title: Activation of N-methyl-D-aspartate receptor glycine site temporally ameliorates neuropsychiatric symptoms of Parkinson's disease with dementia.
abstract: OBJECTIVE
  We have previously found that sarcosine, a glycine transporter I inhibitor, can improve the psychiatric symptoms of schizophrenia. In this study, we aimed to investigate whether the agent can also ameliorate neuropsychiatric symptoms of Parkinson's disease (PD) patients with dementia.
  
  
  METHODS
  An 8-week, double-blind, placebo-controlled trial was conducted in patients who had PD with dementia (PD-D). Neuropsychiatric manifestations were measured before and at week 2 (V1), week 4 (V2) and week 8 (V3) after treatment. Linear regression with the generalized estimating equations was applied for data analysis.
  
  
  RESULTS
  Fifteen patients were randomized into a sarcosine group; the other 15 into a placebo group. The generalized estimating equations model revealed significant differences in Hamilton Depression Rating Scale score (P = 0.049) at V1 and Neuropsychiatry Inventory (P = 0.039) at V2 between the treatment and placebo groups. By excluding the advanced patients from analysis, there were significant differences in Unified Parkinson's Disease Rating Scale V2 (P = 0.004) and V3 (P = 0.040), Hamilton Depression Rating Scale V1 (P = 0.014) and V2 (P = 0.047), Neuropsychiatry Inventory V1 (P = 0.002) and V2 (P < 0.001) and Behavior Pathology in Alzheimer's Disease Rating Scale V2 (P = 0.025) in favor of sarcosine.
  
  
  CONCLUSIONS
  Sarcosine temporally improved depression and neuropsychiatric symptoms in PD-D patients without exacerbating the motor or cognitive features; the beneficial effects were more prominent in patients with mild-moderate severity. Enhancement of N-methyl-D-aspartate receptor-glycine cascade may lead to a novel path for the management of PD-D.
authors.affiliation: Department of Neurology, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan; School of Medicine, Medical College, China Medical University, Taichung, Taiwan.
authors.forename: Chon-Haw
authors.initials: CH
authors.lastname: Tsai
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Huang
authors.forename: Bey-Ling
authors.initials: BL
authors.lastname: Liu
authors.forename: Chia-Ing
authors.initials: CI
authors.lastname: Li
authors.forename: Ming-Kuei
authors.initials: MK
authors.lastname: Lu
authors.forename: Xianxiu
authors.initials: X
authors.lastname: Chen
authors.forename: Mu-Chieh
authors.initials: MC
authors.lastname: Tsai
authors.forename: Yu-Wan
authors.initials: YW
authors.lastname: Yang
authors.forename: Hsien-Yuan
authors.initials: HY
authors.lastname: Lane
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003704:Dementia / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists*; D012521:Sarcosine / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D012521:Sarcosine
keywords: N-methyl-D-aspartate; Parkinson's disease; dementia; hallucination; neuropsychiatry