Infratentorial cerebral microbleeds and brain age gap in stroke patients: a cross-sectional neuroimaging study

Stroke survivors often face long-term cognitive and motor deficits. Brain age gap (BAG), the difference between chronological age and age estimated based on MRI data, has emerged as a biomarker for neurodegeneration. While prior work links BAG to stroke outcomes, the relationship between BAG and cerebral microbleeds (CMBs), particularly infratentorial CMBs common in hypertensive arteriopathy, remains unclear. The sensorimotor network (SMN) is highly susceptible to both direct and remote injury after stroke and is structurally and functionally interconnected with infratentorial regions via pathways such as the corticospinal tract. Vascular disruption in the cerebellum or brainstem may therefore have downstream effects on supratentorial SMN regions, making this network a biologically relevant target for investigating BAG-CMB relationships. We analyzed data from 1725 stroke patients in the Stroke Outcomes Optimization Projects. Two trained raters manually counted infratentorial CMBs on susceptibility-weighted MRI images (SWI), while BAG was computed using the automated volBrain BrainStructureAges pipeline on T1-weighted images. Spearman correlations tested associations between CMB count and regional BAG in 14 a priori brain regions of interest (ROI) and results were conditioned for age, sex, race, white matter hyperintensities, hypertension, type of scanner, and total ischemic lesion volume. Infratentorial CMB count was positively correlated with BAG in 9/14 sensorimotor regions: right precentral gyrus medial segment (r (213) = 0.186, p = 0.007), left precentral gyrus medial segment (r (213) = 0.186, p = 0.007), right postcentral gyrus medial segment (r (213) = 0.202, p = 0.004), right postcentral gyrus (r (213) = 0.202, p = 0.004), left postcentral gyrus (r (213) = 0.161, p = 0.021), right parietal operculum (r (213) = 0.198, p = 0.004), right central operculum (r (213) = 0.195, p = 0.005), right precentral gyrus (r (213) = 0.184, p = 0.008), and left postcentral gyrus medial segment (r (213) = 0.192, p = 0.006). Our findings suggest that infratentorial microvascular injury is associated with accelerated aging in functionally connected motor cortices. This supports a network-level model of stroke-related brain aging, with implications for predicting sensorimotor outcomes. BAG may serve as a sensitive marker for cerebrovascular injury and guide targeted rehabilitation efforts.