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Introduction: HIV-associated neurocognitive disorders (HAND) are a spectrum of cognitive impairments occurring in chronic HIV infection. HAND are highly prevalent in sub-Saharan Africa (SSA), despite combination antiretroviral therapy (cART). Older people appear to be at increased risk. Cognitive reserve (CR), shown to be protective in neurodegenerative dementias, may also protect against HAND.Aim: To evaluate the association of CR and risk of HAND in an older cART-treated population in SSA.Methods: This was a cross-sectional observational study undertaken at hospital outpatient clinics in Mbeya, Southwest Tanzania. HIV-positive participants aged ≥ 50 years and established on cART underwent diagnostic assessment by operationalised AAN criteria. Assessment included neuropsychological test battery, functional assessment, informant history and depression screen. HIV-negative control participants were attendees of other chronic disease clinics who completed neuropsychological assessments to provide normative scores for HAND diagnosis. CR was measured using the Cognitive Reserve Index (CRI) and other proxy measures including years of formal education.Results: Lower total Cognitive Reserve Index (CRI) score, lack of formal education, unemployment and low-skilled manual work were associated with increased risk of HAND. Lower CRI score and lack of formal education were independent risk factors for HAND but HIV disease severity measures were not.Conclusion: Higher total CRI score and formal education appeared to be protective for HAND, in this cohort. These are potentially modifiable factors, though education may be difficult to modify in later life. Cognitive reserve may be more important than HIV-disease control in risk of HAND in older people with treated HIV.

Objectives: HIV-associated neurocognitive disorders (HAND) are highly prevalent in those ageing with treated HIV. High-income country data suggest that vascular risk factors (VRFs) may be stronger predictors of HAND than HIV-disease severity. This hypothesis is yet to be examined in the population ageing with HIV in sub-Saharan Africa. Our aim was to evaluate relationships of VRFs, vascular end organ damage and HAND in individuals aged ≥50 receiving HIV treatment in TanzaniaDesign: Cross sectional observational study, with systematic sampling.Methods: c-ART-treated individuals were assessed for HAND by consensus criteria. Prevalence of VRFs (hypertension, hypercholesterolemia, obesity, diabetes, and smoking) and end organ damage markers (prior myocardial infarction, stroke, left ventricular hypertrophy, estimated-glomerular filtration rate, ankle-brachial pressure index, retinal arteriovenous ratio) were measured. Independent associations of VRFs, end organ damage and HAND were examined by multivariable logistic regression.Results: Data were available for 153 individuals (median age 56, 67.3% female). HAND was highly prevalent (66.7%, 25.5% symptomatic) despite well-managed HIV (70.5% virally suppressed). Vascular risk factors included hypertension (34%), obesity (10.5%), hypercholesterolemia (33.3%), diabetes (5.3%) and current smoking (4.6%). End organ damage prevalence ranged from 1.3% (prior MI) to 12.5% (LVH). Measured VRFs and end organ damage were not independently associated with HAND, although there was a significant association with lower diastolic BP (p 0.030, OR 0.969 (0.943-0.997).Conclusion: The overall lack of association between vascular risk factors, vascular end organ damage and HAND suggests vascular risk factors are not major drivers of HAND in this setting. Further studies should explore alternative aetiologies such as chronic inflammation.