Human immunodeficiency virus (HIV)-associated dementia, also called HIV-associated neurocognitive disorder, is a chronic cognitive deterioration due to brain infection by HIV. Psychomotor slowing; mood changes, including irritability and difficulty concentrating; and motor deficits, including gait abnormalities, may occur. The diagnosis is suspected based on clinical presentation, routine monitoring of CD4 counts and viral load, and brain imaging (eg, MRI) with lumbar punctures in some patients. Treatment approaches include supportive care and antiretroviral therapy.
(See also Overview of Delirium and Dementia and Dementia.)
Dementia is chronic, global, usually irreversible deterioration of cognition. HIV-associated dementia may occur in the late stages of HIV infection. Unlike almost all other forms of dementia, it typically occurs in younger people.
Dementia should not be confused with delirium, although cognition is disordered in both. The following helps distinguish them:
Dementia affects mainly memory, is typically caused by anatomic changes in the brain, has slower onset, and is generally irreversible.
Delirium affects mainly attention, is typically caused by acute illness or drug toxicity (sometimes life threatening), and is often reversible.
Other specific characteristics also help distinguish the 2 disorders (see table ).
Pure HIV-associated dementia is caused by neuronal damage mediated indirectly by HIV-infected macrophages and microglia in the central nervous system (CNS), which may lead to synaptic dysfunction (1). However, in patients with HIV infection, dementia may also result from other disorders, some of which may be treatable. These disorders include other infections, such as secondary infection with JC virus causing progressive multifocal leukoencephalopathy (PML) and CNS lymphoma. Other opportunistic infections (eg, cryptococcal meningitis, other fungal meningitis, some bacterial infections, tuberculosis meningitis, viral infections, toxoplasmosis) and metabolic- or medication-related causes may also contribute.
The prevalence of dementia in patients with advanced HIV infection ranges from 5 to 15% (2), but a significantly higher percentage of patients may have a milder, more subclinical form. Incidence is inversely proportional to CD4 count.
General references
1. Letendre S. Central nervous system complications in HIV disease: HIV-associated neurocognitive disorder. Top Antivir Med. 2011;19(4):137-142.
2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed, Text Revision (DSM-5-TR). American Psychiatric Association Publishing; 2022.
Symptoms and Signs of HIV-Associated Dementia
Symptoms and signs of HIV-associated dementia may be similar to those of other dementias. Early manifestations include:
Psychomotor slowing (eg, slowed thinking and expression)
Memory deficits
Difficulty concentrating
Apathy
Executive dysfunction
Behavioral manifestations such as mild personality changes, irritability, or social withdrawal are often early clinical features. Insight is preserved, and manifestations of depression are few. Motor movements are slowed; ataxia and weakness may be evident. Memory deficits may occur, particularly for recent events, impairing recall more than recognition. Executive dysfunction may include difficulty planning, multitasking, and problem-solving.
Abnormal neurologic signs may include:
Paraparesis
Lower-extremity spasticity
Ataxia
Extensor-plantar responses
Abnormalities in gait (eg, slow, broad-based gait)
Extrapyramidal signs (eg, bradykinesia and rigidity similar to Parkinson disease)
Mania or psychosis is sometimes present.
Diagnosis of HIV-Associated Dementia
History and physical examination (including a mental status examination)
Measurement of CD4 count and HIV viral load
Prompt evaluation, including MRI and usually lumbar puncture, when deterioration is acute
HIV-associated dementia should be suspected in patients who have (1):
Symptoms of dementia
Known HIV infection or symptoms or risk factors suggesting HIV infection
If patients known to have HIV infection have symptoms suggesting dementia, a general diagnosis of dementia is confirmed based on the usual criteria, including the following:
Cognitive or behavioral (neuropsychiatric) symptoms interfere with the ability to function at work or do usual daily activities.
These symptoms represent a decline from previous levels of functioning.
These symptoms are not explained by delirium or a major psychiatric disorder.
Evaluation of cognitive function involves taking a history from the patient and from someone who knows the patient plus doing a bedside mental status examination or, if bedside testing is inconclusive, formal neuropsychologic testing.
If patients with symptoms of dementia are not known to have HIV infection but have risk factors for HIV infection, they should be tested for HIV infection.
As in other patients with HIV infection, CD4 count and HIV viral load should be measured in patients with suspected HIV-associated dementia. In patients with suspected or confirmed HIV infection and confirmed dementia, these values help determine how likely HIV-associated dementia (and CNS lymphoma and other HIV-associated CNS infections) is contributing to dementia. In patients who have confirmed HIV infection but not dementia, these values help determine how likely HIV-associated dementia is to develop.
If patients have dementia and HIV infection, other processes can cause or contribute to worsening dementia symptoms. Thus, the cause of cognitive decline, particularly sudden, severe decline, whether due to HIV infection or another infection, must be identified as soon as possible.
MRI, with and without contrast, should be done to identify other causes of dementia, and if MRI does not identify any contraindication to lumbar puncture, lumbar puncture should also be done. Cerebrospinal fluid analysis may include cell count, protein, glucose, HIV RNA (when indicated), and targeted microbiologic testing by nucleic acid amplification tests for opportunistic pathogens; cytology should additionally be performed if CNS lymphoma is a diagnostic consideration. Late-stage findings of HIV-associated dementia may include diffuse nonenhancing white matter hyperintensities, cerebral atrophy, and ventricular enlargement.
Diagnosis reference
1. Cornea A, Lata I, Simu M, Rosca EC. Assessment and Diagnosis of HIV-Associated Dementia. Viruses. 2023;15(2):378. Published 2023 Jan 28. doi:10.3390/v15020378
Treatment of HIV-Associated Dementia
Antiretroviral therapy (ART)
The primary treatment of HIV-associated dementia is ART, which suppresses viral replication, improves immune function, and may stabilize or partially reverse cognitive decline (1). Immune reconstitution inflammatory syndrome (IRIS) may cause paradoxical worsening of neurologic and mental status when ART is started (2). IRIS should be anticipated and managed appropriately.
Supportive measures are similar to those for other dementias. For example, the environment should be bright, cheerful, and familiar, and it should be designed to reinforce orientation (eg, placement of large clocks and calendars in the room). Measures to ensure patient safety (eg, signal monitoring systems for patients who wander) should be implemented. Cognitive, motor, and psychiatric symptoms should be treated as needed, and rehabilitation therapies may provide additional benefit.
Treatment references
1. Nabha L, Duong L, Timpone J. HIV-associated neurocognitive disorders: perspective on management strategies. Drugs. 2013;73(9):893-905. doi:10.1007/s40265-013-0059-6
2. Bahr N, Boulware DR, Marais S, Scriven J, Wilkinson RJ, Meintjes G. Central nervous system immune reconstitution inflammatory syndrome. Curr Infect Dis Rep. 2013;15(6):583-593. doi:10.1007/s11908-013-0378-5
Prognosis for HIV-Associated Dementia
Before effective combination ART, untreated HIV-associated dementia was associated with a very poor prognosis, with mean survival of approximately 3 to 6 months after diagnosis. In the ART era, the incidence of severe HIV-associated dementia has declined substantially, and life expectancy among affected patients has improved markedly with ART; patients adherent to modern regimens of ART may survive years with appropriate care.
However, patients with HIV infection and untreated dementia typically have a worse prognosis than those without dementia.
End-of-life issues
Because insight and judgment can deteriorate in patients with dementia, appointment of a family member, guardian, or lawyer to oversee finances may be necessary. Early in the course of dementia, before the patient is incapacitated, the patient’s wishes about care should be clarified, and financial and legal arrangements (eg, durable power of attorney, durable power of attorney for health care) should be made. When these documents are signed, the patient’s capacity should be evaluated, and the evaluation results should be recorded. Decisions about artificial feeding and treatment of acute disorders are best made before the needs develop.
In advanced dementia, care often shifts towards palliative measures with comfort-focused approaches, emphasizing symptom control and quality of life rather than aggressive interventions or repeat hospitalizations.
