Analysis of 38,414 older adults reveals that accumulating modifiable risk factors—including hypertension, diabetes, smoking, depression, and hearing loss—directly correlates with accelerated brain aging. Each additional risk factor increased odds of white matter damage, brain infarcts, and critically, hippocampal atrophy, which emerged as the primary pathway linking lifestyle risks to cognitive decline. The hippocampus, essential for memory formation, showed the strongest mediating effect between cumulative risk burden and declining global cognition, delayed recall, and semantic fluency. This finding challenges the traditional approach of targeting individual risk factors in isolation. Instead, it suggests that cardiovascular health, sensory function, mental health, and education collectively determine brain resilience through shared neurobiological pathways. The dose-response relationship supports aggressive multidomain prevention strategies, potentially offering greater neuroprotective benefits than addressing risks individually. However, this cross-sectional analysis from the National Alzheimer's Coordinating Center cannot establish causation, and the preprint awaits peer review before results are confirmed. The research represents an important step toward understanding how modifiable lifestyle factors compound to influence brain aging, though longitudinal studies are needed to validate the proposed causal mechanisms.