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

Abstract

Objective: To investigate the effect on survival of treatment with memantine in patients with dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD).

Methods: 75 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.

Results: After 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.

Conclusions: Early 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 number: ISRCTN89624516.

Figure 1

Trial profile of the study population (Swedish population in the original RCT). See also figure 3 for further management of the 14 patients in the placebo group. DLB, dementia with Lewy bodies; Parkinson's disease with dementia; RCT, randomised placebo-controlled trial.

Figure 2

Description of the Clinical Global Impression of Change (CGIC) score system.

Figure 3

Trial profile for further management of the original placebo group during the open-label treatment follow-up. See also figure 1.

Figure 4

Kaplan-Meier estimates of the rate of survival in patients with dementia with Lewy bodies and Parkinson's disease with dementia following 24-week placebo-controlled double-blinded treatment with memantine. The group of patients that received treatment with memantine during the first 24 weeks had a higher 3-year survival rate compared with patients in the placebo group (log rank x²=4.021, p=0.045).

Figure 5

(A) Kaplan-Meier estimates of the rate of survival in patients with DLB and PDD following 24-week double-blinded treatment with memantine. The group of patients that responded positively to treatment after 24 weeks had a higher 3-year survival rate compared with non-responders (log rank x²=6.595, p=0.010). (B) Kaplan-Meier estimates of the rate of survival in patients with DLB and PDD following double-blinded treatment with placebo. There was no difference in survival between the patients who responded positively to placebo compared with the non-responders (log rank x²=0.161, p=0.689). CGIC, Clinical Global Impression of Change; DLB, dementia with Lewy bodies; Parkinson's disease with dementia.

Figure 6

Kaplan-Meier estimates of the rate of survival in patients with DLB and PDD following 6-month open-label treatment with memantine. There was no difference in survival between the patients who responded positively to treatment compared with the non-responders (log rank x²=1.834, p=0.176). CGIC, Clinical Global Impression of Change; DLB, dementia with Lewy bodies; Parkinson's disease with dementia.