Brief Report: Body Mass Index and Cognitive Function Among HIV-1-Infected Individuals in China, India, and Nigeria.

BACKGROUND: Risk of cognitive impairment is increased among persons with high or low body mass index in HIV- and HIV+ populations in resource-rich settings. We examined this association among HIV+ patients in 3 resource-limited settings. METHODS: This secondary analysis included data of 761 HIV+ volunteers pooled from 3 prospective cohort studies conducted in China (n = 404; 53%), India (n = 200; 26%), and Nigeria (n = 157; 21%). World Health Organization (WHO) weight classifications were based on body mass index. T scores, adjusted for demographics and practice effects, were derived from a 7-domain neuropsychological battery. Neurocognitive impairment (NCI) was defined as global deficit score of ≥0.5. RESULTS: Overall, prevalence of NCI at baseline was 27.7% (similar across all cohorts). The overweight/obese and underweight constituted 37.3% and 15.5% of the total participants, respectively. In a multivariable logistic regression of pooled longitudinal data, adjusting for clinical and demographic variables, the odds of global NCI were 38% higher among the overweight/obese as compared to normal weight participants [odds ratio: 1.38 (95% confidence interval: 1.1 to 1.72); P = 0.005]. Similarly, the odds of global NCI were 39% higher among the underweight as compared to normal weight participants [odds ratio: 1.39 (95% confidence interval: 1.03 to 1.87); P = 0.029]. CONCLUSIONS: NCI among HIV-1-infected patients was more prevalent in both overweight/obese and underweight than normal weight individuals in 3 resource-limited settings, confirming observations in resource-rich settings. Mechanisms underlying these associations are unclear but likely differ for underweight and overweight persons.

Lower CSF Aß is Associated with HAND in HIV-Infected Adults with a Family History of Dementia.

BACKGROUND: Both family history of dementia (FHD) and lower levels of Aß-42 are indepentently associated with worse neurocognitive functioning in HIVinfected patients. OBJECTIVE: To examine the relationships between cerebrospinal fluid (CSF) Aß-42 and FHD with HIV-associated neurocognitive disorders (HAND). METHODS: One hundred eighty-three HIV+ adults underwent neuropsychological and neuromedical assessments, and determination of CSF Aß-42 concentration and FHD (defined as a self-reported first or second-degree relative with a dementia diagnosis). Univariate analyses and multivariable logistic regressions were used. RESULTS: FHD was not associated with HAND (p = 0.24); however, CSF Aß-42 levels were lower (p = 0.03) in the HAND group, but were not associated with FHD (p = 0.89). Multivariable models showed a main effect of CSF Aß-42 (p = 0.03) and a trend-level (p = 0.06) interaction between FHD and CSF Aß-42, such that lower CSF Aß-42 was associated with HAND in those with FHD (p < 0.01) compared to those without FHD (p = 0.83). An analysis in those with follow-up data showed that higher baseline CSF Aß-42 was associated with lower risk of neurocognitive decline (p = 0.02). While we did not find an FHD X CSF Aß-42 interaction (p = 0.83), when analyses were stratified by FHD, lower CSF Aß-42 was associated at the trend-level with neurocognitive decline in the FHD group (p = 0.08) compared to the no FHD group (p = 0.15). CONCLUSION: FHD moderates the relationship between of CSF Aß-42 and HAND. The findings highlight the complexities in interpreting the relationships between biomarkers of age-related neurodegeneration and HAND.

Asymptomatic HIV-associated neurocognitive impairment increases risk for symptomatic decline.

OBJECTIVE: While HIV-associated neurocognitive disorders (HAND) remain prevalent despite combination antiretroviral therapy (CART), the clinical relevance of asymptomatic neurocognitive impairment (ANI), the most common HAND diagnosis, remains unclear. We investigated whether HIV-infected persons with ANI were more likely than those who were neurocognitively normal (NCN) to experience a decline in everyday functioning (symptomatic decline). METHODS: A total of 347 human participants from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) cohort were NCN (n = 226) or had ANI (n = 121) at baseline. Neurocognitive assessments occurred approximately every 6 months, with median (interquartile range) follow-up of 45.2 (28.7-63.7) months. Symptomatic decline was based on self-report (SR) or objective, performance-based (PB) problems in everyday functioning. Proportional hazards modeling was used to generate risk ratios for progression to symptomatic HAND after adjusting for baseline and time-dependent covariates, including CD4+ T-lymphocyte count (CD4), virologic suppression, CART, and mood. RESULTS: The ANI group had a shorter time to symptomatic HAND than the NCN after adjusting for baseline predictors: adjusted risk ratios for symptomatic HAND were 2.0 (confidence interval [CI] 1.1-3.6; p = 0.02) for SR, 5.8 (CI 3.2-10.7; p < 0.0001) for PB, and 3.2 (CI 2.0-5.0; p < 0.0001) for either SR or PB. Current CD4 and depression were significant time-dependent covariates, but antiretroviral regimen, virologic suppression, and substance abuse or dependence were not. CONCLUSIONS: This longitudinal study demonstrates that ANI conveys a 2-fold to 6-fold increase in risk for earlier development of symptomatic HAND, supporting the prognostic value of the ANI diagnosis in clinical settings. Identifying those at highest risk for symptomatic decline may offer an opportunity to modify treatment to delay progression.

HIV-associated neurocognitive disorders in sub-Saharan Africa: a pilot study in Cameroon.

BACKGROUND: The disease burden of human immunodeficiency virus (HIV)--acquired immunodeficiency syndrome (AIDS) is highest in sub-Saharan Africa but there are few studies on the associated neurocognitive disorders in this region. The objectives of this study were to determine whether Western neuropsychological (NP) methods are appropriate for use in Cameroon, and to evaluate cognitive function in a sample of HIV-infected adults. METHODS: We used a battery of 19 NP measures in a cross-sectional study with 44 HIV+ adults and 44 demographically matched HIV- controls, to explore the validity of these NP measures in Cameroon, and evaluate the effect of viral infection on seven cognitive ability domains. RESULTS: In this pilot study, the global mean z-score on the NP battery showed worse overall cognition in the HIV+ individuals. Significantly lower performance was seen in the HIV+ sample on tests of executive function, speed of information processing, working memory, and psychomotor speed. HIV+ participants with AIDS performed worse than those with less advanced HIV disease. CONCLUSIONS: Similar to findings in Western cohorts, our results in Cameroon suggest that HIV infection, particularly in advanced stages, is associated with worse performance on standardized, Western neurocognitive tests. The tests used here appear to be promising for studying NeuroAIDS in sub-Saharan Africa.