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Neuropathological findings in multiple system atrophy with cognitive impairment

  • Neurology and Preclinical Neurological Studies - Original Article
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Abstract

Cognitive impairment (CI), previously considered an exclusion criterium for the diagnosis of multiple system atrophy (MSA) according to the second consensus criteria, is not uncommon in MSA. Mild cognitive impairment (MCI) has been reported in up to 47% of MSA patients, while severe dementia is rare. We related clinical CI with neuropathological findings in 48 autopsy-proven cases of MSA. This retrospective study included 33 parkinsonism predominant MSA (MSA-P), and 15 cerebellar ataxia-predominant MSA (MSA-C) cases (mean age at death 60.5 ± 7.8; range 46–82 years). Cognitive state was assessed from hospital charts, however, without comprehensive neuropsychological testing. Neuropathological examination, in addition to grading of the MSA pathologies, included semiquantitative assessment of Lewy and Alzheimer-related co-pathologies. Their incidence was compared with 143 age-matched controls (mean age 60.5 ± 7.6 years). MCI reported in ten cases (20.8%) was associated with moderate cortical tau pathology in only three; moderate CI in seven patients (14.5%) was associated with cortical amyloid plaques and moderate cortical tau pathology in six each, and one with probable primary age-related tauopathy (PART); a female aged 82 years with severe dementia showed fully developed Alzheimer disease. Cortical amyloid plaques, observed in eight cases, three of them without tau pathology, were associated with clinical MCI, as was cortical Lewy pathology in five. Two cases with cortical Lewy pathology and neuritic Braak stages II and III, and three with Braak stage IV, without cortical Lewy bodies, had shown moderate CI. Cortical Lewy pathology observed in four cases was not associated with clinical CI. 77.1% of the MSA cases were free of Alzheimer-type lesions, compared to 42% of controls; while Lewy pathology in the MSA cohort (22.9%) was significantly higher than in the control group (8.4%) both p < 0.001. Mild-to-moderate CI, reported in 35.3% of MSA patients, being significantly older than those without CI, were frequently associated with cortical Alzheimer (Braak stages III and IV) and Lewy pathologies, while only one with severe dementia had fully developed Alzheimer disease. In view of these findings in a limited series of MSA patients, further studies to elucidate the pathological basis of cognitive impairment in MSA are warranted.

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Abbreviations

AD:

Alzheimer disease

ADNC:

Alzheimer disease neuropathological changes

Aβ:

β-Amyloid

αSyn:

α-Synuclein

CAA:

Cerebral amyloid angiopathy

CI:

Cognitive impairment

DLB:

Dementia with Lewy bodies

GCI:

Glial cytoplasmic inclusions

MCI:

Mild cognitive impairment

MMSE:

Mini-Mental State Examination

MSA:

Multiple system atrophy

MSA-C:

Cerebellar ataxia-predominant MSA

MSA-P:

Parkinsonism predominant MSA

NCI:

Neuronal cytoplasmic inclusion

OPCA:

Olivopontocerebellar atrophy

PD:

Parkinson disease

PSP:

Progressive supranuclear palsy

SND:

Striatonigral degeneration

TGCGs:

Tau-positive glial cytoplasmic granules

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Acknowledgements

The author would like to thank Mr. E. Mitter-Ferstl, PhD, for secretarial and editorial work.

Funding

The study was partially funded by the Society for the Promotion of Research in Experimental Neurology, Vienna, Austria.

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  1. Institute of Clinical Neurobiology, Alberichgasse 5/13, 1150, Vienna, Austria

    Kurt A. Jellinger

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Jellinger, K.A. Neuropathological findings in multiple system atrophy with cognitive impairment. J Neural Transm 127, 1031–1039 (2020). https://doi.org/10.1007/s00702-020-02201-2

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  • DOI: https://doi.org/10.1007/s00702-020-02201-2

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