Cerebral Small Vessel Disease: Early-Life Antecedents and Long-Term Implications for the Brain, Aging, Stroke, and Dementia

Cerebral small vessel disease is common in older adults and increases the risk of stroke, cognitive impairment, and dementia. While often attributed to midlife vascular risk factors such as hypertension, factors from earlier in life may contribute to later small vessel disease risk. In this review, we summarize current evidence for early-life effects on small vessel disease, stroke and dementia focusing on prenatal nutrition, and cognitive ability, education, and socioeconomic status in childhood. We discuss possible reasons for these associations, including differences in brain resilience and reserve, access to cognitive, social, and economic resources, and health behaviors, and we consider the extent to which these associations are independent of vascular risk factors. Although early-life factors, particularly education, are major risk factors for Alzheimer disease, they are less established in small vessel disease or vascular cognitive impairment. We discuss current knowledge, gaps in knowledge, targets for future research, clinical practice, and policy change.