Brain Lewy-Type Synucleinopathy Density Is Associated with a Lower Prevalence of Atherosclerotic Cardiovascular Disease Risk Factors in Patients with Parkinson's Disease

Background: Some epidemiology studies suggest that atherosclerotic cardiovascular disease (ASCVD) risk factors increase the risk of developing Parkinson's disease (PD). However, conflicting data suggest lower rates of ASCVD in PD. Objective: The objective of this study is to determine, with data from a longitudinal clinicopathological study, whether ASCVD risk factors are associated with a PD diagnosis and/or increased brain or peripheral load of Lewy-type synucleinopathy (LTS). Methods: All subjects were followed to autopsy and neuropathological examination in the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). Multivariable regression models, including age, gender, and smoking history, were used to investigate the association of a PD diagnosis or brain or submandibular gland LTS load with ASCVD risk factors. Results: 150 subjects were included (PD n=60, controls n=90). Univariable comparisons and regression models showed a general trend to inverse associations. The multivariable odds ratio (OR) of brain LTS load for carotid artery disease was 0.93 (95% CI: 0.86 to 0.98; p=0.02), for anticoagulant use 0.95 (95% CI: 0.90 to 0.99; p=0.04) and for abnormal heart weight 0.96 (95% CI: 0.92 to 0.99; p=0.01). Composite clinical and overall (clinical + pathology composite risk scores) composite risk scores were also significantly lower in the PD subjects (p=0.0164 and 0.0187, respectively). Submandibular gland LTS load was not significantly related to ASCVD conditions. Conclusions: This study shows associations of higher brain LTS with lower prevalence of both clinical and pathological indices of ASCVD in PD subjects versus age-similar controls. We suggest that this is due to α-synuclein pathology-induced sympathetic denervation in PD.