Brain Advance Access originally published online on September 16, 2009
Brain 2009 132(11):2947-2957; doi:10.1093/brain/awp234
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A clinico-pathological study of subtypes in Parkinson's disease
1 Queen Square Brain Bank for Neurological Disorders and Institute of Neurology, University College, London, UK 2 Russian State Medical University, Moscow, Russia 3 Reta Lila Weston Institute of Neurological Studies, University College, London, UK 4 Van Cleef Roet Centre for Nervous Diseases, Monash University, Melbourne, Australia 5 Neurosciences Department, Monash Medical Centre, Melbourne, Australia
Correspondence to: Prof. A. J. Lees, Reta Lila Weston Institute of Neurological Studies, 1 Wakefield Street, London, WC1N 1PJ, UK E-mail: alees{at}ion.ucl.ac.uk
We have carried out a systematic review of the case files of 242 donors with pathologically verified Parkinson's disease at the Queen Square Brain Bank for Neurological Disorders in an attempt to corroborate the data-driven subtype classification proposed by Lewis and colleagues (Heterogeneity of Parkinson's disease in the early clinical stages using a data driven approach. J Neurol Neurosurg Psychiatry 2005; 76: 343–8). Cases were segregated into earlier disease onset (25%), tremor dominant (31%), non-tremor dominant (36%) and rapid disease progression without dementia (8%) subgroups. We found a strong association between a non-tremor dominant disease pattern and cognitive disability. The earlier disease onset group had the longest duration to death, and greatest delay to the onset of falls and cognitive decline. Patients with a tremor dominant disease pattern did not live significantly longer than non-tremor dominant patients and showed no difference in mean time to onset of falls and hallucinations. Rapid disease progression was associated with older age, early depression and early midline motor symptoms, and in 70% of the cases, tremulous onset. The non-tremor dominant subgroup had a significantly higher mean pathological grading of cortical Lewy bodies than all other groupings (P < 0.05) and more cortical amyloid-β plaque load and cerebral amyloid angiopathy than early disease onset and tremor dominant groups (P = 0.047). An analysis of cases with pathologically defined neocortical Lewy body disease confirmed the link between bradykinetic onset, cognitive decline and Lewy body deposition in the neocortex. Although neuropathological examination failed to distinguish the other subtypes, the classification scheme was supported by an analysis of clinical data that were independent of the basic subgroup definitions.
Key Words: bradykinesia; Parkinson's disease dementia; Lewy body; tremor dominant phenotype; age of onset
Abbreviations: EDO, earlier disease onset; NTD, non-tremor dominant; QSBB, Queen Square Brain Bank; RDP, rapid disease progression without dementia; TD, tremor dominant
Received April 1, 2009. Revised July 24, 2009. Accepted July 25, 2009.