Fruit Intake and Alzheimer’s Disease: Results from Mendelian Randomization

Abstract

Abstract Background Alzheimer's disease (AD) is the leading cause of dementia in old age, recognized as a global health priority. The number of dementia patients is projected to reach 152 million worldwide by the mid-century. AD can damage thought, memory, and independence, increasing the risk of dependence, disability, and mortality. The aim of the present study is to explore precise causality from fruit intake on risk of AD.Methods To explore the causal effect of fresh fruit intake and dried fruit intake on the liability of AD, this study utilized a genome-wide association study (GWAS) developed by the MRC-IEU for the full UK Biobank and the GWAS from FinnGen round 8 to conduct a Mendelian randomization (MR) analysis. The instrumental variables (IVs) for each fruit intake were selected based on the InSIDE hypothesis and the exposure-outcome datasets were harmonized. The study used inverse variance weighted (IVW), MR‒Egger, and weighted median (WM) approaches for MR estimates, and scatter plots, funnel plots, and leave-one-out plots were generated for statistical inspection of the stability of the results.Results MR analyses were conducted to investigate the causal effects of fresh fruit and dried fruit intake on Alzheimer's disease (AD) using targeted genome-wide association study datasets. Little evidence suggested a potential causal relationship between fresh fruit intake and AD (OR (95%CI) = 0.97 (0.50, 1.91), P-value = 0.939), while a significant and intensive causality was indicated between dried fruit intake and AD (OR (95%CI) = 4.09 (2.07, 8.10), P-value < 0.001). Stability evaluations showed no heterogeneity and pleiotropy affecting the interpretability and credibility of the primary analyses.Conclusions We strengthened the evidence supporting the positive causality from dried fruit intake to the liability of Alzheimer’s disease, while the association between fresh fruit intake and the risk of Alzheimer’s disease failed to be demonstrated. Further validation focusing on underlying molecular mechanisms and expansility of ethnicity could strengthen the reliability of the diet intervention throughout the prevention on AD.