A - 115 Cognitive Predictors of Phosphorylated Skin Nerve α-Synuclein Deposition in Patients with Suspected Synucleinopathy

Abstract Objective Synucleinopathies are a group of neurodegenerative diseases caused by abnormal α-Synuclein aggregates and characterized by motor, autonomic, and cognitive changes, including Parkinson’s disease, Lewy Body disease, and Multiple System Atrophy. Due to variability in presentation, clinical phenotyping is challenging for diagnosis and treatment planning. Phosphorylated α-Synuclein (P-syn) detected in nerve fibers using skin biopsy shows promise in clinical phenotyping of synucleinopathies. However, cognitive predictors of P-syn deposition in synucleinopathies have not been fully explored. This study aimed to examine the utility of cognitive testing in predicting P-syn deposition in a clinical sample. Method A chart review of 52 older adults (Mean age = 72.8 years) referred to an outpatient neurology clinic for a diagnostic dementia workup was conducted. Clinical variables were collected, including skin biopsy (Syn-One) and cognitive test scores (Short Test of Mental Status [STMS]). P-syn was detected in 22 patients (42%) and at 68%, 41%, and 55% of central (neck) and distal (thigh and calf) biopsy sites, respectively. Results Overall cognition (STMS Total) did not significantly differ between patients with (Mean = 30.5) and without (Mean = 29.6) P-syn (p = 0.51). Within the P-syn positive group, STMS Registration-Trials and Calculation scores significantly predicted distally deposited P-syn (F(1,18) = 7.54, p = 0.01). This relationship was more pronounced in the thigh compared to the calf biopsy sites. Conclusion STMS Registration-Trials (immediate recall) and Calculation scores were significantly related to distally deposited P-syn. These findings highlight the importance of how cognitive test performance can potentially impact clinical phenotyping in synucleinopathies. Future research will examine the relationship between cognition, clinical features, and other neurodegenerative disease biomarkers.