Vascular Contributions to Cognitive Impairment and Brain Health: Clinical Update and Mechanistic Considerations: A...

This scientific statement updates the first American Heart Association and American Stroke Association scientific statement published in 2011, which presented evidence for vascular contributions to cognitive impairment and dementia and positioned vascular risk factors as therapeutic targets in the causal pathway of neurodegenerative disorders. This updated scientific statement provides a synthesis of current knowledge, identifies knowledge gaps, and proposes directions for future research in vascular contributions to cognitive impairment and dementia. Age-related cognitive impairment is established as a multiple-cause process driven by interactions between vascular factors and the interconnected hallmarks of aging. Evidence from single-domain and multidomain interventions indicates that reducing vascular risk alone does not fully restore brain health, underscoring the need for complementary strategies that halt or reverse the vascular-driven acceleration of aging hallmarks. However, the inherent biological heterogeneity of aging and the dynamic time-dependent nature of age-related changes create significant knowledge gaps that hinder the identification of effective complementary therapeutic targets. Elucidating the multimechanistic origins of vascular contributions to cognitive impairment and dementia and time-appropriate interventions to complement vascular risk factor modification is vital to maintaining brain health and preserving cognitive function across the life span. Achieving this goal requires a deeper understanding of the time-varying mechanisms of cellular injury and repair in individuals susceptible, resistant, and resilient to vascular contributions to cognitive impairment and dementia. Circulating molecular factors hold promise as dynamic readouts of these mechanistic processes, thereby informing the timing and nature of targeted interventions. Until then, intensifying control of modifiable vascular risk factors remains the most effective strategy to preserve brain health.