Many patients with AIDS develop HIV-associated dementia (HAD). HAD usually develops after overt AIDS, although in many patients the dementia can present at the same time, or before other manifestations of AIDS.

In some patients, dementia may be the only clinical sign of HIV infection at the time of diagnosis. HAD remains one of the most common causes of dementia in patients younger than age 40 years. Therefore, HIV testing should be included in the evaluation of a young patient with unexplained dementia.

The incidence of HAD has declined from approximately 21% to almost 10% in the era of combination antiretroviral therapy.

The onset of dementia is usually insidious, although some patients may experience an abrupt, rapid worsening of their condition, before sudden onset of dementia. In some patients, a rapidly accelerating dementia may occur in association with systemic illness.

Early symptoms and signs include:

Cortical features such as aphasia, apraxia, alexia, and agraphia are less common. Mild disturbances of eye movements are often present.

Late manifestations include severe dementia, ataxia, motor weakness, incontinence, tremor, mutism, and frontal release signs (e.g., rooting reflex and grasp response).

Some patients have an associated retinopathy, myelopathy, or peripheral neuropathy.

Laboratory studies. HAD typically occurs in the setting of moderately severe immunosuppression. Mean CD4 counts are usually below 200 mm³. Cerebrospinal fluid (CSF) is abnormal in approximately half of the patients, and shows elevated protein levels, pleocytosis, and oligoclonal bands. Computed tomography (CT) or MRI scans are essential to rule out other focal conditions associated with AIDS (these conditions will be described later). Classic findings include atrophy, enlargement of cortical sulci, enlarged ventricles, and white-matter abnormalities. The detection of cerebral atrophy also has been reported among asymptomatic HIV patients, and is therefore not diagnostic of HAD. The electroencephalogram (EEG) is usually normal in the early stages of AIDS dementia complex.

Pathologic abnormalities result from direct viral invasion of the subcortical white matter, thalamus, and basal ganglia with relative sparing of the cerebral cortex. Neuron loss and astrocytosis are secondary effects of the viral invasion. An infiltration of macrophages is characteristic; these cells are believed to mediate much of the local damage via immunologic mechanisms. HAD is generally a diagnosis of exclusion.

One must rule out other possible causes of dementia and delirium, including metabolic or drug-induced encephalopathy, cryptococcal meningitis, tuberculosis, intracranial mass lesion, neurosyphilis, encephalitis secondary to herpes simplex virus (HSV), varicella zoster virus (VZV), and cytomegalovirus (CMV).

Most experts recommend initiation of combination antiretroviral therapy in patients with HAD. Data demonstrating consistent improvements in HAD following therapy, unfortunately, are limited.