Stroke-Related Acceleration of Brain Atrophy Beyond Aging in the Framingham Study: Paired Pre and Post MRI Evidence and Cognitive Associations

Introduction: Stroke induces structural brain disruption, accelerating cognitive decline. Using data from the Framingham Heart Study (FHS), we sought to separate aging-only versus aging plus stroke atrophy rates and its cognitive correlates. Methods: We included cognitively intact FHS participants with first incident stroke. We include pre- and post-index MRIs in both stroke cases and matched controls (2:1), allowing us to estimate aging-only versus aging plus stroke atrophy rates. We computed annualized rates of change in brain volume metrics and cognitive decline, adjusting for relevant factors. Results: We included 45 stroke cases (67.8±10.3 years, 17(38%) female). Compared to controls, accelerated ipsilesional brain atrophy (adjusted Δ=-2.39 mm3/year, p<0.001) and white matter hyperintensity progression (adjusted Δ=0.71 mm3/year, p=0.003) were observed. Voxel-based analysis revealed maximal atrophy subcortically. Accelerated atrophy correlated with global cognition and executive function decline among stroke survivors but not controls. Discussion: This paired-MRI study provides preliminary evidence that stroke modestly accelerates ipsilesional atrophy, predominantly in subcortical regions plausibly linked to processing-speed decline. These findings are hypothesis-generating and require validation in larger prospective studies before firm conclusions can be drawn.