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


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Authors

Howlett, David R 
Whitfield, David 
Johnson, Mary 
Attems, Johannes 
O'Brien, John T 

Abstract

Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are characterized by the presence of α-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 α-synuclein, phosphorylated tau (phosphotau) and Aβ 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 α-synuclein load. Patients also had varying degrees of senile Aβ plaque and phosphotau pathology. Regression analyses pointed to a combined pathology (Aβ plaque plus phosphotau plus α-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 α-synuclein-induced neurodegeneration alone but senile plaque and phosphorylated tau pathology also contribute to the overall deficits.

Description

Keywords

Alzheimer's disease, Lewy body dementia, Parkinson's disease dementia, cognitive decline, dementia with Lewy bodies, Aged, Aged, 80 and over, Amyloid beta-Peptides, Brain, Cognition Disorders, Female, Humans, Lewy Body Disease, Male, Neurofibrillary Tangles, Phosphorylation, Plaque, Amyloid, alpha-Synuclein, tau Proteins

Journal Title

Brain Pathol

Conference Name

Journal ISSN

1015-6305
1750-3639

Volume Title

25

Publisher

Blackwell Publishing Ltd
Sponsorship
The main fundingwas provided by the Alzheimer’s SocietyUK and the BUPA Foundation. The research in Newcastle was supported in part by the Dunhill Medical Trust (R173/1110). Tissue for this study was provided by (i) the Newcastle Brain Tissue Resource; (ii) the London Neurodegenerative Brain Bank; and (iii) the Thomas Willis Oxford Brain Collection. All three resources are funded in part by grants from the UK Medical Research Council and by Brains for Dementia Research, a joint venture between Alzheimer’s Society and Alzheimer’s Research UK. In Singapore, funding was provided by a Centre grant (NMRC/CG/NUHS/2010) and a Clinical Scientist Award (NMRC/CSA/032/2011) from the National Medical Research Council.