AIDS Dementia Complex
Dementia is a brain disorder that affects a person's ability to think clearly and can impact his or her daily activities. AIDS dementia complex (ADC) -- dementia caused by HIV infection -- is a complicated syndrome made up of different nervous system and mental symptoms. These symptoms are somewhat common in people with HIV disease.
The frequency of ADC increases with advancing HIV disease and as CD4+ cell counts decrease. It is fairly uncommon in people with early HIV disease, but it's more common in people with severely weakened immune systems and symptoms of advanced disease. Severe ADC is almost exclusively seen only in people with advanced HIV disease.
ADC consists of many conditions that can be of varying degrees and may progressively worsen. These conditions can easily be mistaken for symptoms of other common HIV-associated problems including depression, drug side effects or opportunistic infections that affect the brain like toxoplasmosis or lymphoma. Symptoms of ADC may include poor concentration, forgetfulness, loss of short- or long-term memory, social withdrawal, slowed thinking, short attention span, irritability, apathy (lack of caring or concern for oneself or others), weakness, poor coordination, impaired judgment, problems with vision and personality change.
Because ADC varies so much from person to person, it is poorly understood and has been reported and described in many conflicting ways. This publication will shed light on some of these issues as well as the available treatments for ADC.
What Is ADC?
ADC is characterized by severe changes in four areas: a person's ability to understand, process and remember information (cognition); behavior; ability to coordinate muscles and movement (motor coordination); or emotions (mood). These changes are called ADC when they're believed to be related to HIV itself rather than other factors that might cause them, like other brain infections, drug side effects, etc.
In ADC, cognitive impairment is often characterized by memory loss, speech problems, inability to concentrate and poor judgment. Cognitive problems are often the first symptoms a person with ADC will notice. These include the need to make lists in order to remember routine tasks or forgetting, in mid-sentence, what one was talking about.
Behavioral changes in ADC are the least understood and defined. They can be described as impairments in one's ability to perform common tasks and activities of daily living. These changes are found in 30-40% of people with early ADC.
Motor impairment is often characterized by a loss of control of the bladder; loss of feeling in and loss of control of the legs; and stiff, awkward or obviously slowed movements. Motor impairment is not common in early ADC. Early symptoms may include a change in handwriting.
Mood impairments are defined as changes in emotional responses. In ADC, this impairment is associated with conditions, such as severe depression, severe personality changes (psychosis) and, less commonly, intense excitability (mania).
How Does HIV Cause ADC?
While it is clear that HIV can cause serious nervous system disease, how it causes ADC is unclear. In general, nervous system and mental disorders are caused by the death of nerve cells. While HIV does not directly infect nerve cells, it's thought that HIV can somehow kill them indirectly.
Macrophages -- white cells that are prevalent in the brain and act as large reservoirs for HIV -- appear to be HIV's first target in the central nervous system. HIV-infected macrophages can carry HIV into the brain from the bloodstream. Test tube studies offer these hypotheses about how macrophages may help destroy nerve cells:
Anecdotal reports indicate that there are fewer people with ADC since anti-HIV therapy became standard. People who develop ADC today tend to be "sicker" than those who developed it before the use of anti-HIV therapy. One early study from England supports this theory.
The British study found that only 2% of people with AIDS taking AZT developed ADC from 1982-1988, compared to 20% of those not on AZT. The incidence of ADC dropped from 53% in 1987 (before the arrival of AZT) to 3% in 1988 (after the arrival of AZT).
Early in the epidemic, many new AIDS cases were attributed to ADC. These newly-diagnosed people often had ADC but no other AIDS-related condition. Many doctors report that they are no longer seeing people who have just ADC. It has increasingly become a disease of late-stage AIDS when people suffer from multiple infections.
Three tests are required to diagnose ADC accurately: a mental status exam, one of the standard scans (CT and/or MRI) and a spinal tap. These may also help tell ADC apart from other brain disorders like toxoplasmosis, PML (progressive multifocal leukoencephalopathy) or lymphoma. Care should be taken, however, as ADC may occur along with the symptoms of other brain disorders. Diagnosing both conditions at the same time can be more difficult.
The main way to detect and evaluate ADC is through a mental status exam. The examination is designed to reveal problems like short- or long-term memory loss, problems with orientation, concentration and abstract thinking as well as swings in mood. Imaging of the brain with scans (like an x-ray) is also used. Certain lab tests can also be useful like examining cerebrospinal fund (CSF), obtained by a spinal tap (also called lumbar puncture).
CT and MRI scans are routinely used in the detection of ADC. CT scans are x-rays that use special beams to produce detailed images of organs and structures within the body. In people with ADC these scans usually show signs of destroyed brain tissue. MRI, or Magnetic Resonance Imaging, is a sensitive brain scan that is used when CT findings are not conclusive. Results from both of these tests are helpful in ruling out other causes for the symptoms.
Tests of CSF may help determine if someone has ADC, but they are not conclusive. Mostly they're used to rule out other causes of the symptoms of ADC, and that's why they're important. Many people with ADC have higher levels of certain proteins or white blood cells in their CSF. However, not everyone with these levels turn out to have ADC. Also, people with advanced ADC are generally more likely to have higher HIV levels in their CSF, although people with no symptoms of brain disorders sometimes have high HIV levels in their CSF.
The best therapies to treat ADC appear to be anti-HIV drugs, and high-dose AZT is the most studied drug for it. However, many specialists contend that how well a potent regimen controls HIV reproduction overall is more important than the actual drugs used in the regimen. This may or may not include using standard, or even high-dose, AZT as part of the regimen.
Generally speaking, creating an anti-HIV regimen with the extra goal of treating ADC follows three basic principals:
It's believed -- based on findings that high-dose AZT (1,000-1,200mg/daily) can cross the blood-brain barrier and effectively treat ADC -- that an anti-HIV drug that crosses the blood-brain barrier might help prevent or treat ADC. To date, AZT is the best understood treatment available for ADC. Several groups have reported improvements in cognitive functions with AZT as well as prevention of HIV infection of the brain. Larger doses (1,000mg compared to the now-standard 600mg per day) of AZT appear to be necessary for treating ADC. However, high-dose AZT may present problems since many people with HIV, particularly those who are the sickest, are often unable to tolerate its side effects.
While AZT may be the most researched drug for treating ADC, other anti-HIV drugs that cross the blood-brain barrier may be equally useful. These include -- in addition to AZT -- d4T, abacavir, nevirapine, amprenavir, atazanavir and to a lesser degree indinavir and 3TC. Efavirenz has not been shown to cross this barrier to a significant degree, but some experts speculate that it may be useful in treating ADC.
Anti-HIV therapies are best used in combinations. It may also be important to consider a drug's ability to cross into the brain when constructing an effective regimen. For information on developing long-term strategies and creating potent anti-HIV therapy regimen, call Project Inform's Hotline at 1-800-822-7422 or email a question.
Treating the Symptoms of ADC
Psycho-active drugs are often used to treat the symptoms of ADC. These include anti-psychotics, anti-depressants, anxiolytics, psycho-stimulants, anti-manics, and anti-convulsants. These drugs do not treat the underlying cause of ADC, or even stop its progression. However, they may ease some of its symptoms. Haloperidol (Haldol) is often used for easing ADC symptoms, though it has many side effects. People with ADC are sensitive to Haldol, so small doses of 5-10mg daily should be used to avoid severe side effects.
Ritalin (methylphenidate) has been used with success in people with ADC to ease apathy and to increase energy, concentration and appetite. Daily doses of 5-10mg are often sufficient.
In cases of severe behavior disorders, anti-psychotics like thorazine and mellaril can be used to control agitation. Lorazepam (Ativan) and diazepam (Valium) may also be used for sedation and controlling anxiety. Other drugs include perphenazine (Trilafon), thiothixene (Navane), molindole (Moban), and fluoxetine (Prozac) with bupropion (Wellbutrin).
Many of the therapies listed here may have potential drug interaction with commonly used anti-HIV therapies as well as therapies to treat or prevent HIV-related conditions. For more information about drug interactions, call Project Inform's National HIV/AIDS Treatment Hotline at 1-800-822-7422 or email a question.
New treatments for ADC are desperately needed. It's also important that new anti-HIV drugs be fully evaluated for their usefulness in treating ADC. At the same time, promising drugs that may work to treat the underlying causes of ADC also need to be investigated.
This material has been produced as a result of a collaboration between Project Inform and Gay Men's Health Crisis. For more information about Project Inform, call the Project Inform Hotline at 1-800-822-7422. For more information about Gay Men's Health Crisis in New York, call 212-367-1451. Special thanks goes to Dr. Richard Price of University of California's San Francisco General Hospital, Neurology Services and Dr. Justin McArthur, Professor of Neurology and Epidemiology at John Hopkin's University in Baltimore for their editorial support.
This article was provided by Project Inform. Visit Project Inform's website to find out more about their activities, publications and services.