Changes in motor subtype and risk for incident dementia in Parkinson's disease

Abstract

The objective of this study was to assess the temporal relationship between changes in predominant motor symptoms and incident dementia in Parkinson's disease (PD). A community-based sample of 171 nondemented patients with PD was followed prospectively and examined at baseline and after 4 and 8 years. The motor subtype of Parkinsonism was classified into tremor-dominant (TD), indeterminate, or postural instability gait difficulty (PIGD) subtype at each visit, based on defined items in the Unified Parkinson's Disease Rating Scale, subscales II and III. Dementia was diagnosed according to DSM-III-R criteria, based on clinical interview, cognitive rating scales, and neuropsychological examination. Logistic regression was used to analyze the relationship between subtype of Parkinsonism and dementia. Transition from TD to PIGD subtype was associated with a more than threefold increase in the rate of Mini-Mental State Examination decline. Compared to patients with persistent TD or indeterminate subtype, the odds ratio for dementia was 56.7 (95% CI: 4.0-808.4; P = 0.003) for patients changing from TD or indeterminate subtype to PIGD subtype, and 80.0 (95% CI: 4.6-1400.1; P = 0.003) for patients with persistent PIGD subtype. Patients with TD subtype at baseline did not become demented until they developed PIGD subtype, and dementia did not occur among patients with persistent TD subtype of Parkinsonism. In a substantial proportion of PD patients who develop postural instability and gait disorder during the course of the disease, this transition is associated with accelerated cognitive decline and highly increased risk for subsequent dementia. These findings raise the question whether PIGD and dementia share common or parallel neuropathology.

Heterogeneity of Cholinergic Denervation in Parkinson's Disease without Dementia

“…Cholinergic system degeneration may also provide a conceptual framework to explain why patients with higher postural instability and gait disturbances in PD are at an increased risk of developing dementia (Alves et al, 2006;Taylor et al, 2008). However, we did not find a specific association between thalamic cholinergic activity and cognitive performance in our study.…”

Sex differences in LRRK2 G2019S and idiopathic Parkinson's Disease

“…While not universal,34 certain reports suggest a slower disease progression in female patients. A benign phenotype has also been suggested to be related to a more common occurrence of tremor‐dominant subtype in women, which in turn has been associated with slower disease progression and less cognitive impairment 35, 36. In our sample, men and women with IPD had similar rates of tremor‐dominant subtype (30.3% in IPD women vs. 25.47% in men, P = 0.59).…”

History of falls in Parkinson disease is associated with reduced cholinergic activity

“…27 Studies have also shown an association between the postural instability and gait difficulty motor phenotype in PD and increased risk of dementia. 28,29 These findings raise the question whether postural instability and gait difficulty and PD dementia share a common cholinergic mechanism contributing to these 2 clinical manifestations.…”

“…Subjects with a Mini-Mental State Examination (MMSE) score of 24 or less were not eligible for the study. 10 The mean MMSE score was 29.0 Ϯ 1.4 (range [25][26][27][28][29][30].…”