The Role of N-Methyl-D-Aspartate Receptor Neurotransmission and Precision Medicine in Behavioral and Psychological Symptoms of Dementia

Abstract

While the world's population is aging, the prevalence of dementia and the associated behavioral and psychological symptoms of dementia (BPSD) rises rapidly. BPSD are associated with worsening of cognitive function and poorer prognosis. No pharmacological treatment has been approved to be beneficial for BPSD to date. Dysfunction of the N-methyl-D-aspartate receptor (NMDAR)-related neurotransmission leads to cognitive impairment and behavioral changes, both of which are core symptoms of BPSD. Memantine, an NMDAR partial antagonist, is used to treat moderate to severe Alzheimer's disease (AD). On the other hand, a D-amino acid oxidase inhibitor improved early-phase AD. Whether to enhance or to attenuate the NMDAR may depend on the phases of dementia. It will be valuable to develop biomarkers indicating the activity of NMDAR, particularly in BPSD. In addition, recent reports suggest that gender difference exists in the treatment of dementia. Selecting subpopulations of patients with BPSD who are prone to improvement with treatment would be important. We reviewed literatures regarding the treatment of BPSD, focusing on the NMDAR-related modulation and precision medicine. Future studies examining the NMDAR modulators with the aid of potential biomarkers to tailor the treatment for individualized patients with BPSD are warranted.

Keywords: Alzheimer’s disease; N-methyl-D-aspartate receptor; behavioral and psychological symptoms of dementia; gender difference; precision medicine.