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Diana De Ronchi, MD; Irma Faranca, MD; Domenico Berardi, MD; Paolo Scudellari, MD; Marco Borderi, MD; Roberto Manfredi, MD; Laura Fratiglioni, MD, PhD

Arch Neurol. 2002;59:812-818.

Context  Although it is well established that acquired immunodeficiency syndrome dementia complex mainly develops in patients with advanced human immunodeficiency virus 1 (HIV-1) infection and severe immunosuppression, other factors that might increase the risk of early neuropsychological abnormalities are controversial.

Objective  To identify risk factors for HIV-1–related cognitive impairment.

Design  Case-control study.

Setting  Division of Infectious Diseases, University of Bologna.

Participants  We studied 272 consecutive individuals: 90 HIV-1–seronegative, 88 asymptomatic HIV-1–seropositive, and 94 symptomatic HIV-1–seropositive persons.

Main Outcome Measures  Cognitive impairment was defined as poor performance on at least 2 of the 7 neuropsychological tests included in the battery. Cutoff scores for poor performance on a test were established as 2 or more SDs lower than the mean of the seronegative group in the corresponding risk behavior strata: injecting drug users, hemophiliacs, and other risk behaviors. The following risk factors were studied: age, sex, education, risk behaviors, HIV-1 stage, lymphocyte count, and antiretroviral therapy.

Results  Compared with individuals with higher levels of education, those with less than 6 years of schooling had an odds ratio (OR) of 17.2 (95% confidence interval [CI], 3.6-83.3) for cognitive impairment, independent of age, sex, disease stage, antiretroviral therapy, and risk behavior. Compared with injecting drug users, homosexual/bisexual and heterosexual participants had ORs of 9.6 (95% CI, 2.2-42.7) and 6.3 (95% CI, 2.2-18.3), respectively, for cognitive impairment. Use of antiretroviral treatment (any vs none) was associated with lower prevalence of cognitive impairment (OR, 0.1; 95% CI, 0.0-0.3). Compared with persons with high CD4⁺ cell counts (500/µL), those with low (<200/µL) and moderate (200-499/µL) CD4⁺ cell counts had adjusted ORs of 8.6 (95% CI, 1.0-71.0) and 6.9 (95% CI, 1.0-48.4), respectively. The presence of prominent depressive symptoms did not change the results.

Conclusions  Low educational level, low CD4⁺ cell count, and homosexual/bisexual and heterosexual risk behaviors are risk factors for cognitive impairment in HIV-1–seropositive persons. Antiretroviral therapy exerts a beneficial effect against cognitive impairment in symptomatic individuals. Homosexual/bisexual and heterosexual persons who survive longer are expected to be the group at highest risk for cognitive impairment. However, the protective effect of antiretroviral therapy may balance this increased risk.

From the Institute of Psychiatry (Drs De Ronchi, Faranca, Berardi, and Scudellari) and the Division of Infectious Diseases, Department of Clinical and Experimental Medicine (Drs Borderi and Manfredi), University of Bologna, Bologna, Italy; and the Division of Geriatric Epidemiology, NEUROTEC, Karolinska Institutet, Stockholm, Sweden (Drs De Ronchi and Fratiglioni).

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