Cognitive Intra-individual Variability in Cognitively Healthy APOE ε4 Carriers, Mild Cognitive Impairment, and Alzheimer’s Disease: a Meta-analysis

Abstract

Intra-individual variability (IIV) quantifies an individual’s scatter in performances across a test battery (dispersion) or across reaction times within a single task (consistency). No studies have meta-analyzed the cross-sectional IIV literature in those with mild cognitive impairment (MCI) and Alzheimer’s dementia (AD). An additional aim of this meta-analysis was to examine IIV in APOE ε4 + healthy control (HC) samples. A systematic search strategy was applied to six databases (Academic Search Complete, PsycINFO, MEDLINE, CINAHL Complete, ERIC, and ProQuest Dissertations & Theses) to identify studies comparing the extent of dispersion- and consistency-based cognitive IIV between clinical (MCI, AD) and HC samples. Thirty-five studies met the inclusion criteria for our random-effects cross-sectional meta-analysis. Hedges’ g was used to aggregate between-group effect sizes, with higher positive values indicating clinical > HC IIV. Meta-regression and subgroup-analyses were conducted to evaluate continuous and categorical moderator variables, respectively. Omnibus models yielded analogous moderate-strength, albeit heterogeneous, effects for dispersion and consistency (g = 0.65). Clinical severity was a robust moderator of dispersion (MCI = 0.47, AD = 1.16) and consistency (MCI = 0.51, AD = 1.31) effects. Supplemental analysis of APOE ε4 status in HCs revealed a nonsignificant trend of elevated overall (i.e., dispersion + consistency) IIV in APOE ε4 + vs. APOE ε4 − HC samples (g = 0.24). Cognitive IIV is sensitive to the presence of AD-related genetic risk as well as neurocognitive impairment across the neurocognitive disorder severity spectrum, with a graded-pattern of HC < MCI < AD samples.