Beyond Alzheimers: Memantine for treatment of behavioral disturbance in otherwise unspecified major neurocognitive disorder

Introduction Major neurocognitive dysfunction (NCD) currently affects up to 5.7 million people in the United States, with numbers expected to rise above 13 million by 20501. Unfortunately, behavioral disturbances are exceedingly common in patients with major NCD, representing a significant source of morbidity and mortality in this population. This is particularly burdensome to patients in hospitals and assisted-living facilities (ALFs), leading to increased lengths of stay and decreased quality-of-life measures2. Furthermore, behavioral disturbance increases psychological stress and fatigue imposed on family and caregivers. Despite the overwhelming consequences of behavioral disturbance in major NCD, we have relatively few options for treatment, with many of these lacking robust supportive data. Memantine, an NMDA antagonist used in moderate-to-severe Alzheimer dementia (AD), has been shown to improve behavioral disturbance in AD patients3. In this case report, we describe the use of memantine for the treatment of behavioral disturbance in a patient with unspecified major NCD. Methods This is a case of a 76-year-old man with bipolar 1 disorder who presented with unspecified major NCD with behavioral disturbance characterized by threatening staff at his ALF when food preferences were not accommodated. He reported no symptoms and showed no signs of a manic or depressive episode. His initial MoCA score was 16/30. In the hospital, he exhibited a disruptive and confrontational attitude, hyperphagia with excessive carbohydrate consumption, forgetfulness with perseveration on requests for denture cream and Chapstick, and disinhibited sexual commentary concerning for frontotemporal dementia, but also had concern for vascular dementia given his hypertension and atrial fibrillation. He had a gradual decline in memory function over a period of several years, with MMSE scores trending from 29/30 to 20/30 over the past 7 years, raising concern for possible AD. He also exhibited intermittent paranoia. He refused brain MRI. Memantine 5 mg daily was started and increased by 5 mg each week until reaching 20 mg daily (10 mg BID). Results After beginning treatment with memantine, patient exhibited reductions in social isolation, disruptive/disinhibited behavior, intrusiveness, perseverative requests, and paranoia. MoCA score improved by 2 points after 2 weeks of therapy, and by 5 points after 7 weeks of treatment. Conclusions It was concluded that memantine may have the potential to improve behavioral disturbances in patients with unspecified major NCD. Furthermore, the clinically significant improvement in this patient's paranoia suggests that memantine may also augment the potency of clozapine. Notable also is memantine's favorable side-effect profile, making it a relatively safe drug without significant associated risks. Given the observed efficacy in this clinical case as well as the medication's safety, memantine warrants further exploration as a potential therapy to improve behavioral disturbance in patients with major NCD. Funding N/A