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.
Keywords: Alzheimer's disease; Parkinson's disease; family history; vascular dementia.
© 2023 International Parkinson and Movement Disorder Society.