Intrinsic Capacity Defined Using 4 Domains, Genetic Risk, and Incident Parkinson Disease

Intrinsic capacity (IC), a World Health Organization-defined measure of healthy aging, has been linked to several neurologic disorders but has not been extrapolated to Parkinson disease (PD). The study aimed to explore the association between IC and incident PD and whether genetic risk modulated this association. This longitudinal analysis used data from the UK Biobank, a prospective cohort study designed to investigate the impact of genetic and environmental factors on health outcomes. Participants were voluntarily recruited from 22 assessment centers across the United Kingdom between 2006 and 2010. Individuals with IC component data and without pre-existing PD or dementia at baseline were included. The IC deficit score was derived from 4 domains: psychological (exhaustion and sleep duration), sensory (visual and hearing impairments), vitality (grip strength and weight loss), and locomotor function (walking speed), while the cognitive domain was not assessed. Genetic risk was estimated by polygenic risk score, and incident PD was identified using an algorithm. Cox proportional hazard models were used to calculate the hazard ratios (HRs) and 95% CIs. Of the 401,791 participants (mean age [SD], 56.6 [8.0] years; 53.8% female) included, 2,763 (0.69%) developed PD during a median follow-up of 12.3 years. The HR (95% CI) for incident PD was 1.82 (1.50-2.20) in individuals with IC deficit scores of 4+ compared with those with 0. Each 1-point increment in IC deficit was associated with a 16% (95% CI 12%-20%) increased risk of PD. Low IC was associated with a 68% (95% CI 48%-91%) higher risk of incident PD. Individuals with low IC and high genetic risk were at the highest PD risk (HR = 3.01; 95% CI 2.40-3.78). High genetic risk attenuated the protective role of high IC (HR [95% CI]: 0.45 [0.35-0.58] in low risk vs 0.72 [0.59-0.88] in high risk; P for interaction = 0.002), but high IC was still associated with a diminished risk of PD in the high-risk group. High IC was associated with a decreased risk of PD, even in genetically high-risk individuals. The absence of the cognitive domain may limit understanding of the association.