Effects of age, HIV, and HIV-associated clinical factors on neuropsychological functioning and brain regional volume in HIV+ patients on effective treatment

Abstract

It is yet unclear if people infected with human immunodeficiency virus (HIV+) on stable, combined antiretroviral therapies (cARTs) decline with age at the same or greater rate than healthy people. In this study, we examined independent and interactive effects of HIV, age, and HIV-related clinical parameters on neuropsychological functioning and brain regional volume in a sizable group of Polish HIV+ men receiving cART. We also estimated the impact of nadir CD4 cell count, CD4 cell count during participation in the study, duration of HIV infection, or duration of cART along with age. Ninety-one HIV+ and 95 control (HIV−) volunteers ages 23–75 completed a battery of neuropsychological tests, and 54 HIV+ and 62 HIV− of these volunteers participated in a brain imaging assessment. Regional brain volume in the cortical and subcortical regions was measured using voxel-based morphometry. We have found that HIV and older age were independently related to lower attention, working memory, nonverbal fluency, and visuomotor dexterity. Older age but not HIV was associated with less volume in several cortical and subcortical brain regions. In the oldest HIV+ participants, age had a moderating effect on the relationship between the duration of cART and visuomotor performance, such as that older age decreased speed of visuomotor performance along with every year on cART. Such results may reflect the efficacy of cART in preventing HIV-associated brain damage. They also highlight the importance of monitoring neuropsychological functioning and brain structure in HIV+ patients. This is particularly important in older patients with long adherence to cART.Electronic supplementary materialThe online version of this article (10.1007/s13365-018-0679-4) contains supplementary material, which is available to authorized users.

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

“…Regression analysis also showed that older age was associated with poorer performance in both tests. However, no interaction effect was observed Gawron et al (2018) [ 35 ] Cross-sectional Age as continuous variable and HIV serostatus Standard 6 Test (raw score) No premature age effect Both HIV and age independently contributed to the lower performance in NP test results although their interaction effect was not observed Cysique et al (2011) [ 39 ] Cross-sectional Age as continuous variable and HIV serostatus Standard 6 Global impairment score and Frascati No premature age effect Both age and HIV status were independently associated in the expected direction to the global impairment score. However, their interaction effect was not clear.…”

“…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.…”

“…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.…”

Cognitive ageing is premature among a community sample of optimally treated people living with HIV

“…Studies that recruited unrepresentatively healthy HIV participants within their country (i.e. highly educated, stable on cART, with undetectable viral load and no neuropsychological confounds) did not observe premature cognitive ageing [33,34]. A Polish study [33] did not observe the premature cognitive ageing effect amongst 91 HIV‐positive and 95 HIV‐negative participants (age range: 23–75 years) who were recruited from an infectious disease hospital and received standard neuropsychological testing.…”

“…highly educated, stable on cART, with undetectable viral load and no neuropsychological confounds) did not observe premature cognitive ageing [33,34]. A Polish study [33] did not observe the premature cognitive ageing effect amongst 91 HIV‐positive and 95 HIV‐negative participants (age range: 23–75 years) who were recruited from an infectious disease hospital and received standard neuropsychological testing. All the participants in this study were males who were highly educated (≥12 years of education), and clinically stable (no active OI, active syphilis, current hepatitis C coinfection, alcohol or substance abuse, major psychiatric illnesses, liver or renal insufficiency, and had viral load < 60 copies/mL).…”