Circulating Omega3 Polyunsaturated Fatty Acids and Subclinical Brain Abnormalities on MRI in Older Adults: The Cardiovascular Health Study

Consumption of tuna or other broiled or baked fish, but not fried fish, is associated with fewer subclinical brain abnormalities on magnetic resonance imaging (MRI). We investigated the association between plasma phospholipid omega 3 polyunsaturated fatty acids (PUFAs), objective biomarkers of exposure, and subclinical brain abnormalities on MRI. Methods and Results  In the community based Cardiovascular Health Study, 3660 participants aged less than or equal to 65 underwent brain MRI in 1992 to 1994, and 2313 were rescanned 5 years later. MRIs were centrally read by neuro radiologists in a standardized, blinded manner. Participants with recognized transient ischemic attacks or stroke were excluded. Phospholipid PUFAs were measured in stored plasma collected in 1992 to 1993 and related to cross sectional and longitudinal MRI findings. After multivariable adjustment, the odds ratio for having a prevalent subclinical infarct was 0.60 (95 per cent CI, 0.44 to 0.82) in the highest versus lowest long chain omega 3 PUFA quartile. Higher long chain omega 3 PUFA content was also associated with better white matter grade, but not with sulcal or ventricular grades, markers of brain atrophy, or with incident subclinical infarcts. The phospholipid intermediate chain omega 3 PUFA alpha linolenic acid was associated only with modestly better sulcal and ventricular grades. However, this finding was not supported in the analyses with alpha linolenic acid intake. Conclusions    Among older adults, higher phospholipid long chain omega 3 PUFA content was associated with lower prevalence of subclinical infarcts and better white matter grade on MRI. Our results support the beneficial effects of fish consumption, the major source of long chain omega 3 PUFAs, on brain health in later life. The role of plant derived alpha linolenic acid in brain health requires further investigation. (Authors abstract)
Findings on magnetic resonance imaging (MRI), including subclinical (lacunar) infarcts, white matter abnormalities (leukoaraiosis), and ventricular and sulcal enlargement, that is, brain atrophy, are common in the elderly. Circulating biomarkers of omega 3 PUFAs provide objective measures that reflect both dietary consumption (eg, fish and fish oil) and relevant biologic processes (eg, elongation of the intermediate chain omega 3 PUFA alpha linolenic acid [ALA] to longer chain omega  3 PUFAs). Biomarker levels also permit direct assessment of specific individual omega 3 PUFAs, including the long chain eicosapentaenoic acid (EPA, 20 5n  3), docosapentaenoic acid (DPA, 22 5n  3), and docosahexaenoic acid (DHA, 22 6n  3), and the intermediate chain ALA (18 3n  3), for which prior data on brain health is limited and conflicting. Yet few studies have investigated associations between circulating omega 3 PUFAs and MRI findings.  The association of plasma phospholipid omega 3 PUFAs, a biomarker for longer term circulating concentrations, with subclinical brain abnormalities in older adults, including both cross sectional and prospective analyses based on serial MRIs was assessed. In this study among older men and women, plasma phospholipid long chain omega 3 PUFAs, and in particular DHA, were associated with specific findings consistent with better brain health, including lower risk of prevalent subclinical (lacunar) infarcts, better white matter grade, and lower risk of worsening white matter. The phospholipid long chain omega 3 PUFAs were not associated with other MRI metrics, such as markers of brain atrophy, that is, sulcal and ventricular grades. Phospholipid ALA, an intermediate chain omega 3 PUFA from plants, only had borderline associations with better sulcal and ventricular grades. The associations observed for phospholipid ALA were of borderline statistical significance, and our secondary analyses with dietary ALA did not support the findings observed with phospholipid ALA. Thus, these findings should be interpreted cautiously, and confirmation in additional studies is needed, especially in populations with low fish intake. On the other hand, because the majority of dietary ALA is oxidized and used for energy dietary ALA does not correlate well with circulating ALA concentrations. Thus, circulating ALA concentrations have other metabolic determinants that could at least partly explain the different results for phospholipid versus dietary ALA. Few studies have investigated the associations between ALA and MRI findings. There is a need for further investigation to elucidate the potential role of ALA in brain health. A potential limitation of the study was the availability of circulating PUFA measurements at only 1 time, which may cause bias by misclassification because of changes in PUFA concentrations over time and thus attenuate the associations toward the null in longitudinal analyses. The participants who underwent MRI scans were somewhat healthier than those who did not, so results may not be fully applicable to the sickest individuals in a general elderly population. In conclusion, the findings in these older men and women suggest that circulating long chain omega 3 PUFA concentrations, a biomarker of regular fish consumption, are associated with lower risk and could be beneficial for the prevention of certain subclinical brain abnormalities that are commonly observed in the elderly. The potential role of the plant based, intermediate chain omega 3 PUFA ALA is less evident. The results support the need for additional prospective observational studies using fatty acid biomarkers, as well as randomized intervention studies to evaluate the role of omega 3 PUFAs in subclinical brain health and disease later in life.  (Editors comments)