Characterizing the cognitive phenotype of Parkinson’s disease

Abstract

AbstractBackgroundParkinson’s disease (PD) is a complex neurodegenerative disease in which combinations of motor and non‐motor symptoms result in a wide range of phenotypic presentations and disease progression. Precise characterization of these clinical endophenotypes can guide clinical practice. Such endophenotypes can also be powerful to identify genetic factors for complex diseases, like PD. Given the prevalence and impact of cognitive impairment in PD, we aimed to characterize cognitive endophenotypes in a cohort of PD patients with longitudinal assessments.MethodWe reviewed the medical records of 1028 individuals diagnosed with PD by a movement disorders specialist at our institution. We extracted scores from all available Mini‐Mental Status Examinations (MMSE). We fit proportional odds models with patient specific random effects to estimate odds ratios for higher versus lower cognition in association with age, sex and follow‐up time.ResultAmong the 237 patients with at least one MMSE, 108 had ≥2 time points and 118 were cognitively impaired (MMSE<27). The mean age was 71 years, 63 (27%) were female and the mean follow‐up time was 2.56 years. Overall, females with PD had higher MMSE scores than males with an odds ratio at age 70 of 2.43 (95% CI: 1.29, 4.97). However, MMSE scores decline with age at a faster rate in females than males (p=0.002) with ORs for a 1 year of 0.85 (0.79, 0.91) and 0.94 (95%CI: 0.91, 0.97), respectively. Within patients, declines in MMSE per year had an OR of 0.76 (0.60, 0.97) for females and 0.85 (0.75, 0.95) for males though this difference was not statistically significant. Corresponding expected MMSE trajectories are shown in the figure.ConclusionOur findings demonstrate sex differences in the cognitive phenotypes of PD. In particular, cognitive scores tend to be higher in females compared to males, but decline faster in females. These findings have clinical implications regarding counseling of patients with PD. We are currently expanding this approach to specific cognitive domains, other validated tests of cognition, and investigating the influence of genetic risk factors, such as APOE on cognitive decline in PD.