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

Abstract

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, placebocontrolled 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. 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.

Identification of a Circulating Amino Acid Signature in Frail Older Persons with Type 2 Diabetes Mellitus: Results from the Metabofrail Study

“…Sarcosine, the N-methylated derivative of glycine, is an important intermediate of one-carbon metabolism [62]. Recent studies have investigated the association between sarcosine levels and age-related conditions in humans with conflicting results [63][64][65][66]. In a comparative metabolomics analysis, circulating sarcosine was found to be reduced with aging and increased by dietary restriction in both rodents and humans [67].…”

Sarcosine Is Uniquely Modulated by Aging and Dietary Restriction in Rodents and Humans

“…Elevated sarcosine levels in urine (Sreekumar et al, 2009) and serum (Koutros et al, 2013) have been associated with prostate cancer progression, although this relation has not been observed in other reports (de Vogel et al, 2014; Jentzmik et al, 2011). Elevated urine sarcosine levels were also associated with incident type 2 diabetes (Svingen et al., 2016), while low levels of sarcosine in blood have been linked with advanced arteriosclerosis (Hasokawa et al, 2012) and several neurological disorders, including neuropathic pain (Barthel et al, 2014), cerebral ischemia (Pinto et al, 2014), seizure (Socała et al, 2010), and Parkinson disease (Tsai et al, 2014). More recently, serum sarcosine was shown to be increased by a 10-week aerobic exercise training program in previously untrained male subjects (Felder et al, 2017).…”

“…In support of the former possibility, sarcosine supplementation in humans has produced promising results as a primary therapy for Parkinson’s disease with dementia (Tsai et al, 2014) and as an adjuvant treatment for patients suffering from schizophrenia (Strzelecki et al, 2015; Tsai et al, 2004). Likewise, beneficial effects of sarcosine have been found for learning and memory deficits (Kumar et al., 2016) and depression in rats (Chen et al, 2017).…”

Impairments in face discrimination and emotion recognition are related to aging and cognitive dysfunctions in Parkinson’s disease with dementia

“…Additional inclusion criteria include (1) age between 50-90 years old, (2) laboratory assessments (including blood and biochemical tests) that were clinically insignificant, (3) at least six years of formal education or can communicate effectively and are capable of completing the assessments. Based on our previous report 49 , medications currently used by patients had to be stabilized for at least three months before inclusion and remain unchanged throughout the study period. The PD-D patients received the tasks in the morning while withheld the antiparkinsonian agents www.nature.com/scientificreports www.nature.com/scientificreports/ the night before.…”