Effect of ageing on neurocognitive function by stage of HIV infection: evidence from the Multicenter AIDS Cohort Study

Abstract

Background: The demographics of the HIV epidemic in the USA have shifted towards older age. We aimed to establish the relationship between the processes of ageing and HIV infection in neurocognitive impairment.

Methods: With longitudinal data from the Multicenter AIDS Cohort Study, a long-term prospective cohort study of the natural and treated history of HIV infection among men who have sex with men in the USA, we examined the effect of ageing, HIV infection (by disease stage), and their interaction on five neurocognitive domains: information processing speed, executive function, episodic memory, working memory, and motor function. We controlled for duration of serostatus in a subanalysis, as well as comorbidities and other factors that affect cognition. Analyses were by linear mixed models for longitudinal data.

Findings: 5086 participants (47 886 visits) were included in the analytic sample (2278 HIV-seropositive participants contributed 20 477 visits and 2808 HIV-seronegative control participants contributed 27 409 visits). In an a-priori multivariate analysis with control variables including comorbidities and time since seroconversion, significant, direct negative effects of ageing were noted on all neurocognitive domains (p<0·0001 for all). Similar effects were noted for late-stage HIV disease progression on information processing speed (p=0·002), executive function (p<0·0001), motor function (p<0·0001), and working memory (p=0·001). Deleterious interaction effects were also noted in the domains of episodic memory (p=0·03) and motor function (p=0·02).

Interpretation: A greater than expected effect of ageing on episodic memory and motor function with advanced stages of HIV infection suggests that these two domains are most susceptible to the progression of neurocognitive impairment caused by ageing in individuals with HIV. This deficit pattern suggests differential damage to the hippocampus and basal ganglia (specifically nigrostriatal pathways). Older individuals with HIV infection should be targeted for regular screening for HIV-associate neurocognitive disorder, particularly with tests referable to the episodic memory and motor domains.

Funding: National Institute of Mental Health.

Figure 1. Plots of Adjusted Domain Scores and Fitted Regression Lines from the Multi-Variable Models for the Relationships Observed between Age on Episodic Memory and Motor Function According to Late CDC Disease Stage/AIDS Versus HIV Seronegative Status

This figure shows the adjusted domain scores together with the fitted regression lines for the effect of age in late stage HIV disease (AIDS) versus those with HIV-seronegative status from the multi-variable models for the Full Model/Full Sample Analysis and for the Full Model /Sub-Sample Analysis Adding Time since Seroconversion into the model. The AIDS and HIV-seronegative sub-samples were selected to display the results from the opposite poles of the HIV disease stage variable used here on the domains of episodic memory and motor function. In the model adding time since seroconversion, participants with AIDS (solid line) performed more poorly in older age than the HIV-seronegative control participants (broken line) in both domains. The lack of any pattern in the residual error scattergrams of both groups (aside from the downward trends consistent with the regression on age) supports the validity of the analytic models employed.