Cognitive Functioning of Unaffected First-degree Relatives of Individuals With Late-onset Alzheimer's Disease: A Systematic Literature Review and Meta-analysis
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Published:2022-09-03
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ISSN:1040-7308
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Container-title:Neuropsychology Review
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language:en
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Short-container-title:Neuropsychol Rev
Author:
Ramos Ari AlexORCID, Galiano-Castillo NoeliaORCID, Machado LianaORCID
Abstract
AbstractFirst-degree relatives of individuals with late-onset Alzheimer's disease (LOAD) are at increased risk for developing dementia, yet the associations between family history of LOAD and cognitive dysfunction remain unclear. 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 = 4,086, mean age = 57.40, SD = 4.71) showed significantly inferior cognitive performance (Hedges’ g = -0.16; 95% CI, -0.25 to -0.08; p < .001) compared to controls (n = 2,388, mean age = 58.43, SD = 5.69). 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 ɛ4 carriership was associated with more significant dysfunction in cognition (g = -0.24; 95% CI, -0.38 to -0.11; p < .001) compared to non-carriers (g = -0.14; 95% CI, -0.28 to -0.01; p = .04). Cognitive test type was significantly associated with between-group differences, accounting for 65% (R23 = .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 ɛ4.
Funder
University of Otago Doctoral Scholarship University of Otago
Publisher
Springer Science and Business Media LLC
Subject
Neuropsychology and Physiological Psychology
Reference102 articles.
1. Abulafia, C., Duarte-Abritta, B., Villarreal, M. F., Ladron-de-Guevara, M. S., Garcia, C., Sequeyra, G., Sevlever, G., Fiorentini, L., Baer, K.-J., Gustafson, D. R., Vigo, D. E., & Guinjoan, S. M. (2017). Relationship between cognitive and sleep-wake variables in asymptomatic offspring of patients with late-onset Alzheimer's Disease. Frontiers in Aging Neuroscience, 9, Article 93. https://doi.org/10.3389/fnagi.2017.00093 2. Abulafia, C., Fiorentini, L., Loewenstein, D. A., Curiel-Cid, R., Sevlever, G., Nemeroff, C. B., Villarreal, M. F., Vigo, D. E., & Guinjoan, S. M. (2019a). Executive functioning in cognitively normal middle-aged offspring of late-onset Alzheimer’s disease patients. Journal of Psychiatric Research, 112, 23–29. https://doi.org/10.1016/j.jpsychires.2019.02.016 3. Abulafia, C., Loewenstein, D., Curiel-Cid, R., Duarte-Abritta, B., Sanchez, S. M., Vigo, D. E., Castro, M. N., Drucaroff, L. J., Vazquez, S., Sevlever, G., Nemeroff, C. B., Guinjoan, S. M., & Villarreal, M. F. (2019b). Brain Structural and Amyloid Correlates of Recovery From Semantic Interference in Cognitively Normal Individuals With or Without Family History of Late-Onset Alzheimer’s Disease. Journal of Neuropsychiatry and Clinical Neurosciences, 31(1), 25–36. https://doi.org/10.1176/appi.neuropsych.17120355 4. ALZGENE. (2010). Meta-analysis of all published AD association studies (case-control only) APOE E2/3/4. Retrieved 24 May 2022, from www.alzgene.org/meta.asp?geneID=83 5. Aschenbrenner, A. J., Balota, D. A., Gordon, B. A., Ratcliff, R., & Morris, J. C. (2016). A diffusion model analysis of episodic recognition in preclinical individuals with a family history for Alzheimer’s disease: The adult children study [Article]. Neuropsychology, 30(2), 225–238. https://doi.org/10.1037/neu0000222
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