HIV and age underlie specific patterns of brain abnormalities and cognitive changes in high functioning patients.

Abstract

Objective: Findings on the influence of age and HIV on brain and cognition remain equivocal, particularly in aviremic subjects without other age or HIV-related comorbidities. We aimed to (a) examine the effect of HIV status and age on structural brain measurements and cognition, and (b) apply the machine learning technique to identify brain morphometric and cognitive features that are most discriminative between aviremic subjects with HIV on stable combination antiretroviral therapy (cART) and healthy controls. Method: Fifty-three HIV-seropositive patients and 62 healthy controls underwent neuropsychological testing (executive functions, attention, memory, learning, psychomotor speed, fluency) and volumetric MRI scans. Voxel-based morphometry, ANCOVAs, machine learning, and multivariate regression were conducted to determine the between group differences in terms of relationship of HIV status, age, and their interaction on neurocognitive and structural brain measures. Results: Volume and gray matter (GM) thickness of the caudate, parahippocampus, insula, and inferior frontal gyrus were smaller in seropositive subjects in comparison with healthy controls (HC). They also performed worse in complex attention and cognitive fluency tasks. Support vector machine (SVM) analysis revealed that the best between-groups classification accuracy was obtained based on cognitive scores encompassing complex attention and psychomotor speed, as well as volumetric measures of white matter and total gray matter; third, fourth, and lateral ventricles; amygdala; caudate; and putamen. Both voxel-based morphometry (VBM) and regression analysis yielded that HIV and aging independently increase brain vulnerability and cognitive worsening. Conclusion: Patients with HIV on effective cART demonstrate smaller volumetric measures and worse cognitive functioning relative to seronegative individuals. There is no interaction between HIV infection and aging.

Is There Any Evidence of Premature, Accentuated and Accelerated Aging Effects on Neurocognition in People Living with HIV? A Systematic Review

“…Age was the only primary predictor in all studies, but in eight studies, age was investigated as a co-primary exposure along with a HIV-related variable such as duration of HIV infection [37] or a non-HIV related factor such as education [46] and alcohol use [47]. Neurocognition was also the sole primary outcome of interest in all but five studies [29,30,35,36,48], which also identified the effect of age on changes in neuroimaging.…”

“…The highest prevalence rate of HAND was found in a study where a large proportion (81%) of HIV + participants had substance use disorders [64]. Four out of eight studies [36,37,39,53] classified HAND clinical sub-categories, with ANI being the most prevalent (range: 53%-74%) in three studies, while MND was the predominant classification in one study (55%) [39]. Four of the studies compared HAND prevalence between age groups [37,58,62,64].…”

“…The majority of the studies were conducted in the US while two studies originated from the UK [29,30], Italy [31,32], China [33,34], and Poland [35,36], and one was carried out in Japan [37], Brazil [38], and Australia [39]. No study was conducted in low-income countries.…”

“…Twenty eight studies excluded participants with a major confounding condition for HAND as delineated using in the Frascati Criteria [13] such as major neurological and psychiatric disorders, current substance abuse and history of head trauma with loss of consciousness more than 30 min. Six studies [29,30,36,40,43,44] included men who have sex with men (MSM) participants only, and three [29,30,40] of these recruited only Caucasian participants. Two studies [35,46] included only male participants.…”

“…Two studies [35,46] included only male participants. Two British studies [29,30] and two Polish studies [35,36] enrolled solely virally suppressed HIV + participants (plasma HIVRNA < 50cp/mL). One study [31] included only formally diagnosed HAND cases and compared the distribution of young and old age groups among mild and severe cases of HAND.…”