Activation of N ‐methyl‐ D ‐aspartate receptor glycine site temporally ameliorates neuropsychiatric symptoms of P arkinson's disease with dementia

Aim 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 ( V 1), week 4 ( V 2) and week 8 ( V 3) 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 H amilton D epression R ating S cale score ( P  = 0.049) at V 1 and N europsychiatry I nventory ( P  = 0.039) at V 2 between the treatment and placebo groups. By excluding the advanced patients from analysis, there were significant differences in U nified P arkinson's D isease R ating S cale V 2 ( P  = 0.004) and V 3 ( P  = 0.040), H amilton D epression R ating S cale V 1 ( P  = 0.014) and V 2 ( P  = 0.047), N europsychiatry I nventory V 1 ( P  = 0.002) and V 2 ( P  < 0.001) and B ehavior P athology in A lzheimer's D isease R ating S cale V 2 ( P  = 0.025) in favor of sarcosine. Conclusion 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 .