Circulating Omega-3 and Omega-6 Fatty Acids, Cognitive Decline, and Dementia in Older Adults

J Alzheimers Dis. 2023;95(3):965-979. doi: 10.3233/JAD-230083.

Abstract

Background: Comprising nearly 35% of brain lipids, polyunsaturated fatty acids (PUFA) are essential for optimal brain function. However, the role of PUFA on cognitive health outcomes later in life is largely unknown.

Objective: We investigated prospective associations of plasma phospholipid omega-3 (ALA [18 : 3], EPA [20 : 5], DPA [22 : 5], DHA [22 : 6]) and omega-6 (LA [18 : 2], AA [20 : 4]) PUFA with cognitive decline, risk of cognitive impairment and dementia among adults aged≥65 years in the Cardiovascular Health Study.

Methods: Circulating fatty acid concentrations were measured serially at baseline (1992/1993), 6 years, and 13 years later. Cognitive decline and impairment were assessed using the 100-point Modified Mini-Mental State Examination (3MSE) up to 7 times. Clinical dementia was identified using adjudicated neuropsychological tests, and ICD-9 codes.

Results: Among 3,564 older adults free of stroke and dementia at baseline, cognitive function declined annually by approximately -0.5 3MSE points; 507 participants developed cognitive impairment and 499 dementia over up to 23 years of follow-up. In multivariable models, higher circulating arachidonic acid (AA) concentrations were associated with slower cognitive decline and lower dementia risk, with associations growing stronger with greater length of follow-up (hazard ratio [HR,95% CI] of dementia per interquintile range, 0.74 [0.56-0.97] at 5 years, and 0.53 [0.37-0.77] at 15 years). Circulating docosapentaenoic (DPA) concentrations were associated with slower cognitive decline and lower risk of cognitive impairment (extreme-quintile HR, 0.72 [95% CI: 0.55, 0.95]). Findings were generally null or inconsistent for other omega-3 or omega-6 PUFA.

Conclusion: Circulating AA and DPA, but not other PUFA, are associated with slower rate of cognitive decline and lower risk of dementia or cognitive impairment later in life.

Keywords: Aging; Alzheimer’s disease; cognition; dementia; diet; fatty acids.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Arachidonic Acid
  • Cognitive Dysfunction* / diagnosis
  • Cognitive Dysfunction* / epidemiology
  • Dementia* / diagnosis
  • Dementia* / epidemiology
  • Fatty Acids
  • Fatty Acids, Omega-3*
  • Fatty Acids, Omega-6
  • Fatty Acids, Unsaturated
  • Humans

Substances

  • Fatty Acids, Omega-3
  • Fatty Acids, Unsaturated
  • Fatty Acids, Omega-6
  • Arachidonic Acid
  • Fatty Acids