HIV-associated neurocognitive disorders (HAND) are neurological disorders associated with HIV infection and AIDS. It is a syndrome of progressive deterioration of memory, cognition, behavior, and motor function in HIV-infected individuals during the late stages of the disease, when immunodeficiency is severe. HAND may include neurological disorders of various severity. HIV-associated neurocognitive disorders are associated with a metabolic encephalopathy induced by HIV infection and fueled by immune activation of macrophages and microglia. These cells are actively infected with HIV and secrete neurotoxins of both host and viral origin. The essential features of HIV-associated dementia (HAD) are disabling cognitive impairment accompanied by motor dysfunction, speech problems and behavioral change. Cognitive impairment is characterised by mental slowness, trouble with memory and poor concentration. Motor symptoms include a loss of fine motor control leading to clumsiness, poor balance and tremors. Behavioral changes may include apathy, lethargy and diminished emotional responses and spontaneity. Histopathologically, it is identified by the infiltration of monocytes and macrophages into the central nervous system (CNS), gliosis, pallor of myelin sheaths, abnormalities of dendritic processes and neuronal loss.
HAD typically occurs after years of HIV infection and is associated with low CD4+ T cell levels and high plasma viral loads. It is sometimes seen as the first sign of the onset of AIDS. Prevalence is between 10 and 24% in Western countries and has only been seen in 1–2% of India-based infections. With the advent of highly active antiretroviral therapy (HAART), the incidence of HAD has declined in developed countries, although its prevalence is increasing. HAART may prevent or delay the onset of HAD in people with HIV infection, and may also improve mental function in people who already have HAD.
Dementia only exists when neurocognitive impairment in the patient is severe enough to interfere markedly with day-to-day function. That is, the patient is typically unable to work and may not be able to take care of themself. Before this, the patient is said to have a mild neurocognitive disorder.
Presentation
Cognitive impairments associated with HIV occur in the domains of attention, memory, verbal fluency, and visuospatial construction. Specifically for memory, the lowered activity of the hippocampus changes the basis for memory encoding and affects mechanisms such as long-term potentiation. Severity of impairment in different domains varies depending on whether or not a patient is being treated with HAART or monotherapy. Studies have shown that patients exhibit cognitive deficits consistent with dysfunction of fronto-striatal circuits including associated parietal areas, the latter of which may account for observed deficits in visuospatial function. In addition to cognitive impairments, psychological dysfunction is also noted. For example, patients with HIV have higher rates of clinical depression and alexithymia, i.e., difficulty processing or recognizing one's own emotions. Patients also have more difficulty recognizing facial emotions.
Without combination antiretroviral therapy, cognitive impairments increase with successive stages of HIV. HIV patients in early stages show mild difficulties in concentration and attention. In advanced cases of HIV-associated dementia, speech delay, motor dysfunction, and impaired thought and behavior are observed. Specifically, lower motor speeds were found to correlate with hypertrophy of the right putamen.
The diagnosis of HIV-associated neurocognitive impairment is made using clinical criteria after considering and ruling out other possible causes. The severity of neurocognitive impairment is associated with nadir CD4, suggesting that earlier treatment to prevent immunosuppression due to HIV may help prevent HIV-associated neurocognitive disorders.
Pathophysiology
HIV-associated dementia (HAD) is not a true opportunistic infection; it is one of the few conditions caused directly by HIV itself. However, the cause of HAD can be difficult to discern because the central nervous system can be damaged by a number of other causes related to HIV infection: opportunistic infections AIDS-related lymphoma or metastasis of other AIDS-related cancers direct effects of HIV in the brain toxic effects of drug treatments malnutrition