Cognitive dysfunction, depression, and inflammation as potential pre-diagnostic markers of Parkinson's disease
Appleman, Erica Rose
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Parkinson’s disease (PD) has long been conceptualized as a motor disorder, but significant clinical features arise before motor symptoms are present. Although prospective, longitudinal research offers the most valid approach for determining pre-diagnostic indicators of PD, it is costly and requires a long time-course. Leveraging existing epidemiological datasets offers the opportunity to identify pre-diagnostic features that may predict later PD diagnosis. This project used the Framingham Heart Study (FHS) database of prospective follow-up on a community-based sample that spans over six decades. Regular surveillance identified 156 incident cases of PD. Promising biomarker and other clinical marker candidates were derived from cohort-based samples without prospective follow-up and included cognition, depression, and inflammation. The main hypothesis was that potential markers would discriminate between individuals who did/ did not go on to a later PD diagnosis. The FHS database provided clinical markers (cognition, depression) and fluid biomarkers (levels of plasma inflammation) for interrogation. Cognition was indexed by performance on the Mini-Mental State Examination and a comprehensive neuropsychological assessment, including measures of attention, memory, and executive functioning. Depression was derived from scores on the Center for Epidemiologic Studies Depression Scale (CES-D). Separate means comparison and logistic regression analyses to maximize sample sizes were conducted on available data for candidate (bio)markers at time-points 1-3 years or 1-5 years pre-diagnosis for PD cases (N=7-33) and control participants (N=28-224), in samples matched for age, sex, and education level. No significant differences were found between PD and control participants on any measure of cognitive functioning 1-3 years pre-diagnosis. No significant differences were found for total CES-D scores or levels of plasma inflammation 1-5 years pre-diagnosis. Higher levels of C-reactive protein and TNF-alpha were significantly correlated with increasing age in the total sample but not for PD specifically. These results indicate that cognition, self-reported depression, and plasma inflammation may not be useful as markers of PD risk, and efforts should likely focus on alternative candidate markers. Detecting PD in the earliest stages is an important goal, as it could lead to treatments that attenuate progression, improve clinical prognosis, and enhance the possibility of disease prevention.