyzed for association with blood pressure over time, with adjustment for demographic and health factors.

The caregivers reported high levels of enjoyable activities — most said they spent time outdoors, laughing, watching TV, listening to music, and reading or listening to stories. About half of caregivers said they exercised frequently.

Caregivers who more frequently engaged in pleasant leisure activities had lower mean arterial blood pressure (a measure of average blood pressure). In follow-up analyses, these activities were associated with a significant reduction in diastolic pressure (the second, lower blood pressure number), although not in systolic pressure (the first, higher number).

As expected, caregivers who exercised more frequently had lower blood pressure. However, other types of “more sedentary, reflective” activities also led to reduced blood pressure. These included reading, listening to music, shopping, and recalling past events.

Blood pressure also decreased after nursing home placement or death of the person with Alzheimer’s disease. That was consistent with previous studies showing that caregivers’ health improves after their caregiving duties end.

Being a caregiver for a disabled loved one is a highly stressful experience, associated with an increased risk of cardiovascular disease and death. Stress may contribute to high blood pressure, which is the strongest risk factor for cardiovascular disease. The new results suggest that leisure activities are a behavioral factor that can prevent the development of high blood pressure in Alzheimer’s caregivers.

Dr. Mausbach notes that the study assessed both the frequency and enjoyment of activities. The premise is that rather than recommending certain activities to everyone, it’s important for caregivers to enjoy the activities they do to receive benefit. While the study can’t determine how many activities people should do,

“We believe three to four enjoyed activities each week could have a modest impact on an individual’s blood pressure,” Dr. Mausbach commented.

“From there, the more an individual can do, the better the impact.”

The researchers have been conducting a clinical trial to examine the effect of a therapy to increase pleasant leisure activities.

“We recognize caregivers may have a difficult time engaging in pleasant leisure activities because they are busy with their caregiving duties,” said Dr. Mausbach.

“So we work with caregivers to find activities they can more confidently engage in even when their spouse is present. We also help them monitor their use of time so they know the times during the day when they are most capable of doing activities. Further, if caregivers use respite services, they are in a perfect position to use some of their respite time to engage in these activities.”

Citation

https://www.sciencedaily.com/releases/2017/06/170623100708.htm

Journal Reference:

Brent T. Mausbach, Rosa Romero-Moreno, Taylor Bos, Roland von Känel, Michael G Ziegler, Matthew A. Allison, Paul J. Mills, Joel E. Dimsdale, Sonia Ancoli-Israel, Andrés Losada, María Márquez-González, Thomas L. Patterson, Igor Grant. Engagement in pleasant leisure activities and blood pressure. Psychosomatic Medicine, 2017; 1 DOI: 10.1097/PSY.0000000000000497

 

Anti-epilepsy Drug Restores Normal Brain Activity in Mild Alzheimer’s Disease

(Beth Israel Deaconess Medical Center) In the last decade, mounting evidence has linked seizure-like activity in the brain to some of the cognitive decline seen in patients with Alzheimer’s disease. Patients with Alzheimer’s disease have an increased risk of epilepsy and nearly half may experience subclinical epileptic activity — disrupted electrical activity in the brain that doesn’t result in a seizure but which can be measured by electroencephalogram (EEG) or other brain scan technology.

In a recent feasibility study, clinician-scientists at Beth Israel Deaconess Medical Center (BIDMC) tested an anti-epileptic drug for its potential impact on the brain activity of patients with mild Alzheimer’s disease. The team, led by Daniel Z. Press, MD, of the Berenson-Allen Center for Non-invasive Brain Stimulation at BIDMC, documented changes in patients’ EEGs that suggest the drug could have a beneficial effect. The research was published in the Journal of Alzheimer’s Disease.

“In the field of Alzheimer’s disease research, there has been a major search for drugs to slow its progression,” said Press, an Instructor of Neurology in the Cognitive Neurology Unit at BIDMC and an Associate Professor of Neurology at Harvard Medical School.

“If this abnormal electrical activity is leading to more damage, then suppressing it could potentially slow the progression of the disease.”

In this double-blind within-subject study, a small group of patients with mild Alzheimer’s disease visited BIDMC three times. At each visit, patients were given a baseline (EEG) to measure the electrical activity in the brain. Next, patients were given injections containing either inactive placebo or the anti-seizure drug levetiracetam, at either a low dose (2.5 mg/kg) or a higher dose (7.5 mg/kg). Neither patients nor medical professionals knew which injections patients were receiving, but each patient eventually got one of each type, in a random order.

After receiving the injection, patients underwent another EEG, then magnetic resonance imaging (MRI) — which measures blood flow in the brain, another way to quantify brain activity and determine where in the brain it is taking place. Finally, patients took a standardized cognitive test, designed to measure memory, executive functioning, naming, visuospatial ability and semantic function — capabilities all affected by Alzheimer’s disease.

In the seven patients able to complete the study protocol successfully, Press and colleagues analyzed changes in their EEGs. (Blood flow analysis from the MRI data is still underway.) Overall, higher doses of the anti-seizure drug appeared to normalize abnormalities seen in the patients’ EEG profiles. That is, researchers saw overall increases in brain wave frequencies that had been abnormally low in Alzheimer’s disease patients prior to receiving the higher dose of levetiracetam, and, likewise, saw decreases in those that had been abnormally high.

“It’s worth noting, we did not demonstrate any improvement in cognitive function after a single dose of medication in this study,” said Press.

“It’s too early to use the drug widely, but we’re preparing for a larger, longer study.”

The risk of developing Alzheimer’s disease increases sharply with age. Today, it affects more than 5 million Americans, a figure that is projected to reach 16 million by 2050 as the population ages. In recent years, researchers have focused on developing techniques to clear the brain of amyloid and tau protein plaques that build up and wreak havoc in the brains of patients with Alzheimer’s disease.

“These strategies have not led to new therapies to date,” said Press.

“There have been a lot of disappointments. So our findings represent an interesting new avenue.”

Citation

https://www.sciencedaily.com/releases/2017/06/170623131512.htm

Story Source:

Materials provided by Beth Israel Deaconess Medical Center. Note: Content may be edited for style and length.

Copyright 2017 ScienceDaily or by third parties, where indicated.

 

Alzheimer’s Disease Study Links Brain Health and Physical Activity

(Journal of Alzheimer’s Disease) People at risk for Alzheimer’s disease who do more moderate-intensity physical activity, but not light-intensity physical activity, are more likely to have healthy patterns of glucose metabolism in their brain, according to a new UW-Madison study.

Results of the research were published today online in Journal of Alzheimer’s Disease. Senior author Dr. Ozioma Okonkwo, assistant professor of medicine, is a researcher at the Wisconsin Alzheimer’s Disease Research Center and the Wisconsin Alzheimer’s Institute at the UW School of Medicine and Public Health.

First author Ryan Dougherty is a graduate student studying under the direction of Dr. Dane B. Cook, professor of kinesiology and a co-author of the study, and Dr. Okonkwo. The research involved 93 members of the Wisconsin Registry for Alzheimer’s Prevention (WRAP), which with more than 1,500 registrants is the largest parental history Alzheimer’s risk study group in the world.

Researchers used accelerometers to measure the daily physical activity of participants, all of whom are in late middle-age and at high genetic risk for Alzheimer’s disease, but presently show no cognitive impairment. Activity levels were measured for one week, quantified, and analyzed. This approach allowed scientists to determine the amount of time each subject spent engaged in light, moderate, and vigorous levels of physical activity.

Light physical activity is equivalent to walking slowly, while moderate is equivalent to a brisk walk and vigorous a strenuous run. Data on the intensities of physical activity were then statistically analyzed to determine how they corresponded with glucose metabolism—a measure of neuronal health and activity—in areas of the brain known to have depressed glucose metabolism in people with Alzheimer’s disease. To measure brain glucose metabolism, researchers used a specialized imaging technique called 18F-fluorodeoxyglucose positron emission tomography (FDG-PET).

Moderate physical activity was associated with healthier (greater levels of) glucose metabolism in all brain regions analyzed. Researchers noted a step-wise benefit: subjects who spent at least 68 minutes per day engaged in moderate physical activity showed better glucose metabolism profiles than those who spent less time.

“This study has implications for guiding exercise ‘prescriptions’ that could help protect the brain from Alzheimer’s disease,” said Dougherty.

“While many people become discouraged about Alzheimer’s disease because they feel there’s little they can do to protect against it, these results suggest that engaging in moderate physical activity may slow down the progression of the disease.”

“Seeing a quantifiable connection between moderate physical activity and brain health is an exciting first step,” said Okonkwo.

He explained that ongoing research is focusing on better elucidating the neuroprotective effect of exercise against Alzheimer’s disease. To investigate this further, the team is recruiting individuals with concerns about their memory for a national clinical trial called EXERT to test whether physical exercise can slow the progression of early memory problems caused by Alzheimer’s disease. For more information or to volunteer, contact exercise physiologist Beth Jeanes at 608-265-5752 or by email at emjeanes@medicine.wisc.edu.

The Wisconsin Alzheimer’s Disease Research Center (ADRC) and The Wisconsin Alzheimer’s Institute (WAI) are two collaborative groups working under the UW Initiative to End Alzheimer’s in leading-edge research, education and outreach programs.

The study was supported by the National Institutes of Health, Veterans Administration, Alzheimer’s Association, Wisconsin Alumni Research Foundation, Helen Bader Foundation, Northwestern Mutual Foundation, and Extendicare Foundation.

Citation

http://www.j-alz.com/content/alzheimers-disease-study-links-brain-health-and-physical-activity

Journal of Alzheimer’s Disease is published by IOS Press

Copyright © 2017