Cai_2026_Front.Psychiatry_17_1840039

INTRODUCTION: Alzheimer's disease (AD) is associated with progressive cognitive decline, functional impairment, and reduced quality of life. Although pharmacological treatments such as cholinesterase inhibitors and memantine are commonly used, their clinical benefits remain limited and heterogeneous. Cognitive stimulation therapy (CST) may provide additional benefits when combined with standard pharmacotherapy. This randomized controlled trial (RCT) aimed to evaluate the clinical efficacy of modified CST combined with standard drug therapy on cognitive function, activities of daily living, and quality of life in patients with mild-to-moderate AD and to explore key predictors of CST efficacy using a multivariate regression model. METHODS: This evaluator-blinded randomized controlled trial enrolled 80 patients with mild-to-moderate Alzheimer's disease (AD), who were randomly assigned in a 1:1 ratio to either the modified CST plus standard pharmacotherapy group (study group, n = 40) or the standard pharmacotherapy-alone group (control group, n = 40).The modified CST program comprised 14 weekly 45-minute sessions. The primary endpoint was the change in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) score from baseline to post-intervention. Secondary measures included the Activities of Daily Living (ADL) scale and the Quality of Life in Alzheimer's disease (QOL-AD) questionnaire. Data were analyzed using an intention-to-treat (ITT) approach. Independent predictors of treatment efficacy were identified using a two-stage screening strategy (univariate screening and stepwise regression). RESULTS: A total of 75 patients completed the study, and 80 were included in the ITT analysis. After 14 weeks of intervention, baseline-adjusted ANCOVA showed that the study group had significantly better post-intervention ADAS-Cog scores than the control group. The adjusted mean difference in ADAS-Cog score was -3.28 points (95% CI: -3.72 to -2.83; P < 0.001), favoring the study group. Significant baseline-adjusted between-group differences were also observed for ADL (adjusted mean difference = -4.93, 95% CI: -8.39 to -1.47; P = 0.006) and QOL-AD (adjusted mean difference = 2.69, 95% CI: 1.01 to 4.37; P = 0.002), both favoring the study group. Higher years of education (beta = -0.54, P < 0.001), regular physical activity (beta = -0.28, P = 0.003), higher baseline Mini-Mental State Examination (MMSE) scores (beta = -0.22, P = 0.001), and active hobbies (beta = -0.20, P = 0.002) were significant independent predictors of CST efficacy. DISCUSSION: Modified CST combined with medication significantly delays cognitive decline and improves QOL-AD in patients with mild-to-moderate AD. Educational attainment, lifestyle factors, and cognitive reserve are key determinants of CST efficacy. Relevant institutions should develop targeted enhancement protocols for patients with lower educational levels or insufficient cognitive reserves when implementing CST. TRIAL REGISTRATION: Chinese Clinical Trial Registry, identifier ChiCTR2600118654, https://www.chictr.org.cn.