A systematic analysis of twelve randomized controlled trials reveals the emerging evidence for combining multidomain lifestyle modifications with targeted supplementation for Alzheimer's prevention. The reviewed studies integrated 2-7 lifestyle domains—spanning exercise, cognitive training, nutrition guidance, and cardiovascular management—with compounds including omega-3 fatty acids, tramiprosate, vitamin D, and epigallocatechin gallate. Seven trials focused on prodromal Alzheimer's or mild cognitive impairment populations.
This combination approach represents a logical evolution from single-intervention studies that have yielded inconsistent results. The multidomain strategy acknowledges Alzheimer's complex etiology involving neuroinflammation, vascular dysfunction, and metabolic dysregulation. Previous landmark trials like FINGER demonstrated lifestyle interventions alone can preserve cognition in at-risk populations, while supplement research has been plagued by mixed outcomes when studied in isolation.
The precision prevention concept—tailoring interventions to individual risk profiles and disease stages—could optimize treatment efficacy. However, the heterogeneity across these twelve trials in terms of intervention components, durations, and outcome measures limits definitive conclusions. The field requires larger, standardized trials to determine which combination protocols deliver clinically meaningful cognitive protection for specific at-risk populations.
