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Original Investigation |

Association of Serum Docosahexaenoic Acid With Cerebral Amyloidosis ONLINE FIRST

Hussein N. Yassine, MD1; Qingru Feng, MSc1; Ida Azizkhanian, MSc1; Varun Rawat, PhD1; Katherine Castor, PhD2; Alfred N. Fonteh, PhD2; Michael G. Harrington, MB, ChB2; Ling Zheng, PhD3; Bruce R. Reed, PhD4; Charles DeCarli, MD4; William J. Jagust, MD5; Helena C. Chui, MD3
[+] 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
JAMA Neurol. Published online August 08, 2016. doi:10.1001/jamaneurol.2016.1924
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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.

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Figure 1.
Association of Docosahexaenoic Acid (DHA) Levels and Apolipoprotein E Genotype With Cerebral Amyloidosis

The relationship between cerebral amyloidosis as assessed by Pittsburgh compound B (PiB) positron emission tomography (PET) scan and serum levels of DHA. A, Box plot of PiB index units in patients with and without APOE ε4 allele. B, Cerebral amyloid load (as indexed by PiB index units) in participants grouped according to the quartiles of their serum DHA levels (percentage of total fatty acids). C, The association of serum DHA levels with PiB index by APOE genotype. Serum DHA explained 10% of the variability in cerebral amyloidosis (R2 = 0.1), whereas both serum DHA and APOE together explained 23% of cerebral amyloidosis (R2 = 0.23). The groups were compared by Wilcox on t test or analysis of variance. The relationship was modeled using a linear regression. Serum DHA units are the percentage of total fatty acids.

aP < .05.

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Figure 2.
Association of Serum Docosahexaenoic Acid (DHA) With Regional Brain Volumes Involved in Cognitive Functions

A, The correlation of hippocampal volume with serum DHA levels in 52 participants from the Aging Brain Study. Serum DHA (percentage of total fatty acids) was associated with hippocampal volume. Serum DHA explained 14% of the variability in hippocampal volumes (R2 = 0.14; P = .005). B, An association between serum DHA and left entorhinal volume was observed and explained 24% of the variability in hippocampal volume (R2 = 0.24; P < .001). The relationships were modeled using a linear regression. Brain volume is reported as a ratio of intracranial volume. Serum DHA units are reported as a percentage of total fatty acids.

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