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Although motor impairments in Parkinson's disease (PD) are attributed to nigrostriatal dopaminergic denervation, postural instability and gait difficulty (PIGD) features are less responsive to dopaminergic medications. PIGD features are a risk factor also for the development of dementia in PD (PDD). These observations suggest that nondopaminergic mechanisms may contribute to axial motor impairments. The aim was to perform a correlative PET study to examine the relationship between neocortical β-amyloid deposition ([(11)C]-Pittsburgh Compound B), nigrostriatal dopaminergic denervation ([(11)C]-dihydrotetrabenazine), and PIGD feature severity in PD patients at risk for dementia. This was a cross-sectional study of 44 PD patients (11 female and 33 male; 69.5 ± 6.6 years of age; 7.0 ± 4.8 years motor disease duration; mean H & Y stage: 2.7 ± 0.5) who underwent PET, motor feature severity assessment using the Movement Disorder Society revised UPDRS, and the Dementia Rating Scale (DRS). Linear regression (R(2)(adj) = 0.147; F(4,39) = 2.85; P = 0.036) showed that increased PIGD feature severity was associated with increased neocortical [(11)C]-Pittsburgh Compound B binding (β = 0.346; t(39) = 2.13; P = 0.039) while controlling for striatal [(11)C]-dihydrotetrabenazine binding, age, and DRS total score. Increased neocortical β-amyloid deposition, even at low-range levels, is associated with higher PIGD feature severity in PD patients at risk for dementia. This finding may explain why the PIGD motor phenotype is a risk factor for the development of PDD. Copyright © 2012 Movement Disorders Society.

Citation

Martijn L T M Müller, Kirk A Frey, Myria Petrou, Vikas Kotagal, Robert A Koeppe, Roger L Albin, Nicolaas I Bohnen. β-Amyloid and postural instability and gait difficulty in Parkinson's disease at risk for dementia. Movement disorders : official journal of the Movement Disorder Society. 2013 Mar;28(3):296-301

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PMID: 23239424

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