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An augmented aging process in brain white matter in HIV.

ABSTRACT: OBJECTIVE:HIV infection and aging are both associated with neurodegeneration. However, whether the aging process alone or other factors associated with advanced age account for the progression of neurodegeneration in the aging HIV-positive (HIV+) population remains unclear. METHODS:HIV+ (n?=?70) and HIV-negative (HIV-, n?=?34) participants underwent diffusion tensor imaging (DTI) and metrics of microstructural properties were extracted from regions of interest (ROIs). A support vector regression model was trained on two independent datasets of healthy adults across the adult life-span (n?=?765, Cam-CAN?=?588; UiO?=?177) to predict participant age from DTI metrics, and applied to the HIV dataset. Predicted brain age gap (BAG) was computed as the difference between predicted age and chronological age, and statistically compared between HIV groups. Regressions assessed the relationship between BAG and HIV severity/medical comorbidities. Finally, correlation analyses tested for associations between BAG and cognitive performance. RESULTS:BAG was significantly higher in the HIV+ group than the HIV- group F (1, 103)?=?12.408, p?=?.001). HIV RNA viral load was significantly associated with BAG, particularly in older HIV+ individuals (R2 ?=?0.29, F(7, 70)?=?2.66, p?=?.021). Further, BAG was negatively correlated with domain-level cognitive function (learning: r?=?-0.26, p?=?.008; memory: r?=?-0.21, p?=?.034). CONCLUSIONS:HIV infection is associated with augmented white matter aging, and greater brain aging is associated with worse cognitive performance in multiple domains.

SUBMITTER: Kuhn T

PROVIDER: S-EPMC5951745 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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An augmented aging process in brain white matter in HIV.

Kuhn Taylor T Kaufmann Tobias T Doan Nhat Trung NT Westlye Lars T LT Jones Jacob J Nunez Rodolfo A RA Bookheimer Susan Y SY Singer Elyse J EJ Hinkin Charles H CH Thames April D AD

Human brain mapping 20180227 6

<h4>Objective</h4>HIV infection and aging are both associated with neurodegeneration. However, whether the aging process alone or other factors associated with advanced age account for the progression of neurodegeneration in the aging HIV-positive (HIV+) population remains unclear.<h4>Methods</h4>HIV+ (n = 70) and HIV-negative (HIV-, n = 34) participants underwent diffusion tensor imaging (DTI) and metrics of microstructural properties were extracted from regions of interest (ROIs). A support ve ...[more]

PMID: 29488278

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Project description:Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia activity in various brain regions upon healthy aging and Alzheimer's disease (AD)-related pathology in both human and mouse samples. In purified microglia isolated from aging mouse brains, we found a profound gene expression pattern related to pro-inflammatory processes, phagocytosis, and lipid homeostasis. Particularly in white matter microglia of 24-month-old mice, abundant expression of phagocytic markers including Mac-2, Axl, CD16/32, Dectin1, CD11c, and CD36 was detected. Interestingly, in white matter of human brain tissue the first signs of inflammatory activity were already detected during middle age. Thus quantification of microglial proteins, such as CD68 (commonly associated with phagocytosis) and HLA-DR (associated with antigen presentation), in postmortem human white matter brain tissue showed an age-dependent increase in immunoreactivity already in middle-aged people (53.2 ± 2.0 years). This early inflammation was also detectable by non-invasive positron emission tomography imaging using [11C]-(R)-PK11195, a ligand that binds to activated microglia. Increased microglia activity was also prominently present in the white matter of human postmortem early-onset AD (EOAD) brain tissue. Interestingly, microglia activity in the white matter of late-onset AD (LOAD) CNS was similar to that of the aged clinically silent AD cases. These data indicate that microglia-induced neuroinflammation is predominant in the white matter of aging mice and humans as well as in EOAD brains. This white matter inflammation may contribute to the progression of neurodegeneration, and have prognostic value for detecting the onset and progression of aging and neurodegeneration.

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An augmented aging process in brain white matter in HIV.

Publications

An augmented aging process in brain white matter in HIV.

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