| HIV-Associated Dementia and Minor Cognitive Motor DisorderJuly 2006 | Background | | The HIV virus is neurotropic and directly invades brain tissue shortly after infection.
Accordingly, HIV may cause cognitive difficulties, including HIV-associated dementia
(HAD), also called AIDS dementia complex (ADC). In the United States in past years, HAD
was the most common neurologic complication of AIDS, affecting 40-60% of all AIDS
patients. In recent years, the incidence of HAD has declined, probably because of the
use of potent combination antiretroviral therapy (ART). Other HIV-related opportunistic
infections of the central nervous system (CNS) (eg, toxoplasmosis, cytomegalovirus
encephalitis) and malignancies (eg, lymphoma) have declined in frequency even more
sharply than HAD. The fact that HAD has not declined as much as other HIV-related CNS
disease suggests that the CNS may be an important reservoir for HIV and that current
antiretroviral medications do not protect the CNS as well as they protect the rest of
the body. The HIV viral load in the CNS is correlated with cognitive decline; however,
it is not correlated with plasma viral load and cannot be estimated from plasma viral
load. The American Psychiatric Association describes dementia as "an organic mental disorder
defined as a loss of intellectual abilities of sufficient severity to interfere with
social or occupational functioning." The clinical presentation of dementia varies.
Patients may develop ambulation or gait problems, mania, panic, psychosis, social
isolation, or anxiety. Dementia is progressive but with a variable course; some patients
have a rapid progression, whereas others have a slow decline in function. Many patients
with HIV-related neurocognitive impairments are acutely aware of their deterioration and
may develop an adjustment disorder characterized by profound fear, anxiety, or
depression. Some HIV-infected patients may develop a milder form of cognitive disorder, called minor
cognitive motor disorder (MCMD), which is not necessarily an early stage of dementia.
The distinction between MCMD and dementia is important and may have a major
psychological impact on the patient. | |
| SOAP (Subjective, Objective, Assessment, Plan) | | | Assessment | | | Partial Differential Diagnosis | | | Other CNS conditions, such as toxoplasmosis, fungal infection,
Mycobacterium avium complex (MAC), lymphoma, cytomegalovirus
ventriculitis or encephalitis, normal-pressure hydrocephalus, neurosyphilis,
tuberculosis, or Cryptococcus neoformans. Many of these are treatable. | | | Depression, which can present as cognitive impairment. | | | Other medical causes, such as nutritional deficiencies (eg, vitamin B12),
metabolic disorders (eg, hypothyroidism), toxins (eg, chronic alcohol use), or
infections (eg, tertiary syphilis). | | | Delirium, which is an acute manifestation of cognitive impairment with
inability to maintain attention. Delirium can be due to many medical conditions,
but is also commonly caused by medications, including those with anticholinergic
adverse effects, such as amitriptyline (Elavil), promethazine (Phenergan),
prochlorperazine (Compazine), and diphenhydramine (Benadryl). An anticholinergic
delirium is characterized by visual or tactile hallucinations, confusion, and
sometimes agitation. Other medications that may cause delirium include
prednisone, meperidine (Demerol), lithium (at toxic levels, which may occur in a
stable patient with a serious opportunistic infection or dehydration),
agonist-antagonist analgesics such as pentazocine (Talwin), and short-acting
benzodiazepines such as midazolam (Versed) and triazolam (Halcion). | | | Intoxication or withdrawal. | |
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Table 1 describes the states of HAD. Table 1. Stages and Characteristics of HIV-Associated DementiaStage | Characteristics
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Source: Bartlett JG, Gallant JE. 2005-2006 Medical Management of HIV Infection. Baltimore: Johns Hopkins University Division of Infectious Diseases; 2005. Available online at hopkins-aids.edu/mmhiv/order.html. |
Stage 0 (normal) |
Normal mental and motor function |
Stage 0.5 (subclinical) |
Equivocal symptoms of cognitive or motor dysfunction; no
impairment of work or activities of daily living (ADL) |
Stage 1 (mild) |
Evidence of intellectual or motor impairment, but able to
perform most ADL |
Stage 2 (moderate) |
Unable to work, but can manage self-care |
Stage 3 (severe) |
Major intellectual incapacity or motor disability |
Stage 4 (end-stage) |
Nearly vegetative | | |
| Plan | | | Check thyroid function, vitamin B12, folate, rapid plasma reagin (RPR), blood
chemistries and electrolytes, liver function tests (LFTs), complete blood count
(CBC), and testosterone level. | | | Order computed tomography (CT) scan or magnetic resonance imaging (MRI).
(Cortical atrophy, similar to that seen in Alzheimer dementia, may be visible in
very late stages of HAD.) Rule out masses and space-occupying lesions. | | | Check cerebrospinal fluid (CSF): In patients with HAD, the CSF will show
increased protein and mononuclear pleocytosis. It may be valuable to check the
HIV viral load in the CSF, because sometimes the CSF viral load is high
regardless of the plasma viral load; this may explain the patient's
central deficits. | | | Perform an electroencephalogram (may show mild, nonspecific slowing). | | | Refer the patient to a psychiatrist and neurologist for further evaluation and
neuropsychological testing. | |
| Treatment | | | Pharmacotherapy | | ART may be helpful in treating MCMD and HAD and should be recommended for all
patients, unless there are contraindications. The ability of particular
antiretroviral drugs to penetrate the blood-brain barrier may be less important to
treatment success than the overall potency of the regimen and the ability of the
patient to adhere to it. Studies from the 1980s showed that zidovudine monotherapy was beneficial in patients
with HAD, so some clinicians include it in the ART regimen for anyone with
neurocognitive impairment. Others suggest using at least 2 drugs that cross the
blood-brain barrier (eg, zidovudine, stavudine, abacavir, lamivudine, and
nevirapine). Efavirenz, didanosine, and lamivudine cross to a lesser degree. As a
class, protease inhibitors (PIs) have poor blood-brain barrier penetration.
Nevertheless, patients have shown neurocognitive improvement while taking
PI-containing regimens, perhaps because of indirect effects on HIV activity in the
CNS. Treat depressive symptoms with low dosages of selective serotonin reuptake inhibitors
(SSRIs) (see chapter Depression for details). Antipsychotic medications may be useful in treating agitation and hallucinations, but
patients with these conditions are often extremely sensitive to anticholinergic
adverse effects and extrapyramidal symptoms. Newer neuroleptic or antipsychotic
agents, such as olanzapine and risperidone, have lower rates of significant side
effects compared with older drugs. The starting dosage of olanzapine is 2.5 mg
orally at bedtime; that for risperidone is 0.5-1 mg orally at bedtime. Note that
these drugs may interact with antiretroviral medications, especially ritonavir, and
can cause weight gain and other metabolic adverse effects. Avoid benzodiazepines,
which tend to increase confusion and decrease concentration. Consult with a
knowledgeable psychiatrist or pharmacist. Psychostimulants such as methylphenidate (Ritalin) and dextroamphetamine (Dexedrine)
have been used to improve attention, concentration, and psychomotor function.
Dosages of methylphenidate start at 5 mg for a test dose, then 2.5-5.0 mg twice
daily, increasing by doses of 5 mg every other day until the desired effect is
achieved. Usual dosages are in the range of 20-30 mg per day. Monitor blood
pressure, heart rate, and symptoms of restlessness, agitation, nausea, and
psychosis. No data are available regarding the use of atomoxetine (Strattera) to
improve attention and concentration in patients with HAD. | |
| Psychosocial interventions | | For a patient who is knowledgeable about HIV, a dementia workup or diagnosis often
precipitates a crisis, with an increased risk of suicide. Carefully screen for
depression and suicidality, and treat these if they develop. Behavioral management strategies may assist the patient with early manifestations of
dementia to continue living with some degree of independence and safety in the home.
Memory aids such as posted notes, calendars, alarmed pill-boxes, and other
environmental cues may help. It is critical to enlist the support of family members and significant others at an
early stage of the illness. Because the disease is frightening and may be
progressive, the patient and members of the support system need assistance in
anticipating and planning for the future. Plans for assisted living or other in-home
custodial care should be made early. Severe or late dementia causes fear,
misunderstanding, and frustration for both the patient and care givers. All involved
will require help from visiting nurses, social workers, hospice workers, and
physicians. Recommend the preparation of an advance directive for the patient with
early manifestations of dementia. | |
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| Patient Education | | |
| Patients should maintain their support system as much as possible. | | | Refer patients to a support group or an HIV-experienced counselor who can respond
to their fears and concerns. | | | ART has helped some people with HAD. Patients who are candidates for ART, should
find someone to help with their antiretroviral medications, if at all possible.
Enlist family members or roommates to help the patient take the medications as
scheduled. Educate them about adverse effects, and whom to call with problems and
questions. | | | Teach patients to use cues (eg, notes, calendars, alarms) to help themselves keep
track of medicines, appointments, social events, and other important activities.
Help them identify ways to make the house safer and to maintain as much
functionality and dignity as possible. | |
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| References | | | The appearance of external hyperlinks does not constitute endorsement by the Department of Veterans Affairs of the linked Web sites, or the information, products or services contained therein. | | |
| Bartlett JG, Gallant JE. 2005-2006 Medical Management of HIV Infection. Baltimore: Johns Hopkins University Division of Infectious Diseases; 2005. Available online at hopkins-aids.edu/mmhiv/order.html. | | | McArthur JC, Hoover DR, Bacellar H, et al. Dementia in AIDS patients: incidence and risk factors. Multicenter AIDS Cohort Study. Neurology. 1993 Nov;43(11):2245-52. | | | McDaniel JS, Purcell DW, Farber EW. Severe mental illness and HIV-related medical and neuropsychiatric sequelae. Clin Psychol Rev. 1997;17(3):311-25. | | | McGuire D. Neurologic Manifestations of HIV. In: Peiperl L, Coffey S, Volberding PA, eds. HIV InSite Knowledge Base[textbook online]; San Francisco: UCSF Center for HIV Information; June 2003. | | | Neuenburg JK, Brodt HR, Herndier BG, et al. HIV-related neuropathology, 1985 to 1999: rising prevalence of HIV encephalopathy in the era of highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2002 Oct 1;31(2):171-7. | | | Price RW. AIDS Dementia Complex. In: Peiperl L, Coffey S, Volberding PA, eds. HIV InSite Knowledge Base[textbook online]; San Francisco: UCSF Center for HIV Information; June 1998. | | | Price, RW. Management of the Neurologic Complications of HIV-1 Infection and
AIDS. In: Sande MA, Volberding PA, eds. The Medical Management of AIDS, 6th ed.
Philadelphia: WB Saunders; 1999:217-240. | | | Sacktor N, Skolasky RL, Tarwater PM, et al. Response to systemic HIV viral load suppression correlates with psychomotor speed performance. Neurology. 2003 Aug 26;61(4):567-9. | |
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