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In this well-designed case-cohort study of age-matched HIV-infected and -uninfected older adults with HIV from the MACS group, a measurable decline in cognitive function was seen in older infected patients. Five domains of cognition were measured and all were affected with increasing age compared to the uninfected controls. Older subjects with late-stage HIV-infection showed severe declines in the two domains of episodic memory and motor function. The authors recommend screening all older HIV-infected patients for HIV-associated neurocognitive disorder, with special focus on these two domains.