Dementia has become an all-important disease because the population is aging rapidly and the cost of health
care associated with dementia is ever increasing. In addition to cognitive function impairment, associated behavioral and
psychological symptoms of dementia (BPSD) worsen patient’s quality of life and increase caregiver’s burden.
Alzheimer’s disease is the most common type of dementia and both behavioral disturbance and cognitive impairment of
Alzheimer’s disease are thought to be associated with the N-methyl-D-aspartate (NMDA) dysfunction as increasing
evidence of dysfunctional glutamatergic neurotransmission had been reported in behavioral changes and cognitive decline
in Alzheimer’s disease. We review the literature regarding dementia (especially Alzheimer’s disease), BPSD and relevant
findings on glutamatergic and NMDA neurotransmission, including the effects of memantine, a NMDA receptor
antagonist, and NMDA-enhancing agents, such as D-serine and D-cycloserine. Literatures suggest that behavioral
disturbance and cognitive impairment of Alzheimer’s disease may be associated with excitatory neurotoxic effects which
result in impairment of neuronal plasticity and degenerative processes. Memantine shows benefits in improving cognition,
function, agitation/aggression and delusion in Alzheimer's disease. On the other hand, some NMDA modulators which
enhance NMDA function through the co-agonist binding site can also improve cognitive function and psychotic
symptoms. We propose that modulating NMDA neurotransmission is effective in treating behavioral and psychological
symptoms of Alzheimer’s disease. Prospective study using NMDA enhancers in patients with Alzheimer’s disease and
associated behavioral disturbance is needed to verify this hypothesis.