Clinical Guide > Neuropsychiatric Disorders > Dementia

HIV-Associated Dementia and Other Neurocognitive Disorders

January 2011

Chapter Contents


HIV is a neurotropic virus that directly invades the brain shortly after infection. HIV replicates in brain macrophages and microglia, causing inflammatory and neurotoxic host responses. HIV may cause cognitive, behavioral, and motor difficulties. These difficulties may range in severity from very mild to severe and disabling; if moderate or severe, they constitute minor cognitive motor disorder (MCMD) or HIV-associated dementia (HAD), respectively. These conditions are distinguished from the milder cognitive changes seen in some people with HIV infection by the greater impact and duration of the functional deficits. MCMD is thought to involve neuronal cell dysfunction, whereas HAD often involves actual cell death.

A note on nomenclature: There have been multiple shifts in the nomenclature used to describe HIV-associated neurocognitive disorders. The most recent proposed system, published in the journal Neurology in 2007, suggests three categories: asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HAD. However, the diagnoses of ANI and MND require neuropsychological testing that is more likely to be available in research settings as opposed to clinical settings. This chapter will therefore address the clinical diagnoses of MCMD and HAD.

Both MCMD and HAD are AIDS-defining conditions (listed as "Encephalopathy, HIV related" in the classification system used by the U.S. Centers for Disease Control and Prevention), and are risk factors for death. Neurocognitive disorders associated with HIV are among the most common and clinically important complications of HIV infection. However, they are diagnoses of exclusion, and other medical causes must be ruled out.

Risk factors for developing an HIV-associated neurocognitive disorder include the following:

The use of effective antiretroviral therapy (ART) that maintains the plasma HIV RNA at undetectable or low values is the best way to prevent and treat HIV-related neurocognitive disorders. Thus, it is essential to choose an ART regimen that takes into consideration resistance testing and adherence issues.

Minor Cognitive Motor Disorder

MCMD is characterized by mild impairment in functioning and may escape diagnosis by the clinician. The course and onset of MCMD can vary dramatically. The more demanding the activities of a particular individual, the more likely that person would be to notice the difficulties. MCMD does not necessarily progress to dementia.

HIV-Associated Dementia

HAD is characterized by symptoms of cognitive, motor, and behavioral disturbances. There is often a progressive slowing of cognitive functions, including concentration and attention, memory, new learning, sequencing and problem solving, and executive control. HAD also can present with behavioral changes, which mainly take the form of apathy, loss of motivation, poor energy, fatigue, and social withdrawal. Motor changes, including slowing, clumsiness, unsteadiness, increased tendon reflexes, and deterioration of handwriting may occur.

S: Subjective

If a neurocognitive disorder is suspected, obtain a history of the patient's symptoms (see below). Whenever possible, obtain a parallel history of the patients past history and recent mental status changes from significant others or caretakers.

Patient self-reports of cognitive problems and bedside cognitive status tests may be insensitive, particularly to subtler forms of impairment.

To help clarify factors that may be causing the changes in mental status, inquire about the following:

Ask about the following symptoms:

Table 1. Symptoms of MCMD and HAD

Minor Cognitive Motor Disorder (MCMD)HIV-Associated Dementia (HAD)
* American Academy of Neurology, AIDS Task Force (see "References," below)

Patients may complain of:

  • Difficulty with complex tasks
  • Mild memory problems
  • Distractibility/confusion
  • A need to make lists
  • Problems with adherence to medications

Diagnostic Criteria*

The patient displays at least two of the following symptoms for >1 month:

  • Impaired attention/concentration
  • Mental slowing
  • Impaired memory
  • Slowed movements
  • Impaired coordination
  • Personality change, irritability, or emotional lability

Patients may present with:

  • Memory problems
  • Distractibility
  • Anger, irritability, or emotional lability
  • Fatigue, psychomotor slowness
  • Sadness
  • Poor balance, clumsiness
  • Decreased attention or concentration
  • Social withdrawal
  • Reduced speed of information processing
  • Executive dysfunction (e.g., in realms of abstraction, divided attention, shifting cognitive sets)
  • Language problems
  • Visuospatial difficulties
  • Apraxias
  • Psychotic symptoms (in late stage)
  • Severe verbal memory loss (in late stage)
  • Seizures (in late stage)
  • Mutism (in late stage)

Diagnostic Criteria*

The patient displays at least two of the following cognitive symptoms for >1 month:

  • Impaired attention/concentration
  • Slowing in processing information
  • Difficulty with abstraction/reasoning
  • Difficulty with visuospatial skills
  • Impaired memory/learning
  • Impaired speech/language


At least one of the following:

  • Acquired abnormality in motor function by clinical examination or neuropsychological testing
  • Decline in motivation, emotional control, or social behavior

O: Objective

Figure 1: Modified HIV Dementia Scale

Maximum ScoreScoreActivity/Test

Maximum score: 12 points; a score of <7.5 points suggests possible HAD (note, this test is not specific)

Adapted from McArthur JC. Minor cognitive motor disorder: Does it really exist? Hopkins HIV Rep. Nov 1996;8(4):8.

n/an/aMemory/Registration: State four words for the patient to recall (dog, hat, green, peach), pausing 1 second between each each. Then ask the patient to restate all four.

Psychomotor Speed: Ask the patient to write the alphabet in upper case letters horizontally across the page; record time: ________ seconds.

≤21 sec = 6

21.1 - 24 sec = 5

24.1 - 27 sec = 4

27.1 - 30 sec = 3

30.1 - 33 sec = 2

33.1 - 36 sec = 1

> 36 sec = 0


Memory Recall: Ask the patient to restate the four words from Memory/Registration above. Give one point for each correct response. For words not recalled, prompt with a "semantic" clue, as follows: animal (dog); piece of clothing (hat), color (green), fruit (peach). Give 1/2 point for each correct after prompting.

2(_______)Construction: Copy the cube below; record time: _____ seconds. (<25 sec = 2; 25 - 35 sec = 1; >35 sec = 0)
line drawing of a cube

A: Assessment

A differential diagnosis includes the following medical conditions, which may present with cognitive changes or delirium:

P: Plan

Laboratory and Diagnostic Evaluation

A change in the mental status of an HIV-infected person should prompt a thorough search for underlying biological causes. As noted above, HIV-related neurocognitive disorders are diagnoses of exclusion, and other causes of the patient's symptoms should be ruled out.

Perform the following tests:

Table 2. Tests for Identifying and Staging HIV-Related Neurocognitive Impairment

HIV Dementia Scale
  • Screens for the memory and attention deficits and psychomotor slowing that are typical of HAD
  • Requires training to administer and, therefore, may not be ideal for a clinic setting
Modified HIV Dementia Scale
  • Designed specifically for use by non-neurologists and, therefore, may be more useful than the HIV Dementia Scale for a primary care setting
  • Requires approximately 5 minutes to administer
  • See Figure 1, above.
Mental Alternation Test
  • Useful for assessing patients with early dementia, who will show impairments in timed trials
Memorial Sloan-Kettering (MSK) Scale
  • Can be used for assessing severity
  • Combines the functional impact of both cerebral dysfunction (dementia) and spinal cord dysfunction (myelopathy); the two entities can be separated and staged independently
Trail Making Test, Parts A and B (from the Halstead-Reitan Neuropsychological Battery)
  • May be used as a screening tool, but results require interpretation by a neuropsychologist
  • May be used at the bedside to track a patient's response to ART over time
Grooved Pegboard (dominant and nondominant hand)
  • May be used as a screening tool and does not require literacy


There are no specific treatments for HIV-associated neurocognitive disorders, but ART may reverse the disease process, and a number of therapies may be helpful. The treatment of MCMD and HAD ideally utilizes a multidisciplinary approach that may involve HIV specialists, neurologists, psychiatrists, psychologists, nurse practitioners, social workers, and substance-use counselors.

Neurocognitive impairment in patients with HIV infection often is multifactorial. In addition to treating HIV-associated neurocognitive disorders themselves, it is important to correct, as much as possible, all medical conditions that may adversely affect the brain (e.g., psychiatric comorbidities, endocrinologic abnormalities, adverse medication effects). For patients using alcohol or illicit or nonprescribed drugs, implement strategies to reduce their use; these agents can further impair cognition.

Pharmacologic Management of HIV-Associated Neurocognitive Disorders

Nonpharmacologic Management of MCMD and Mild HAD

Nonpharmacologic Management of Moderate to Severe HAD

The strategies noted above should be utilized, but additional measures are needed.

Management of patients with severe or late-stage HAD requires an evaluation of their safety and a determination of the environment and level of supervision that are needed. The clinician should attend to the following:

Additional helpful strategies for managing patients who are confused, agitated, or challenged by their experience include the following:

Patient Education