The moderating effect of diet on the relationship between depression and Alzheimer’s disease‐related blood‐based biomarker

Abstract Background Interplay between diet, depression, and Alzheimer's disease (AD) shows promise as an important area of study for early intervention and therapy. Associations between both depression and diet and heightened AD risk underscore the need to examine the moderating effect of dietary patterns on the relationship between depression, and AD‐related blood‐based biomarkers. Method Data from cognitively unimpaired older adults (n=89; age ≥60 years) enrolled in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study were included. Participants completed a food frequency questionnaire, self‐report measures of depression, and had AD‐related blood‐based biomarker levels for phosphorylated tau (ptau181) 181, Aβ40, Aβ42, Neurofilament Light Chain (NfL), and Glial Fibrillary Acidic Protein (GFAP). Scores for two dietary patterns, 1) Mediterranean diet (MeDi), and 2) western diet were generated for each individual. Moderation and simple slope analyses were used to examine the interactions between dietary patterns, depression, and biomarker levels. Result Depression was positively associated with NfL levels in males with lower than mean MeDi score adherence (β=3.759, SE=1.248, p=0.005). Depression was also positively associated with NfL levels in Apolipoprotein E (APOE) ε4 allele non‐carriers with lower than mean and mean MeDi score adherence (β=7.384, SE=1.972, p<0.001; β=3.797, SE=1.004, p<0.001, respectively). Moreover, depression was positively associated with Aβ40 levels in APOE ε4 allele non‐carriers with lower than mean and mean MeDi score adherence (β=16.837, SE=5.242, p=0.002; β=7.502, SE=2.669, p=0.005, respectively). No moderating effects of MeDi on the relationship between depression and levels of ptau181, Aβ42, and GFAP were observed. Furthermore, western diet had no moderating effect on the relationship between depression, and AD‐related blood‐based biomarkers. Conclusion This study highlights MeDi adherence as a potential moderator of the relationship between mood and AD‐related blood‐based biomarker levels. These findings also emphasize the importance of gender‐ and genotype‐specific approaches to depression‐cognition‐diet research and highlight the need for further investigation.