Of 70 autopsied patients with the acquired immune deficiency syndrome (AIDS), 46 suffered progressive dementia that was frequently accompanied by motor and behavioral dysfunction. Impaired memory and concentration with psychomotor slowing represented the most common early presentation of this disorder, but in nearly one half of the patients either motor or behavioral changes predominated. Early motor deficits commonly included ataxia, leg weakness, tremor, and loss of fine-motor coordination, while behavioral disturbances were manifested most commonly as apathy or withdrawal, but occasionally as a frank organic psychosis. The course of the disease was steadily progressive in most patients, and at times was punctuated by an abrupt acceleration. However, in 20% of patients a more protracted indolent course was observed. In the most advanced stage of this disease, patients exhibited a stereotyped picture of severe dementia, mutism, incontinence, paraplegia, and in some cases, myoclonus. The high incidence and unique clinical presentation of this AIDS dementia complex is consistent with the emerging concept that this complication is due to direct brain infection by the retrovirus that causes AIDS.

In order to define the histopathological substrate of the dementia that frequently complicates the acquired immune deficiency syndrome (AIDS), we analyzed the neuropathological findings in 70 autopsied adult AIDS patients, 46 of whom had suffered clinically overt dementia. Less than 10% of the brains were histologically normal. Abnormalities were found predominantly in the white matter and in subcortical structures, with relative sparing of the cortex. Their frequency and severity generally correlated well with the degree and duration of clinical dementia. Most commonly noted was diffuse pallor in the white matter, which in the pathologically milder cases was accompanied by scanty perivascular infiltrates of lymphocytes and brown-pigmented macrophages, and in the most advanced cases by clusters of foamy macrophages and multinucleated cells associated with multifocal rarefaction of the white matter. However, in nearly one third of the demented cases the histopathological findings were remarkably bland in relation to the severity of clinical dysfunction. In addition, similar mild changes were noted in over one half of the nondemented patients, consistent with subclinical involvement. Vacuolar myelopathy was found in 23 patients and was generally more common and severe in patients with advanced brain pathology. Evidence of cytomegalovirus (CMV) infection was noted in nearly one quarter of the brains and was associated with a relative abundance of microglial nodules, but correlated neither with the major subcortical neuropathology nor with the clinical dementia, indicating that CMV infection likely represented a second, superimposed process. This study establishes the AIDS dementia complex as a distinct clinical and pathological entity and, together with accumulating virological evidence, suggests that it is caused by direct LAV/HTLV-III brain infection.

Objective To determine whether cognitive impairment and brain injury as measured by proton magnetic resonance spectroscopy (MRS) persist in the setting of highly active antiretroviral therapy (HAART). Design This study is an observational cohort study. Methods MRS was performed in 268 patients: HIV-negative controls (N=28), HIV-positive neuroasymptomatic (NA) subjects (N=124), and subjects with AIDS Dementia Complex (ADC; N=50) on stable ART with a mean duration of infection of 12 years and CD4 of 309 cells/mm3. Four metabolites were measured over creatine (Cr): N-acetyl aspartate (NAA), marker of neuronal integrity; Choline (Cho), myoinositol (MI), markers of inflammation, and glutamate and glutamine (Glx) in the basal ganglia (BG), frontal white matter (FWM) and mid-frontal Cortex (MFC). Analyses included ANOVA, ANCOVA, linear and nonparametric regression models. Results Cognitive impairment was found in 48% of HIV infected subjects. Both HIV positive groups showed significant increases in MI/Cr or Cho/Cr in all brain regions when compared to controls; a significant decrease in Glx/Cr in the FWM was observed in the NA group; only ADC subjects showed a significant reduction in NAA/ Cr although a significant trend for decreasing NAA/Cr in the BG was found across the groups. Effects related to aging and duration of infection but not central nervous system penetration effectiveness (CPE) were observed. Conclusions Brain inflammatory changes remain ubiquitous among HIV-infected subjects whereas neuronal injury occurs predominantly in those with cognitive impairment. Together these findings indicate that despite the widespread use of HAART, HIV-associated cognitive impairment and brain injury persist in the setting of chronic and stable disease.

Background-Cerebral atrophy is a well described, but poorly understood complication of HIV infection. Despite reduced prevalence of HIV-associated dementia in the HAART era, HIV continues to affect the brains of patients with chronic infection. In this study we examine patterns of brain volume loss in HIV infected patients on HAART, and demographic and clinical factors contributing to it. We hypothesized that nadir CD4+ lymphocyte count, duration of HIV infection and age would be associated with reduced cortical volumes.