Literature Review
Among APOE ε4 carriers, moderate seafood consumption significantly correlates with lesser Alzheimer’s disease neuropathology, according to research published February 2 in JAMA. This association does not exist in people who do not carry the Alzheimer’s disease risk gene, however. In addition, seafood consumption correlates with higher brain levels of mercury, but these mercury levels do not correlate with brain neuropathology, researchers said.
Concerns About Mercury
Prior studies have found protective associations between seafood consumption and dementia, but mercury contamination in seafood has raised concerns. To study the association between seafood consumption, brain mercury level, and brain neuropathology in older adults, Martha Clare Morris, ScD, Director of Nutrition and Nutritional Epidemiology at Rush University Medical Center in Chicago, and colleagues conducted cross-sectional analyses of deceased participants in the Memory and Aging Project. The investigators included 286 participants from the clinical neuropathologic cohort study who had completed a dietary assessment, died between 2004 and 2013, and had a brain autopsy performed.
Martha Clare Morris, ScD
Mean age at death was 89.9, 67% of subjects were women, and average educational attainment was 14.6 years. Sixty-five participants (22.7%) had the APOE ε4 allele. The participants were residents of retirement communities and subsidized housing in Chicago.
Participants reported seafood intake by completing a food frequency questionnaire at a mean of 4.5 years before death. Mean seafood consumption in this cohort was 1.3 seafood meals per week in the lowest tertile and 2.7 seafood meals per week in the highest tertile.
Investigators assessed dementia-related pathologies, including Alzheimer’s disease, Lewy bodies, and the number of macroinfarcts and microinfarcts. They measured tissue concentrations of mercury and selenium using instrumental neutron activation analyses in a subsample of 203 cases.
Pathologic Hallmarks
As in prior studies, seafood consumption did not correlate with Alzheimer’s disease outcomes in a linear way, and the investigators only presented findings where seafood was modeled as an indicator variable (ie, one or more meals per week vs less). After adjusting for age, sex, education, and total energy intake, eating one or more seafood meals per week was significantly associated with less Alzheimer’s disease pathology, including lower density of neuritic plaques and less severe and widespread neurofibrillary tangles in APOE ε4 carriers.
Brain mercury levels positively correlated with the number of seafood meals consumed per week, but levels did not correlate with neuropathology. “To our knowledge, this is the first study to report on the relationship between brain concentrations of mercury and brain neuropathology or diet,” said Dr. Morris and colleagues. “The finding of no deleterious correlations of mercury on the brain is supported by a number of case–control studies that found no difference between Alzheimer’s disease patients and controls in mercury concentrations in the brain, serum, or whole blood.”
Reassuring Data
That higher mercury levels do not correlate with dementia or Alzheimer’s disease pathology “is reassuring because ingested mercury accumulates in the body over decades, and brain levels hence result from exposure, which likely precedes any Alzheimer’s disease or dementia development,” said Edeltraut Kröger, PhD, and Robert Laforce Jr, MD, PhD, of Université Laval in Quebec City, Canada, in an accompanying editorial.
“Patients and their families may be hopeful that interventions such as seafood consumption may help reduce clinical manifestations of Alzheimer’s disease or dementia, and the report by Morris et al provides reassurance that seafood contamination with mercury is not related to increased brain pathology,” they said. “Eating fatty fish may continue to be considered potentially beneficial against cognitive decline in at least a proportion of older adults, a strategy that now generally should not be affected by concerns about mercury contamination in fish.”
Drs. Kröger and Laforce noted that large randomized clinical trials are needed before recommending dietary interventions, such as a Mediterranean-style diet, to improve cognitive health. In addition, relating brain pathology, including amyloid deposition, to clinical disease may be more complicated than previously thought. “Ultimately, proof of the brain pathological concepts of Alzheimer’s disease and other dementias will be based on data from clinical trials confirming that preventive or therapeutic interventions on these elements of brain neuropathology will reduce clinical manifestations of Alzheimer’s disease and other dementias,” they said.
The study cohort was very old and largely non-Hispanic white, and the findings might not apply to younger adults or other racial or ethnic groups, the investigators said. The results also cannot be generalized to populations with higher seafood consumption or mercury exposure.
