title: Cortical Lewy bodies and Aβ burden are associated with prevalence and timing of dementia in Lewy body diseases.
abstract: Our main objective was to determine the neuropathological correlates of dementia in patients with Lewy body disease (LBD). Furthermore, we used data derived from clinical, neuropathological and genetic studies to investigate boundary issues between Dementia with Lewy bodies (DLB) and Parkinson's disease with (PDD) and without (PDND) dementia.
  
  
  
  One hundred and twenty-one cases with a neuropathological diagnosis of LBD and clinical information on dementia status were included in the analysis (55 PDD, 17 DLB and 49 PDND). We carried out topographical and semi-quantitative assessment of Lewy bodies (LB), Aβ plaques and tau-positive neuropil threads (NT). The APOE genotype and MAPT haplotype status were also determined.
  
  
  
  The cortical LB (CLB) burden was the only independent predictor of dementia (OR: 4.12, P < 0.001). The total cortical Aβ plaque burden was an independent predictor of a shorter latency to dementia from onset of motor signs (P = 0.001). DLB cases had a higher LB burden in the parietal and temporal cortex, compared to PDD. Carrying at least one APOE ϵ4 allele was associated with a higher cortical LB burden (P = 0.02), particularly in the neocortical frontal, parietal and temporal regions.
  
  
  
  High CLB burden is a key neuropathological substrate of dementia in LBD. Elevated cortical LB pathology and Aβ plaque deposition are both correlated with a faster progression to dementia. The higher CLB load in the temporal and parietal regions, which seems to be a distinguishing feature of DLB, may account for the shorter latency to dementia and could be mediated by the APOE ϵ4 allele.
authors.affiliation: Neuroepidemiology and Ageing Research Unit, School of Public Health, Imperial College, London, UK.|Centro Parkinson, Istituti Clinici di Perfezionamento di Milano, Milano, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Ruffmann
authors.affiliation: Neuroepidemiology and Ageing Research Unit, School of Public Health, Imperial College, London, UK.
authors.forename: F C F
authors.initials: FC
authors.lastname: Calboli
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College, London, UK.
authors.forename: I
authors.initials: I
authors.lastname: Bravi
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College, London, UK.
authors.forename: D
authors.initials: D
authors.lastname: Gveric
authors.affiliation: Neuroepidemiology and Ageing Research Unit, School of Public Health, Imperial College, London, UK.
authors.forename: L K
authors.initials: LK
authors.lastname: Curry
authors.affiliation: Genomics of Common Disease, School of Public Health, Imperial College, London, UK.|Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: de Smith
authors.affiliation: Genomics of Common Disease, School of Public Health, Imperial College, London, UK.|Department of Molecular Virology, Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: S
authors.initials: S
authors.lastname: Pavlou
authors.affiliation: Section of Investigative Medicine, Department of Medicine, Imperial College, London, UK.
authors.forename: J L
authors.initials: JL
authors.lastname: Buxton
authors.affiliation: Section of Investigative Medicine, Department of Medicine, Imperial College, London, UK.
authors.forename: A I F
authors.initials: AI
authors.lastname: Blakemore
authors.affiliation: Neuroepidemiology and Ageing Research Unit, School of Public Health, Imperial College, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Takousis
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Molloy
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Piccini
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College, London, UK.
authors.forename: D T
authors.initials: DT
authors.lastname: Dexter
authors.affiliation: Institute of Brain Behaviour and Mental Health, University of Manchester, Manchester, UK.
authors.forename: F
authors.initials: F
authors.lastname: Roncaroli
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College, London, UK.
authors.forename: S M
authors.identifier: 0000-0002-7131-4643
authors.initials: SM
authors.lastname: Gentleman
authors.affiliation: Neuroepidemiology and Ageing Research Unit, School of Public Health, Imperial College, London, UK.
authors.forename: L T
authors.initials: LT
authors.lastname: Middleton
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism; D002540:Cerebral Cortex / Q000473:pathology*; D003704:Dementia / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D005260:Female; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology*; D020961:Lewy Body Disease / Q000150:complications / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications / Q000473:pathology*; D015995:Prevalence
chemical_list: D016229:Amyloid beta-Peptides
keywords: Aβ; Lewy bodies; Parkinson's disease; alpha-synuclein; dementia; neuropathology