Abstract Introduction Sleep EEG is a promising tool to measure brain aging in vulnerable populations such as people with HIV, who are high risk of brain aging due to co-morbidities, increased inflammation, and antiretroviral neurotoxicity. Our lab previously developed a machine learning model that estimates age from sleep EEG (brain age, BA), which reliably predicts chronological age (CA) in healthy adults. The difference between BA and CA, the brain age index (BAI), independently predicts mortality, and is increased by cardiovascular co-morbidities. Here, we assessed BAI in HIV+ compared to matched HIV- adults. Methods Sleep EEGs from 43 treated HIV+ adults were gathered and matched to controls (HIV-, n=284) by age, gender, race, alcoholism, smoking and substance use history. We compared BAI between groups and used additional causal interference methods to ensure robustness. Individual EEG features that underlie BA prediction were also compared. We performed a sub-analysis of BAI between HIV+ with or without a history of AIDS. Results After matching, mean CA of HIV+ vs HIV- adults were 49 and 48 years, respectively (n.s.). The mean HIV+ BAI was 3.04 years higher than HIV- (4.4 vs 1.4 yr; p=0.048). We found consistent and significant results with alternative causal inference methods. Several EEG features predictive of BA were different in the HIV+ and HIV- cohorts. Most notably, non-REM stage 2 sleep (N2) delta power (1-4Hz) was decreased in HIV+ vs. HIV- adults, while theta (4-8Hz) and alpha (8-12Hz) power were increased. Those with AIDS (n=19, BAI=4.40) did not have significantly different BAI than HIV+ without AIDS (n=23, BAI=5.22). HIV+ subjects had higher rates of insomnia (56% vs 29%, p<0.001), obstructive apnea (47% vs 30%, p=0.03), depression (49% vs 23%, p<0.001), and bipolar disorder (19% vs 4%, p<0.001). Conclusion HIV+ individuals on ART have excess sleep-EEG based brain age compared to matched controls. This excess brain age is partially due to reduction in delta power during N2, suggesting decreased sleep depth. These results suggest sleep EEG could be a valuable brain aging biomarker for the HIV population. Support This research is supported by the Harvard Center for AIDS Research HU CFAR NIH/NIAID 5P30AI060354-16.
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