PT  - JOURNAL ARTICLE
AU  - Natalie Busby
AU  - Janina Wilmskoetter
AU  - Ezequiel Gleichgerrcht
AU  - Chris Rorden
AU  - Rebecca Roth
AU  - Roger Newman-Norlund
AU  - Argye Elizabeth Hillis
AU  - Simon S. Keller
AU  - Christophe de Bezenac
AU  - Sigfus Kristinsson
AU  - Julius Fridriksson
AU  - Leonardo Bonilha
TI  - Advanced Brain Age and Chronic Poststroke Aphasia Severity
AID  - 10.1212/WNL.0000000000201693
DP  - 2023 Mar 14
TA  - Neurology
PG  - e1166--e1176
VI  - 100
IP  - 11
4099  - http://n.neurology.org/content/100/11/e1166.short
4100  - http://n.neurology.org/content/100/11/e1166.full
SO  - Neurology2023 Mar 14; 100
AB  - Background and Objectives Chronic poststroke 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 chronologic 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 poststroke language impairments, above and beyond chronologic age, and lesion characteristics.Methods This cohort study retrospectively evaluated participants from the Predicting Outcomes of Language Rehabilitation in Aphasia clinical trial (NCT03416738), recruited through local advertisement in South Carolina (US). Primary inclusion criteria were left hemisphere stroke and chronic aphasia (≥12 months after 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 Wechsler Adult Intelligence Scale Matrices subtest, before completing 6 weeks of language therapy. The PNT was repeated 1 month after therapy. We leveraged modern neuroimaging techniques to estimate brain age and computed a proportional difference between chronologic age and estimated brain age. Multiple linear regression models were used to evaluate the relationship between proportional brain age difference (PBAD) and behavior.Results Participants (N = 93, 58 males and 35 females, average age = 61 years) had estimated brain ages ranging from 14 years younger to 23 years older than chronologic 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 PBAD (T = −2.0474, p = 0.0468, 9% of variance explained).Discussion 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 PBAD, albeit only among participants with advanced brain aging. These findings corroborate the importance of brain age as a determinant of poststroke 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.TE=echo time; TI=inversion time; PBAD=proportional brain age difference; PNT=Philadelphia Naming Test; PPTT=Pyramids and Palm Trees Test; POLAR=Predicting Outcomes of Language Rehabilitation in Aphasia; TR=repetition time; WAB-AQ=Western Aphasia Battery–Aphasia Quotient; WAB-R=Western Aphasia Battery–Revised; WAIS=Wechsler Adult Intelligence Scale