Gait impairment and cholinergic dysfunction in early PD: Does vascular risk play a moderating role?

Abstract

[Poster] Objective: To compare the relationship between short latency afferent inhibition (SAI) and quantitative gait characteristics in Parkinson's (PD) subjects with high and low vascular risk. Background: Cholinergic dysfunction contributes to gait impairment in PD. Recently, cardiovascular risk factors have been implicated in higher level gait disorders in PD. We hypothesised that the relationship between gait and SAI would be moderated by cerebrovascular damage to cholinergic pathways. Methods: Forty one incident PD subjects and 44 age-matched controls were assessed as part of the ongoing ICICLE-GAIT study, a collaborative study with ICICLE-PD. Mean age 69.3 ± 10.1 years in PD, 68.5 ± 8.4 years in controls (p=0.695). Subjects’ past medical history was obtained and relative cardiovascular risk quantified as 10 year risk compared to expected risk for age and sex, using the QRISK2 calculator. This was used as a proxy for risk of cerebrovascular damage. Low risk was defined as a relative risk ratio ≤1 and high risk as a ratio >1, or existing cardiovascular disease. Cholinergic function was quantified by short latency afferent inhibition (SAI). A 7m instrumented walkway (GAITrite) measured 16 gait characteristics, including: gait speed, step length, stance time, gait variability and asymmetry. SPSS 21 was used to perform Pearson's bivariate correlations and linear regression models. Results: SAI was higher (more impaired) in PD than controls (75.53 ± 23.72 vs. 58.67 ± 22.17, p=0.001). Gait was impaired in PD subjects, who showed reduced velocity (p=0.005), step length (p=0.005), increased step length variability (p=0.017) and stance time asymmetry (p=0.027). There was no difference in SAI or gait characteristics between high (n=17) and low risk (n=24) PD groups (p=0.611) . Despite this, SAI explained 45.7% of variance in step length in high risk PD compared to only 2.6% in low risk PD and 0.2% in high risk controls. Conclusions: Our findings suggest that vascular burden may underpin gait impairment associated with cholinergic dysfunction in PD. This relationship was only observed in those with PD and high vascular risk and was not observed in high risk control participants so is unlikely to be related to fitness or cerebrovascular burden alone. Rather, it may represent a cumulative burden of cerebrovascular parenchymal damage, dopaminergic loss, and cholinergic dysfunction, with implications for early gait impairment