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Association Between Orthostatic Hypotension and Dementia in Patients With Parkinson Disease and Multiple System Atrophy

Barrio, Iñigo Ruiz; Miki, Yasuo; Jaunmuktane, Zane T; Warner, Thomas; De Pablo-Fernandez, Eduardo; (2023) Association Between Orthostatic Hypotension and Dementia in Patients With Parkinson Disease and Multiple System Atrophy. Neurology , 100 (10) e998-e1008. 10.1212/WNL.0000000000201659. Green open access

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Abstract

BACKGROUND AND OBJECTIVES: orthostatic hypotension (OH) increases dementia risk in patients with Parkinson's disease (PD) although the underlying mechanisms and whether a similar association between OH and cognitive impairment exists in other synucleinopathies remain unknown. The aim is to evaluate the association between OH and dementia risk in patients with PD, and cognitive impairment risk in patients with multiple system atrophy (MSA), and to explore relevant clinical and neuropathologic factors to understand underlying pathogenic mechanisms. METHODS: Retrospective cohort study. Medical records throughout the entire disease course of consecutive patients with neuropathology-confirmed PD and MSA from the Queen Square Brain Bank- were systematically reviewed. Time of onset and severity of OH-related symptoms were documented and their association with other clinical and neuropathologic variables was evaluated. Dementia risk for patients with PD and cognitive impairment risk for patients with MSA were estimated using multivariable hazard regression. RESULTS: 132 patients with PD and 137 with MSA were included. Patients with MSA developed OH more frequently, earlier in the disease course and with more severe symptoms. Cumulative dementia prevalence was higher in patients with PD. Multivariable adjusted regression models showed that early OH, but not its symptom severity, increased dementia risk in patients with PD by 14% per year (HR = 0.86; 95% CI, 0.80 - 0.93) and cognitive impairment risk in patients with MSA by 41% per year (HR = 0.59; 95% CI, 0.42 - 0.83). Early OH was not associated with increased α-synuclein, amyloid-β, tau, Alzheimer's or cerebrovascular pathologies. No significant associations were found between severity of OH symptoms and other clinical or neuropathologic variables. DISCUSSION: early OH, but not its symptom severity, increases the risk of cognitive impairment in patients with PD and MSA. OH is not associated to more extensive Lewy, amyloid-β, tau, Alzheimer's or cerebrovascular pathologies. It is likely that OH contributes to cognitive impairment in patients with PD and MSA by hypoxia-induced non-specific neurodegeneration. Further research should evaluate whether improving brain perfusion by treating OH may modify the risk of dementia in these conditions.

Type: Article
Title: Association Between Orthostatic Hypotension and Dementia in Patients With Parkinson Disease and Multiple System Atrophy
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1212/WNL.0000000000201659
Publisher version: https://doi.org/10.1212/WNL.0000000000201659
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Autonomic diseases, Parkinson's disease/Parkinsonism, Parkinson's disease with dementia, Multiple system atrophy, MCI (mild cognitive impairment)
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10162639
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