Public Health

Previous evidence suggests that different types of dietary fat-including saturated fatty acids (SFA, primarily from animal products) and unsaturated fats (monounsaturated [MUFA] and polyunsaturated fatty acids [PUFA])-may have distinct effects on brain health and cognition. However, the underlying mechanisms remain poorly understood. This study examines the association between dietary fat intake, neuronal cytoskeletal biomarkers (total tau [t-tau]), and cognition in an aging population cohort.

Data were analyzed from 755 participants in the Chicago Health and Aging Project (CHAP). Global cognition was assessed using a composite score incorporating episodic memory, perceptual speed, and the Mini-Mental State Examination (MMSE). Dietary fat intake was measured using a 144-item food frequency questionnaire and expressed as a percentage of total energy intake. Serum t-tau levels were quantified using a single-molecule array (Simoa) bead-based platform at Quanterix Corporation (Billerica, MA). Longitudinal mixed-effects regression models were used to examine the associations between dietary fat intake, blood t-tau levels, and cognitive decline, adjusting for age, sex, education, and total calorie intake.

Participants had a mean age of 79 years (SD = 6.3), with 54% Black and 61% female. The mean follow-up was 5.5 years. Dietary fat intake as a percentage of total energy was 30.3% for total fat, 9.8% for SFA, 11.4% for MUFA, and 6.3% for PUFA. Mean circulating total tau levels were 0.41 pg/mL (SD = 0.22). Total fat, vegetable fat, and MUFA significantly modified the association between total tau levels and global cognitive decline (p for interaction = 0.023, <0.001, and 0.01, respectively). A 1% increase in total fat, vegetable fat, and MUFA was associated with a slower rate of cognitive decline (β = 0.0046 ± 0.02, β = 0.0071 ± 0.0026, and β = 0.013 ± 0.005, respectively), translating to a 9% slower decline for total fat, 12.5% for vegetable fat, and 24% for MUFA. No significant effect modification was observed for SFA or PUFA.

Dietary fat intake significantly modified the association between blood neurodegenerative cytokines and cognition, suggesting that diet-tau interactions may influence cognitive function in older adults.