Plasma phospholipid very-long-chain SFAs in midlife and 20-year cognitive change in the Atherosclerosis Risk in Communities (ARIC): A cohort study

Danni Li, Jeffrey R. Misialek, Ma Jing, Michael Y. Tsai, John H. Eckfeldt, Lyn M. Steffen, David Knopman, Lisa Wruck, Rebecca Gottesman, Tom H. Mosley, A. Richey Sharrett, Alvaro Alonso

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


BACKGROUND: Very-long-chain SFAs (VLSFAs) have recently gained considerable attention as having beneficial effects on health and aging.

OBJECTIVES: The objective of this study was to assess the associations of plasma phospholipid VLSFAs [arachidic acid (20:0), behenic acid (22:0), tricosanoic acid (23:0), and lignoceric acid (24:0)] with 20-y cognitive decline in the Atherosclerosis Risk in Communities (ARIC) participants. Furthermore, this study compared the associations of plasma phospholipid VLSFAs with 5 common groups of fatty acids [i.e., total SFAs, total MUFAs, total ω-3 (n-3) PUFAs, total marine-derived ω-3 PUFAs, total ω-6 PUFAs].

METHODS: This study used a cohort study design of 3229 ARIC participants enrolled at the Minnesota field center. Fatty acids were measured at visit 1 (1987-1989); and cognition was assessed at visits 2 (1990-1992), 4 (1996-1998), and 5 (2011-2013) using 3 tests: the Delayed Word Recall Test (DWRT), the Digit-Symbol Substitution Test (DSST), and the Word Fluency Test (WFT).

RESULTS: Higher proportions of plasma phospholipid total VLSFAs and each individual VLSFA were associated with less decline in WFT, a test of verbal fluency. For example, 1 SD higher in total VLSFAs at baseline was associated with 0.057 SD (95% CI: 0.018, 0.096, P = 0.004) less cognitive decline over 20 y as measured by WFT score. None of the 5 common fatty acid groups were associated with change in WFT, but a higher proportion of plasma phospholipid total MUFAs was associated with greater decline in DWRT; higher total ω-6 PUFAs with less decline in DWRT; and higher total ω-3 and total marine-derived ω-3 PUFAs with less decline in DSST.

CONCLUSIONS: This study suggests that higher proportions of plasma phospholipid VLSFAs in midlife may be associated with less 20-y cognitive decline.

Original languageEnglish (US)
Pages (from-to)1252-1258
Number of pages7
JournalAmerican Journal of Clinical Nutrition
Issue number6
StatePublished - Jun 1 2020

Bibliographical note

Funding Information:
Supported by National Institute on Aging of the NIH awards R21AG059068, R01AG059654, and R21AG061372 (to DL). The Atherosclerosis Risk in Communities (ARIC) study has been supported in whole or in part with federal funds from the National Heart, Lung, and Blood Institute, NIH, Department of Health and Human Services, under contract nos. HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, and HHSN268201700004I.

Funding Information:
The authors’ responsibilities were as follows—DL and AA: designed the research and had primary responsibility for the final content; JRM and AA: performed the statistical analysis; DL, JRM, and AA: wrote the paper; MJ, MYT, JHE, DK, LW, RG, THM and ARS: contributed to collection of ARIC data used in the study; LYS: contributed to the study design; and all authors: read and approved the final manuscript. DK serves on a Data Safety Monitoring Board for the Dominantly Inherited Alzheimer’s Network (DIAN) study; is an investigator in clinical trials sponsored by Biogen, Lilly Pharmaceuticals, and the University of Southern California; and receives research support from the NIH. All other authors report no conflicts of interest.

Publisher Copyright:
Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.


  • Delayed Word Recall Test (DWRT)
  • Digit-Symbol Substitution Test (DSST)
  • Word Fluency Test (WFT)
  • cognitive change
  • midlife
  • plasma phospholipid very-long-chain saturated fatty acids (VLSFAs)
  • Fatty Acids/blood
  • Prospective Studies
  • Humans
  • Middle Aged
  • Cognition
  • Fatty Acids, Unsaturated/blood
  • Phospholipids/blood
  • Eicosanoic Acids/blood
  • Female
  • Aged
  • Cognition Disorders/blood
  • Atherosclerosis/blood
  • Longitudinal Studies
  • Cohort Studies

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural


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