Disentangling the Effects of Comorbidity and Polypharmacy on Cognitive Function and Physical Frailty in Individuals With HIV

Objective: To estimate the extent to which comorbidity, polypharmacy, and anticholinergic/sedative burden interrelate to influence cognitive ability, perceived cognitive deficits (PCD), and physical frailty in people living with HIV. Design: Cross-sectional Structural Equation Modeling of data from 824 older people living with HIV in Canada, participating in the Positive Brain Health Now study. Method: Structural Equation Modeling was used to link observed variables, including comorbidity, polypharmacy, anticholinergic, and sedative burden, to cognitive ability and 2 latent constructs-physical frailty and PCD. The model was adjusted for age, sex, education, nadir CD4, duration of HIV, and symptoms of anxiety/depression. Maximum Likelihood with Robust standard errors and bootstrapping were used to test the robustness and significance of the model's indirect effects. Results: Anticholinergic burden had a direct significant negative relationship with cognitive ability (beta std = -0.21, P < 0.05) and indirect effect on PCD (beta std = 0.16, P < 0.01) and frailty (beta std = 0.06, P < 0.01) through sedative burden. Sedative burden was directly associated with PCD (beta std = 0.18, P < 0.01) and indirectly with frailty through PCD (beta std = 0.07, P < 0.01). Comorbidity and polypharmacy exerted indirect effects on PCD and physical frailty through anticholinergic and sedative burden. The model fits the data well (CFI: 0.97, TLI: 0.94, RMSEA: 0.05, SRMR: 0.04). Conclusions: Anticholinergic and sedative burden function as a pathway through which polypharmacy and comorbidities influence physical frailty and PCD. Reducing the use of anticholinergic and sedative medications could help prevent and manage cognitive impairment and frailty in older people living with HIV.