Vascular disease and vascular risk factors in relation to motor features and cognition in early Parkinson's disease

Abstract

ObjectiveThe 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.

α‐Synuclein real‐time quaking‐induced conversion in the cerebrospinal fluid of uncertain cases of parkinsonism

“…18,19 Finally, the positive test result in 1 control subject remains unexplained, as detailed review of this subject's clinical chart did not reveal any signs of prodromal parkinsonism. Although all VaP patients had unambiguous vascular magnetic resonance imaging abnormalities combined with a clinical presentation suggestive of VaP (eg, lower body parkinsonism), we cannot exclude that these patients had a mixed α-synucleinopathy and vasculopathy, as described previously for PD patients.…”

Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders

“…For example, cerebrovascular disease plays a part in the pathogenesis of PD 52 , the second most common neurodegenerative disorder, which is characterized by accumulation of α-synuclein and degeneration of dopaminergic neurons in the substantia nigra. Vascular disease and vascular risk factors aggravate motor dysfunction and cognitive impairment in PD 59 . Cerebrovascular disease, BBB impairments and neurovascular abnormalities are also found in HD 60,61 , an autosomal-dominant neurodegenerative disease with motor, cognitive, psychiatric, and metabolic abnormalities caused by the aggregation of mutant huntingtin protein.…”

Disease Modification in Parkinson's Disease: Current Approaches, Challenges, and Future Considerations

“…To date, 3 important trials, the Multidomain Alzheimer Preventive Trial, the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability, and the Dutch Prevention of Dementia by Intensive Vascular Care trial, have shown somewhat variable results but suggest that targeting interventions to individuals at increased risk for dementia might be effective . The evidence that patients with PD have a higher incidence of vascular risk factors and cerebrovascular disease is limited, but there is reason to believe that those patients with this combination have a greater occurrence of certain levodopa‐resistant features such as cognitive decline and axial motor dysfunction even in the early clinical stages of the disease . Furthermore, statin therapy was found to be underutilized in those with high or medium cardiovascular risk (60% of recent‐onset patients in one study from Scotland), thus not only increasing the threat of vascular morbidity and mortality but also potentially accentuating cognitive and motor features associated with their disease.…”