Family History of AD/Dementia, Polygenic Risk Score for AD, and Parkinson's Disease

Background Co-occurrence of Alzheimer's disease (AD) and Parkinson's disease (PD) has been observed. However, there is limited knowledge on how family history of AD is associated with PD.Objectives To prospectively examine the associations of family history of AD/dementia and polygenic risk score for AD (AD-PRS) with PD risk.Methods The study included 477,190 participants from UK Biobank who were free of PD at baseline (2006-2010) and had complete data on the studied exposure variables, family history of AD and AD-PRS. Cox proportional hazards model was used to examine the hazard ratios (HRs) and their 95% confidence intervals (CIs) of family history of AD/dementia and AD-PRS for PD risk. We also conducted mediation analysis to examine the proportion of the association between family history of AD/dementia and PD risk that could be mediated by AD-PRS.Results During a median follow-up of 12.5 years, we identified 2550 incidences of PD. Family history of AD/dementia (adjusted HR = 1.21; 95% CI 1.09-1.35) and AD-PRS (adjusted HR = 1.10 per 1 unit increment; 95% CI 1.05-1.14) were associated with PD risk, after adjustment for age, sex, lifestyle factors, and other potential confounders. The association between family history of AD/dementia and PD risk was mediated by 13.1% by the AD-PRS. As expected, we observed significant associations of family history of AD/dementia and AD-PRS with risks of dementia and AD (P < 0.001 for all).Conclusions Family history of AD/dementia appeared to be associated with PD risk, and this association could be mediated partially by AD-related genetic factors.