AIDS Dementia Complex

 

AIDS dementia complex (ADC), also known as HIV encephalopathy or HIV-associated neurocognitive disorder (HAND), is a complication of advanced HIV infection characterized by a significant loss of memory, cognitive function, judgment, and verbal fluency. It typically occurs when a person with HIV is severely immunocompromised (as measured by the loss of CD4 T-cells).

ADC is among the list of AIDS-defining conditions classified by the Centres for Disease Control and Prevention (CDC).  It is less commonly seen today than it was during the height of the AIDS pandemic of the 1980s and 1990s due to the advent of combination antiretroviral therapy.

Even so, between 4% and 15% of people living with HIV will experience some form of neurocognitive impairment as a direct result of HIV infection. This not only includes people with an untreated infection but also those on long-term HIV therapy.

The symptoms of ADC are similar to those of other types of dementia. By definition, dementia is a chronic disorder caused by brain disease or injury that manifests with memory problems, personality changes, and impaired reasoning.

Symptoms of ADC

The symptoms can vary from one person to the next but may include:

  • Forgetfulness
  • Memory loss
  • Mood changes
  • Personality changes
  • Apathy
  • Difficulty concentrating
  • Impaired reasoning and judgment
  • Confused thinking
  • Difficulty following instructions
  • Difficulty generating or communicating ideas
  • Inability to describe or recognize emotions
  • Delayed or absent verbal responses
  • Reduced awareness of one’s surroundings
  • Mutism and catatonia

The hallmark of later-stage ADC (or any form of advanced dementia) is the inability to recognize one’s own symptoms.

With that said, the symptoms of ADC can often fluctuate, particularly in response to a person’s immune status and an HIV-associated illness. This makes it different from neurodegenerative forms of dementia in which the decline tends to be constant and irreversible.

In addition to cognitive impairment (the loss of one’s conscious intellectual capacity), ADC commonly manifests with psychological problems, particularly as the neurological symptoms become more profound.

Changes to the neural network of the brain can manifest with physical symptoms, particularly in people with severe ADC. These include:

  • Paraparesis (partial paralysis of the lower extremity)
  • Ataxia (characterized by slurred speech, stumbling, falling, and clumsiness)
  • Hyperreflexia (overresponsive reflexes)
  • Extensor-plantar response (the abnormal curving of the toes and feet when stroked)

AIDS dementia complex is associated with advanced HIV infection. It tends to affect people whose CD 4 Count is below 200 cells per microliter (cells/mL)—the CDC definition of AIDS. ADC is primarily seen with untreated HIV infection. People over 50 are most commonly affected. Some studies have shown that women with HIV are at greater risk than men, although it is unclear why.

The relationship between HIV infection and ADC is not well understood, but it is thought that HIV affects the brain directly and indirectly in several ways.

Viral Infiltration

From the earliest stage of infection, HIV is able to cross the blood-brain barrier, that separates the brain from the rest of the body. Once the virus enters the brain, it immediately establishes hidden reservoirs in a type of nerve cell called a microglia.  However, rather than generating new viruses, this hidden virus (called a provirus) will replicate silently alongside the host cell, unseen by the immune system and largely untouched by antiretroviral therapy.

Even so, toxic proteins produced by the virus can start to damage microglia and nearby cells called astrocytes. These are the cells in the central nervous system that regulate nerve signaling and transmission (synapses), protect nerve cells from oxidative damage, and maintain the integrity of the blood-brain barrier.

Beyond the toxic effect that HIV has on these cells, the increased permeability of the blood-brain barrier leaves the brain exposed to the indirect ravages of HIV infection.

Immune Activation and Inflammation

The direct damage caused by HIV only plays a part in the onset of ADC. It is, in fact, the indirect mechanisms triggered by HIV that appear to play the bigger role.

When HIV infection occurs, the immune system will activate and release inflammatory proteins called cytokines that trigger a defensive inflammatory response.  Even during the latent stage of infection when the disease is largely asymptomatic, chronic inflammation will persist, causing ongoing injury to nerve cells and the axons that connect them.

This is evidenced by structural changes to the brain in people with long-term HIV infection. Even those on effective antiretroviral therapy will often experience changes in the subcortical parts of the brain (including the basal ganglia and hippocampus) that regulate emotions, learning, and memory formation.   Under the burden of untreated HIV, the increased circulation of cytokines—paired with the destruction of the blood-brain barrier—can compound the damage to these parts of the brain, often irreversibly.

AIDS dementia complex is diagnosed by the characteristic symptoms and features of the disorder as well as the exclusion of all other possible causes.  The diagnostic process can be complicated since most people will present with mild cognitive dysfunction rather than the catastrophic loss of memory and executive function.

There are no lab tests or imaging studies that can definitively diagnose ADC; rather, it is diagnosed based on clinical criteria and an expert review of evidence.

The frontline treatment of AIDS dementia complex is antiretroviral therapy. The combination of drugs blocks multiple stages in the life cycle of HIV, preventing the replication of the virus. The resulting drop in the viral load, ideally to undetectable levels, alleviates the inflammatory burden on the body while allowing the immune system to rebuild itself.

The combination typically involves three different drugs taken daily to maintain a consistently high concentration in the blood.