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Regional Multiple Pathology Scores Are Associated with Cognitive Decline in Lewy Body Dementias

Lookup NU author(s): Professor Johannes Attems, Professor John O'Brien, Dr Dag Aarsland, Dr Clive Ballard



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are characterized by the presence of -synuclein-containing Lewy bodies and Lewy neurites. However, both dementias also show variable degrees of Alzheimer's disease (AD) pathology (senile plaques and neurofibrillary tangles), particularly in areas of the cortex associated with higher cognitive functions. This study investigates the contribution of the individual and combined pathologies in determining the rate of cognitive decline. Cortical -synuclein, phosphorylated tau (phosphotau) and A plaque pathology in 34 PDD and 55 DLB patients was assessed semi-quantitatively in four regions of the neocortex. The decline in cognition, assessed by Mini Mental State Examination, correlated positively with the cortical -synuclein load. Patients also had varying degrees of senile A plaque and phosphotau pathology. Regression analyses pointed to a combined pathology (A plaque plus phosphotau plus -synuclein-positive features), particularly in the prefrontal cortex (BA9) and temporal lobe neocortex with the superior and middle temporal gyrus (BA21, 22), being a major determining factor in the development of dementia. Thus, cognitive decline in Lewy body dementias is not a consequence of -synuclein-induced neurodegeneration alone but senile plaque and phosphorylated tau pathology also contribute to the overall deficits.

Publication metadata

Author(s): Howlett DR, Whitfield D, Johnson M, Attems J, O'Brien JT, Aarsland D, Lai MKP, Lee JH, Chen C, Ballard C, Hortobagyi T, Francis PT

Publication type: Article

Publication status: Published

Journal: Brain Pathology

Year: 2015

Volume: 25

Issue: 4

Pages: 401-408

Print publication date: 01/07/2015

Online publication date: 30/10/2014

Acceptance date: 25/07/2014

Date deposited: 25/08/2015

ISSN (print): 1015-6305

ISSN (electronic): 1750-3639

Publisher: Wiley-Blackwell


DOI: 10.1111/bpa.12182


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Funder referenceFunder name
Alzheimer's Society
Alzheimer's Society UK
UK Medical Research Council
Alzheimer's Research UK
BUPA Foundation
NMRC/CG/NUHS/2010National Medical Research Council
NMRC/CSA/032/2011National Medical Research Council
R173/1110Dunhill Medical Trust