title: 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.affiliation: Department of Radiology, University of Michigan, Ann Arbor, Michigan 48105, USA. mtmuller@med.umich.edu
authors.forename: Martijn L T M
authors.initials: ML
authors.lastname: Müller
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Frey
authors.forename: Myria
authors.initials: M
authors.lastname: Petrou
authors.forename: Vikas
authors.initials: V
authors.lastname: Kotagal
authors.forename: Robert A
authors.initials: RA
authors.lastname: Koeppe
authors.forename: Roger L
authors.initials: RL
authors.lastname: Albin
authors.forename: Nicolaas I
authors.initials: NI
authors.lastname: Bohnen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D003430:Cross-Sectional Studies; D003704:Dementia / Q000150:complications*; D005260:Female; D020233:Gait Disorders, Neurologic / Q000209:etiology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications* / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography; D004856:Postural Balance / Q000502:physiology*; D011569:Psychiatric Status Rating Scales; D012678:Sensation Disorders / Q000209:etiology*; D012720:Severity of Illness Index; D013747:Tetrabenazine / Q000031:analogs & derivatives; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D002247:Carbon Isotopes; D013844:Thiazoles; C032811:dihydrotetrabenazine; D013747:Tetrabenazine