RT Journal Article
SR Electronic
T1 Neuropathology of dementia in patients with Parkinson’s disease: a systematic review of autopsy studies
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP 1234
OP 1243
DO 10.1136/jnnp-2019-321111
VO 90
IS 11
A1 Callum Smith
A1 Naveed Malek
A1 Katherine Grosset
A1 Breda Cullen
A1 Steve Gentleman
A1 Donald G Grosset
YR 2019
UL http://jnnp.bmj.com/content/90/11/1234.abstract
AB 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.Trial registration number CRD42018088691.