Diet, Exercise Can Affect the Brain 'at the Molecular Level,' Reducing Amyloid Buildup

Deborah Brauser

August 23, 2016

Modifiable risk factors, such as exercise and consuming a Mediterranean-style diet (MedDiet), can reduce amyloid plaque in patients with mild cognitive impairment (MCI), lowering their risk for conversion to Alzheimer's disease, suggests new imaging research.

The small study of 44 participants with MCI or subjective memory impairment (SMI) showed that those with a higher adherence to a MedDiet had significantly lower positron emission tomography (PET) measures of amyloid plaques and tau tangles than those with a lower adherence.

In addition, the patients with MCI who reported higher levels of physical activity had lower PET measures of amyloid and tau binding, whereas those with a higher body mass index (BMI) had higher measures of binding.

"To date, there really hadn't been a look at the molecular pathology of this disease before it's diagnosed," lead author David A. Merrill, MD, PhD, assistant clinical professor of psychiatry at the University of California-Los Angeles Health System, told Medscape Medical News.

"The findings, especially showing that those who more regularly ate a Mediterranean-style diet had lower levels of these plaques and tangles, represent 'smoking gun' evidence of the molecular fingerprint of this disease process — and that there's less of this binding when you strive to live healthily," added Dr Merrill.

The study is published in the September issue of the American Journal of Geriatric Psychiatry.

"The authors are starting to address an important issue," said Heather M. Snyder, PhD, senior director of medical and scientific operations at the Alzheimer's Association, when asked for comment. "How lifestyle behaviors may play a role in the underlying biology of Alzheimer's disease is a big question.

"This is a relatively small study with preliminary data, but it's starting to move in an important direction," added Dr Snyder.

Cutting Risks to Cut AD Cases Worldwide

The investigators note that approximately 50% of all Alzheimer's cases are associated with modifiable dementia risk factors and that reducing these risks by 10% to 25% could potentially cut 500,000 cases in the United States and 1 to 3 million cases worldwide.

"To support efforts of such modifiable risk factor reduction, there is a growing interest in establishing the extent to which lifestyle factors impact…pathology in predementia states," they write.

For the current study, the investigators wanted to assess how some of these factors "are associated with a PET ligand that binds to and provides a measure of both amyloid and tau, namely 2-(1-(6-[(2-[F-18]fluorethyl)(methyl)amino]-2-naphthyl)ethylidene)malononitrile (FDDNP)."

Enrollment consisted of 44 volunteers who had registered memory problems. All underwent FDDNP-PET to measure plaque/tangle binding in the frontal, parietal, medial and lateral temporal, and posterior cingulate regions.

They also underwent physical and mental status examinations and a battery of neuropsychological testing. The investigators determined that 20 of the patients had MCI (65% women; mean age, 62 years) and 24 had SMI (66.7% women; mean age, 63.1 years).

The mean BMI was similar between the MCI and SMI groups (25.6 vs 25.9, respectively). However, 54.2% of the patients with SMI had an above-normal BMI, defined as greater than 25, vs 36.8% of those with MCI.

In addition, the International Physical Activity Questionnaire for the Elderly was used to determine "high" or "low" activity levels (based on a standard of 600 metabolic equivalent-minutes/week). And the patients were split into subgroups that "rarely" or "often" adhered to a MedDiet, based on a five-point Likert scale.

Exercise, Diet Prescriptions?

As with BMI, physical activity and MedDiet adherence levels were similar between the two cognitive groups. The MCI group, however, had significantly higher regional brain FDDNP-PET binding than did the SMI group (P = .02).

Regardless of cognitive status, the patients who adhered often to a MedDiet had lower levels of FDDNP-PET binding than did those who rarely adhered to the diet (P = .04).

A high vs low activity level was also significantly associated with lower FDDNP-PET binding in those with MCI (P = .004) — but not in those with SMI. And the MCI group members with a BMI greater than 25 had higher binding than those with a BMI of 25 or less (P = .002), while the SMI group showed no links between BMI and FDDNP-PET binding.

Overall, "we found moderate but significant associations" between the factors assessed and FDDNP-PET binding levels, note the investigators.

"These findings are consistent with those derived from other…studies finding that lifestyle behaviors affecting BMI influence AD and related dementia risk and multifactorial health strategies might delay onset of AD symptoms," they write.

The study "lends key insight not only into the ability of patients to prevent Alzheimer's disease, but also physicians' ability to detect and image these changes," said Dr Merrill in a press release.

"I will actually write a prescription for physical exercise and give it to patients, and I will prescribe a healthy diet. And we have both university- and community-based resources to help with that," he told Medscape Medical News.

"Love Your Brain"

"This particular study used a specific way of visualizing proteins in the brain. So it's hard to know exactly what the brain changes are that [the investigators] are seeing within these individuals based on these behaviors," commented Dr Snyder.

Still, she credited the researchers for assessing specific risk factors, such as BMI, to see how it can affect brain pathology in these patients.

"We've seen other studies that have looked at levels of physical activity and the changes in the levels of different brain protectants, particularly brain-derived neurotropic factor, or BDNF," said Dr Snyder. "But what's unique about this study is the idea of being able to use imaging and some of the developing and emerging tools as a way to look at cases."

She noted that in 2015, the Alzheimer's Association completed a "survey of the landscape about what we understand about lifestyle behaviors" and how they might affect brain health.

On the basis of this, the organization released "10 Ways to Love Your Brain," which included a list of factors that can reduce cognitive decline and may reduce dementia.

However, Dr Snyder pointed out that a lot of emerging data are suggesting that "it's not just one factor or another, but more a combination and how you put these things together in an overall healthy lifestyle recipe. And I believe that's a direction where we're going to see the field go."

In fact, she noted that the large FINGER study from Finland, which was reported in 2014, showed that a group undergoing a healthy lifestyle recipe intervention (including nutritional guidance, physical activity, cognitive training, and management of cardiac risk factors) had less cognitive decline than the group that received just regular health advice.

"The 10 Ways to Love Your Brain checklist was released for a consumer audience, but it also gives physicians a tool that they can share with their patients and say, 'here are some things you can do, based on the science, that's beneficial to keeping your brain as healthy as you can as you age,'" Said Dr Snyder.

The study was funded by grants from the National Institutes of Health (NIH) and by the Department of Energy, the Larry L. Hillblom Foundation, the Fran and Ray Stark Foundation Fund for Alzheimer's Disease Research, the Ahmanson Foundation, the Lovelace Foundation, the National Science Foundation, the UCLA Claude Pepper Older Americans Independence Center through funding by the National Institute on Aging, the American Federation of Aging Research, the John A. Hartford Foundation, the Centers of Excellence National Program, and the NIH/National Center for Advancing Translational Science. Dr Merrill reports having received lecture fees from Assurex Health. Disclosures for the coauthors are in the original paper.

Am J Geriatr Psychiatry. Published online May 13, 2016. Abstract

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