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From the Institute for Clinical Neuroanatomy (Drs. Braak, Rüb, and Del Tredici), J.W. Goethe University, Frankfurt/Main, Germany; and Department of Neurology MST Hospital Group (Dr. Jansen Steur) and Laboratorium Pathologie Oost Nederland (Dr. de Vos), Enschede, The Netherlands.
Address correspondence and reprint requests to Prof. Heiko Braak, J.W. Goethe University, Institute for Clinical Neuroanatomy, Theodor Stern Kai 7, 60590 Frankfurt/Main, Germany; e-mail: Braak{at}em.uni-frankfurt.de
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 
-synuclein semiquantitatively in sections from 18 brain regions. In silver-stained sections and sections immunostained for tau and ß-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 ß-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.
Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the April 26 issue to find the title link for this article.
* Drs. Del Tredicgips de Vos are joint last authors.
Supported by the Deutsche Forschungsgemeinschaft (DFG).
Received March 26, 2004. Accepted in final form January 6, 2005.
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