Cross-sectional associations of amyloid burden with semantic cognition in older adults without dementia: A systematic review and meta-analysis

Previous research suggests the presence of subtle semantic decline in early stages of Alzheimer's disease. This study investigated associations between amyloid burden, a biomarker for Alzheimer's disease, and tasks of semantic impairment in older individuals without dementia. A systematic search in MEDLINE, PsycINFO, and Embase yielded 3691 peer-reviewed articles excluding duplicates. After screening, 41 studies with overall 7495 participants were included in the meta-analysis and quality assessment. The overall weighted effect size of the association between larger amyloid burden and larger semantic impairment was 0.10 (95% CI [-0.03; 0.22], p = 0.128) for picture naming, 0.19 (95% CI [0.11; 0.27], p < 0.001) for semantic fluency, 0.15 (95% CI [-0.15; 0.45], p = 0.326) for vocabulary, and 0.10 (95% CI [-0.14; 0.35], p = 0.405; 2 studies) for WAIS Information. Risk of bias was highest regarding comparability, as effect sizes were often not calculated on covariate-adjusted statistics. The relevance of the indicated amyloid-related decline in semantic fluency for research and clinical applications is likely negligible due to the effect's small magnitude. Future research should develop more sensitive metrics of semantic fluency to optimize its use for early detection of Alzheimer's disease-related cognitive impairment.