Different Brain Atropy Patterns May Explain Variability in Alzheimer’s Disease

(Massachusetts General Hospital) Imaging studies imply that most patients, at-risk individuals show a combination of atrophy factors.

Mathematical modeling of the brain scans of patients with Alzheimer’s disease and others at risk for the devastating neurodegenerative disorder has identified specific patterns of brain atrophy that appear to be related to the loss of particular cognitive abilities.

In their report that has been published online in the Proceedings of the National Academy of Sciences, a team of researchers at Massachusetts General Hospital (MGH) and the National University of Singapore describe how different atrophy patterns may explain the different ways that Alzheimer’s disease can be manifested in individual patients.

“The symptom severity and neurodegeneration can vary widely across patients in Alzheimer’s disease,” says Thomas Yeo, PhD, of the Martinos Center for Biomedical Imaging at MGH.

“Our work shows that participants in this study exhibit at least three atrophy patterns – cortical, temporal or subcortical – that are associated with variability in cognitive decline not only in patients diagnosed with Alzheimer’s but also in individuals with mild cognitive impairment or those who are cognitively normal but are at risk for Alzheimer’s.”

In addition to his affiliation with the Martinos Center, Yeo is an assistant professor in the Department of Electrical and Computer Engineering, Clinical Imaging Research Centre and Singapore Institute for Neurotechnology at the National University of Singapore.

The study analyzed data collected as part of the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a multi-institutional project to develop biomarkers – including blood tests, cerebrospinal fluid tests, and imaging studies – that can be used for diagnosis or in clinical trials.

Yeo and his team – including investigators at the MGH and in Singapore – analyzed MR images taken of the brains of 378 ADNI participants when they enrolled in the study. Of these participants, 188 had been diagnosed with Alzheimer’s disease; the others – 147 with mild cognitive impairment and 43 who were cognitively normal – were at increased risk based on levels in their brains of the beta-amyloid plaques that are characteristic of the disease.

As a first step, the research team analyzed data from the baseline structural MRIs using a mathematical model that estimated the probability that particular details of each image were associated with atrophy of a specific location within the brain.

Based on the location of atrophy factors, they determined three atrophy factor patterns: cortical – representing atrophy in most of the cerebral cortex; temporal – indicating atrophy in the temporal cortex (the cortical lobe behind the ears), hippocampus and amygdala; and subcortical, indicating atrophy in the cerebellum, striatum and thalamus, structures at the base of the brain.


Mathematical modeling of brain scans of patients with Alzheimer’s disease and others at risk for the disorder has allowed the identification of three atrophy factor patterns, based on the loss of gray matter throughout major areas of the brain, which may help explain the variations in symptoms occurring in individual patients. (Xiuming Zhang, National University of Singapore)

Analysis of study participant scans taken two years later indicated that atrophy factor patterns were persistent in individuals and did not reflect different stages of disease. Most participants – including those in the mild cognitive impairment and cognitively normal groups – showed levels of more than one atrophy factor.

Behavioral and cognitive tests of study participants taken at six-month intervals indicated associations between particular atrophy factor patterns and specific cognitive deficits.

Individuals in whom temporal atrophy predominated had greater problems with memory, while cortical atrophy was associated with difficulties with executive function – the ability to plan and to accomplish goals. Individual differences in how atrophy factors are distributed within the brain may allow prediction of the rate at which cognitive abilities would be expected to decline.

“Most previous studies focused on patients already diagnosed, but we were able to establish distinct atrophy patterns not only in diagnosed patients but also in at-risk participants who had mild impairment or were cognitively normal at the outset of the study,” Yeo says.

“That is important because the neurodegenerative cascade that leads to Alzheimer’s starts years, possibly decades, before diagnosis. So understanding different atrophy patterns among at-risk individuals is quite valuable.

He adds, “Previous studies assumed that an individual can only express a single neurodegenerative pattern, which is highly restrictive since in any aged person there could be multiple pathological factors going on at the same time – such as vascular impairment along with the amyloid plaques and tau tangles that are directly associated with Alzheimer’s. So individuals who are affected by multiple, co-existing pathologies might be expected to exhibit multiple atrophy patterns.”

Future research could further determine whether and how these atrophy patterns relate to the distribution of amyloid and tau and the mechanisms by which they affect specific cognitive abilities, Yeo explains. The same analytic approach also could be applied to other types of patient data and extended to other neurodegenerative disorder that produce varying symptom patterns, such as Parkinson’s disease and autism.



Journal Reference:

Xiuming Zhang, Elizabeth C. Mormino, Nanbo Sun, Reisa A. Sperling, Mert R. Sabuncu, B. T. Thomas Yeo. Bayesian model reveals latent atrophy factors with dissociable cognitive trajectories in Alzheimer’s disease. Proceedings of the National Academy of Sciences, 2016; 201611073 DOI: 10.1073/pnas.1611073113

Copyright © 2007-2016. The General Hospital Corporation. All Rights Reserved.



Brain Cell ‘Executioner’ Identified

(Johns Hopkins Medicine) Common culprit may cause damage in stroke, brain injury, neurodegenerative disease.

Despite their different triggers, the same molecular chain of events appears to be responsible for brain cell death from strokes, injuries and even such neurodegenerative diseases as Alzheimer’s. Now, researchers at Johns Hopkins say they have pinpointed the protein at the end of that chain of events, one that delivers the fatal strike by carving up a cell’s DNA. The find, they say, potentially opens up a new avenue for the development of drugs to prevent, stop or weaken the process.

A report on the research appears in the Oct. 7 issue of the journal Science.

The new experiments, conducted in laboratory-grown cells, build on earlier work by research partners Ted Dawson, M.D., Ph.D., now director of the Institute for Cell Engineering at the Johns Hopkins University School of Medicine, and Valina Dawson, Ph.D., professor of neurology.

Their research groups found that despite their very different causes and symptoms, injury, stroke, Alzheimer’s disease, Parkinson’s disease and the rare, fatal genetic disorder Huntington’s disease have a shared mechanism of a distinct form of “programmed” brain cell death they named parthanatos after the personification of death in Greek mythology and PARP, an enzyme involved in the process.

“I can’t overemphasize what an important form of cell death it is; it plays a role in almost all forms of cellular injury,” Ted Dawson says.

His and Valina Dawson’s research groups have spent years delineating each of the links in the parthanatos chain of events and the roles of the proteins involved.

The current study, they say, has completed the chain. From previous studies, the researchers knew that when a protein called mitochondrial apoptosis-inducing factor, or AIF, leaves its usual place in the energy-producing mitochondria of the cell and moves to the nucleus, it sparks the carving up of the genome housed in the nucleus and leads to cell death.

But AIF itself, they say, can’t cut DNA. So then-postdoctoral fellow Yingfei Wang, Ph.D., now an assistant professor at the University of Texas Southwestern Medical Center, used a protein chip to screen thousands of human proteins to find those that interacted most strongly with AIF. Working with the 160 candidates she uncovered, she then used custom molecules called small interfering RNAs to stop each of those proteins’ manufacture, one by one, in lab-grown human cells to see if doing so would prevent cell death.


Nucleus of a cell undergoing parthanatos.
Credit: Yingfei Wang and I-Hsun Wu/Johns Hopkins Medicine

One of the 160 proteins, known as macrophage migration inhibitory factor (MIF), was a winner.

“We found that AIF binds to MIF and carries it into the nucleus, where MIF chops up DNA,” Ted Dawson says. “We think that’s the final execution step in parthanatos.”

The group reports that in work to be published, it also identified a few chemical compounds that block MIF’s action in the lab-grown cells, protecting them from parthanatos. Dawson says they plan to test these in animals, and modify them to maximize their safety and effectiveness.

He cautions that while parthanatos is known to cause cell death in many brain conditions, MIF’s ability to chop up DNA has so far only been definitively linked with stroke — when the MIF gene was disabled in mice, the damage caused by a stroke was dramatically reduced.

“We’re interested in finding out whether MIF is also involved in Parkinson’s, Alzheimer’s and other neurodegenerative diseases,” he says.

If so, and if an inhibitor of MIF proves successful in testing, it could have implications for treating many conditions, he says.



Journal Reference:

Y. Wang, R. An, G. K. Umanah, H. Park, K. Nambiar, S. M. Eacker, B. Kim, L. Bao, M. M. Harraz, C. Chang, R. Chen, J. E. Wang, T.-I. Kam, J. S. Jeong, Z. Xie, S. Neifert, J. Qian, S. A. Andrabi, S. Blackshaw, H. Zhu, H. Song, G.-l. Ming, V. L. Dawson, T. M. Dawson. A nuclease that mediates cell death induced by DNA damage and poly(ADP-ribose) polymerase-1. Science, 2016; 354 (6308): aad6872 DOI: 10.1126/science.aad6872

©2016 Newswise, Inc


Research Hints at Underlying Cause for Alzheimer’s Drug Trial Failures

(University of Kentucky) Because Alzheimer’s disease (AD) is the leading cause of dementia, many people use the two terms interchangeably. But inadequate blood flow to the brain due to microinfarcts, mini-strokes, or strokes is a hallmark of a disease called Vascular Cognitive Impairment and Dementia (VCID). VCID is the second most common cause of dementia, and the two are not mutually exclusive – researchers estimate that 40-60% of Alzheimer’s disease patients also have VCID.

A paper recently published in the Journal of Neuroscience by Donna Wilcock, PhD, of the University of Kentucky Sanders-Brown Center on Aging, reports that a certain form of immunotherapy targeted to Alzheimer’s patients may be ineffective when that patient also has VCID.

“These findings are important in that they provide a possible explanation for why clinical trials of anti-Aβ immunotherapy for Alzheimer’s disease have been historically unsuccessful,” Wilcock said.

“If up to 40 percent of people with Alzheimer’s also have VCID, treatment candidates that target only the AD physiology won’t be effective in those patients. It’s like treating only half the disease.”

Most researchers agree that the formation of brain plaques containing amyloid β (Aβ) peptides is an initial step in the development of Alzheimer’s disease, which has led to a race to identify and test treatments that reduce the levels of these plaques. Anti-Aβ immunotherapy, which uses antibodies against A to clear it from the brain, has been a leading approach.

While these drugs showed promise in animal studies, clinical trials have failed to show similar benefits in human patients.

“There has been one failure after another in clinical trials, which has been really disheartening for the scientific community and for patients, Wilcock said. “My work might shed some early light on why they failed and eventually open the door for a combination treatment for VCID and AD.”

Without a suitable animal model, testing this hypothesis would not have been possible. Fortunately, Wilcock and her research team had already developed an innovative model of combined AD and VCID. Using this mouse model, together with its parent model of AD without VCID, Wilcock evaluated the ability of an anti-Aβ antibody to enhance cognitive capabilities in both models. While Aβ levels were reduced in both groups, cognitive function was not improved in the groups with combined AD and VCID.

“The failure of anti-Aβ immunotherapy in the mixed AD-VCID model suggests that both disease processes have to be treated to have a successful outcome,” Wilcock said.

“The missing link has been that our animal models usually possess the hallmarks of only one disease, which has led to failure of successful translation to clinic.”

By developing a model that more accurately reflects the brain changes we see in the human brain with dementia, we can better develop our treatment approaches and increase our chances of successful translation. Our next step is to add a treatment for VCID on top of the Aβ immunotherapy to try to overcome the inability to produce a meaningful improvement in learning and memory.”

Research reported in this publication was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under award numbers F31NS092202 and 1RO1NS079637. This content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.



© 2016 University of Kentucky College of Medicine


Mediterranean Diet Could Lower Risk of Cardiovascular Disease in UK

(University of Cambridge) Britons eating a Mediterranean diet could lower their risk of developing heart disease and stroke, according to research published in the open access journal BMC Medicine.

In this study, the first of its kind carried out in a UK population, the researchers found that healthy individuals with greater adherence to a Mediterranean-type diet had 6 to 16% lower risk of future cardiovascular disease compared to individuals who had poor adherence.

Dr Nita Forouhi, lead author from the Medical Research Council Epidemiology Unit at the University of Cambridge, UK, said:

“We estimate that one in 25 of all new cardiovascular disease cases or one in eight cardiovascular deaths in our UK based study population could potentially be avoided if this population increased their adherence to the Mediterranean diet.”

The Mediterranean diet is typically high in fruits, vegetables, whole grains, nuts and olive oil, while low in red meats and moderate in dairy, fish, poultry and wine. The UK National Institute for Health and Care Excellence (NICE) recommends a Mediterranean style diet for people already diagnosed with cardiovascular disease to prevent further episodes of heart attack or stroke. However, the association of the Mediterranean diet with preventing  cardiovascular disease in the first instance or preventing further episodes has not been examined in the UK until now.

Dr Forouhi adds:

“The benefits of the Mediterranean diet for cardiovascular health are well documented in countries of the Mediterranean region, but this is the first study to evaluate this in the UK. If our findings are broadly representative of the overall UK population, then we can assume that higher level of adherence to the Mediterranean diet could have significant impact in lowering the cardiovascular disease burden in the UK.”

The researchers collected data from 23,902 initially healthy Britons taking part in the EPIC-Norfolk prospective cohort study. The participants’ diets were measured using food frequency questionnaires and participants were followed up for an average of 12 to 17 years to investigate the association between adherence to the Mediterranean diet and the occurrence of new-onset CVD and deaths during that time.

The Mediterranean diet was defined using a 15 point score based on guideline recommendations from a Mediterranean dietary pyramid published by the Mediterranean Diet Foundation. This is the first time these guidelines have been tested for their associations with health. There are other definitions of what constitutes a Mediterranean diet, but when alternative definitions were used in this study, the findings were broadly similar.

Dr Forouhi adds:

“Encouraging greater adoption of the Mediterranean diet looks like a promising component of a of a wider strategy to help prevent cardiovascular disease, including other important factors such as not smoking and maintaining a healthy weight, blood cholesterol and blood pressure.”

The authors acknowledge that these findings are based on an observational study and so a cause and effect relationship cannot be assumed. However, they were careful to make comprehensive adjustments for lifestyle and other factors that could potentially distort the findings, and together with the consistency of results with other studies elsewhere, their current findings provide robust evidence for a link.

Dr Forouhi concludes:

“Our study shows that higher versus lower adherence to a Mediterranean-type diet is linked with lower future CVD risk in the UK but our challenge now is to understand the social, economic and cultural factors that might support or prevent people being able to keep to this dietary pattern in the UK.”



EPIC-Norfolk study is supported by the Medical Research Council and Cancer Research UK.

Adapted from a press release by BioMed Central.

Tong, T et al. Prospective association of the Mediterranean diet with cardiovascular disease incidence and mortality and its population impact in a non-Mediterranean population: the EPIC-Norfolk Study. BMC Medicine; 29 Sept 2016; DOI: 10.1186/s12916-016-0677-4

© 2016 University of Cambridge


Trial Helps Doctors Tell Lewy Body Dementia From Alzheimer’s, Parkinson’s

(The Ohio State University Wexner Medical Center) Knowing that many clinicians find it difficult to correctly diagnose patients with Lewy body dementia, researchers at The Ohio State University Wexner Medical Center set out to develop a clinical profile for these patients. Their findings are published online in the Journal of Alzheimer’s Disease.

The study compared 21 patients with Lewy body dementia to 21 patients with Alzheimer’s disease and 21 patients with Parkinson’s disease. The patients were carefully matched by age, gender, education, race, degree of cognitive impairment, and degree of motor (physical) impairment. Pairs were compared using cognitive, functional, behavioral and motor measures.

“Many clinicians find it difficult to diagnose Lewy body dementia patients, often confusing them and misdiagnosing them as Alzheimer¹s disease or Parkinson¹s disease patients. Our study findings showed that the clinical profiles of Lewy body dementia patients can be differentiated from Alzheimer’s and Parkinson’s patients,” said Dr. Douglas Scharre, director of the division of cognitive neurology at Ohio State’s Wexner Medical Center and principal investigator of the study.

“Since treatments and prognosis differ between these conditions, it’s important to correctly diagnose the patient from the start.”

Researchers with Ohio State’s Center for Cognitive and Memory Disorders found that the diagnosis is likely Lewy body dementia if the patient is characterized by a specific cognitive profile (retrieval memory disturbance and deficits in visuospatial and executive domains), along with axial (trunk/body) posture impairments & gait/balance instability.

Compared to Alzheimer’s patients, Lewy body dementia patients have more executive and visuospatial deficits and less amnesia and disorientation, and also show more daytime sleepiness, cognitive/behavioral fluctuations, hallucinations and obstructive sleep apnea than either Alzheimer’s or Parkinson’s patients. Significant correlations were noted between axial motor, balance and gait disturbances and executive functioning, visuospatial abilities and global cognitive deficits.

Lewy body dementia is characterized by Parkinsonism (stiffness and trouble with gait), memory loss, and visual processing difficulties. Fluctuations and visual hallucinations are not uncommon. Mental degradation progresses as in people with Alzheimer’s disease. The disease usually appears after age 60.

Lewy bodies are collections of proteins (alpha-synuclein) that accumulate abnormally in the brain, that are not typically seen in Alzheimer’s, and are deposited in different parts of the brain than in Parkinson’s. These toxic alpha-synuclein proteins accumulate gradually, impact specific brain regions leading to its unique clinical symptoms and disease course, and need to be treated and managed differently than those with Alzheimer’s or Parkinson’s.

 “It’s vitally important that patients are correctly diagnosed so that they can be prescribed the proper medications that may help slow down the course of the disease or improve symptoms,” Scharre said.

The correct diagnosis of Lewy body dementia will prompt evaluation and treatment for commonly co-existing associated conditions such as autonomic conditions, sleep apnea, REM sleep behavior disorder, fluctuations of attention and alertness, gait disturbance and fall risk.

This research is supported by a grant from the Mangurian Foundation.

Other Ohio State researchers involved in the study include Shu-Ing Chang, Haikady N. Nagaraja, Ariane Park, Anahita Adeli, Punit Agrawal, Anne Kloos, Deb Kegelmeyer, Shannon Linder, Nora Fritz, Sandra K. Kostyk, and Maria Kataki.



Journal Reference:

Douglas W. Scharre, Shu-Ing Chang, Haikady N. Nagaraja, Ariane Park, Anahita Adeli, Punit Agrawal, Anne Kloos, Deb Kegelmeyer, Shannon Linder, Nora Fritz, Sandra K. Kostyk, Maria Kataki. Paired Studies Comparing Clinical Profiles of Lewy Body Dementia with Alzheimer’s and Parkinson’s Diseases. Journal of Alzheimer’s Disease, 2016; DOI: 10.3233/JAD-160384

Copyright The Ohio State University Wexner Medical Center


For Women, Caffeine Could be Ally in Warding Off Dementia

(University of Wisconsin-Milwaukee) Higher caffeine intake in women is associated with reduced odds of developing dementia or cognitive impairment, according to the results of a new study published in The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences.

Among a group of older women, self-reported caffeine consumption of more than 261 mg per day was associated with a 36 percent reduction in the risk of incident dementia over 10 years of follow-up. This level is equivalent to two to three 8-oz cups of coffee per day, five to six 8-oz cups of black tea, or seven to eight 12-ounce cans of cola.

“The mounting evidence of caffeine consumption as a potentially protective factor against cognitive impairment is exciting given that caffeine is also an easily modifiable dietary factor with very few contraindications,” said Ira Driscoll, PhD, the study’s lead author and a professor of psychology at the University of Wisconsin-Milwaukee.

“What is unique about this study is that we had an unprecedented opportunity to examine the relationships between caffeine intake and dementia incidence in a large and well-defined, prospectively-studied cohort of women.”

The findings come from participants in the Women’s Health Initiative Memory Study, which is funded by the National Heart, Lung, and Blood Institute. Driscoll and her research colleagues used data from 6,467 community-dwelling, postmenopausal women aged 65 and older who reported some level of caffeine consumption. Intake was estimated from questions about coffee, tea, and cola beverage intake, including frequency and serving size.

In 10 years or less of follow-up with annual assessments of cognitive function, 388 of these women received a diagnosis of probable dementia or some form of global cognitive impairment.

Those who consumed above the median amount of caffeine for this group (with an average intake of 261 mg per day) were diagnosed at a lower rate than those who fell below the median (with an average intake of 64 mg per day).

The researchers adjusted for risk factors such as hormone therapy, age, race, education, body mass index, sleep quality, depression, hypertension, prior cardiovascular disease, diabetes, smoking, and alcohol consumption.

“While we can’t make a direct link between higher caffeine consumption and lower incidence of cognitive impairment and dementia, with further study, we can better quantify its relationship with cognitive health outcomes,” Driscoll said.

“Research on this topic will be beneficial not only from a preventative stand point but also to better understand the underlying mechanisms and their involvement in dementia and cognitive impairment.”


https://uwm.edu/news/ women-caffeine-ally-warding-off-dementia/

Copyright University of Wisconsin-Milwaukee


Can Lifestyle Changes Reduce Your Risk of Dementia?

(BrightFocus Foundation) The August 22 issue of Time magazine talks about ways to protect the brain as it ages. Research is showing that exercise and other lifestyle interventions work to stave off normal cognitive decline seen with aging and to a limited extent might even help keep Alzheimer’s disease (AD) and other forms of dementia at bay.

One of the experts quoted in the article is BrightFocus’ 2010-14  Alzheimer’s Disease Research (ADR) grantee Kristine Yaffe, MD, professor of psychiatry, neurology and epidemiology and vice chair of research in psychiatry at the University of California, San Francisco (UCSF). Her epidemiologic research, supported by ADR and others, has made her one of the country’s leading authorities on preventable risk factors for AD and other forms of dementia.

Time also goes into the clinic with Harvard-trained neurologist Majid Fatuhi, MD, PhD, who has established three-month personalized AD prevention “boot camps” near Washington, DC. The program enrolls adults with mild cognitive impairment (MCI), a condition that resembles normal aging but sometimes progresses to AD.

After initial cognitive assessment, participants undergo three months of training that has them exercising, meditating, eating a Mediterranean diet, and using techniques to reduce stress and improve sleep habits. There’s also brain training and “talk therapy” accompanied by neuroimaging, so patients can actually see their neurons firing in response to stimulation.

Fatuhi and colleagues just published their initial results from 127 patients Journal of Prevention of Alzheimer’s Disease, 2016). The majority of participants (84 percent) had significant improvement in at least three areas of cognitive function. In a subgroup of 17 patients who had pre- and post-MRIs, half the group (nine patients) had modest hippocampal growth consistent with a 1-2 year reversal of normal age-related cognitive decline.

Fatuhi’s approach is among a handful of programs cropping up in the United States and worldwide. Leading the way for these clinical applications was the FINGER trial in Finland, a large, publicly-subsidized effort to assess a multidomain program of exercise, diet and other behavioral changes in normal older adults who are at risk of developing AD.

Two-year results showed that strict adherence to the program significantly improved overall cognitive functioning in subjects versus controls (Ngandu et al, Lancet, 2015, or read our earlier report). The principal investigator of that trial, Miia Kivalpelto, MD, a neurologist based at the Karolinska Institutet outside Stockholm, acknowledged in an interview that what “works” in Finland may not work everywhere. However, she expressed the hope that FINGER’s basic findings might be adapted for use in the United States and elsewhere.

Yaffe Links Diabetes and Heart Disease Risk with Alzheimer’s

The BrightFocus ADR program also is funding research into the science behind behavioral changes that might improve brain health and reduce Alzheimer’s risk. See our sidebar list of some current ADR grant projects on this topic.

A pioneer in this area, Kristine Yaffe, MD, received ADR funding to investigate causative links between poor glucose control and/or adult onset diabetes (Type 2) and the risk of AD. The brain uses glucose as a primary energy source, and cognitive function becomes impaired when blood glucose drops to low levels. Severe hypoglycemia may cause neuronal damage, Yaffe and colleagues speculated.  This association was borne out in a large study of 783 older Americans with diabetes, who were followed for 12 years. Those who experienced a hypoglycemic event had a two-fold increased risk for developing dementia, compared with those who did not (Yaffe et al, JAMA Intern Med, 2013).

That study was followed by several others, including Yaffe’s 2014 study showing that cardiovascular risk factors in early adulthood, including elevated glucose and high blood pressure, are linked with significantly worse cognitive function in middle age compared with having none of those risk factors (Yaffe et al,Circulation, 2014; read our summary).

“Heart-disease risk factors have a big effect on brain health,” Time quotes Yaffe as saying. “My prediction is that one day, hopefully, Alzheimer’s will be handled like cardiovascular disease, with a combination of drugs and lifestyle factors.”

Yaffe’s research also has linked sleep disorders, depression, post-traumatic stress disorder, and other conditions to increased risk for AD. Her wide-ranging epidemiologic studies have reinforced the concept that because Alzheimer’s is influenced by modifiable risk factors, the disease may be, to some degree, preventable.

In 2011, Yaffe coauthored a study (also quoted in the Time article) which projected that seven modifiable risk factors are responsible for up to half of all cases of late-life dementia, and that targeted interventions could reduce up to one-third of AD-related dementia worldwide, a total of nearly 10 million cases (Barnes D and Yaffe K, Lancet Neurol., 2011). The seven risk factors are diabetes, mid-life hypertension and obesity, smoking, depression, low educational attainment, and physical inactivity.

“Lifestyle factors are so important,” Yaffe is quoted in Time, “even though they sound sort of soft, and a lot of people therefore think they can’t possibly be that effective. But I’m not so sure.

“They’re not expensive, they don’t have side effects, and they’re good for the body too. So why wouldn’t you make lifestyle changes?”

What Lifestyle Changes Are Beneficial?

Below are some lifestyle changes that may help protect brain health and reduce AD risk, as highlighted in the Time article, and in other reports.

What’s good for the heart is good for the brain. Fotuhi describes the brain as a “sea of blood vessels.” Some 20 percent of all blood pumped by the heart goes to provide the brain with sufficient oxygen so that its 100 billion neurons can fire properly. Thus, for our brains to work best, any condition that interferes with blood flow—such as hypertension, obesity, Type 2 diabetes, high cholesterol, or hyperlipidemia—needs to be treated or, even better, prevented. Part of the reason exercise is so good for us as we age is because it increases blood flow.

Exercise helps reverse brain shrinking and improves cognition. The hippocampus, a region of the brain that is essential for memory, normally shrinks about one-half a percent each year after age 40. That’s part of normal aging; however, smaller hippocampus regions have been associated with increased risk of Alzheimer’s. The good news is that aerobic exercise and meditation may actually help to reverse this trend and “grow” hippocampal volume by modest amounts. Research has shown that in older adults with MCI, there were improvements in cognitive function after an extended period of high-intensity aerobic exercise (45 minutes, four times a week, for six months). In addition, the oldest age group had significant reduction in “bad” tau, which is believed to be a key driver that advances AD.

Keep your mind and spirit in the game.  Engaging with the world intellectually, through such activities as reading and writing (even letters), has been linked to better cognition in old age. In terms of emotional engagement, rich social lives are linked with higher levels of cognition, whereas loneliness and depression are linked to cognitive decline and poorer brain health.

Realize the benefit of a good night’s sleep. Sleep cycles are when the brain does its housekeeping, clearing out damaged neurons and toxic substance, like toxic tau and amyloid beta. Poor sleep contributes to AD, and improving sleep habits can reduce risk.

Modify your diet. Although not specifically covered in the Time article, a Mediterranean-style diet rich in fresh food, including berries and nuts, leafy greens, fish (at least once a week), whole grains, and olive oil, appears to be beneficial. Martha Clare Morris, ScD, a nutritional expert who coined the MIND diet (for “Mediterranean-DASH Intervention for Neurodegenerative Delay” ) has published research showing that it can delay cognitive aging and cut Alzheimer’s risk (Morris et al, Alzheimers Dement, 2015).

A modified Mediterranean diet was part of the FINGER study and also is followed in Fatuhi’s AD prevention “boot camps.”



By Martha Snyder Taggart

Copyright 2016 BrightFocus Foundation. All rights reserved.


Alzheimer’s Beginnings Prove to be a Sticky Situation

(Michigan State University) Laser technology has revealed a common trait of Alzheimer’s disease — a sticky situation that could lead to new targets for medicinal treatments.

Alzheimer’s statistics are always staggering. The neurodegenerative disease affects an estimated 5 million Americans, one in three seniors dies with Alzheimer’s or a form of dementia, it claims more lives than breast and prostate cancers combined, and its incidence is rising.

To help fight this deadly disease, Lisa Lapidus, Michigan State University professor of physics and astronomy, has found that peptides, or strings of amino acids, related to Alzheimer’s wiggle at dangerous speeds prior to clumping or forming the plaques commonly associated with Alzheimer’s.

“Strings of 40 amino acids are the ones most-commonly found in healthy individuals, but strings of 42 are much more likely to clump,” said Lapidus, who published the results in the current issue of ChemPhysChem.

“We found that the peptides’ wiggle speeds, the step before aggregation, was five times slower for the longer strings, which leaves plenty of time to stick together rather than wiggle out of the way.”

This so-called “wiggle” precedes clumping, or aggregating, which is the first step of neurological disorders such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. Lapidus pioneered the use of lasers to study the speed of protein reconfiguration before aggregation.

If reconfiguration is much faster or slower than the speed at which proteins bump into each other, aggregation is slow. If reconfiguration is the same speed, however, aggregation is fast. She calls the telltale wiggle that she discovered the “dangerous middle.”

“The dangerous middle is the speed in which clumping happens fastest,” Lapidus said.

“But we were able to identify some ways that we can bump that speed into a safer zone.”

Lapidus and her team of MSU scientists, including Srabasti Acharya, Kinshuk Srivastava and Sureshbabu Nagarajan, found that increasing pH levels kept the amino acids wiggling at fast, safe speeds. Also, a naturally occurring molecule, curcumin (from the spice turmeric), kept the peptide out of the dangerous middle.

While this is not a viable drug candidate because it does not easily cross the blood-brain barrier, the filter that controls what chemicals reach the brain, they do provide strong leads that could lead to medicinal breakthroughs.

Along with new drug targets, Lapidus’ research provides a potential model of early detection. By the time patients show symptoms and go to a doctor, aggregation already has a stronghold in their brains. Policing amino acids for wiggling at dangerous speeds could tip off doctors long before the patient begins to suffer from the disease.

This research was funded by the National Institutes of Health.



Journal Reference:

Srabasti Acharya, Kinshuk Raj Srivastava, Sureshbabu Nagarajan, Lisa Jill Lapidus. Monomer dynamics of the Alzheimer peptides and Kinetic Control of Early Aggregation in Alzheimer’s Disease. ChemPhysChem, 2016; DOI: 10.1002/cphc.201600706

© Michigan State University