Objective:

To investigate the association between frailty and Parkinson’s disease (PD) during the prodromal phase compared to controls.

Background:

Frailty is a decline in physical function, reserve, and resistance to stressors. PD is a multisystem neurodegenerative disease. Coexistence of PD and frailty drives clinical complexity. Understanding the relationship between frailty and prodromal PD may allow for earlier intervention in at-risk individuals in order to delay or prevent complications and reduce mortality.

Design/Methods:

We conducted a population-based case-control study of incident PD cases (N=82,560) and controls (N=96,482) age 70-90 identified in 2009. We used Medicare data 2004-2009 and examined frailty in five 12-month time windows during the prodromal period using claims-based frailty index (CFI) (range: 0-1 and categorized as nonfrail (<0.25), mildly frail (0.25–0.34), moderately-to-severely frail (≥0.35)). For each time window, we calculated odd ratios (ORs) and 95% confidence intervals (CIs) for the association between frailty as an exposure and the outcome of PD, adjusted for age, sex, race/ethnicity, smoking, and healthcare utilization. We examined variables in CFI that were positively associated with PD in the 12-months prior to diagnosis.

Results:

Mild frailty (OR=1.70, 95% CI: 1.62-1.78) and moderate-to-severe frailty (OR=1.29, 95% CI: 1.16-1.43) were positively associated with PD five years prior to diagnosis. This association strengthened in the final year prior to diagnosis both with mild frailty (OR=7.75, 95% CI: 7.51-7.99) and moderate-to-severe frailty (OR=10.22, 95% CI: 9.63-10.80). In the 12-months prior to diagnosis, the CFI variable “organic psychotic conditions”, which includes diagnoses for dementia, depression, and anxiety, had the most marked association with PD (OR=4.63, 95% CI: 4.50-4.77).

Conclusions:

PD cases are frailer than controls in the prodromal period for at least 5 years prior to diagnosis. Common psychiatric symptoms of PD had the strongest association with PD in the 12 months prior to diagnosis.