Cognitive decline of aging is modulated by chronic inflammation and comorbidities. In people with HIV-infection (PWH) it may also be affected by HIV-induced inflammation, lifestyle and long-term effects of antiretroviral therapies (ART). The role of genetics in the susceptibility to HIV-associated neurocognitive disorders (HAND) is not fully understood. Here we explored the possible relations among variants in 3 genes involved in inflammation and neurodegenerative disorders (APOE: epsilon 2/epsilon 3/epsilon 4; HFE: H63D; C9ORF72: hexanucleotide expansions >= 9 repeats), cognitive/functional impairment (MiniMental State Examination MMSE, Clock Drawing Test CDT, Short Physical Performance Battery SPPB), comorbidities and HIV-related variables in a cohort of > 50 years old PWH (n = 60) with at least 10 years efficient ART. Patients with diabetes or hypertension showed significantly lower MMSE (p = .031) or SPPB (p = .010) scores, respectively, while no relations between HIV-related variables and cognitive/functional scores were observed. Patients with at least one APOE epsilon 3 allele had higher CDT scores (p = .019), APOE epsilon 2/epsilon 4 patients showing the lowest scores in all tests. Patients with HFE-H63D variant showed more frequently hypertriglyceridemia (p = .023) and those harboring C9ORF72 expansions > 9 repeats had higher CD4(+)-cell counts (p = .032) and CD4% (p = .041). Multiple linear regression analysis computed to verify possible associations among cognitive/functional scores and all variables further suggested positive association between higher CDT scores and the presence of at least one APOE epsilon 3 allele (2,2; 95% CI [0,03 0,8]; p = .037), independent of other variables, although the model did not reach the statistical significance (p = .14). These data suggest that in PWH on efficient ART cognitive abilities and physical performances may be partly associated with comorbidities and genetic background. However, further analyses are needed to establish whether they could be also dependent and influenced by comorbidities and genetic background.
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