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 and physical frailty in people living with HIV. Design: Cross-sectional Structural Equation Modeling (SEM) of data from 824 older people living with HIV in Canada, participating in the Positive Brain Health Now study. Method: SEM was used to link observed variables, including comorbidity, polypharmacy, anticholinergic and sedative burden, to cognitive ability and two latent constructs - physical frailty and perceived cognitive deficits (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 (βstd = -0.21, p<0.05) and indirect effect on PCD (βstd = 0.16, p<0.01) and frailty (βstd = 0.06, p<0.01) through sedative burden. Sedative burden was directly associated with PCD (βstd = 0.18, p<0.01) and indirectly with frailty through PCD (βstd = 0.07, p<0.01). Comorbidity and polypharmacy exerted indirect effects on PCD and physical frailty through anticholinergic and sedative burden. The model fit the data well (CFI: 0.97, TLI: 0.94, RMSEA: 0.05, SRMR: 0.04). Conclusion: Anticholinergic and sedative burden function as a pathway through which polypharmacy and comorbidities influence physical frailty and perceived cognitive deficits. Reducing the use of anticholinergic and sedative medications could help prevent and manage cognitive impairment and frailty in older people living with HIV.