People living with HIV (PLWHIV) and declining cognition exhibit hyperinsulinemia, as well as abnormal cholesterol and lipid metabolism compared with PLWHIV who have normal, stable cognition, indicating that interventions to restore brain insulin sensitivity may help preserve these patients’ cognitive performance, according to a study published in Neurology.
This study was designed to identify associations between metabolic status and insulin sensitivity and declining cognition in PLWHIV, using data obtained from participants in the Central Nervous System HIV Anti-Retroviral Therapy Effects Research Study (CHARTER). Data from patients with comorbid psychiatric conditions, diabetic and cholesterol-lowering medications, and current recreational drug use were excluded from analysis. Cognitive performance was longitudinally and serially assessed to group patients into declining cognition or stably normal categories.
Patients with declining cognition had elevated insulin levels compared with stably normal patients (95.5±34.6 vs 60.3±25.2 pmol/L) as well as higher c-peptide levels (2.8 ±1.6 vs 1.5 ±0.74 ng/mL). Insulin was shown to be the only predictor of cognitive status (P =.003) in a multivariable logistic regression model that included body mass index and protease inhibitor and was associated with increased odds of cognitive decline (odds ratio =1.44; 95% CI, 1.14–1.83). Insulin was also shown to be the only predictor in a separate multivariable logistic regression model that included both current CD4+ T cells and insulin as predictors (odds ratio 1.43; 95% CI, 1.13–1.80; P =.003 per 10-unit increase). These results were confirmed by similar results from the data analysis of a second cohort of PLWHIV.
Although patients in the declining cognition group exhibited elevated plasma c-peptide levels and baseline hyperinsulinemia, these individuals had normal c-peptide/insulin ratios, which suggested that increased insulin production but normal insulin clearance. These associations between hyperinsulinemia and worsening cognition were further supported by data showing low high-density lipoprotein, high low-density lipoprotein/high-density lipoprotein ratios, and elevated cholesterol/high-density lipoprotein ratios in the worsening cognition group compared with the stably normal group.
Limitations to this study included restriction of data generalizability by the clinical and demographic characteristics used to match patients, limited sample size, and a lack of women in the discovery cohort.
Study investigators concluded, “Our data suggest that hyperinsulinemia and abnormalities in lipid and cholesterol metabolism are important factors associated with worsening cognition in HIV-infected patients. Interventions that restore brain insulin sensitivity could be useful therapies for HIV-associated impairments in cognition.”
Khuder SS, Chen S, Letendre S, et al. Impaired insulin sensitivity is associated with worsening cognition in HIV-infected patients [published online February 20, 2019]. Neurology. doi: 10.1212/WNL.0000000000007125