Xie_2026_J.Alzheimers.Dis__13872877261471921

BackgroundMild cognitive impairment (MCI) represents a critical window for both pharmacological therapies and non-pharmacological interventions to delay cognitive decline.ObjectiveTo evaluate whether combining pharmacotherapy with multicomponent behavioral interventions enhances outcomes relative to behavioral interventions alone.MethodsThe sample included people with MCI (pwMCI) of any etiology who completed the HABIT Healthy Action to Benefit Independence & Thinking((a)) program. Baseline pharmacotherapy (acetylcholinesterase inhibitor and/or glutamate regulators) use was dichotomized (yes/no). Multivariate linear mixed-effects models examined changes from baseline in care partner-reported everyday functional skills, quality of life, self-efficacy, anxiety, depression, and HABIT compliance at post-intervention, 6 months, and 12 months, adjusting for baseline cognitive impairment severity and relevant demographic covariates.ResultsAmong 1074 pwMCI, 413 (38.5%) were receiving pharmacotherapy at baseline. Pharmacotherapy use was more prevalent among White than non-White participants (39.4% versus 23.3%, p = 0.01). At baseline, pharmacotherapy users had more severe cognitive impairment and lower utilization of rehabilitation strategies (all p < 0.05). Both groups demonstrated significant improvements across all outcomes at post-intervention. During follow-up (mean score change compared to baseline), pharmacotherapy users showed greater increases in HABIT compliance at 6 months (3.2 versus 2.0) and 12 months (2.1 versus 1.4). In contrast, by 12 months, pharmacotherapy users experienced greater worsening of everyday functional skills related to memory (-2.1 versus -1.3) and executive function (-5.8 versus-3.7).ConclusionspwMCI undergoing pharmacotherapy entered the HABIT program with more advanced cognitive impairment. The pharmacotherapy was not associated with greater intervention-related benefit or attenuation of long-term cognitive decline.