Is Reversible Cognitive Frailty a Unified Syndrome? Insights from a Bifactor Exploratory Structural Equation Model in People with HIV

Reversible cognitive frailty, defined as co-occurring self-reported cognitive difficulty and prefrailty or frailty, may mark an early window for intervention in people with HIV. However, whether this construct reflects a unified syndrome or independent co-occurring processes remains unclear. We tested whether a general reversible cognitive frailty factor underlies shared variance between physical frailty and self-reported cognitive difficulty indicators using a bifactor exploratory structural equation modelling (bifactor-ESEM) framework in the Positive Brain Health Now cohort. Participants (N = 824; mean age 53.0 years; 63.6% ≥50 years; 84.7% male) completed the Perceived Deficits Questionnaire, modified Fried-based frailty indicators, and RAND-36 health surveys. Four prespecified measurement models were compared. The bifactor-ESEM showed a superior fit (Comparative Fit Index = 1.000, Tucker-Lewis Index = 0.999, Root Mean Square Error of Approximation = 0.010, Standardized Root Mean Square Residual = 0.009) and identified a prominent general factor spanning cognitive and physical indicators, alongside smaller cognitive-specific and physical-specific factors. Reliability and dimensionality indices supported a shared but not strictly unidimensional construct (general Explained Common Variance = 0.496; Omega Hierarchical = 0.590). The latent structure was stable across age groups with configural, metric, and partial scalar invariance. In adjusted regressions, the general factor was strongly related to poorer health-related quality of life, as indicated by RAND-36 Mental Component Summary and Physical Component Summary scores (b = -9.58 and b = -6.94, both p < .001), with domain-specific factors adding incremental variance. Sensitivity analyses using adjusted composites and partial least squares structural equation modelling produced convergent results. Reversible cognitive frailty represents a unified but multidimensional syndrome. Integrated screening combining cognitive complaints, exhaustion, and mobility indicators can identify at-risk individuals for interventions targeting both shared and domain-specific vulnerabilities.