Abstract
<title>Abstract</title> <p>Background Alzheimer's disease (AD) has become a major global public health crisis, with > 99% failure rate of disease-modifying therapies in phase III trials. Late initiation of intervention is the core issue. Approximately 40% of dementia cases are preventable through risk factor intervention, and AD pathology begins 20–30 years before clinical symptoms. Evidence from 2024 identifies ages 18–39 as a critical prevention window. Objective To systematically synthesize evidence on life-course AD prevention, construct a "Cognitive Fortress" theoretical framework, and develop community-based assessment tools and intervention pathways. Methods Systematic searches of PubMed, Cochrane, and Web of Science (inception to March 2026) yielded 90 included studies (18 RCTs, 52 cohorts, 20 systematic reviews). Quality was assessed using PRISMA, RoB 2.0, ROBINS-I, and AMSTAR-2. Evidence levels followed OCEBM 2011 criteria. Results ① Risk factors across four life stages were identified: early life (< 18y) low education (Level I); young adulthood (18-39y) hypertension, obesity, smoking/TBI, inflammatory markers, hearing loss (Level II); midlife (40-65y) hypertension, type 2 diabetes (Level I); late life (> 65y) hearing loss, depression (Level I). ② The four-line "Cognitive Fortress" framework was constructed: Line 1 Cognitive Reserve (early life), Line 2 Risk Surveillance (young adulthood), Line 3 Neuroprotection (midlife), Line 4 Compensatory Mechanisms (late life). ③ A 10-item risk scale and three-tier intervention pathway were developed. Conclusions AD prevention must transcend the "geriatric disease" mindset. A life-course, multi-stage intervention strategy can effectively delay or prevent clinical AD onset. The four-line framework provides actionable theoretical guidance for community-based AD prevention.</p>