Abstract
Objective: A pooled post hoc analysis of ADCS-ADL19 scores from two, 24-week, placebo-controlled trials was performed to evaluate the impact of combining memantine with ChEI treatment on daily functioning and assess potential clusters of functional tasks that improved together. Background: Moderate to severe Alzheimers disease is frequently treated with a cholinesterase inhibitor (ChEI) in combination with memantine. Methods: Data were pooled from trials MEM-MD-02 and MEM-MD-50 (placebo+ChEI, n=525; memantine+ChEI, n=531). Factors were derived using a principal components analysis based on change-from-baseline item values (placebo and memantine groups combined), varimax rotation, maximum loading for each item, and eigenvalues of ≥1 for each factor with a designated maximum of 4 factors. Between-group comparisons of item and factor score changes used a mixed-effects model with repeated measures (MMRM; OC and LOCF) analysis. Results:At Week 24, there were significant advantages of memantine+ChEI treatment over placebo+ChEI for grooming (P<0.001), conversing (P=0.010), and finding belongings (P=0.002). The 4 subscales identified were: basic ADLs (eating, walking, toileting, bathing, grooming, dressing; loading value range [LVR]: 0.41-0.71), higher-level ADLs requiring communication/comprehension skills (using telephone, watching television, conversing, finding belongings, traveling, left alone; LVR: 0.37-0.58), simple praxis (faucet on, faucet off, light on; LVR: 0.53-0.80), and praxis items requiring visuo-spatial and memory skills (clearing table, obtaining beverage, disposing of litter, light off; LVR: 0.35-0.63). At Week 24, the memantine+ChEI group declined less than placebo+ChEI on each subscale: basic ADLs (least squares difference [LSDiff]=0.376; P=0.017), higher level ADLs (LSDiff=0.265; P=0.156), simple praxis (LSDiff=0.077; P=0.043), and praxis items requiring visuo-spatial and memory skills (LSDiff=0.300; P=0.017). Conclusions:The addition of memantine to stable ChEI treatment was associated with significant improvements in grooming, conversing, and finding belongings. The factor analysis identified 4 subscales, and significant advantages of memantine+ChEI treatment over placebo+ChEI for basic ADLs, simple praxis, and praxis items requiring visuo-spatial and memory skills.