title: Lewy- and Alzheimer-type pathologies in Parkinson's disease dementia: which is more important?
abstract: The relative importance of Lewy- and Alzheimer-type pathologies to dementia in Parkinson's disease remains unclear. We have examined the combined associations of α-synuclein, tau and amyloid-β accumulation in 56 pathologically confirmed Parkinson's disease cases, 29 of whom had developed dementia. Cortical and subcortical amyloid-β scores were obtained, while tau and α-synuclein pathologies were rated according to the respective Braak stages. Additionally, cortical Lewy body and Lewy neurite scores were determined and Lewy body densities were generated using morphometry. Non-parametric statistics, together with regression models, receiver-operating characteristic curves and survival analyses were applied. Cortical and striatal amyloid-β scores, Braak tau stages, cortical Lewy body, Lewy neurite scores and Lewy body densities, but not Braak α-synuclein stages, were all significantly greater in the Parkinson's disease-dementia group (P<0.05), with all the pathologies showing a significant positive correlation to each other (P<0.05). A combination of pathologies [area under the receiver-operating characteristic curve=0.95 (0.88-1.00); P<0.0001] was a better predictor of dementia than the severity of any single pathology. Additionally, cortical amyloid-β scores (r=-0.62; P=0.043) and Braak tau stages (r=-0.52; P=0.028), but not Lewy body scores (r=-0.25; P=0.41) or Braak α-synuclein stages (r=-0.44; P=0.13), significantly correlated with mini-mental state examination scores in the subset of cases with this information available within the last year of life (n=15). High cortical amyloid-β score (P=0.017) along with an older age at onset (P=0.001) were associated with a shorter time-to-dementia period. A combination of Lewy- and Alzheimer-type pathologies is a robust pathological correlate of dementia in Parkinson's disease, with quantitative and semi-quantitative assessment of Lewy pathology being more informative than Braak α-synuclein stages. Cortical amyloid-β and age at disease onset seem to determine the rate to dementia.
authors: Queen Square Brain Bank for Neurological Disorders, UCL Institute of Neurology, WC1N 3BG, London, UK.|Movement Disorders Unit, Neurology Service, Institut Clínic de Neurociències, Hospital Clínic de Barcelona, IDIBAPS, CIBERNED, 08036 Barcelona, Catalonia, Spain.
authors: Yaroslau
authors: Y
authors: Compta
authors: Queen Square Brain Bank for Neurological Disorders, UCL Institute of Neurology, WC1N 3BG, London, UK.
authors: Laura
authors: L
authors: Parkkinen
authors: Queen Square Brain Bank for Neurological Disorders, UCL Institute of Neurology, WC1N 3BG, London, UK.
authors: Sean S
authors: SS
authors: O'Sullivan
authors: Reta Lila Weston Institute, UCL Institute of Neurology, WC1N 3BG, London, UK.
authors: Jana
authors: J
authors: Vandrovcova
authors: Queen Square Brain Bank for Neurological Disorders, UCL Institute of Neurology, WC1N 3BG, London, UK.
authors: Janice L
authors: JL
authors: Holton
authors: Reta Lila Weston Institute, UCL Institute of Neurology, WC1N 3BG, London, UK.
authors: Catherine
authors: C
authors: Collins
authors: Queen Square Brain Bank for Neurological Disorders, UCL Institute of Neurology, WC1N 3BG, London, UK.
authors: Tammaryn
authors: T
authors: Lashley
authors: Forensic Psychiatry Research Unit, Queen Mary, University of London, E1 4NS, London, UK.
authors: Constantinos
authors: C
authors: Kallis
authors: Queen Square Brain Bank for Neurological Disorders, UCL Institute of Neurology, WC1N 3BG, London, UK.|Van Cleef Roet Centre for Nervous Diseases, Monash University, Commercial Rd, 3004, Melbourne, Victoria, Australia.
authors: David R
authors: DR
authors: Williams
authors: Reta Lila Weston Institute, UCL Institute of Neurology, WC1N 3BG, London, UK.
authors: Rohan
authors: R
authors: de Silva
authors: Queen Square Brain Bank for Neurological Disorders, UCL Institute of Neurology, WC1N 3BG, London, UK.|Reta Lila Weston Institute, UCL Institute of Neurology, WC1N 3BG, London, UK.
authors: Andrew J
authors: AJ
authors: Lees
authors: Queen Square Brain Bank for Neurological Disorders, UCL Institute of Neurology, WC1N 3BG, London, UK.
authors: Tamas
authors: T
authors: Revesz
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