Bridging the gap: Efficacy of combined therapies for cognitive, behavioral, and functional outcomes in Alzheimer's disease - results from a systematic review and network meta-analysis

Abstract

BackgroundEvidence regarding efficacy of combined pharmaco- and non-pharmacotherapies and their comparative effectiveness for Alzheimer's disease (AD) is limited.ObjectiveTo estimate the comparative efficacy of pharmacotherapies, non-pharmacotherapies, and combined therapies for improving cognitive, behavioral, and functional outcomes in patients with AD.MethodsRelevant studies were identified from Medline via PubMed and Scopus databases (March 2021-December 2022). Randomized-controlled trials were eligible if they assessed the efficacy of pharmacotherapies, non-pharmacotherapies, or combined therapies in patients aged 60 years or older, and measuring cognitive, behavioral, or functional outcomes. A network meta-analysis was conducted to estimate relative treatment effects, and interventions were ranked using surface under the cumulative ranking (SUCRA) curve. Confidence in the findings was evaluated using the Confidence in Network Meta-Analysis (CINeMA) framework.ResultsA total of 153 randomized-controlled trials were analyzed. Compared to placebo/usual care, donepezil plus cognitive therapy and rivastigmine plus cognitive rehabilitation significantly improved Mini-Mental State Examination scores. Behavioral outcomes were improved by rivastigmine plus cognitive stimulation, brain stimulation plus exercise, and occupational therapy. Functional status improved significantly with rivastigmine plus cognitive stimulation and exercise. Based on SUCRA ranking, rivastigmine plus cognitive rehabilitation ranked highest for cognitive improvement (92.8%), brain stimulation plus exercise ranked highest for the behavioral outcome (93.1%), and rivastigmine plus cognitive stimulation ranked highest for functional improvement (94.1%).ConclusionsDonepezil plus cognitive therapy and rivastigmine plus cognitive rehabilitation were the most effective treatments for improving cognitive outcomes. Rivastigmine plus cognitive stimulation ranked highest for both behavioral and functional outcomes, while exercise remains an important strategy for supporting daily functioning in patients with AD.