Cognitive and Functional Trajectories in Older Adults With Prediagnostic Parkinson Disease

There is increasing interest in characterizing the earliest phases of Parkinson’s Disease (PD). However, few studies have investigated prediagnostic trajectories of cognition and function. Our objective was to describe prediagnostic cognitive and functional trajectories in PD in older women and men.We studied 9,595 women and 5,795 men from two prospective cohort studies of community-dwelling elders followed up to 20 years. In individuals without prevalent PD, we estimated the associations of incident PD diagnosis with rates of change in cognition and function before and after diagnosis compared to healthy older adults using multivariate mixed-effects models.Over follow-up, 297 individuals developed incident PD. Interactions between the terms in our model and sex were statistically significant for the three outcomes (p<0.001 for all), so we stratified results by sex. Compared to older men without PD, men who developed PD exhibited faster decline in global cognition (0.04 SD more annual change, p<0.001), executive function (0.05 SD more annual change, p<0.001), and functional status (0.06 SD more annual change, p<0.001) in the prediagnostic period. Women who developed PD compared to women without PD displayed faster decline in executive function (0.02 SD more annual change, p=0.006) and functional status in the prediagnostic period (0.07 SD more annual change, p<0.001).Individuals with incident PD exhibit cognitive and functional decline during the prediagnostic phase that exceeds rates associated with normal aging. Better understanding heterogeneity in prodromal PD is essential to enable earlier diagnosis and identify impactful nonmotor symptoms in all subgroups.