Olfactory Function Predicts Cognitive Deficits and Decline in Early Parkinson's Disease (S5.007)

OBJECTIVE: To evaluate the association of baseline olfaction with both cross-sectional and longitudinal assessments of motor symptoms, non-motor symptoms (NMS) and other biomarkers (radiologic, CSF) in early Parkinson’s disease (PD). BACKGROUND: Biomarkers for diagnosis and prognosis remain a major unmet need in PD research and clinical management. Olfactory impairment is common in PD with a prevalence of 70-90[percnt] and is often one of the first manifestations of the disease, which, along with the ease of assessment, make it an attractive predictive biomarker. METHODS: Parkinson’s Progression Marker’s Initiative (PPMI) participants underwent baseline olfactory testing with the University of Pennsylvania Smell Identification Test (UPSIT). Serial assessments included measures of motor symptoms, NMS, neuropsychological assessment, CSF biomarkers, and dopamine transporter (DAT) imaging. Up to three years follow-up data were included. RESULTS: Worse olfaction was associated with more severe NMS, including anxiety and autonomic symptoms. DAT imaging demonstrated a linear trend toward lower uptake in the putamen and striatum in those with worse olfaction. Aβ1-42 was significantly lower in those with worse olfaction, while Tau/Aβ1-42 ratio was higher. In longitudinal analysis, UPSIT score was associated with greater decline over time in Montreal Cognitive Assessment (MoCA) score (β=0.02, p=0.001), as were composite measures of UPSIT score and Aβ1-42 (β= -0.48, p<0.001) or Tau/Aβ1-42 ratio (β= -0.27, p=0.014). In a Cox proportional hazards model, a composite measure of olfaction and Tau/Aβ1-42 ratio was a significant predictor of conversion to mild cognitive impairment (MCI; MoCA<26), with subjects most affected on both measures being 79[percnt] more likely to develop new-onset MCI compared with the least affected subjects (HR=1.79, p=0.02). CONCLUSIONS: Worse baseline olfaction is associated with future cognitive decline and progression to MCI in early PD. The addition of CSF biomarkers to olfactory testing may increase the likelihood of identifying those at highest risk for cognitive decline. Disclosure: Dr. Fullard has nothing to disclose. Dr. Tran has nothing to disclose. Dr. Xie has nothing to disclose. Dr. Scordia has nothing to disclose. Dr. Linder has nothing to disclose. Dr. Purri has nothing to disclose. Dr. Weintraub has received license fee payments from the University of Pennsylvania. Dr. Duda holds stock in General Electric and Celgene, Inc., Dr. Chahine has nothing to disclose. Dr. Morley has nothing to disclose.