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Emerging evidence indicates that specific genetic variants may affect the susceptibility to cognitive impairment in individual patients. In this systematic review we summarize the evidence for genetic variants on cognitive outcomes following brain insults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic search was conducted in PubMed, Embase, PsycINFO, bioRxiv, medRxiv, reference lists, and ClinicalTrials.gov to identify studies published before June 14, 2023, reporting associations between genetic variants and cognitive outcomes following brain insults. Only studies conducted in humans and published in English were included. A broad definition of brain insults was applied, with a primary focus on stroke, traumatic brain injury (TBI), and brain tumors. All articles underwent bias assessment using the JBI critical appraisal tools.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of the 121 studies included, 80 (66%) were rated as low risk of bias. The\n                      <jats:italic>APOE<\/jats:italic>\n                      gene was investigated in 56% of TBI studies, 52% of stroke studies, and 43% of studies on other brain injuries. Of the 74 studies on\n                      <jats:italic>APOE<\/jats:italic>\n                      , 50 (68%) focused on the\n                      <jats:italic>\u03b5<\/jats:italic>\n                      4 allele, with 39 studies (87%) reporting associations between the\n                      <jats:italic>\u03b5<\/jats:italic>\n                      4 allele and worse cognitive outcomes. The\n                      <jats:italic>BDNF<\/jats:italic>\n                      rs6265 polymorphism was examined in 18 studies, 15 of which reported significant effects on cognitive outcomes. However, the direction of these effects was inconsistent, with seven studies linking the G allele and seven the A allele to worse cognitive outcomes. For the\n                      <jats:italic>COMT<\/jats:italic>\n                      rs4680 polymorphism, nine out of 12 studies reported worsened cognitive outcomes linked to the G allele, while several reported a protective association for the A allele. Injury\u2010 and population\u2010specific patterns were not consistent.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This systematic review suggests that\u00a0\n                      <jats:italic>APOE\u2010<\/jats:italic>\n                      \u03b54\u00a0and potentially\u00a0the G allele of\n                      <jats:italic>COMT<\/jats:italic>\n                      rs4680 are associated with poor cognitive outcomes following brain insults. The type of brain injury does not appear to influence whether genetic variants predispose to favorable or unfavorable cognitive outcomes. Future research may benefit from focusing on\u00a0these markers, particularly in larger datasets, to validate these findings.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71173","type":"journal-article","created":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T03:03:53Z","timestamp":1767236633000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic Risk Factors for Poor Cognitive Outcome Following Brain Insult\u2014A Systematic Review"],"prefix":"10.1002","volume":"16","author":[{"given":"Tora","family":"Dun\u00e5s","sequence":"first","affiliation":[{"name":"Department of Clinical Neuroscience, Institute of Neuroscience and Physiology Sahlgrenska Academy, University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Leiss","sequence":"additional","affiliation":[{"name":"Department of Clinical 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