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More HIV-infected individuals are living longer; however, how their brain function is affected by aging is not well understood. One hundred twenty-two men (56 seronegative control [SN] subjects, 37 HIV subjects with normal cognition [HIV+NC], 29 with HIV-associated neurocognitive disorder [HAND]) performed neuropsychological tests and had acceptable functional magnetic resonance imaging scans at 3 Tesla during tasks with increasing attentional load. With older age, SN and HIV+NC subjects showed increased activation in the left posterior (reserve, "bottom-up") attention network for low attentional-load tasks, and further increased activation in the left posterior and anterior ("top-down") attention network on intermediate (HIV+NC only) and high attentional-load tasks. HAND subjects had only age-dependent decreases in activation. Age-dependent changes in brain activation differed between the 3 groups, primarily in the left frontal regions (despite similar brain atrophy). HIV and aging act synergistically or interactively to exacerbate brain activation abnormalities in different brain regions, suggestive of a neuroadaptive mechanism in the attention network to compensate for declined neural efficiency. While the SN and HIV+NC subjects compensated for their declining attention with age by using reserve and "top-down" attentional networks, older HAND subjects were unable to compensate which resulted in cognitive decline., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Highly active antiretroviral therapy (HAART) has increased life expectancy among HIV-infected individuals, and by 2015, at least half of all HIV-infected individuals will be over 50 years of age. Neurodegenerative processes associated with aging may be facilitated by HIV-1 infection, resulting in premature brain aging. This review will highlight brain abnormalities in HIV patients in the setting of aging, focusing on recent neuroimaging studies of the structural, physiological, functional and neurochemical changes. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy studies performed during the pre-HAART era or on antiretroviral-naive subjects suggest an accelerated aging process, while those on HAART-treated subjects suggest premature brain atrophy. Diffusion tensor imaging studies yielded conflicting findings on the relationship between HIV and age in neuroasymptomatic individuals. Functional MRI studies found evidence of premature or accelerated aging processes in the brains of HIV subjects. Lastly, many age-related illnesses such as diabetes, stroke, and depression, as well as comorbid substance abuse, may further exacerbate the aging process in the HIV-infected brain, leading to premature or accelerated age-related brain changes. Given the different pathologic or physiologic changes in the brain assessed by the different neuroimaging techniques, using a multimodal approach in longitudinal follow-up studies is recommended for future studies.