AIDS Dementia Complex Diagnosis & Care
The following is from a 1996 article in patient care. it's a little out of date. However, it is still a nice summary of AIDS Dementia Complex symptoms and care. NTII's memantine is the most promising drug in clinical trials for ADC. NTII, if all goes well, could be filing for FDA approval next year.
John de C
By J. HAMPTON ATKINSON, MD, LISA CAPALDINI, MD, JEROME F. LEVINE, MD, RICHARD W. PRICE, MD
Fifteen years into the AIDS epidemic, many of the opportunistic mysteries of HIV disease are yielding to research. New drugs are available, and many others are in development. Treatment regimens are being refined. Life expectancy has increased.
But what of the quality of life during those months to years of survival? Patients with HIV infection are subject to a variety of neurologic, psychological, and cognitive problems that can interfere with functioning. Neurologic disturbances can result from the direct or indirect effects of the virus on CNS function, side effects of drugs, and opportunistic infections. Motor control may be affected, and the results may range from barely detectable to utterly devastating.
A number of psychiatric disorders can develop as primary and secondary manifestations of the disease. Depression is particularly common. And, of course, patients face the psychological devastation associated with any chronic, life-threatening disease as well as the particular difficulties associated with AIDS, such as stigmatization and abandonment.
These neuropsychiatric and psychological concerns today assume a prominent position in the overall care of HIV-infected patients. As the primary care provider, you are ideally situated to play a key role in helping the patient cope. You are likely to be familiar with the patient's needs and problems as they develop and to be accessible at these times. With an empathetic attitude, an awareness of ancillary resources, and a little time, you can make an enormous difference in the patient's life.
DEMENTIA
It became apparent early in the AIDS epidemic that immune system compromise often was accompanied by cognitive and motor changes ranging from mild impairment to dementia approaching the severity of Alzheimer's disease. As researchers have sought to categorize various aspects of AIDS during the past 15 years, they have also worked to clarify the nature and impact of the so-called AIDS dementia complex (ADC). A staging scheme has been developed (see Table 1).1 Full-fledged dementia generally is associated only with advanced AIDS and severe immunosuppression and is a poor prognostic sign. The overall prevalence of dementia in people with frank AIDS is estimated at 5-15%.
TABLE 1 Staging of AIDS dementia complex
Stage Characteristics
0 Normal Normal mental and motor function
0.5 Subclinical Minimal symptoms of cognitive or motor dysfunction but no impairment of work or performance of daily duties
1 Mild Unequivocal evidence of functional, intellectual, or motor impairment but able to perform all but the more demanding aspects of work; fully ambulatory
2 Moderate Unable to perform demanding daily activities but can accomplish basic self-care activities; ambulatory but may require a single prop
3 Severe Major intellectual incapacity or motor disability
4 End-stage Nearly vegetative and/or mute; paraparetic or paraplegic with double incontinence
Adapted with permission of Little, Brown & Co, from Sidtis JJ, Price RW: Early HIV-1 infection and the AIDS dementia complex. Neurology 1990;40:323-326.
ADC is in part a diagnosis of exclusion. Ruling out other causes of neuropsychological disturbance such as CNS infection or lymphoma is, of course, important. The workup includes a good history and physical and careful neurologic examination; when indicated by the clinical findings and circumstances, laboratory tests such as serum VDRL and cryptococcal antigen assays also should be ordered. A lumbar puncture and MRI of the brain are sometimes indicated. Older patients appear to be more at risk for neurologic changes because of the aging brain's increasing vulnerability to injury. Children are also at particular risk-the developing brain is susceptible to viral damage that leads to encephalopathy.
Mild impairment Although frank dementia is not common, as many as one half of all symptomatic AIDS patients exhibit a mild degree of neurocognitive impairment known as minor cognitive-motor disorder (see Table 2).2 A typical observation is that patients have difficulty concentrating or completing tasks that had been routine. This may manifest as forgetfulness, feeling "spaced out," or having difficulty functioning efficiently at work.
TABLE 2 Diagnostic criteria for mild HIV-associated cognitive-motor disorder
1. Cognitive/motor/behavioral abnormalities (both A and B)
A. At least two of the following: Impaired attention or concentration, mental slowing, impaired memory, slowed movements, incoordination, or personality change
B. Acquired cognitive/motor abnormality verified by clinical neurologic examination or neuropsychological testing (may include tests for fine motor speed, manual dexterity, perceptual motor skills, attention/concentration, speed of processing information, abstraction/reasoning, visuospatial skills, memory/learning, or speech/language)
2. The cognitive/motor/behavioral disturbances cause mild impairment of work or activities of daily living
3. Patient does not meet criteria for AIDS dementia complex (see Table 3, page 134)
4. No evidence of active CNS opportunistic infection, malignancy, or severe systemic illness; cognitive/motor/behavioral disturbances are not attributable solely to substance abuse or other psychiatric disorders
Note: All four major criteria must be met for the diagnosis of mild HIV-associated cognitive-motor disorder.
Adapted with permission from Stern Y: Neuropsychological evaluation of the HIV patient. Psychiatr Clin North Am 1994;17:125-134.
Seropositive but asymptomatic patients may also experience minor cognitive-motor changes, but this is rare. This milder form of impairment may present a particular challenge to the primary care physician. When are the changes important? Do they suggest a need for more aggressive antiretroviral treatment? How often do they relate to depression rather than early ADC?
Evidence suggests that zidovudine (AZT) can be beneficial in reversing or slowing the progress of clinically overt dementia.3 Although there have been no controlled trials evaluating the clinical effects of other antiretroviral drugs on neurologic function, HIV infects the CNS. It is therefore reasonable to assume that lessening the systemic and CNS viral load would help preserve CNS functioning. The potential role of the new protease inhibitors also needs to be evaluated in HIV patients.
Optimal antiretroviral treatment is desirable because maintaining immune function can help improve cognitive and motor function. This can enhance emotional health and quality of life, which may, in turn, improve immune system function. Mortality also may be affected, with even milder impairment possibly being associated with shortened survival time.
It's important to keep in mind that mild or early cognitive impairment can be one of the most distressing aspects of HIV disease for patients and families. Patients may be acutely aware of what is happening to them-and what may lie ahead. In no facet of AIDS care is empathy more important, and your role is crucial. Let the patient know that you will continue to be available for support and help, regardless of what comes. Reassure the patient and family that mild cognitive or motor difficulties do not necessarily progress to full-blown dementia. Issues of dignity and autonomy may be very much on the patient's mind, and your influence can be great.
When symptoms worsen
The diagnosis of dementia as set out in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), requires that the patient exhibit difficulties with memory and one other area of mental functioning, such as aphasia, apraxia, or a decrease in the executive functions of judgment, synthesis, and action. Diagnostic criteria for ADC also have been specified, and since 1986 dementia has been considered an AIDS-defining condition (see Table 3).4 The condition must have a significant impact on the patient's life, usually involving the inability to work and care for oneself adequately.
TABLE 3 Diagnostic criteria for AIDS dementia complex
1. Acquired abnormality in at least two of the following cognitive abilities: attention/concentration, speed of processing information, abstraction/reasoning, visuospatial skills, memory/learning, and speech/language
2. Cognitive impairment causes impairment in work or activities of daily living
3. One of the following:
A. Acquired abnormality in motor functioning verified by clinical examination and/or neuropsychological tests
B. Decline in motivation or emotional control
4. Cognitive deficit demonstrable in the absence of clouding of consciousness
5. If another potential cause is present (such as depression or substance abuse), it is not the cause of the cognitive, motor, or behavioral symptoms or signs
Note: All five major criteria must be present for a diagnosis of AIDS dementia complex.
Adapted with permission from Stern Y: Neuropsychological evaluation of the HIV patient. Psychiatr Clin North Am 1994;17:125-134.
Various tests are used to evaluate dementia, but these are often time-consuming, requiring 2-6 hours of formal testing. To facilitate the diagnosis of HIV-related dementia, a group of investigators recently designed a quick bedside test, the Mental Alternation Test.5 The patient is asked to count to 20, recite the alphabet, and then alternate between the two: 1-A, 2-B, 3-C, etc. The investigators reported that the test was perhaps more sensitive than the Mini-Mental State Exam. Its specificity is lower than standard tests, but the investigators note that false-positive results will be screened out by more extensive testing. They concluded that the Mental Alternation Test could be useful in primary care in determining the need for neurologic referral.
The patient's demeanor and behavior also may suggest worsening dementia, such as when a formerly reliable patient suddenly begins missing office appointments. The patient may seem unable to connect with you or the surroundings, and motor control and balance may be noticeably impaired. Symptoms of dementia tend to fluctuate, so keep in mind that the person who appears completely lucid may not always be so. Conversely, even the most demented-appearing person may have periods of lucidity. Any discussions therefore should be conducted with the assumption that the patient is aware of what is being said.
What can be done
Along with optimal antiretroviral treatment, environmental and behavioral strategies can help the patient with mild to moderate cognitive impairment to maximize function. Simplifying routines and avoiding time pressures can help alleviate the frustration of cognitive impairment. Many people find that making lists helps keep them focused. The environment should be kept uncluttered and as familiar as possible. Numerous community resources such as social service agencies and AIDS programs are available for patients and caregivers.
With disease progression and worsening dementia, however, come more severe difficulties. The patient with end-stage AIDS and severe dementia may be too much for the family to cope with-or there may be no family support to enlist. Nursing homes often are unwilling to take these patients. They may linger in the acute care setting to little benefit and at great cost. Hospice involvement becomes all-important.
There is reason for optimism, however. Researchers are now looking at possible pharmacologic options for improving cognitive functioning in AIDS patients, and phase II studies are under way. The calcium channel blocker memantine HCl, for example, is being tested. This agent is not active against the virus itself, but in vitro it reverses HIV-induced disruptions in calcium metabolism and impedes cytokine activity that may destabilize neuronal function. Its clinical usefulness awaits further study. |
