Abstract
Regional neuron loss following stroke can result in remote brain changes due to diaschisis and secondary brain atrophy. Whole brain changes post-stroke can be captured by the predicted brain age difference (brain-PAD), a neuroimaging-derived biomarker of global brain health previously associated with poorer chronic stroke outcomes. We hypothesized that greater lesion damage would be longitudinally associated with worsening brain-PAD during subacute stroke, and conversely, that poorer baseline brain-PAD would be associated with enlarged lesion damage. We prospectively collected MRIs from 47 stroke patients across three sites within 3 weeks (baseline) and at 3 months (follow-up) post-stroke. Predicted brain age was estimated via a pretrained ridge regression model using 77 morphological features. Brain-PAD was calculated as predicted age minus chronological age. Robust linear mixed effects regression models were used to examine relationships between infarct volume and brain-PAD, adjusting for age, sex, time, and intracranial volume at baseline. Larger baseline infarct volume was associated with accelerated brain aging at 3 months (β=0.87, p=0.023). Conversely, larger baseline brain-PAD predicted larger increase in infarct volume at 3 months (β=0.02, p=0.009). These findings reveal a bidirectional relationship between focal stroke damage and global brain health during the subacute period, underscoring the importance of assessing both.