Vascular risk factors and the effect of white matter lesions on extrapyramidal signs in Alzheimer's disease

Background: Extrapyramidal signs (EPSs), which are important characteristics of Parkinson's disease (PD), occur frequently in Alzheimer's disease (AD). Although AD and PD share common clinical features such as EPSs, these diseases vary with respect to vascular risk factors. The presence of vascular risk factors increases the risk of AD; however, these factors have been known to be inversely associated with PD. We aimed to assess the effect of vascular risk factors and white matter lesions (WMLs) on EPSs in AD. Methods: We recruited 1,187 AD patients and 333 controls with neither cognitive impairment nor EPSs. All participants underwent detailed clinical evaluations which included assessments of vascular risk factors, cognitive function, and EPSs, as well as WMLs on brain MRIs. EPS subtypes were classified into tremor-dominant, postural instability gait difficulty, or indeterminate; WMLs subtypes were classified into periventricular WML (pvWML) or deep WML (dWML). Results: EPSs were present in 17.9% of subjects with AD and were significantly associated with vascular risk factors such as age, male gender, diabetes mellitus, and WMLs. Additionally, a multivariate logistic regression analysis showed that EPSs in AD were associated with pvWML (odds ratio (OR), 1.61-2.52), not with dWML. With respect to EPS subtypes, the majority (78.4%) of EPSs in AD were postural instability gait difficulty, which was also associated with WMLs (OR 1.84-2.41), pvWML (OR 2.09-3.14), and dWML (OR 1.83-3.42). Conclusions: EPSs in AD are associated with selected vascular risk factors as well as WMLs.