Abstract
Frailty, broadly defined as diminished physiological resilience to stressors, is increasingly recognized as a significant determinant of outcomes in acute ischemic stroke (AIS). While physical frailty is characterized by functional decline and vulnerability, brain frailty refers to reduced neurophysiological reserve, reflected in imaging markers such as cortical atrophy, leukoaraiosis, and chronic infarcts. These conditions may coexist but represent distinct constructs, each influencing post-stroke recovery. This review synthesizes eight key studies examining the impact of brain frailty on AIS outcomes following reperfusion therapies, including intravenous thrombolysis and endovascular thrombectomy. Evidence from post hoc analyses of major trials and prospective cohorts shows that brain frailty is independently associated with greater initial stroke severity, poorer functional recovery, and worse cognitive outcomes. Furthermore, both physical and brain frailty mediate the association between age and recovery, reinforcing the importance of biological age over chronological age in prognostication. The limitations of conventional tools like the modified Rankin Scale (mRS) are discussed, as mRS may not capture the etiology or reversibility of prestroke disability. Treatment decisions based solely on age or mRS can lead to under-treatment of older or frail individuals, despite evidence showing selected patients can benefit from reperfusion therapy. Integrating frailty assessments, both clinical and imaging-based, into AIS management may enhance patient selection, promote treatment equity, and optimize outcomes. Future protocols should adopt a nuanced approach that considers biological age and cerebral functional reserve alongside traditional metrics like infarct volume and location.
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