Abstract
BACKGROUND: Cardiovascular comorbidities are a known risk factor for impaired mobility in elderly individuals. Motor impairments in Parkinson disease are conventionally ascribed to nigrostriatal dopaminergic denervation although progressive gait and balance impairments become more common with aging and often show limited response to dopaminergic replacement therapies. METHODS: We explored the association between elevated cardiovascular risk factors and performance on the Timed Up and Go test in cross-sectional of Parkinson disease subjects (n = 83). Cardiovascular risk factor status was estimated using the Framingham General Cardiovascular Disease risk-scoring algorithm in order to dichotomize the cohort into those with and without elevated modifiable cardiovascular risk compared with normative scores for age and gender. All subjects underwent clinical and neuroimaging evaluations including a 3-m Timed Up and Go test, [(11)C]dihydrotetrabenazine positron emission tomography imaging to estimate nigrostriatal dopamine terminal loss, and an magnetic resonance imaging assessment of leukoaraiosis. A similar analysis was performed in 49 healthy controls. RESULTS: After adjusting for disease duration, leukoaraiosis, and nigrostriatal dopaminergic denervation, Parkinson disease subjects with elevated Framingham risk scores (n = 61) displayed slower Timed Up and Go test performance (β = 1.86, t = 2.41, p = .018) compared with subjects with normal range Framingham risk scores (n = 22). When age ≥65 was added to the model in a post hoc analysis, the strength of effect seen with older age (β = 1.51, t = 2.44, p = .017) was similar to that of elevated Framingham risk scoring (β = 1.87, t = 2.51, p = .014). In a multivariable regression model studying the healthy control population, advanced age (t = 2.15, p = .037) was a significant predictor of Timed Up and Go speed though striatal [(11)C]dihydrotetrabenazine (t = -1.30, p = .19) and elevated Framingham risk scores (t = 1.32, p = .19) were not. CONCLUSIONS: Modifiable cardiovascular risk factors and older age may independently exacerbate balance-related disability in Parkinson disease and may exert additive or synergistic pathological effects. The pathophysiology of these impairments cannot be explained completely by nigrostriatal dopaminergic denervation or leukoaraiosis burden and may relate to systemic factors seen with accelerated aging.