Abstract
ABSTRACTObjectiveThe purpose of this study was to examine the relationship between vascular disease (and vascular risk factors), cognition and motor phenotype in Parkinson's disease (PD).MethodsRecently diagnosed PD cases were enrolled in a multicenter prospective observational longitudinal cohort study. Montreal cognitive assessment (normal >23, mild cognitive impairment 22 to 23 or lower but without functional impairment, and dementia 21 or less with functional impairment) and Movement Disorder Society Unified PD Rating Scale part 3 (UPDRS 3) scores were analyzed in relation to a history of vascular events and risk factors.ResultsIn 1759 PD cases, mean age 67.5 (standard deviation 9.3) years, mean disease duration 1.3 (standard deviation 0.9) years, 65.2% were men, 4.7% had a history of prior stroke or transient ischemic attack, and 12.5% had cardiac disease (angina, myocardial infarction, heart failure). In cases without a history of vascular disease, hypertension was recorded in 30.4%, high cholesterol 27.3%, obesity 20.7%, diabetes 7.2%, and cigarette smoking in 4.6%. Patients with prior stroke or transient ischemic attack were more likely to have cognitive impairment (42% vs 25%) and postural instability gait difficulty (53.5% vs 39.5%), but these findings were not significant after adjustment for age, sex, and disease duration (P = .075). The presence of more than 2 vascular risks was associated with worse UPDRS 3 motor scores (beta coefficient 4.05, 95% confidence interval 1.48, 6.61, p = .002) and with cognitive impairment (ordinal odds ratio 2.24, 95% confidence interval 1.34, 3.74, p = .002). In 842 patients (47.8%) with structural brain imaging, white matter leukoaraiosis, but not lacunar or territorial infarction, was associated with impaired cognition (p = .006) and postural instability gait difficulty (p = .010).ConclusionVascular comorbidity is significantly associated with cognitive and gait impairment in patients with early PD, which may have prognostic and treatment implications. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Highlights
Cognitive impairment and dementia are recognized consequences of the evolving neurodegenerative processes underlying Parkinson’s disease (PD) and represent a significant management issue
Because the prevalence of cerebrovascular disease and vascular risk factors increases with age, in high-income countries, it seems likely that they contribute to cognitive impairment and motor disability in PD
An association of the postural instability gait difficulty (PIGD) phenotype with cognitive impairment is well documented in PD,[8] and gait impairment is common after ischemic stroke and occurs in the absence of acute cerebrovascular events.[9,10]
Summary
Cognitive impairment and dementia are recognized consequences of the evolving neurodegenerative processes underlying Parkinson’s disease (PD) and represent a significant management issue. Gait impairment and falls result, in part, from motor dysfunction in PD and are more likely in patients with axial involvement, recognized clinically as the postural instability gait difficulty (PIGD) motor phenotype, distinct from the tremor dominant (TD) motor phenotype.[7] An association of the PIGD phenotype with cognitive impairment is well documented in PD,[8] and gait impairment is common after ischemic stroke and occurs in the absence of acute cerebrovascular events.[9,10] in PD, subclinical cerebrovascular disease was linked to greater motor severity and increased gait impairment in two small, but detailed, studies that included structural MRI and functional dopaminergic imaging.[11,12] Axial impairment increased in relation to the white matter cerebrovascular burden with a stronger relationship than that between white matter changes and bradykinesia, and there was no relationship with either tremor or rigidity.[12] An overlap syndrome between PD and cerebrovascular disease may create a mixed motor phenotype and explain the limited responsiveness of some of these motor and cognitive features to antiparkinsonian therapy Because some of these risk factors are modifiable,[13] reducing the direct effects of ischemia-related neuronal loss would be one aim of this approach to limit the damaging effects from comorbid cerebrovascular disease on cognition and gait. Our objective was to test the hypothesis that vascular and metabolic factors are associated with cognitive and motor features in recent onset PD, with the aim of explaining differences in PD phenotype that arise from these comorbidities
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