Treatment effect of memantine on survival in dementia with Lewy bodies and Parkinson's disease with dementia: a prospective study

Abstract

ObjectiveTo investigate the effect on survival of treatment with memantine in patients with dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD).Methods75 patients with DLB and PDD were included in a prospective double-blinded randomised placebo-controlled trial (RCT) of memantine, of whom long-term follow-up was available for 42. Treatment response was recorded 24 weeks from baseline and measured by Clinical Global Impression of Change (CGIC). The participants were grouped as responders (CGIC 1–3) or non-responders (CGIC 4–7). The 24-week RCT was followed by open-label treatment and survival was recorded at 36 months.ResultsAfter 36-month follow-up, patients in the memantine group had a longer length of survival compared with patients in the placebo group (log rank x²=4.02, p=0.045). Within the active treatment group, survival analysis 36 months from baseline showed that the memantine responders, based on CGIC, had higher rates of survival compared with the non-responders (log rank x²=6.595, p=0.010). Similar results were not seen in the placebo group.ConclusionsEarly treatment with memantine and a positive clinical response to memantine predicted longer survival in patients with DLB and PDD. This suggests a possible disease-modifying effect and also has implications for health economic analysis. However, owing to the small study sample, our results should merely be considered as generating a hypothesis which needs to be evaluated in larger studies.Trial registration numberISRCTN89624516.

The prognosis of dementia with Lewy bodies

“…Of interest with regard to treatment decisions, one randomized placebocontrolled trial of the glutamate inhibitor memantine in DLB and PDD patients showed a positive impact on survival 43 . Although this evidence is too weak to be the basis of treatment decision-making this finding does indicate the potential role of this treatment approach in DLB and may warrant further investigation to establish the underlying mechanism for improved survival.…”

Evidence-Based Review of Therapeutic Approaches in Dementia with Lewy Bodies

“…A study looked at the difference in treatment response between patients who had mixed AD-DLB pathology and those with pure Dementia with Lewy Bodies. It showed an enhanced response with acetylcholine esterase inhibitors in those with pure DLB when compared to those with concomitant AD pathology [21][22][23][24].…”

“…In a follow-up open-label extension phase, patients who were started on memantine in the original RCT were shown to have a better 3 year survival compared to those on placebo (p=0.045) [23,24].…”

Efficacy of memantine on neuropsychiatric symptoms associated with the severity of behavioral variant frontotemporal dementia: A six-month, open-label, self-controlled clinical trial

“…In addition, memantine has been demonstrated to ease or improve behavioral and cognitive manifestations of these forms of dementia, in particular various behavioral disturbances (irritability, agitation, aggression and difficulty eating) (7)(8)(9). Previously reviewed studies have observed that NMDA receptors are upregulated in FTLD and suggest that aberrant glutamatergic neurotransmission and glutamate excitotoxicity mediating cellular dysfunction may be implicated in the pathogenesis of FTLD (10).…”

“…Patients were divided into the following groups according to their MMSE score: Mild bvFTD (MMSE score, 21-26); and moderate-to-severe bvFTD (MMSE score, [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20].…”