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Seafood Found Neuroprotective for Alzheimer's in Those with the Risk Gene

ARTICLE IN BRIEF

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THE STUDY found an associated benefit from eating even a modest amount of seafood — as little as one serving a week — among those with the risk gene for Alzheimers disease.

A Rush University study found that people who carry the apolipoprotein e4 risk gene for Alzheimer's had an associated neuroprotective benefit against the amyloid deposits and neurofibrillary tangles indicative of the disease, but there was no associated benefit for people who did not carry the risk gene.

Eating at least one seafood meal a week can help protect the brains of persons at heightened risk for Alzheimer's disease, and there seems to be no downside from the levels of mercury found in fish, according to an analysis of autopsied brain tissue from 286 elderly persons who had filled out food diaries as part of a longitudinal study on aging and memory.

The Rush University study found that the benefits of eating seafood applied only to people who carried the apolipoprotein E4 (APOE e4) gene, which is linked to an elevated risk of Alzheimer's disease. For persons who did not have the genetic variant, seafood consumption did not afford protection against the amyloid deposits and neurofibrillary tangles indicative of Alzheimer's.

“We found that seafood consumption was associated with higher brain levels of mercury, but that mercury was not correlated with brain neuropathologies of any type associated with dementia,” said Martha Clare Morris, ScD, lead author of the study, published in the February 2 edition of the Journal of the American Medical Association (JAMA).

Other studies have likewise suggested that seafood may help fend off Alzheimer's-related dementia, but there has been a worry that the mercury found in fish could harm the brain. Mercury is known to be neurotoxic at high levels. [There have also been concerns about fish levels of a toxin, alpha-amino-beta-methylaminopropionic acid (BMAA), produced by blue-green algae blooms, but the current study did not screen for that.]

Dr. Morris, a professor of epidemiology at Rush University, told Neurology Today that her team's findings suggest that “patients don't have to be all that concerned that the mercury they are getting from fish may be having a bad effect on the brain.”

From an everyday practical standpoint, it was noteworthy that the study found a benefit from eating even a modest amount of seafood — as little as one serving a week. Seafood is high in long-chain omega-3, or n-3 fatty acids, which are important to normal neuronal function.

“Such a simple strategy is encouraging in the light of the lack of evidence on protection against many neurodegenerative diseases such as Alzheimer's disease and Parkinson disease, another cause of dementia,” the authors of an editorial that accompanied the JAMA report wrote.

STUDY METHODOLOGY

The new report comes from the Rush Memory and Aging Project, an ongoing clinical and neuropathological cohort study of older adults that began in 1997 with residents of retirement communities and subsidized housing in Chicago. Volunteers were dementia- free at enrollment and agreed to undergo annual clinical neurological exams and have their brains autopsied at death. Beginning in 2004, the participants filled out annual dietary questionnaires.

This latest report from the project included an analysis of brain tissue from 286 persons who died between November 2004 and November 2013 and completed at least one dietary assessment. The average age at death was 89.9, and 67 percent of participants were women. The average number of years of education was 14.6 years, and 22.7 percent of participants were positive for the APOE e4 gene.

The study was designed to answer multiple questions: Was there a correlation between seafood consumption and brain neuropathologies that are indicative of dementia? Was seafood consumption correlated with higher mercury levels in brain tissue? And were those elevated levels associated with any neuropathologies?

Brain tissue was analyzed for amyloid plaques, neurofibrillary tangles, Lewy bodies, microinfarcts, and macroinfarcts. The extent of Alzheimer's disease pathology was scored using a standardized scale, from 1 (low disease pathology) to 4 (high).

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DR. MARTHA CLARE MORRIS: “We found that seafood consumption was associated with higher brain levels of mercury, but that mercury was not correlated with brain neuropathologies of any type associated with dementia.”

Levels of mercury and selenium, another metal found in fish, were also measured in the brain tissue. Autopsy results were compared with information from the dietary questionnaires, which asked about the frequency of eating four seafood items — a tuna sandwich, fish sticks, cakes or sandwich; fresh fish as a main dish; and shrimp, lobster or crab. The questionnaire also asked about use of fish oil supplements. On average 2.4 years passed from the time the last questionnaires was completed until death.

Among the findings:

  • weekly consumption of seafood and dietary intake of long-chain n-3 fatty acids were inversely correlated with Alzheimer's disease pathology, including lower density of neuritic plaques, less severe and widespread neurofibrillary tangles, and lower neuropathologically defined Alzheimer's disease, but only among APOE e4 carriers.
  • APOE e4 carriers who ate fish weekly scored, on average, half a point lower on the scale for Alzheimer's disease pathology than those who did not.
  • While at least one serving of fish a week was correlated with less Alzheimer disease, more intake was not associated with an increasingly lower risk of Alzheimer's neuropathologies.
  • Dietary intake of seafood and long-chain n-3 fatty acids did not seem to protect against brain infarcts or Lewy bodies.
  • Seafood intake did correlate with higher levels of mercury in the brain, but higher mercury levels did not correlate with negative neuropathologies.

“To our knowledge, this is the first study to report on the relationship between brain concentrations of mercury and brain neuropathologies or diet,” the researchers reported.

Why seafood consumption did not appear to benefit persons who were not APOE e4 carriers is not clear, Dr. Morris said. It is possible the study was not large enough to detect more subtle differences in brain pathology among person not at high risk for Alzheimer's.

The study also could not prove a cause and effect between seafood consumption and risk of Alzheimer's disease, though the findings were consistent with previous observational studies that found an association between eating seafood and lower risk of dementia.

While it is not reported in the study, Dr. Morris said her team did not find that one category of seafood was better than another. Other studies have suggested that dark oily fish, such as tuna or salmon, are most beneficial.

Dr. Morris said her research team will explore the connection between seafood consumption and other markers of brain health such as synaptic proteins. In the meantime, Dr. Morris said she believes the case is strong for recommending seafood in the diet.

“Everybody is concerned about protecting their brain against cognitive decline and Alzheimer's disease,” she said. “Diet is one thing we have control over.”

Table

ASSOCIATIONS BETWEEN DIETARY INTAKE OF SEAFOOD AND ALZHEIMERS DISEASE (AD) NEUROPATHOLOGY: Odds Ratio (95% CI)

EXPERTS COMMENT

Researchers not involved with the study agreed that the findings bolster the arguments in favor of a seafood-rich diet.

“I think this study is very important,” said Yian Gu, PhD, an assistant professor of neuropsychology in Columbia University's neurology department, who coauthored a study published online in Neurology in October that found a connection between a Mediterranean diet and brain volume as measured on MRI. The study, which included 674 elderly persons, found that those who had a Mediterranean-style diet (more fish and plant-based food and less red meat and dairy) showed less brain shrinkage than those who did not follow such a diet. The difference in brain shrinkage between the two groups was tantamount to about five years of aging.

Dr. Gu said the new finding that the level of mercury that comes with eating seafood is not deleterious to the brain is reassuring. “When it comes to the risk of Alzheimer's disease, you cannot change your genetics,” she said. “But there are things you can do to make things better.”

A 2013 report from the cognitive sub-study Women's Health Study, with nearly 6,000 women followed longitudinally, found that consumption of tuna or dark-meat fin fish once a week or more was associated with a lower decline in verbal memory over a period of four years.

“The good news from these studies is that we are talking about modest levels of intake,” not a dramatic overhaul in diet, said Olivia Okereke, MD, an associate professor of psychiatry at Harvard University and a geriatric psychiatrist at Brigham and Women's Hospital, who was a senior author of the Women's Health Study report.

The question of whether taking fish oil supplements is good for the brain is still debatable, though Dr. Okereke said long-term, large-sample randomized controlled clinical trials should help answer the question. At Brigham and Women's Hospital, such a trial is underway to evaluate, among other things, whether fish oil supplements can protect against cognitive decline.

As with any lifestyle change, it is difficult to get people to adjust their eating habits and stick to new routines. Also, it is not known when is the most critical point to intervene with dietary changes to stave off the neurologic changes associated with Alzheimer's disease.

“We now know it takes many years or even decades for this type of pathology to accumulate in the brain,” said Dr. Okereke said.

EXPERTS: ON THE FINDING THAT MERCURY LEVELS IN FISH ARE NOT ASSOCIATED WITH ALZHEIMER'S PATHOLOGY

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DR. YIAN GU said the new finding that the level of mercury that comes with eating seafood is not deleterious to the brain is reassuring. “When it comes to the risk of Alzheimers disease, you cannot change your genetics. But there are things you can do to make things better.”

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DR. OLIVIA OKEREKE said the question of whether taking fish oil supplements is good for the brain is still debatable, though long-term, large-sample randomized controlled clinical trials should help answer the question.

LINK UP FOR MORE INFORMATION:

•. Morris MC, Brockman J, Schneider JA, et al. Association of seafood consumption, brain mercury level and APOE e4status with brain neuropathology in older adults http://jama.jamanetwork.com/article.aspx?articleid=2484683. JAMA 2016;315(5):489–497.
    •. Kröger E, LaForce R Jr. Editorial: Fish consumption, brain mercury, and neuropathology in patients with Alzheimer disease and dementia http://jama.jamanetwork.com/article.aspx?articleid=2484661. JAMA 2016; 315(5):465–466.