Cross-sectional and longitudinal associations of smoking behavior with measures of subclinical vascular brain injury and microvascular function

The National Heart, Lung, and Blood Institute awarded Vassar College $222,750 under the Cardiovascular Diseases Research program (CFDA 93.837) on August 1, 2026, to examine cross-sectional and longitudinal associations of smoking behavior with subclinical vascular brain injury and microvascular function.

The award funds research leveraging the longitudinal, community-based Framingham Heart Study to investigate how cigarette smoking and cessation affect vascular brain injury and peripheral and microvascular function. Aim 1 will relate smoking status, intensity, and cessation duration to cross-sectional and longitudinal changes in MRI-based measures of vascular brain injury, including fractional anisotropy, free water, and peak width of skeletonized mean diffusivity. Aim 2 will assess whether smoking behavior and cessation patterns are associated with peripheral vascular and microvascular remodeling and whether putative effects operate through shared hemodynamic pathways.

This is a Project Grant awarded through the NIH peer-review process. The period of performance runs from August 1, 2026 through July 31, 2028. Work is performed in Poughkeepsie, New York.

Abstract

Cigarette smoking remains one of the most pervasive and preventable causes of vascular disease worldwide. Although smoking prevalence has declined, nearly 50 million adults in the united states continue to smoke, and millions more are former smokers who retain residual vascular risk. Growing evidence indicates that vascular injury occurs years before the onset of clinical symptoms and that early subclinical changes in brain structure and function may represent modifiable pathways to cognitive impairment and dementia. Within the vascular contributions to cognitive impairment and dementia framework, cigarette smoking is a potent vascular toxin that promotes endothelial dysfunction, large artery stiffening, and impaired microvascular tone, which are hallmarks of vascular aging. However, the mechanisms linking smoking exposure to subclinical cerebrovascular injury remain poorly characterized, and the degree to which these effects are reversible with cessation is unknown. We recently showed that measures of central arterial hemodynamics vary with smoking behavior and improve with longer cessation. Building off this work during my K01 award period, we will leverage the longitudinal, community-based framingham heart study to examine how cigarette smoking and cessation affect subclinical vascular brain injury as well as peripheral vascular and microvascular function and if these putative effects are through shared hemodynamic pathways. Aim 1 will relate smoking status, intensity, and cessation duration to cross-sectional and longitudinal changes in MRI-based measures of vascular brain injury (fractional anisotropy, free water, and peak width of skeletonized mean diffusivity); and aim 2 will assess whether smoking behavior and cessation patterns are associated with peripheral vascular and microvascular remodeling and dysfunction (via flow-mediated dilation, digital peripheral arterial tonometry, and brachial flow velocities measures). By integrating cerebrovascular, peripheral vascular, and microvascular measures within a single, well- characterized cohort, this project will identify systemic vascular coupling mechanisms that connect smoking to subclinical brain injury. The results will clarify whether vascular injury processes are reversible with cessation, generate preliminary data for future R01 studies, and advance nhlbi's mission to uncover tractable vascular pathways linking cardiovascular health to cognitive decline and dementia.