Immunosenescence and its impact on ischemic stroke risk and outcomes in older adults: a systematic review

Background: Age is a major risk factor for ischemic stroke (IS), with immunosenescence-age-related immune system dysfunction - contributing to worse outcomes. Immunosenescence impairs immune responses, heightens inflammation, and increases susceptibility to infections, all of which affect stroke prognosis. This review investigates the association between immunosenescence, immune cell dysfunction, and IS risk and outcomes. Methods: A systematic review was conducted to identify cohort studies examining immunosenescence in IS patients aged 60 and above. Databases PubMed and Embase were searched up to 10 August 2024. Studies were included if they analyzed immune cell markers or inflammatory markers in relation to IS risk or outcomes. A total of 11 studies met the inclusion criteria. Results: Elevated inflammatory markers such as interleukin (IL)-6, high-sensitivity C-reactive protein (hs-CRP), and Th17 cells were significantly associated with poorer stroke outcomes. Studies indicated an imbalance between pro-inflammatory Th17 cells and regulatory T cells (Treg) post-stroke. Higher neutrophil-to-lymphocyte ratio (NLR) and alterations in B-cell subsets were also observed in older stroke patients, further contributing to the inflammatory response. These immune dysregulations were linked to increased mortality and poor recovery. Conclusion: Immunosenescence plays a crucial role in IS pathogenesis and recovery, with chronic inflammation and immune dysfunction exacerbating stroke outcomes in older adults. Targeting immune markers, particularly IL-6 and the Th17/Treg imbalance, may offer new therapeutic approaches to improve stroke prognosis in aging populations. Further research is needed to develop interventions that address immunosenescence in IS. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024583142.