The effect of 12-week open-label memantine treatment on cognitive function improvement in patients with alcohol-related dementia

Abstract

There is compelling evidence that alcohol-induced neurotoxicity is related to glutamate excitotoxicity. It was hypothesized that the low-affinity NMDA receptor antagonist memantine would improve the cognitive function of patients with alcoholic dementia. The aim of this study was to test this hypothesis and to evaluate the effect of memantine on the cognitive improvement of patients with alcohol-related dementia (ARD). The study was designed as a 12-wk open-label study investigating the efficacy of 20 mg memantine, a low-affinity NMDA receptor antagonist, as a treatment for cognitive and behavioural problems in 19 patients with probable ARD according to the criteria for ARD proposed by Oslin and colleagues. The CERAD-K (Consortium to Establish a Registry for Alzheimer's Disease - Korean version) and several clinical assessment scales were completed before and after the 12-wk memantine treatment period. Significant improvements in the mean scores from baseline to final assessment were observed in the Global Deterioration Scale (p<0.05), Brief Psychiatric Rating Scale (p<0.01), Geriatric Quality of Life - Dementia scale (p<0.01) and Neuropsychiatric Inventory (p<0.01) at the end of week 12. The CERAD-K subscales of word list recall (p<0.05), word list recognition (p<0.05), time orientation (p<0.01), drawing an interlocking pentagon (p<0.05), and the total MMSE-K (Mini Mental State Examination - Korean version) scores (p<0.01) of the patients all showed significant improvement following the memantine trial. In this open-label study, patients with ARD treated with 20 mg/d memantine for 12 wk showed improvement on global cognition, quality of life and behavioural symptoms. The result of this study suggests the possible usefulness of memantine for the treatment of ARD. As this was an open-label study, the possibility that participants improved cognitively on their own due to protracted abstinence from alcohol cannot be discounted.

Alcohol-Related Dementia and Neurocognitive Impairment: A Review Study

“…A 12-week study on patients with probable ARD showed significant improvements on global cognition, quality of life and behavioral symptoms (76). Another memantine trial on WKS patients also showed improvement in cognition (word list recall, word list recognition, time orientation, drawing an interlocking pentagon and the total Mini Mental State Examination - Korean version) of all the patients (77).…”

Neuroscience of Behavioral and Pharmacological Treatments for Addictions

“…Pathological gambling also demonstrates clinical and biological similarities with drug addictions (Holden, 2010; Potenza, 2006; Potenza, 2008). Consistently, treatments, particularly those with proposed mechanisms of action (e.g., modulation of neurotransmission in the meso-limbic dopamine pathway by opioid receptor antagonists like naltrexone or nalmefene or enhancing cognitive function via glutamatergic agents like memantine) that target features observed across addictions, appear efficacious for both substance and gambling addictions (Brewer et al, 2008b; Cheon et al, 2010; Grant et al, 2010a; Potenza, 2008). Furthermore, among individuals with pathological gambling, response to an opioid receptor antagonist appears strongly related to a family history of alcoholism (Grant et al, 2008), suggesting a possible endophenotype common to pathological gambling and alcoholism.…”

Ethanol and Cognition: Indirect Effects, Neurotoxicity and Neuroprotection: A Review

“…When thiamine-induced glutamate release is combined with ethanol-induced glutamate receptor up-regulation, the potential for excitotoxicity would be compounded. In anecdotal reports patients with Wernicke-Korsakoff syndrome have experienced symptomatic improvement following treatment with the glutamate NMDA receptor antagonist memantine [21,22]. (They have also reportedly improved after treatment with cholinergic agents such as donepezil and rivastigmine [23,24].…”

“…In an open label study of 19 patients with probable ethanol-related dementia, cognitive improvement followed treatment with the glutamate NMDA receptor antagonist memantine [21]. (As noted, Wernicke-Korsakoff syndrome also reportedly benefits from memantine therapy [22]. )…”