Use of memantine (akatinol) for the correction of cognitive impairments in Parkinson's disease complicated by dementia

Abstract

This study addresses the effects of 52 weeks of treatment with the NMDA glutamate receptor antagonist memantine on motor, cognitive, and mental disorders in patients with Parkinson's disease complicated by dementia, as compared with a control group of patients not treated with memantine. Patients of the experimental group (32 subjects) received memantine (20 mg/day), while patients in the control group continued on antiparkinsonism treatment alone. Cognitive, psychiatric, and motor symptoms were assessed before the study and then at the ends of weeks 12, 24, and 52, using clinical assessment, rating scales, and neuropsychological tests. Plasma homocysteine levels were measured by HPLC. Patients treated with memantine had better measures on the MMSE (p < 0.05), ADAS-cog (p < 0.05), clock drawing test (p < 0.05), and FAB (p < 0.01) as compared with the control group by the end of study week 24. Members of the group of patients with high homocysteine levels mounted significantly better responses with memantine treatment, as compared with patients of the control group with high homocysteine levels but not receiving memantine, at the ends of study weeks 24 and 52, in terms of all rating scales (UPDRS, MMSE, ADAS-cog, D-KEFS Verbal Fluency Test, FAB. NPI, and DAD, p < 0.05). By the end of week 52, significant changes in points scores on the NPI-12 scale from baseline were in favor of patients receiving memantine, this applying to the disinhibition (p = 0.006), irritability (p = 0.04), anxiety (p = 0.04), and hallucinations (p = 0.048) subscales. The presence of hyperhomocysteinemia may indicate faster progression of both motor and cognitive impairments in Parkinson's disease. Prolonged memantine treatment of patients with Parkinson's disease complicated by dementia leads to improvements in cognitive functions, stabilization of motor impairments, and decreases in the severity of mental disorders, especially in patients with hyperhomocysteinemia.