Dietary N-6 Polyunsaturated Fatty Acid Intake and Brain Health in Middle-Aged and Elderly Adults

Background: Dietary intake of polyunsaturated fatty acids (PUFA) plays a significant role in the onset and progression of neurodegenerative diseases. Since the neuroprotective effects of n-3 PUFA have been widely validated, the role of n-6 PUFA remains debated, with their underlying mechanisms still not fully understood. Methods: In this study, 169,295 participants from the UK Biobank were included to analyze the associations between dietary n-6 PUFA intake and neurodegenerative diseases using Cox regression models with full adjustments for potential confounders. In addition, multiple linear regression models were utilized to estimate the impact of n-6 PUFA intake on brain imaging phenotypes. Results: Results indicated that low dietary n-6 PUFA intake was associated with increased risks of incident dementia (hazard ratio [95% confidence interval] = 1.30 [1.13, 1.49]), Parkinson’s disease (1.42 [1.16, 1.74]), and multiple sclerosis (1.65 [1.03, 2.65]). Moreover, the low intake was linked to diminished volumes of various brain structures, including the hippocampus (β [95% confidence interval] = −0.061 [−0.098, −0.025]), thalamus (−0.071 [−0.105, −0.037]), and others. White matter integrity was also found to be compromised in individuals with low n-6 PUFA intake. Conclusions: These findings enhanced our understanding of how dietary n-6 PUFA intake might affect neurological health, thereby providing epidemiological evidence for future clinical and public health interventions.