Cognitive Functioning of Unaffected First‑degree Relatives of Individuals With Late‑onset Alzheimer's Disease: A Systematic Literature Review and Meta‑analysis
Metadatos
Mostrar el registro completo del ítemEditorial
Springer
Materia
Alzheimer disease APOE ɛ4 Cognitive dysfunction Neuropsychological tests Risk factors Family history
Fecha
2022-09-03Referencia bibliográfica
Ramos, A.A., Galiano-Castillo, N. & Machado, L. Cognitive Functioning of Unaffected First-degree Relatives of Individuals With Late-onset Alzheimer's Disease: A Systematic Literature Review and Meta-analysis. Neuropsychol Rev (2022). [https://doi.org/10.1007/s11065-022-09555-2]
Patrocinador
University of Otago Doctoral ScholarshipResumen
First-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% (R2
3 = .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.