M J R Aliberti, J E Paiva
Dementia is a growing global health challenge driven by population aging and unequal exposure to biological, behavioral, social, and environmental determinants across the life course. Existing evidence demonstrates that these factors accumulate and interact from fetal development through old age, shaping cognitive reserve, brain resilience, and vulnerability to neurodegeneration. However, current models rarely integrate these multilevel influences in a structured manner. This study proposes a comprehensive multilevel conceptual framework for dementia that maps determinants across seven levels (biological, behavioral, psychological, individual, family, community, and national) and across all life stages, from prenatal development to late life. The framework is organized along a bi-axial structure that aligns levels of influence with temporal windows of exposure, allowing a clear visualization of how early-life and midlife factors contribute to dementia in older age. Two illustrative pathways are explored in depth. The first describes the development of cognitive reserve, highlighting the roles of maternal health, education, health literacy, social engagement, and lifelong learning in delaying symptom onset despite neuropathological burden. The second focuses on cerebrovascular integrity, demonstrating how prenatal vascular development, lifestyle behaviors, and cardiovascular risk profiles influence vascular cognitive impairment and interact with Alzheimer-related pathologies. The framework distinguishes modifiable population-level determinants, such as education quality and public health policies, from more fixed biological factors, thereby identifying critical intervention points. By integrating life-course epidemiology with multilevel determinants, this model provides a structured approach for understanding dementia etiology and supports the development of targeted prevention strategies across individual, community, and societal domains.