Genetic Factors, Brain Atrophy, and Response to Rehabilitation Therapy After Stroke. (February 2022)

• Record Type: Journal Article
• Authors: Cramer, Steven C.; See, Jill; Liu, Brent; Edwardson, Matthew; Wang, Ximing; Radom-Aizik, Shlomit; Haddad, Fadia; Shahbaba, Babak; Wolf, Steven L.; Dromerick, Alexander W.; Winstein, Carolee J.
• Is Part Of: Neurorehabilitation & neural repair. Volume 36:Number 2(2022)
• Page Start: 131
• Page End: 139
• Publication Date: 2022-02
• Subjects: stroke -- rehabilitation -- imaging -- genetics -- biomarker -- endophenotype; Nervous system -- Diseases -- Patients -- Rehabilitation -- Periodicals; Brain damage -- Patients -- Rehabilitation -- Periodicals; Spinal cord -- Wounds and injuries -- Patients -- Rehabilitation -- Periodicals; Nervous system -- Regeneration -- Periodicals; Neuroplasticity -- Periodicals; 616.804305
• DOI: 10.1177/15459683211062899
• Languages: English
• ISSNs: 1545-9683

Abstract

Objective: Patients show substantial differences in response to rehabilitation therapy after stroke. We hypothesized that specific genetic profiles might explain some of this variance and, secondarily, that genetic factors are related to cerebral atrophy post-stroke. Methods: The phase 3 ICARE study examined response to motor rehabilitation therapies. In 216 ICARE enrollees, DNA was analyzed for presence of the BDNF val 66 met and the ApoE ε4 polymorphism. The relationship of polymorphism status to 12-month change in motor status (Wolf Motor Function Test, WMFT) was examined. Neuroimaging data were also evaluated (n=127). Results: Subjects were 61±13 years old (mean±SD) and enrolled 43±22 days post-stroke; 19.7% were BDNF val 66 met carriers and 29.8% ApoE ε4 carriers. Carrier status for each polymorphism was not associated with WMFT, either at baseline or over 12 months of follow-up. Neuroimaging, acquired 5±11 days post-stroke, showed that BDNF val 66 met polymorphism carriers had a 1.34-greater degree of cerebral atrophy compared to non-carriers (P=.01). Post hoc analysis found that age of stroke onset was 4.6 years younger in subjects with the ApoE ε4 polymorphism (P=.02). Conclusion: Neither the val 66 met BDNF nor ApoE ε4 polymorphism explained inter-subject differences in response to rehabilitation therapy. The BDNF val 66 met polymorphism was associated with cerebral atrophy at baseline, echoing findings in healthy subjects, and suggesting an endophenotype. The ApoE ε4 polymorphism was associated with younger age at stroke onset, echoing findings in Alzheimer's disease and suggesting a common biology. Genetic associations provide insights useful to understanding the biology of outcomes after stroke.