Fast track — ArticlesMemantine in patients with Parkinson's disease dementia or dementia with Lewy bodies: a double-blind, placebo-controlled, multicentre trial
Introduction
25 milion people worldwide have dementia, including 700 000 in the UK. Dementia with Lewy bodies (DLB) and dementia associated with Parkinson's disease (PDD) have similar clinical and neuropathological symptoms and account for 15–20% of the global incidence of dementia.1 The complex courses of DLB and PDD include motor, cognitive, attentional, and psychiatric symptoms, and make these forms of dementia particularly challenging in terms of quality of life for patients and carers, admission to nursing homes, and health-related costs.1 Modest clinical benefits are seen in cognition, function, and neuropsychiatric symptoms with rivastigmine,2, 3 but not all patients respond to or can tolerate cholinesterase inhibitors. Better single or combination therapies are, therefore, urgently needed.
Memantine is an N-methyl D-aspartate (NMDA) receptor antagonist that affects glutamatergic neuronal transmission and prevents the toxic effects of raised concentrations of the excitatory neurotransmitter glutamate.4 Memantine has proven efficacy as a treatment for Alzheimer's disease.5 Altered glutamatergic markers have been identified in patients with DLB,6 providing a rationale for therapy with memantine for these individuals. However, preliminary evidence based on case reports has been highly variable and implicates not only the potential for memantine to improve cognitive and motor symptoms in patients with DLB,7 but also the possibility of adverse events, including worsening in cognition8 and psychosis.9 Controlled trials are clearly needed to establish whether memantine has a potential role in the treatment of DLB and PDD; therefore, we did a placebo-controlled study to test the hypothesis that memantine is more effective than placebo for treating the symptoms of patients with PDD or DLB.
Section snippets
Patients
Patients with mild or moderate PDD or DLB (ie, a mini-mental state examination [MMSE]10 score of 12 points or higher) were recruited at four psychiatric and neurological outpatient clinics in Norway, Sweden, and the UK during 2005–08. Patients were included if they fulfilled the UK Parkinson's Disease Society Brain Bank clinical diagnostic criteria for Parkinson's disease (PD) and subsequently developed dementia according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition
Results
75 patients were randomly assigned, and 72 (40 with PDD and 32 with DLB) started study medication (figure 1). Of these, 34 were assigned to memantine and 38 to placebo. 16 withdrew before the end of the study owing to adverse events, although five of these attended the 12-week visit, and 56 completed 24 weeks. There were no significant differences in any of the demographic or clinical variables or treatment characteristics between the treatment groups for the randomised (table 1) or LOCF
Discussion
The main finding of this study is that the patients who received memantine improved more than the patients who received placebo. A moderate-to-substantial improvement was reported by eight (27%) patients in the memantine group; no patients in the placebo group reported more than a slight improvement. The difference in CGIC scores between the groups was 0·7, and the effect size was 0·52, which is usually thought to be a medium-sized effect.22 This difference compares favourably with the results
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