title: Cognitive status correlates with neuropathologic stage in Parkinson disease.
abstract: OBJECTIVE
  To study the association of cognitive status with the stages of a published neuropathologic staging procedure for sporadic Parkinson disease (PD) in a cohort of 88 patients with PD from a single neurologic unit. None had received the clinical diagnosis of dementia with Lewy bodies (DLB).
  
  
  METHODS
  The authors assessed Lewy neurites/bodies (LNs/LBs) immunoreactive for alpha-synuclein semiquantitatively in sections from 18 brain regions. In silver-stained sections and sections immunostained for tau and beta-amyloid protein, the authors semiquantitatively evaluated comorbidities potentially contributing to cognitive decline, e.g., Alzheimer disease (AD), argyrophilic grain disease (AGD), and cerebral vascular disease. The authors analyzed four Mini-Mental State Examination (MMSE) subgroups ranging from marginally impaired cognition to severe dementia using nonparametric tests.
  
  
  RESULTS
  It was possible to assign all patients to one of the PD stages. MMSE scores correlated with neuropathologic stages (p < 0.005) and this association showed a linear trend (p < 0.025). Median MMSE test scores for women were lower than those for men. Cognitively impaired individuals displayed higher stages of AD-related neurofibrillary pathology (p < 0.05) and beta-amyloid deposition (p < 0.05) than cognitively unimpaired persons. MMSE scores did not correlate significantly with AGD, disease duration, age at disease onset, or age at death. Hoehn and Yahr scores, however, correlated with PD stages (p < 0.0005) and MMSE scores (p < 0.0005).
  
  
  CONCLUSIONS
  The decrease in median Mini-Mental State Examination scores between PD stages 3 to 6 indicates that the risk of developing dementia increases with disease progression. In some individuals, however, cognitive decline can develop in the presence of mild Parkinson disease-related cortical pathology and, conversely, widespread cortical lesions do not necessarily lead to cognitive decline.
authors.affiliation: Institute for Clinical Neuroanatomy, J.W. Goethe University, Frankfurt/Main, Germany. Braak@em.uni-frankfurt.de
authors.forename: H
authors.initials: H
authors.lastname: Braak
authors.forename: U
authors.initials: U
authors.lastname: Rüb
authors.forename: E N H
authors.initials: EN
authors.lastname: Jansen Steur
authors.forename: K
authors.initials: K
authors.lastname: Del Tredici
authors.forename: R A I
authors.initials: RA
authors.lastname: de Vos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology; D002561:Cerebrovascular Disorders / Q000473:pathology / Q000503:physiopathology; D003072:Cognition Disorders / Q000209:etiology* / Q000473:pathology* / Q000523:psychology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology; D008297:Male; D016874:Neurofibrillary Tangles / Q000473:pathology; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000150:complications* / Q000473:pathology* / Q000523:psychology; D058225:Plaque, Amyloid / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D012737:Sex Factors