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Original Investigation
October 2016

Association of Serum Docosahexaenoic Acid With Cerebral Amyloidosis

Author Affiliations
  • 1Division of Endocrinology, Department of Medicine, University of Southern California, Los Angeles
  • 2Huntington Medical Research Institute, Pasadena, California
  • 3Department of Neurology, University of Southern California, Los Angeles
  • 4Department of Neurology, University of California Davis, Sacarmento
  • 5Helen Wills Neuroscience Institute, University of California Berkeley

Copyright 2016 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.

JAMA Neurol. 2016;73(10):1208-1216. doi:10.1001/jamaneurol.2016.1924
Key Points

Question  Is there an association between serum docosahexaenoic acid levels and cerebral amyloidosis?

Findings  In this study of 61 older adults without cognitive impairment who underwent amyloid Pittsburgh Compound B positron emission tomography imaging, participants at the lowest quartile of serum docosahexaenoic acid levels had significantly more cerebral amyloidosis.

Meaning  Limited seafood intake may increase the risk of brain amyloid deposition and Alzheimer disease.


Importance  Higher dietary intake of the essential fatty acid docosahexaenoic (DHA) has been associated with better cognitive performance in several epidemiological studies. Animal and in vitro studies also indicate that DHA prevents amyloid deposition in the brain.

Objective  To determine the association between serum DHA levels, cerebral amyloidosis, and the volumes of brain areas affected by Alzheimer disease.

Design, Settings, and Participants  Cross-sectional analysis of serum DHA levels together with measures of amyloid deposition (Pittsburgh Compound B index), brain volumes, and neuropsychological testing scores from 61 participants in the Aging Brain Study. The study was conducted between June 2008 and May 2013, and the data were analyzed between October 2015 and April 2016. Linear models were adjusted for age, sex, years of education, and apolipoprotein E status.

Main Outcomes and Measures  Serum DHA levels with cerebral amyloidosis measured using PIB PET.

Results  Samples were available from 61 Aging Brain Study participants (41 women and 20 men) who underwent amyloid PET imaging. The mean (SD) age of the participants was 77 (6) years and ranged from 67 to 88 years. Serum DHA levels (percentage of total fatty acids) were 23% lower in participants with cerebral amyloidosis than those without (0.97 vs 1.25, P = .007) and were inversely correlated with brain amyloid load (r = −0.32, P = .01) independent of age, sex, apolipoprotein E genotype, and years of education. Moreover, greater serum DHA levels were positively associated with brain volume in several subregions affected by AD, in particular the left subiculum (r = 0.38, P = .005) and the left entorhinal volumes (r = 0.51, P = .001). Serum DHA levels were also associated with nonverbal memory scores (r = 0.28, P = .03).

Conclusions and Relevance  In this study, serum DHA levels were associated with pathogenesis of cerebral amyloidosis and with preservation of entorhinal and hippocampal volumes. These findings suggest an important role for DHA metabolism in brain amyloid deposition during the preclinical or early symptomatic stages of Alzheimer disease.