Disease course and pathology are variable in early HIV infection. A mononucleosis-like illness occurs within days to weeks of presumed HIV exposure, with symptoms such as fatigue, fever, lymphadenopathy, and occasionally a rash. These symptoms usually re-solve as an immune response to HIV develops and the levels of plasma viremia decrease. Patients who present years later with the clinical syndrome of AIDS do not always recall such a prodrome. For untreated
Figure 9–1. The initial psychiatric consultation to an HIV or AIDS patient: a hierarchical approach.
Abbreviations: 1o=primary; 2o=secondary; APA=American Psychiatric Association; DDx=differential diagnosis; Q=question.
patients, the median time from initial infection to the development of clinical disease is approximately 10 years (Fauci and Lane 2001). The rate of disease progression is directly correlated with HIV RNA lev-els. Those with high levels of HIV RNA in plasma progress to symptomatic disease faster than do those with low levels.
The virus crosses the blood–CSF barrier early in the infection. Neuropathological findings include ce-rebral atrophy, myelin pallor, chronic perivascular in-flammation, multinucleated giant cells derived from HIV-infected macrophages and microglia, microglial nodules, and reactive gliosis (Jay 2000). Although typ-ically managed by neurologists, HIV-associated de-mentia complex (HADC) may imitate conditions as varied as neurosyphilis, Alzheimer’s disease, depres-sion, anxiety disorders, psychotic disorders, and sub-stance abuse. Furthermore, HADC patients evolve varied neuropsychiatric complications, such as anxi-ety, depression, mania, and psychosis.
The classification system for HIV infection by the Centers for Disease Control and Prevention empha-sizes the clinical importance of the CD4+
T-lym-phocyte count in categorizing HIV-related clinical conditions. The American Academy of Neurology cat-egorization of HIV-related central nervous system (CNS) disease has become the standard (see Box 9–3).
HADC is a multifaceted syndrome consisting of cognitive, affective, motor, and behavioral abnormali-ties in HIV-infected persons (synonyms: AIDS demen-tia complex, AIDS encephalopathy, HIV encephalopa-thy). DSM-IV-TR (American Psychiatric Association 2000a) specifically uses the term dementia due to HIV disease (code 294.1x). The definitional criteria for HADC according to the American Academy of Neu-rology AIDS Task Force are listed in Box 9–3. Al-though it is not as widely used, we have found the Me-morial Sloan-Kettering Cancer Center staging system for HADC also useful in the clinical description of HADC and its progression (Table 9–2).
Deficits of HADC
Cognitive deficits of HADC include mental slowing (less verbal, less spontaneous, not as quick); poor concentra-tion and attenconcentra-tion (e.g., losing track of conversaconcentra-tions);
Box 9–2. Assessing HIV risk behavior: a checklist of behaviors and attitudes Take a specific behavioral history:
❑ Frequency of sexual intercourse (vaginal, anal, oral)
❑ Number, gender, and known HIV risk of sex partners
❑ Whether the patient has traded sex (for money, drugs, a place to stay, cigarettes)
❑ Past and current symptoms of sexually transmitted infections
❑ Use of condoms and other contraceptive methods
❑ Use of drugs, particularly those that are injected or sniffed
❑ Sharing of needles, syringes, or other injection equipment
Does the person perceive himself/herself to be at risk for HIV infection? (If there is no perception of risk, there will be little motivation for behavioral change.)
Does the person believe that changing behavior will have an impact on preventing infection?
Does the seropositive person care about infecting others or benefit by avoiding reexposure?
Is there an Axis I condition? Would treatment for it improve the ability to cooperate with medical advice (e.g., would adherence improve if depression were treated and resolved)?
Assess predisposition to persistent high-risk sexual behavior, especially:
❑ Drug or alcohol abuse
❑ Borderline personality disorder
❑ Axis I disorder
❑ History of childhood sexual abusea
Is the patient autonomous or fatalistic about the illness? (See Chapter 13.)
aSexual compulsivity, revictimization, substance abuse, and chronic depression enhance the vulnerability to HIV infection of adult survi-vors of sexual abuse (Goodman and Fallot 1998; Lenderking et al. 1997). Survivor characteristics: trauma intrusion phenomena, dissociative phenomena, somatization, sexual dysfunction (Hutton et al. 2001).
Box 9–3. Definitional criteria for HIV-associated dementia complex (HADC) and cognitive impairment (American Academy of Neurology AIDS Task Force)
Probable (must have each of the following)
1. a. Acquired abnormality in at least two of the following cognitive abilities (present for at least 1 month), verified by reliable history and mental status examination, with history obtained from an informant, supplemented by neuropsychological testing:
• attention/concentration
• speed of processing of information
• visuospatial skills
• memory/learning
• speech/language
• abstraction/reasoning b. Cognitive dysfunction causing impairment of work or activities of daily living 2. At least one of the following:
a. Abnormality in motor function or performance verified by clinical exam (e.g., slowed rapid movements, abnormal gait, limb incoordination, hyperreflexia, hypertonia, or weakness); neuropsychological tests (e.g., fine motor speed, manual dexterity, perceptual motor skills)
b. Decline in motivation or emotional control, or change in social behavior (e.g., change in personality with apathy, inertia, irritability, emotional lability) or new onset of impaired judgment (e.g., socially
inappropriate behavior or disinhibition)
3. Absence or clouding of consciousness of sufficient interval to establish criterion 1, above
4. Other etiologies ruled out, including active CNS opportunistic infection or malignancy, psychiatric disorders (e.g., depressive disorder), substance use or withdrawal.
If another potential etiology (e.g., major depression) is present, it cannot be the cause of the above cognitive, motor, or behavioral symptoms and signs in order to diagnose HADC
Possible (must have one of the following)
1. Other potential etiology present (must have each of the following):
a. Same as criteria 1, 2, and 3 in Probable
b. Another potential etiology is present, but the cause of criterion 1 above is uncertain.
2. Incomplete clinical evaluation (must have each of the following):
a. Same as criteria 1, 2, and 3 in Probable
b. Etiology cannot be determined (appropriate laboratory or radiologic investigations pending).
Source. Adapted from Janssen RS, Cornblath DR, Epstein LG, et al.: “Nomenclature and Research Case Definitions for Neurological Man-ifestations of Human Immunodeficiency Virus–Type 1 (HIV-1) Infection: Report of a Working Group of the American Academy of Neu-rology AIDS Task Force.” NeuNeu-rology 41:778–785, 1991.
Table 9–2. Adapted Memorial Sloan-Kettering Cancer Center staging system for HIV-associated dementia complex
Stage Description 0.5
Equivocal
Subclinical cognitive motor impairment
Either minimal or equivocal symptoms of cognitive or motor dysfunction, or mild signs (snout response, slowed extremity movements) but without impairment of work or capacity to perform activities of daily living (ADLs). Gait and strength are normal.
1 Mild
Minor cognitive-motor disorder
Unequivocal evidence (symptoms, signs, neuropsychological test performance) of functional
intellectual or motor impairment, but able to perform all but the more demanding aspects of work or ADLs. Can walk without assistance.
2–4
Moderate to end stage
HIV-associated dementia complex
Stage 2: Cannot walk or maintain the more demanding ADLs, but can perform basic ADLs of self-care;
ambulatory, but may require a single prop
Stage 3: Major intellectual incapacity or motor disability Stage 4: Nearly vegetative
forgetfulness (appointments, names, historical details);
confusion (time, place); and difficulties in abstraction, problem solving, or manipulating acquired knowledge.
Behavioral deficits seen in HADC include apathy, social withdrawal; personality changes; and agitated psychosis.
Motor deficits associated with HADC include loss of coordination; fine motor difficulties (e.g., impaired handwriting); eye movement abnormalities; unsteady gait; leg weakness; and tremor.
HIV-Associated Minor Cognitive-Motor Disorder
The diagnosis of HIV-associated minor cognitive-motor disorder (MCMD) is reserved for individuals who demonstrate cognitive or motor dysfunction not severe enough to interfere with activities of daily liv-ing or to qualify for a full-blown dementia syndrome.
Prevalence estimates made in 1995 (Heaton et al. 1995) are listed in Table 9–3. An important clinical question remains: do MCMD and HADC differ in underlying pathogenesis and clinical course, as well as in sever-ity? Encouragingly, only a minority of patients (about 17%) with MCMD developed HADC in a study by Marder et al. (1998). Trials are under way to determine the impact of HAART on the natural history of both MCMD and HADC.
The symptoms of HADC are often subtle and in-sidious in onset; slowed decision making is most prominent. This presentation differs from the amne-sia, language disturbance, and agnosia typifying the early stages of senile dementia of the Alzheimer type (SDAT). SDAT is a cortical-type dementia. HADC fol-lows a different pattern: it is closer to “subcortical
de-mentia,” which has been described in Parkinson’s dis-ease, Huntington’s disdis-ease, Wilson’s disdis-ease, and other disorders. Although cognitive functioning is eventually globally impaired, insight is often pre-served until late in the illness. Depression is common (see Table 9–4). Luckily, dementia is a complication of advanced HIV infection, rarely developing in the early stages of infection (Jay 2000). Table 9–4 compares fea-tures of cortical and subcortical dementia.
Assessment
Cognitive slowing appears to be the first cognitive dis-turbance of HIV infection. Most useful are test batter-ies that will assess the following: psychomotor speed, information encoding, information retrieval, concen-tration, and attention. Baseline and longitudinal neu-ropsychological testing have become the standard for evaluating and tracking cognitive function in seropos-itive patients. Although the selection of formal neu-ropsychological test instruments is beyond the scope of this chapter, a few points are worth noting:
Table 9–3. CDC stage and MCMD
CDC stage
Approximate percentage of patients
meeting criteria for MCMD
A 5%
B 27%
C 21%–24%
Note. CDC =Centers for Disease Control and Prevention; MCMD=
minor cognitive-motor disorder.
Source. Data from Heaton et al. 1995.
Table 9–4. A comparison of subcortical and cortical dementia Mental status
domain
Subcortical dementia (HADC, Parkinson’s disease)
Cortical dementia (Alzheimer’s disease)
Appearance Disheveled, ill-appearing Alert, healthy
Activity Slow Normal
Posture Distorted Erect
Speech Abnormal articulation: dysarthria, muteness, etc. Normal articulation
Language Normal production Dysnomia, paraphasia
Cognition Cannot plan or sequence cognitive operations in problem solving Unable to manipulate knowledge
Memory Disorder of retrieval Disorder of learning
Visuospatial Sloppy due to movement problems Constructional disturbance
Emotional state Apathetic, lacking drive Unaware, unconcerned
Note. HADC=HIV-associated dementia complex.
Source. From Cummings JL (ed.): Subcortical Dementia. Copyright 1990 Jeffrey L. Cummings. Used by permission of Oxford University Press.
The Mini-Mental State Examination (MMSE) is not sufficiently sensitive for detecting HIV-associated neurocognitive dysfunction, particularly early MCMD, because it omits assessing response time. Even late in the dementing disease, MMSE scores may underesti-mate HADC cognitive dysfunction.
The American Psychiatric Association Practice Guideline (American Psychiatric Association 2000b) recommends baseline screening using any one of the three tests listed in Table 9–5. Patients should be re-evaluated regularly as part of the treatment plan. If there is evidence of early cognitive impairment, for-mal neuropsychological testing is useful for docu-menting areas of cognitive dysfunction as well as ar-eas of relative cognitive strength.
Clinical Course
HADC is a dementia of variable progression and dura-tion. Some HADC patients develop other systemic AIDS manifestations during the course of the dementia.
Others have a more indolent, prolonged, and relatively stable course. Some patients may compensate for cogni-tive loss, whereas others deteriorate rapidly to a severe vegetative dementia over a period of weeks. It is not possible to predict the clinical course for a given patient.
Patients with HADC complain that their thinking is slowed and their concentration diminished. They may report, for example, losing track of the conversation while speaking to people and having to reread a para-graph or page to get it to “sink in.” Additionally, they complain of forgetfulness, usually for day-to-day events.
In the early stages, individuals may report that they can-not keep up with their personal finances or business ac-tivities, describing a state of “puzzlement.” Neurobe-havioral abnormalities may soon follow, such as motor complaints of clumsiness, sloppy handwriting, tremor, and poor balance, especially with rapid head turns.
• Caution. In psychotherapy, the apathy and social withdrawal of insidious-onset HADC may resem-ble and coincide with psychodynamically moti-vated phenomena like resistance, denial, and re-pression.
Case Example of Subtle-Onset HADC Ms. A was a 38-year-old single mother of two who contracted HIV after a sexual assault by a neighbor at the age of 33, for which she had “no memory.” She had been relatively adherent to her medical care, in-cluding a recommendation for an antidepressant and supportive psychotherapy. In the past year, however, Ms. A had become more forgetful about her appointments, joking that “it must be the start of menopause,” or “I guess I didn’t want to talk about something last week.” She would forget to bring in her insurance forms so that sessions could be billed, but also began to misplace items unrelated to psy-chotherapy, such as her children’s medical forms and lunch vouchers. Although she initially attrib-uted these reactions to “what was being discussed in psychotherapy,” the patient could no longer remem-ber what was discussed from session to session. The patient’s sister became concerned that the patient was “acting senile,” that is, apathetic, forgetful, eas-ily confused, “not herself.” Neurological workup later revealed that the patient was in the early stages of HADC.
Comment: HADC-related cognitive changes are some-times distinguishable by “forgetfulness” that is not limited to the psychotherapy sessions or psychody-namically valent material. Such memory and prob-lem-solving deficits will adversely affect the patient’s ability to follow through and maintain continuity in psychotherapy. Sometimes insight regarding intellec-tual decline is preserved until late in the illness, and patients may experience reactions of fear, anxiety, and mourning.
Table 9–5. Clinician-administered tests recommended by the American Psychiatric Association Mental Alternation Test (MAT) Patients count to 20, say the alphabet, and then alternate between numbers/
letters. Score: correct number/letter alterations in 30 seconds (e.g., 1-A, then 2-B, then 3-C= 3). Maximum score: 52 points. Score < 15 correlates with HIV-related cognitive impairment. Confounding conditions: subnormal intelligence; delirium; poor concentration (Jones et al. 1993).
HIV Dementia Scale (HDS) (see Figure 9–2)
Four subtests: timed written alphabet, four-item recall in 5 minutes, cube copy time, and antisaccadic task. Score≤10 correlates with HIV-related cognitive impairment (Power et al. 1995).
The Executive Interview (EXIT25) 25 executive cognition tasks in 15 minutes (e.g., abstract thinking; ability to plan, initiate, sequence, monitor, and stop complex behavior). Available from Dr.
Donald Royall ([email protected]) (Berghuis et al. 1999; Royall et al. 1992;
Schillerstrom et al. 2003).
Differential Diagnosis
HADC is in the differential diagnosis of any psychiat-ric symptom occurring in an HIV-infected individual.
Advanced cases are easy to spot and are characterized by global cognitive deterioration, gross impairment of social functioning, disorientation, agitation, mutism, vacant stare, spasticity and myoclonus, bowel and bladder incontinence, and, rarely, coma. The symp-toms of early HADC, however, may be easily misdiag-nosed as depression, particularly in the initial phases when symptoms coincide with affective changes of depression, including dysphoria, anxiety, irritability, apathy, and social withdrawal. Predominance of
dys-phoric thought content, such as low self-esteem, irra-tional guilt, and self-denigration, may help distin-guish depressive syndromes from HADC. However, these negative self-perceptions are not pathogno-monic and may also reflect patients’ awareness of de-clining cognitive abilities.
Psychotic ideation and inappropriate behavior are relatively uncommon early features of HADC. More typical is the insidious onset of apathy or social with-drawal in a previously healthy seropositive individ-ual. Nonetheless, HADC has also been mistaken for primary psychotic disorders, mania, SDAT, and anxi-ety and adjustment disorders.
Max
Score Score
4 (___) MEMORY – REGISTRATION
Give four words to recall (dog, hat, green, peach), 1 second to say each. Then ask the patient all 4 after you have said them.
4 (___) ATTENTION
Antisaccadic eye movement task1: 20 commands. __ errors in 20 trials (SCORE: ≤ 3 errors=4; 4 errors=3; 5 errors=2; 6 errors=1; >6 errors=0)
6 (___) PSYCHOMOTOR SPEED
Ask patient to write the alphabet in upper case letters horizontally across the page (use back of this record form) and record time: ___ seconds
(SCORE: ≤ 21 sec=6; 21.1 sec=5; 24.1–27 sec=4; 27.1–30 sec=3; >36 sec=0)
4 (___) MEMORY – RECALL
Ask for 4 words from Registration above. For words not recalled, prompt with “semantic clue,”
as follows: animal (dog); piece of clothing (hat); color (green); fruit (peach).
(SCORE: 1 point for each correct unprompted word, ½ point if correct after prompting.)
2 (___) CONSTRUCTION
Copy the cube below; record time: ___ seconds.
(SCORE: < 25 sec = 2; 25–35 sec = 1; > 35 sec = 0)
16 Max
(___) Total Score
(≤10 suggestive of cognitive impairment)
Figure 9–2. HIV Dementia Scale.
1Antisaccadic eye movement task: patient focuses on the examiner’s (E) nose and looks to and from the E’s moving index finger and nose, using alternating hands. E’s hands positioned at the patient’s shoulder width and eye height. Patient must maintain focus on E’s unmoving index finger (i.e., antisaccades). After practice trial, patient is then asked to perform 20 serial anti-saccades. 1 error = looking at moving finger.
Source. Power C, Selnes O, Grim J, et al.: “HIV Dementia Scale: A Rapid Screening Test.” Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 8:273–278, 1995. Used with permission from the publisher.