Objective: To systematically review the literature for evidence of an association between orthostatic hypotension (OH) and cognitive impairment (CI) in α-synucleinopathies and to discuss possible mechanisms and implications of this relationship.

Background: Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA) are characterized by abnormal α-synuclein accumulation. These α-synucleinopathies share clinical features including parkinsonism and non-motor symptoms such as OH and CI. OH causes transient cerebral hypoperfusion and it is possible that repeated episodes of decreased cerebral blood flow may contribute to progression of CI in patients with α-synucleinopathies.

Methods: We systematically reviewed the literature by searching the Medline database using a combination of keywords relating to CI and OH in either PD, DLB or MSA. The abstracts of 332 articles were surveyed and 76 articles selected for review. An additional 55 articles were identified from this initial review resulting in a total of 131 articles being reviewed. Two tiers of articles were identified: ‘first rank papers’ if designed to assess the direct relationship of OH and CI in α-synucleinopathies and ‘second rank papers’ if they added information about the clinical or mechanistic association between OH and CI in α-synucleinopathies, but were designed with a different primary objective.

Results: Our review yielded 10 ‘first rank papers’ and 13 ‘second rank papers.’ All ten of the first rank papers involved patients with PD. Seven of these papers reported a relationship between OH and CI. The 13 ‘second rank papers’ included PD, DLB and MSA patients and 8 of 13 described an association between OH and CI. The papers that did not find an association between OH and CI used insensitive measurements of cognition.

Conclusions: A relationship between OH and CI in patients with α-synucleinopathies exists, but the nature of this relationship is unclear. It is possible that in this population, the presence of OH and CI predict more diffuse brain deposition of α-synuclein. Alternatively, transient episodes of cerebral hypoperfusion may lead to progressive deficits in cognition. In order to better characterize this relationship, clinical trials to determine the effect of management of OH on CI in patients with α-synucleinopathies are warranted.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/association-or-causation-orthostatic-hypotension-and-cognitive-impairment-in-synucleinopathies-a-systematic-review/