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

Abstract

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.

Keywords: dietary factors; genetic risk; gray matter; n-6 polyunsaturated fatty acids; neurodegenerative disease; white matter.

Figure 1

Study workflow. This study analyzed data from 169,295 UK Biobank participants, tracking outcomes for three neurodegenerative diseases, with brain structural alterations considered as secondary outcomes. (A) the study cohort, including population flowchart and baseline characteristics. (B) dietary intake of n-6 PUFAs. (C) Cox proportional hazards regression models were applied to examine associations between low n-6 PUFA intake and neurodegenerative diseases risk. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were calculated in our analyses. Subgroup analyses were conducted stratified by age (<65/≥65), sex (male/female), waist-hip ratio (poor/ideal), and others. Further analyses were also utilized to estimate the relationships of PUFA intake with impairments of brain gray and white matter by multiple linear regression models.

Figure 2

Associations between dietary n-6 PUFA intake and neurodegenerative diseases by genetic risks. A total of 169,295 participants were included to evaluate the relationship between low dietary n-6 PUFA intake and the incidence of dementia, Parkinson’s disease, and multiple sclerosis using the Cox proportional hazards regression model. Subgroup analyses were categorized into four groups: the overall population, low polygenic risk score (PRS), moderate PRS, and high PRS. Results for the overall population were presented in red, and those for the other subgroups were displayed in blue. Model 1 adjusted baseline characteristics including age, sex, and IMD. Model 2 further adjusted WHR and healthy lifestyle factors. Model 3 added adjustments for blood pressure, metabolic biomarkers, dietary n-3 PUFA intake and dietary n-3/n-6 PUFA intake ratio. Results were presented as HRs ± 95% CIs.

Figure 3

Associations between dietary n-6 PUFA intake and the volume of brain gray matter. The relationships between dietary n-6 PUFA intake and the volumes of the brain subcortex and cortex were assessed using multiple linear regression models among 20,506 participants with available MRI data from the UK Biobank. Results are presented as β values, with significance determined by p values. Furthermore, the results of stratified analyses by sex are presented at the bottom. Regions marked in red denote positive correlations, while those in blue denote negative correlations. The color from light to dark indicates that the absolute value of the effect value changes from small to large. The brain structure is in bold font and with an asterisk which indicates the association of statistical significance.

Figure 4

Associations between dietary n-6 PUFA intake and brain white matter integrity. The relationships between dietary n-6 PUFA intake and the integrity of white matter tracts were evaluated using multiple linear regression models among 20,504 participants with available MRI data from the UK Biobank. The fractional anisotropy (FA), mean diffusivity (MD), and intra-cellular volume fraction (ICVF) of white matter tracts were utilized as reference metrics. Results are presented as β values, with significance determined by p values. Furthermore, the results of stratified analyses by sex are presented on the right. Regions marked in red denote positive correlations, while those in blue denote negative correlations. The color from light to dark indicates that the absolute value of the effect value changes from small to large. The brain structure is in bold font and with an asterisk which indicates the association of statistical significance.