Background:  With current treatments, persons with HIV survive longer, raising the possibility that there may be additive or interactive effects on the brain. We assessed the relation of aging and HIV infection (HIV⁺) on cerebral blood flow using arterial spin labeling magnetic resonance imaging (ASL-MRI) within the visual cortex. We hypothesized that older HIV⁺ patients would have more abnormalities in cerebral blood flow due to ongoing inflammation and oxidative stress.

Methods: CBF measurements were obtained from 17 seronegative controls and 18 HIV⁺ subjects at 3 Tesla (General Electric) scanner using ASL-MRI. Subjects were further subdivided into either older (> 50 years old (yo)) or younger (< 35 yo) subgroups. cerebral blood flow were recorded for a resting condition and a functional paradigm consisting of a checkerboard stimulus flashing at 8Hz. A manually drawn visual cortex region-of-interest was chosen based on previous MRI aging studies. An analysis of variance (ANOVA) was performed that assessed the effects of age, HIV serostatus, and their interaction on both resting and functional cerebral blood flow changes with subsequent paired t tests utilized.

Results:  HIV⁺ subjects were predominantly male (56%); were taking ART (78%); and had undetectable viral loads (72%). The breakdown of groups consisted of 9 younger seronegative controls (mean 27 years old), 8 older seronegative controls (mean 54 years), 10 younger HIV⁺ (mean 27 years), and 8 older HIV⁺ (mean 55 years). An ANOVA revealed that both age (p = 0.03) and HIV⁺ status (p = 0.04) affected baseline cerebral blood flow. Subsequent paired t test comparisons demonstrated that older HIV⁺ subjects had a greater decline in baseline cerebral blood flow than either younger seronegative controls (p = 0.02) or older seronegative controls (p = 0.04). An ANOVA also revealed an effect of age (p = 0.03) on functional cerebral blood flow changes. Older HIV⁺ subjects also had greater functional cerebral blood flow changes than any other all group (p = 0.01) on paired t test comparisons. There was no correlation between nadir CD4, current CD4, or HIV RNA levels and cerebral blood flow measures within HIV⁺ subjects.

Conclusions:  There may be an additive effect aging and HIV on brain function with the greatest changes in cerebral blood flow occurring within older HIV⁺ subjects. Observed differences do not correlate with existing markers of HIV disease and could reflect ongoing inflammation and oxidative stress that continue to occur despite relatively good virologic control by ART. Cerebral blood flow measurements may therefore act as a non-invasive surrogate biomarker for assessing effects of HIV in the aging brain.