Cognition in individuals at risk for Parkinson's: Parkinson associated risk syndrome (PARS) study findings

Objectives: The Parkinson Associated Risk Syndrome Study identified a cohort of healthy adults with hyposmia and dopamine transporter binding reduction to characterize individuals at risk for Parkinson's disease (PD). We describe the cognitive profile of this cohort. Methods: Individuals older than 50 y without PD were recruited. Two hundred twenty-five completed cognitive testing and were included in the final analysis. A neuropsychological test battery was administered and normative scores created for global cognition, memory, executive function/working memory, processing speed/attention, visuospatial abilities, and language domains. Other non-motor symptoms (constipation, depression, anxiety, and rapid eye movement sleep behavior disorder) were assessed through questionnaires. Results: Individuals with both hyposmia and reduced dopamine transporter binding (n=38) had lower mean scores for global cognition, executive function/working memory, and memory compared with all other participants (n=187). In separate multivariate logistic regression models, lower global cognition (odds ratio, 1.97, P=0.004), and specifically executive function/working memory (odds ratio, 1.84, P=0.004) scores were associated with membership in the hyposmia with dopamine transporter reduction group. Combining hyposmia with relative impairment on specific cognitive domains increased the odds of dopamine transporter binding reduction compared with hyposmia alone, with the greatest increase in odds for hyposmia plus executive function/working memory relative impairment (68% increase in odds from 4.14 to 6.96). Conclusion: Changes in global cognitive abilities, and specifically executive function/working memory, are present in individuals at risk for PD. Combining non-motor features, including cognition, improves prediction of dopamine transporter binding reduction.