β-Amyloid and postural instability and gait difficulty in Parkinson's disease at risk for dementia.

Abstract

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.

• Authors: Martijn L T M Müller, Kirk A Frey, Myria Petrou, Vikas Kotagal, Robert A Koeppe, Roger L Albin, Nicolaas I Bohnen
• Journal: Movement disorders : official journal of the Movement Disorder Society (Mov Disord) Vol. 28 Issue 3 Pg. 296-301 (Mar 2013) ISSN: 1531-8257 [Electronic] United States
• PMID: 23239424 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2012 Movement Disorders Society.

Chemical References

• 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
• Amyloid beta-Peptides
• Aniline Compounds
• Carbon Isotopes
• Thiazoles
• dihydrotetrabenazine
• Tetrabenazine

Topics

• Aged
• Aged, 80 and over
• Amyloid beta-Peptides (metabolism)
• Aniline Compounds
• Carbon Isotopes (pharmacokinetics)
• Cross-Sectional Studies
• Dementia (complications)
• Female
• Gait Disorders, Neurologic (etiology)
• Humans
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Parkinson Disease (complications, diagnostic imaging, metabolism)
• Positron-Emission Tomography
• Postural Balance (physiology)
• Psychiatric Status Rating Scales
• Sensation Disorders (etiology)
• Severity of Illness Index
• Tetrabenazine (analogs & derivatives)
• Thiazoles