Neuropathology of dementia in patients with Parkinson’s disease: a systematic review of autopsy studies

Smith, C. R., Malek, N. M., Grosset, K. A., Cullen, B. , Gentleman, S. M. and Grosset, D. G. (2019) Neuropathology of dementia in patients with Parkinson’s disease: a systematic review of autopsy studies. Journal of Neurology, Neurosurgery and Psychiatry, 90(11), pp. 1234-1243. (doi: 10.1136/jnnp-2019-321111) (PMID:31444276)

Abstract

Background: Dementia is a common, debilitating feature of late Parkinson’s disease (PD). PD dementia (PDD) is associated with α-synuclein propagation, but coexistent Alzheimer’s disease (AD) pathology may coexist. Other pathologies (cerebrovascular, transactive response DNA-binding protein 43 (TDP-43)) may also influence cognition. We aimed to describe the neuropathology underlying dementia in PD. Methods: Systematic review of autopsy studies published in English involving PD cases with dementia. Comparison groups included PD without dementia, AD, dementia with Lewy bodies (DLB) and healthy controls. Results: 44 reports involving 2002 cases, 57.2% with dementia, met inclusion criteria. While limbic and neocortical α-synuclein pathology had the strongest association with dementia, between a fifth and a third of all PD cases in the largest studies had comorbid AD. In PD cases with dementia, tau pathology was moderate or severe in around a third, and amyloid-β pathology was moderate or severe in over half. Amyloid-β was associated with a more rapid cognitive decline and earlier mortality, and in the striatum, distinguished PDD from DLB. Positive correlations between multiple measures of α-synuclein, tau and amyloid-β were found. Cerebrovascular and TDP-43 pathologies did not generally contribute to dementia in PD. TDP-43 and amyloid angiopathy correlated with coexistent Alzheimer pathology. Conclusions: While significant α-synuclein pathology is the main substrate of dementia in PD, coexistent pathologies are common. In particular, tau and amyloid-β pathologies independently contribute to the development and pattern of cognitive decline in PD. Their presence should be assessed in future clinical trials where dementia is a key outcome measure.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cullen, Dr Breda and Grosset, Professor Donald and Smith, Callum and Grosset, Dr Katherine
• Authors: Smith, C. R., Malek, N. M., Grosset, K. A., Cullen, B., Gentleman, S. M., and Grosset, D. G.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing; College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Journal of Neurology, Neurosurgery and Psychiatry
• Publisher: BMJ Publishing Group
• ISSN: 0022-3050
• ISSN (Online): 1468-330X
• Published Online: 23 August 2019
• Copyright Holders: Copyright © 2019 the author or their employers
• First Published: First published in Journal of Neurology, Neurosurgery and Psychiatry 90:1234-1243
• Publisher Policy: Reproduced in accordance with the publisher copyright policy