title: Regional Multiple Pathology Scores Are Associated with Cognitive Decline in Lewy Body Dementias.
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.
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London, UK.
authors.forename: David R
authors.initials: DR
authors.lastname: Howlett
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Whitfield
authors.affiliation: Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Mary
authors.initials: M
authors.lastname: Johnson
authors.affiliation: Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Johannes
authors.initials: J
authors.lastname: Attems
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: John T
authors.initials: JT
authors.lastname: O'Brien
authors.affiliation: Department of Neurobiology, Ward Sciences and Society, Karolinska Institute, Stockholm, Sweden.|Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Dag
authors.initials: D
authors.lastname: Aarsland
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Mitchell K P
authors.initials: MK
authors.lastname: Lai
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Jasinda H
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Christopher
authors.initials: C
authors.lastname: Chen
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London, UK.
authors.forename: Clive
authors.initials: C
authors.lastname: Ballard
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London, UK.|Department of Neuropathology, Institute of Pathology, University of Debrecen, Debrecen, Hungary.
authors.forename: Tibor
authors.initials: T
authors.lastname: Hortobágyi
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London, UK.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Francis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology* / Q000473:pathology*; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000150:complications* / Q000473:pathology; D008297:Male; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D051844:alpha-Synuclein / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D051844:alpha-Synuclein; D016875:tau Proteins
keywords: Alzheimer's disease; Lewy body dementia; Parkinson's disease dementia; cognitive decline; dementia with Lewy bodies
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