title: Rivastigmine versus placebo in hyperhomocysteinemic Parkinson's disease dementia patients.
abstract: The effects of rivastigmine versus placebo in Parkinson's disease dementia (PDD) patients with elevated or normal/low plasma homocysteine were determined. In this prospective analysis of a 24-week, randomly assigned, placebo-controlled study of rivastigmine in PDD, subpopulations comprised patients with plasma homocysteine >or=14 micromol/L (elevated) or <14 micromol/L (normal/low). Coprimary outcomes were the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Alzheimer Disease Cooperative Society-Clinical Global Impression of Change (ADCS-CGIC). Secondary outcomes included additional measures of cognition, including attention and executive function, daily function, and neuropsychiatric symptoms. Adverse events (AEs) were monitored. In total, 342 of 541 patients provided samples for analysis, from which 72% had elevated plasma homocysteine. Hyperhomocysteinemic patients showed treatment differences (rivastigmine vs. placebo) of 4.0 on ADAS-cog and 0.7 on ADCS-CGIC (both P < 0.01), and significant treatment differences on secondary outcomes. Rivastigmine- and placebo-treated hyperhomocysteinemic patients (16.5% and 14.6%) discontinued the study because of AEs. Patients with normal/low homocysteine showed no treatment differences on primary or secondary outcomes (1.4 on the ADAS-cog and 0.1 on ADCS-CGIC, both P = ns); 16.7% and 10.3% rivastigmine- and placebo-treated patients discontinued because of AEs. Elevated homocysteine was associated with greater rivastigmine treatment differences than normal/low homocysteine.
authors.affiliation: Dipartimento di Scienze Neurologiche, Università Federico II di Napoli, Naples, Italy. barone@unina.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Barone
authors.forename: David J
authors.initials: DJ
authors.lastname: Burn
authors.forename: Teus
authors.initials: T
authors.lastname: van Laar
authors.forename: Chuanchieh
authors.initials: C
authors.lastname: Hsu
authors.forename: Werner
authors.initials: W
authors.lastname: Poewe
authors.forename: Roger M
authors.initials: RM
authors.lastname: Lane
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D003704:Dementia / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications / Q000188:drug therapy; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D048448:Phenylcarbamates / Q000627:therapeutic use*; D011446:Prospective Studies; D000068836:Rivastigmine; D012720:Severity of Illness Index
chemical_list: D018696:Neuroprotective Agents; D048448:Phenylcarbamates; D006710:Homocysteine; D000068836:Rivastigmine