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Historically, older patients have shown a higher risk of HIV-1-associated dementia (HIVD). The objective of this study was to evaluate the association of aging with HIVD and minor cognitive motor disorders (MCMDs) during the late-highly active antiretroviral therapy (HAART) era and to analyze characteristics, predictive factors, and survival of older HIV-1-infected individuals affected by these disorders. A nested longitudinal study was designed for a cohort of HIV-1-infected individuals with neurological diseases. Multiple logistic regression and Cox regression for survival were employed. From 2000 to 2003, 195 patients with HIVD (53%) or MCMD (47%) were enrolled. The cumulative prevalence of these two disorders was 21%, with an increasing rate for calendar year (p0.001). Previous antiretroviral exposure occurred in 46% of patients. Mean CD4(+) cell count and plasma HIV-1 RNA were 144 cells/microl and 4.5 log10 copies/ml, respectively. The mean age was 44 years (SD, 9.9), with 35% of patients aged 20-39 years (I), 45% aged 40-49 years (II), and 20% aged/=50 years (III). Among drug-naive patients, the prevalence of HIVD progressively increased in older subjects: 7.2% (I), 15.3% (II), and 27.3% (III) (p0.001), whereas no significant increase in HIVD with older age was observed in drug-treated subjects. Older age was independently associated with an increased risk of HIVD (odds ratio, 6.44; 95% confidence interval, 2.82-14.69) in naive but not in experienced individuals, but had no significant effect on survival. No significant effect of age was observed for MCMD. We conclude that in our cohort, HAART seems to alter the relationship between aging and HIVD, conferring a neuroprotective effect to older patients. These results may have significant implications for the clinical management of the older HIV population.