Seafood Linked to Less AD Pathology Despite Mercury

Pauline Anderson

February 03, 2016

Consuming moderate amounts of seafood increases brain levels of mercury, but these levels aren't linked to brain neuropathology, a new study has found. Rather, moderate seafood consumption was associated with lesser burden of brain Alzheimer disease (AD) neuropathology, although only in APOE ε4 carriers.

This is good news for patients who avoid fish because they fear mercury contamination, Martha Clare Morris, ScD, director of nutrition and nutritional epidemiology, Rush University, Chicago, Illinois, told Medscape Medical News.

Exposure to toxic levels of mercury has been shown to cause problems with cognition. "What we didn't know is whether an accumulation over time of consistent seafood consumption was detrimental to an adult's brain," said Dr Morris.

The study was published in the February 2 issue of JAMA.

To look at this issue, the researchers used the autopsied brains of 286 participants from the Rush Memory and Aging Project study who were initially free from dementia at enrollment. The mean age of participants at death was 89.9 years, and 67% were women.

In this group, 22.7% were positive for the APOE ε4 allele that is associated with a doubling of the risk for AD, noted Dr Morris.

Before death, participants had completed annual food-frequency questionnaires, which included questions on the consumption of seafood. Although seafood is high in the long-chain n-3 fatty acid docosahexaenoic acid (DHA), which is important for normal neuronal function, it's also a source of mercury, a neurotoxin that can impair neurocognitive development. Selenium reduces mercury toxicity.

From information in the questionnaires, researchers calculated daily intake of DHA and another long-chain n-fatty acid, α-linolenic acid, which is found in plants and seafood. The questionnaire also included a query about intake of fish oil supplements.

About 44% of the sample completed one of the annual questionnaires, 20.3% completed two, and 36% completed three. The mean time between the first questionnaire and death was 4.5 years.

Dementia Pathology

Investigators assessed dementia-related pathology, including amyloid plaques and neurofibrillary tangles, Lewy bodies, macroinfarcts, and microinfarcts. They measured mercury and selenium concentrations in the inferior temporal and midfrontal cortical regions of the brain.

The researchers found that eating at least one seafood meal per week was positively correlated with brain mercury. However, higher levels of mercury were not correlated with more AD or dementia brain pathology.

Higher dietary intake of α-linolenic acid was correlated with lower risk for cerebral macro-infarcts (odds ratio for highest vs lowest levels of intake, 0.51; 95% confidence interval, 0.27 - 0.94; P = .03), and of micro-infarcts, after adjustment for age at death, sex, and education. It was not associated with other neuropathologic markers.

Dr Morris noted that a previous large study in the Netherlands had linked α-linolenic acid intake to lower incidence of stroke.

In the current study, weekly consumption of seafood was correlated with less AD pathology, including lower neuritic plaque density and neurofibrillary tangle severity, compared with those who consumed lower amounts, but only among APOE ε4 carriers. For example, carriers who consumed seafood weekly had a likelihood score for AD that was lower by 0.53 units (on the AD Diagnostic Score).

"Although this is the largest study of autopsied brains and seafood consumption so far, it's still a relatively small number, and we can't rule out that seafood also would benefit people who are ε4 negative," commented Dr Morris.

There was no correlation between use of fish oil supplements and brain neuropathology. However, said Dr Morris, "we had so few fish oil supplement users that it's not strong evidence one way or the other. There just wasn't enough information to have confidence in the findings."

Out of almost 300 participants, only 49 indicated in any 1 year that they were taking fish oil supplements, and only 31 of those 49 consumers reported it only once, she added.

"The message here," she concluded, "is that there isn't evidence that moderate seafood consumption — and the increased mercury that one gets from that — is detrimental in terms of neuropathologies associated with dementia."

Important Information

In an accompanying editorial, Edeltraut Kröger, PhD, Centre of Excellence in Aging and Laval University, Quebec City, Canada, and Robert Laforce Jr, MD, PhD, University Hospital Center, Quebec City, and Laval University, described the new study results "important" and "reassuring," saying they contribute important information.

"This appears to be the first study showing an absence of an increased risk of Alzheimer's disease or dementia related to mercury based on the level of brain pathology, suggesting that seafood can be consumed without substantial concern of mercury contamination diminishing its possible cognitive benefit in older adults," they write.

The differences in correlations between fish or n-3 fatty acids and AD or dementia brain pathology according to APOE ε4 status "underscore the present limits in understanding Alzheimer disease and other dementias resulting from neurodegenerative processes," they say.

The role of APOE ε4 and other genes has been the subject of research and debate, they said. A "better understanding of the genetic underpinnings of neurodegenerative pathologies, and robust epidemiological studies are needed to clarify and refine current concepts," they write.

Eating fatty fish may continue to be considered as possibly preventing cognitive decline in at least some older adults, a strategy that now generally shouldn't be affected by concerns about mercury contamination, they note.

"Such a simple strategy is encouraging in the light of the lack of evidence on protection against many neurodegenerative diseases."

This study was supported by the National Institutes of Health. Dr Morris and the editorial writers have disclosed no relevant financial relationships.

JAMA. 2016;315:489-497. Abstract Editorial

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