Objective:

To compare the cognitive effects of multimodal lifestyle interventions (MMLIs) and monoclonal antibody (MAB) therapies in patients with mild cognitive impairment (MCI) and early Alzheimer’s disease (AD) using Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog) outcomes.

Background:

MMLIs, which combine exercise, diet, stress management, sleep, and cognitive training, and MAB therapies targeting amyloid-β pathology are both disease-modifying approaches. However, their relative clinical efficacy has not been systematically evaluated across trials using a common cognitive measure.

Design/Methods:

We reviewed randomized controlled trials (RCTs) through July 2025 that included either MMLIs or FDA-approved MABs (aducanumab, lecanemab, donanemab) and reported ADAS-Cog outcomes. Secondary endpoints included other cognitive, functional, imaging, and biomarker outcomes, as well as safety profiles.

Results:

Five MMLI RCTs reported ADAS-Cog improvements of 1.3 to 2.6 points, indicating measurable cognitive gains. Benefits were sustained beyond intervention in some trials and were accompanied by improvements in executive function, mood, gait speed, quality of life, and biomarkers (e.g., increased Aβ42/40 ratios, hippocampal volume growth, enhanced cerebral perfusion).
Three large Phase 3 RCTs of MABs demonstrated preservation of 1.4 to 1.5 points on ADAS-Cog relative to placebo, reflecting modest slowing of decline. While MABs achieved robust amyloid clearance, their clinical benefit was limited. Relative benefit analysis showed 27–32% preservation with MABs versus >200% benefit with MMLIs.

Conclusions:

MMLIs consistently improve cognition and confer broad health benefits, whereas MAB therapies robustly clear amyloid plaques but modestly preserve cognition. Future trials should directly compare and combine lifestyle and pharmacologic strategies. As with diabetes and cardiovascular disease, integrated treatment may provide the most effective approach for MCI and early AD.