Advanced Brain Age and Chronic Poststroke Aphasia Severity

Chronic post-stroke language impairment is typically worse in older individuals or those with large stroke lesions. However, there is unexplained variance that likely depends on intact tissue beyond the lesion. Brain age is an emerging concept which is partially independent from chronological age. Advanced brain age is associated with cognitive decline in healthy older adults, therefore we aimed to investigate the relationship with stroke aphasia. We hypothesized that advanced brain age is a significant factor associated with chronic post-stroke language impairments, above and beyond chronological age and lesion characteristics.This cohort study retrospectively evaluated participants from the POLAR clinical trial (NCT03416738), recruited through local advertisement in South Carolina (US). Primary inclusion criteria were left-hemisphere stroke and chronic aphasia (≥12 months post-stroke). Participants completed baseline behavioral testing including the Western Aphasia Battery-Revised (WAB-R), Philadelphia Naming Test (PNT), Pyramids and Palm Trees Test (PPTT), and the Wechsler Adult Intelligence Scale matrices subtest, before completing 6-weeks of language therapy. The PNT was repeated 1-month post-therapy. We leveraged modern neuroimaging techniques to estimate brain age and computed a proportional difference between chronological age and estimated brain age. Multiple linear regression models were used to evaluate the relationship between proportional brain age difference and behavior.Participants (N=93, 58 males, 35 females, average age=61 years) had estimated brain ages ranging from 14-years younger to 23-years older than chronological age. Advanced brain age predicted performance on semantic tasks (PPTT) and language tasks (WAB-R). For participants with advanced brain aging (n=47), treatment gains (improvement on the PNT) were independently predicted by proportional brain age difference (T=-2.0474,p=0.0468, 9% of variance explained).Through the application of modern neuroimaging techniques, advanced brain aging was associated with aphasia severity and performance on semantic tasks. Notably, therapy outcome scores were also associated with proportional brain age difference, albeit only among participants with advanced brain aging. These findings corroborate the importance of brain age as a determinant of post-stroke recovery and underscore the importance of personalized health factors in determining recovery trajectories, which should be considered during the planning or implementation of therapeutic interventions.