A clinico-pathological study of subtypes in Parkinson's disease

Abstract

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-beta 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.

Dopamine Dysregulation Syndrome in Parkinson’s Disease Patients with Unsatisfactory Switching from Immediate to Extended Release Pramipexole: A Further Clue to Incentive Sensitization Mechanisms?

“…Despite disease duration, patients did not show an evident cognitive dysfunction. Such finding in these patients with tremor-dominant PD is not unusual, while several studies have demonstrated that non-tremor-dominant PD is strongly associated with cognitive deterioration [13,14].…”

Parkinsonian Syndromes

“…Data from the Queen Square Brain Bank suggest that the mean time from diagnosis to death is around 14 years; however, for patients diagnosed in their forties it is 24 years, and for patients in their seventies it is 9.7 years. 13 The mean age of disease onset is 61 years old.…”

Age at onset and Parkinson disease phenotype

“…2 The biological basis of this phenotypic variability is unknown but might be explained by the progressive and diverse accumulation of a-synuclein (a-syn) in different brain structures. 3,4 It has been estimated that PD increases with age, reaching a prevalence of 2.6% in people aged 85 to 89 years. 5 Although current evidence does not support the hypothesis that PD is caused by an acceleration of a natural aging process, 6 age is considered its main risk factor.…”