Memantine in mild cognitive impairment and mild dementia of Alzheimer's disease: theoretical background, clinical trials and recommendations

Memantine, uncompetitive antagonist of NMDA receptor, is currently registered worldwide for the treatment of moderate to advanced dementia in the course of Alzheimer's disease and is used either in monotherapy or in combination with cholinesterase inhibitor. Memantine's efficacy has been documented in several clinical trials within cognition, behaviour and activities of daily living domains; the more advanced dementia the bigger effect size is usually seen. Adding memantine to an ongoing cholinesterase inhibitors exerts augmentation. Memantine efficacy in less advanced stages of Alzheimer's dementia is the matter of controversy. It is highly unlikely to see an evident clinical benefit in the group of patients with initial MMSE above 20. Early treatment with memantine is thought to exert long-term consequences as probable disease-modifying effect may come to action. Data supporting this view (and, as a result, early treatment with memantine) is mainly of clinical nature and need to be confirmed with the use of validated disease progression biomarkers. Patients with mild dementia of Alzheimer's type may be rationally treated with memantine monotherapy, even considering probable lack of symptomatic effect, when cholinesterase inhibitors are contraindicated or poorly tolerated. Data supporting the use of memantine in mild cognitive impairment are currently insufficient.