Objective: To analyze neuropathological correlates of cognitive impairment in multiple system atrophy (MSA) and characterize the affected cognitive domains.

Background: Current MSA census criteria delineate dementia as an exclusionary criterion for MSA, but cognitive impairment in individuals with MSA is becoming more readily recognized. The reports of neuropathological correlates of cognitive impairment in MSA are varied and not unambiguously identified.

Method: Alpha-synuclein, amyloid, and tau pathology of autopsy-confirmed MSA brain specimens from New York Brain Bank at Columbia University was examined. Presence of pathology in the entorhinal cortex, prefrontal cortex, temporal cortex, and hippocampus were documented. Clinical charts were retrospectively reviewed for subjective and objective cognitive impairment documentation.

Results: Thirty-eight autopsy-confirmed MSA brains from 1994-2022 were included in this study of which 36.8% (14) reported either subjective or objective cognitive impairment. Of those with cognitive impairment, only 42.9% (6) subjects underwent objective testing of which deficits in executive function/attention, visuospatial, and memory was most readily identified. There was no correlation between neuropathological changes and cognitive deficits.

Conclusion: The reported number of subjects who experience cognitive changes in MSA is consistent with previously reported studies. This study found no neuropathological correlates of cognitive changes. Of the low number of subjects who did undergo objective cognitive testing, executive function/attention, visuospatial, and memory were the most commonly affected cognitive domains.

Patient demographic comparisons

Neuropathological features

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MDS Abstracts - https://www.mdsabstracts.org/abstract/absence-of-identifiable-neuropathological-correlates-of-cognitive-impairment-in-multiple-system-atrophy/