Evidence that intrinsic brain connectivity moderates the association between gait and neurocognitive function in people living with HIV

Globally, a substantial proportion of the approximately 40 million people living with HIV (PLWH) experience some degree of HIV-associated brain injury (HABI), which is often linked to accentuated or accelerated aging in this clinical population. We set out to test the hypothesis that gait speed is associated with cognitive deficits in middle-aged PLWH in a low-middle income (LMIC) setting, and that this is comparable to what is seen in much older healthy adults. In addition, we sought to identify, as a potential marker of HABI, intrinsic functional brain connectivity abnormalities that moderate the association between gait and cognitive function in PLWH. Thirty-nine participants (17 HIV + and 22 HIV-, mean age = 39 +-8.99 years) were recruited from a community health centre in Cape Town. Bivariate and multiple linear regression models compared PLWH and controls with respect to associations between gait speed and neurocognitive domain scores, with relations between these factors and functional connectivity of seven resting state networks assessed within a multivariate regression modelling framework. We found that slower gait speed in PLWH was associated with lower global neurocognitive scores (t = -3.12; p < 0.008), and that this association was replicated in a large public domain cohort of healthy older adults. Moreover, intrinsic connectivity of the frontoparietal network in PLWH was a significant predictor of both gait speed and executive function, a finding that may implicate impaired compensatory mechanisms in this patient population. Our findings underscore the potential utility of gait tests in screening for HABI in PLWH in low resourced settings.