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In this quantitative review, we provide the first meta-analysis on the cognitive profile of unaffected first-degree blood relatives of LOAD-affected individuals compared to controls without a family history of LOAD. A systematic literature search was conducted in PsycINFO, PubMed \/MEDLINE, and Scopus. We fitted a three-level structural equation modeling meta-analysis to control for non-independent effect sizes. Heterogeneity and risk of publication bias were also investigated. Thirty-four studies enabled us to estimate 218 effect sizes across several cognitive domains. Overall, first-degree relatives (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20094,086, mean age\u2009=\u200957.40,\n                    <jats:italic>SD<\/jats:italic>\n                    \u2009=\u20094.71) showed significantly inferior cognitive performance (Hedges\u2019\n                    <jats:italic>g<\/jats:italic>\n                    \u2009=\u2009-0.16; 95% CI, -0.25 to -0.08;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u2009.001) compared to controls (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20092,388, mean age\u2009=\u200958.43,\n                    <jats:italic>SD<\/jats:italic>\n                    \u2009=\u20095.69). Specifically, controls outperformed first-degree relatives in language, visuospatial and verbal long-term memory, executive functions, verbal short-term memory, and verbal IQ. Among the first-degree relatives, APOE \u025b4 carriership was associated with more significant dysfunction in cognition (\n                    <jats:italic>g<\/jats:italic>\n                    \u2009=\u2009-0.24; 95% CI, -0.38 to -0.11;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u2009.001) compared to non-carriers (\n                    <jats:italic>g<\/jats:italic>\n                    \u2009=\u2009-0.14; 95% CI, -0.28 to -0.01;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.04). Cognitive test type was significantly associated with between-group differences, accounting for 65% (\n                    <jats:italic>R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sub>3<\/jats:sub>\n                    \u2009=\u2009.6499) of the effect size heterogeneity in the fitted regression model. No evidence of publication bias was found. The current findings provide support for mild but robust cognitive dysfunction in first-degree relatives of LOAD-affected individuals that appears to be moderated by cognitive domain, cognitive test type, and APOE \u025b4.\n                  <\/jats:p>","DOI":"10.1007\/s11065-022-09555-2","type":"journal-article","created":{"date-parts":[[2022,9,3]],"date-time":"2022-09-03T13:02:31Z","timestamp":1662210151000},"page":"659-674","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Cognitive Functioning of Unaffected First-degree Relatives of Individuals With Late-onset Alzheimer's Disease: A Systematic Literature Review and Meta-analysis"],"prefix":"10.1007","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7117-9728","authenticated-orcid":false,"given":"Ari Alex","family":"Ramos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6825-4213","authenticated-orcid":false,"given":"Noelia","family":"Galiano-Castillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0856-3831","authenticated-orcid":false,"given":"Liana","family":"Machado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,9,3]]},"reference":[{"key":"9555_CR1","doi-asserted-by":"publisher","unstructured":"Abulafia, C., Duarte-Abritta, B., Villarreal, M. 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