Delayed phase in rest-activity rhythms is associated with inflammation and cognitive performance in people living with HIV

Abstract

Study Objectives People living with HIV (PLWH) are at increased risks for chronic inflammation and cognitive impairment. Circadian disruption has been linked to both outcomes in the general populations, but its health relevance in PLWH remains understudied. Methods We analyzed data from 87 PLWH in the UK Biobank who had valid wrist actigraphy recordings and no dementia diagnosis. The phase of circadian rest-activity rhythms, a marker that represents the peak activity timing, was extracted using uniform phase empirical mode decomposition. The associations between circadian phase and two outcomes - cognitive performance (reaction time) and systemic inflammation (C-reactive protein [CRP]) - were assessed using age- and sex-adjusted linear regressions. To correct for the right skewness, the reaction time and CRP were log-transformed. Additionally, potential outliers in both outcomes were examined and excluded using a 3-SD criterion. Results A delayed circadian phase was significantly associated with poorer cognitive performance and elevated CRP levels, with 0.18-0.21 SD increases in the outcomes for each 1-SD delay in circadian phase (both p =. 02). To better put this into the context of aging, the effects of 1-SD delayed circadian phase correspond to the effects of approximately 6-7 years of aging. Exploratory analyses showed no significant association between circadian amplitude and either outcome. Conclusions In PLWH, delayed circadian phase is associated with modest but significant worse cognitive performance in reaction time and an increase in systemic inflammation. These findings highlight the potential role of circadian function in cognitive and inflammatory outcomes among PLWH and warrant further investigation into interventions targeting circadian alignment in this population. Statement of Significance This study investigated the associations between the phase of rest-activity rhythms with cognitive performance and systemic inflammation in people living with HIV (PLWH). Our findings reveal that a delayed phase in rest-activity rhythms is significantly associated with increased systemic inflammation and poorer cognitive performance, with 0.18-0.21 SD increases in the outcomes for each 1-SD delay in circadian phase, which corresponds to the effects of approximately 6-7 years of aging. These results suggest that circadian disruptions such as delayed rest-activity rhythms may exacerbate health issues in PLWH, highlighting the need for further research.