OOCCUUVolume 11 Number 3 February 1996

FF A Guide toAIDSResearch and Counseling

SSThrough a variety of mechanisms, HIV

disease can alter thought, emotion, andbehavior, leading to symptoms of “cogni-tive impairment,” a loss in the ability toprocess, learn, and remember informa-tion. The result is a confusing array ofchanges that inspires fear and helpless-ness in both clients and providers.

Cognitive impairment occurs in 55 per-cent to 65 percent of people with AIDS.1,2

Severe cognitive impairment occurs in thelater stages of HIV infection. There isdisagreement about whether cognitiveimpairment occurs during the early stagesof HIV infection; if it does, it is likely to besubtle and not discernible in activities ofdaily living.3 This article provides anoverview of HIV-related cognitive impair-ment, focusing on the role mental healthproviders play in its treatment.

Treatment ApproachesSome aspects of cognitive impairment are

treatable if addressed quickly; others areuntreatable and rapidly progressive. Whencognitive impairment occurs among peoplewith HIV disease, more than one disordermay be present, a situation that complicatesassessment and treatment. The response tocognitive impairment is four-fold, requiring:accurate diagnosis; coordination of treat-ment and education; aggressive treatmentof the acute causes of cognitive impairment,for example, opportunistic conditions anddelirium; and management through psy-chotherapy and psychopharmacology ofimpairment that is not otherwise treatable.

Accurate diagnosis is crucial to distin-guish among the variety of conditions thatcause HIV-related cognitive changes.* Themost common cause is direct infection of

the brain by HIV. Other causes includeopportunistic conditions, organic affectivedisorders, and conditions—such as deliri-um and substance abuse—that lead totransient impairment.

When questions of cognitive or behav-ioral change arise, psychotherapists shouldencourage clients to contact their physi-cians to rule out or treat reversible causesof impairment. It is useful to lay the foun-dation for coordination with medicalproviders early in the therapeutic relation-ship by obtaining releases from clients.

Once an HIV-related cognitive disorderis diagnosed, education can make thediagnosis less overwhelming and frighten-ing. It can also foster realistic expecta-tions. Providers should seek to demystifyimpairment by explaining the physical,emotional, and cognitive changes that mayoccur, the extent to which these can beameliorated, and the fact that thesechanges are organic and are not within theconscious control of the client.

When cognitive impairment cannot beeliminated through treatment, managementfocuses on psychotherapy and psychophar-macology. There are two psychotherapeuticmodels for managing HIV-related cognitiveimpairment.4,5 The first approach—“Adaptation and Compensation”—is usedfor mild cognitive impairment and aims atreinforcing remaining strengths while help-ing individuals compensate for changes inability. The goal of this approach is to main-tain independence and self-esteem byencouraging full participation in treatmentand life decisions. Supportive psychothera-py including education and problem-solv-ing is most appropriate at this stage.

The second approach—“EnvironmentalEngineering”—best addresses HIV-associ-ated dementia or cognitive impairment ofat least moderate degree. Individuals withdementia lose the ability to deal with thechanging demands of the world and

*See page 5 of thisissue, “Diagnosis ofCognitive Impairment,”for a discussion of thecauses of cognitiveimpairment anddiagnostic techniquesthat can discernamong them.

Treatment of Cognitive ImpairmentPenelope Zeifert, PhD, Mark Leary, MD and Alicia Boccellari, PhD

require structure to decrease fear andconfusion and to ensure safety. With theprogression of dementia, the therapist’srole becomes more active. Psychotherapyat this stage involves educating caregiversregarding management strategies andidentifying community resources to createthe necessary environmental structure.

If an acute psychiatric condition devel-ops, the nonmedical psychotherapist willneed to coordinate treatment with not onlythe primary physician but also a psychia-trist. A psychiatrist can provide consulta-tion about neuropsychiatric disorders,conduct diagnostic work-ups, and managepsychiatric medications. Finally, therapistsshould encourage clients to talk with theirphysicians about antiviral treatment, forexample, zidovudine (ZDV; AZT), which maybe useful in treating cognitive impairment.6

Adaptation and Mild ImpairmentMild impairment occurs most often in

the presence of HIV-associated minorcognitive/motor impairment, which iscaused by direct HIV infection of the brainand which may or may not progress toHIV-associated dementia. Mild impairmentmay also arise from lymphoma or in theearly stages of progressive multifocalleukoencephalopathy (PML) (although boththese conditions may cause much more

severe impairment and death). Individualswith mild impairment have some slownessin their thinking, memory problems, anddecreased problem-solving ability in theface of complex or novel tasks. Mildimpairment, however, does not interferewith the ability to live independently or tointeract meaningfully with others.

Using the Adaptation and Compensationmodel, psychotherapy focuses on settingrealistic goals, facilitating active problem-solving, and compensating for waningskills. In this context, psychotherapy canhelp client identify wishes for the futureand make short- and long-term plans tomeet their goals. It is notable that clientswith mild cognitive impairment can par-ticipate fully in decision-making and thatmaking realistic plans may increase asense of control and competence.

Psychotherapists should encourage indi-viduals with mild HIV-related cognitiveimpairment to be as independent as possi-ble by capitalizing on strengths and com-pensating for limitations. Compensatorystrategies are varied, but they include:performing one task at a time to decreasefrustration and the tendency to make mis-takes; getting enough rest and makingappointments early in the day to minimizefatigue; developing routines and avoidingcrowded public places to prevent overstim-

FOCUS2 February 1996

References1. Price RW, Brew BJ.The AIDS dementiacomplex. Journal ofInfectious Diseases.1988; 158(5): 1079-1083.

2. Heaton RK, Grant I, Butters N, et al. The HNRC 500 -Neuropsychology ofHIV infection atdifferent diseasestages. Journal of the InternationalNeuropsychologicalSociety. 1995; 1(3):231-251.

3. Maj M, Satz P,Janssen R, et al. WHO NeuropsychiatricAIDS Study, cross-sectional phase II:Neuropsychologicaland neurologicalfindings. Archives ofGeneral Psychiatry.1994; 51(1): 51-61.

Late last year, when we pub-lished a monograph on the sub-ject, it had become clear thatcognitive impairment was one ofthe most frightening conditionsassociated with HIV disease. AIDSand the Impact of CognitiveImpairment, by Penelope Zeifert,Mark Leary, and Alicia Boccellari,set out to catalog the state of theart in terms of etiology, diagno-sis, and treatment of the morethan one dozen conditions thatlead to loss of the ability to pro-cess and remember information.

Fears of “losing” one’s mindand the capacity to communi-cate run deep. For clients whohave observed the effects ofdementia, fears revolve aroundthe loss of control; for clientswith less experience, the term

may conjure up images of vio-lence and psychosis. Yet itappears that cognitive impair-ment is often one of the leastlikely issues to be spontaneous-ly raised in psychotherapy, andfor both clients and therapists,one of the least understoodconditions in the pantheon ofHIV-related distress.

For this issue of FOCUS, weasked Zeifert, Leary, andBoccellari to take on the task ofcondensing their opus from 90pages to fewer than 10. Theresult is a primer that defines therange of impairing conditions,the ways in which to distinguishamong them, and most impor-tantly, the variety of ways inwhich to manage and respond.HIV-related cognitive impairment

is in many cases associated withimmune decline and disability,but the important point of thebook and these articles is thatimpairment is often treatableboth with medication andthrough behavioral interventions.

People with cognitive impair-ment can remain connected totheir thoughts, behaviors, andfeelings with the aid of care-givers and providers. By incor-porating environmental andbehavioral cues into their lives,by establishing routine, and byteasing equanimity and self-control out of a discombobulat-ing situation, providers can helptheir clients transcend impair-ment and attain some measureof peace of mind. This under-standing is a boon not only toclients, but also to providersthemselves, who in learningabout these tools, gain comfortin treating people with cognitiveimpairment.

Editorial: Peace of MindRobert Marks, Editor

FOCUS3 February 1996

ulation; using stress reduction techniquesand regular exercise to reduce tension oranxiety; and utilizing adaptive devices suchas appointment or memory books to docu-ment important dates and information.

Environmental Engineering Moderate to severe cognitive impair-

ment—most commonly caused by “HIV-associateddementia”—leads tomemory loss,impaired manipulationand retrieval of infor-mation, and slowedthinking. Behavioralabnormalities includeapathy, depression,and less frequently,manic or hypomanicsymptoms. Motorimpairment may beginwith changes in hand-writing but is mostnotable for leg weak-ness, slowed move-ments, balanceproblems, and generalclumsiness. Withmoderate cognitive

impairment, individuals are no longer ableto work and may need some assistance, butcan still take an active part in their dailycare and can continue to interact withfriends and family. As dementia progress-es, individuals may no longer be able tolive independently, and they may no longerbe able to make reasonable decisions.

In the face of moderate cognitive impair-ment, psychotherapy can no longer bereflective or psychodynamic. The therapistneeds to take a pragmatic and directapproach, be more generous with sugges-tions, and at times even give advice. Theemphasis of therapy shifts from processingfeelings to negotiating the practical issuesof day-to-day living. A session may consistof checking in on basic competencies likethe ability to plan for meals or arrangetransportation, or of discussing recentvisits with doctors and current health sta-tus. The frame of the psychotherapeuticsession may also change in response to theclient’s limitations. For example, the psy-chotherapist may suggest periodicallyincluding the client’s partner or caregiver,meeting less often, or talking by telephone.

At the level of moderate impairment,therapy shifts towards EnvironmentalEngineering—defining and matching theclient’s degree of cognitive impairmentwith the amount of structure necessary. As

the need for assistance increases, the ther-apist can help the client explore both spe-cific needs and personal and communityresources. Discussing a client’s reaction toincreasing dependence and correspondingchanges in interpersonal relationships canoffer a sense of control and support.

As impairment worsens, therapy mayserve to maintain a sense of continuityand support for the client and, increasing-ly, for caregivers. Therapists may take onthe role of consultant to family andfriends, and facilitator between caregiversand health providers. They may be partic-ularly helpful in facilitating a home careplan that incorporates EnvironmentalEngineering interventions.

Managing DementiaManagement of dementia occurs in

three main areas: physical and cognitivechanges; safety concerns; and emotionaland personality changes. The key princi-ple of intervention is to provide externalsupport to the client in order to preservethe highest level of functioning possible.To achieve these goals, therapists shouldwork with clients and their caregivers todevelop and maintain a structured envi-ronment that includes the use of routine,physical cues, and safety devices.

For example, to decrease confusion:maintain a familiar environment; providefrequent orientation cues; limitbackground noise; slow down speech andspeak in simple sentences; and removeclutter. To increase physical mobility: usewalkers or canes; use chairs with arms toaid in sitting and rising; and install ashower bench or raised toilet seat. Toensure safety: remove slip rugs and orga-nize furniture to provide more open space;provide good lighting; safety proof the tubor shower with non-slip surfaces; installmetal plates to cover stove burners; andhave clients carry identification cards andwear identification bracelets.

As impairment progresses, clients arelikely to undergo emotional and personali-ty changes. Ironically, as cognitive impair-ment progresses and interferes with dailyfunctioning, cognitively impaired individu-als often become less anxious about theirsymptoms of progressive dementia.Emotions as well as thinking become sim-plified. The ability to distinguish the finenuances of emotional states and to sustainemotional states decreases. In addition,organic denial may lead to a lack of aware-ness of deficits and poor judgment.

While people with moderate cognitiveimpairment tend to be apathetic, they are

4. Boccellari A.Assessing and diag-nosing AIDS dementiacomplex. In AIDSDementia ComplexTraining Manual.San Francisco: FamilySurvival Project, 1990.

5. Mace N, Rabins P.The 36-Hour Day.Baltimore: JohnHopkins UniversityPress, 1981.

6. Everall IP.Neuropsychiatricaspects of HIV infection. Journal of Neurology,Neurosurgery, andPsychiatry. 1995;58(4): 399-402.

Psychotherapeutictreatment requires

matching approachwith degree of

cognitive impairmentand developing

compensatory orenvironmental

engineering strategies.

AuthorsPenelope Zeifert, PhDis an Assistant ClinicalProfessor of Psychiatryat the University ofCalifornia SanFrancisco and aclinical neuropsycholo-gist at StanfordUniversity and LagunaHonda Hospital in SanFrancisco.

Mark Leary, MD isDeputy Chief ofPsychiatry at SanFrancisco GeneralHospital (SFGH) and anAssistant ClinicalProfessor of Psychiatryat UCSF. He is Co-Chairof the SFGH PsychiatryHIV Task Force.

Alicia Boccellari, PhDis Director of theNeuropsychologyService and theDivision ofPsychosocial Medicineat SFGH and anAssociate ClinicalProfessor ofPsychology at UCSF.She has worked withHIV disease since1985 and has lecturedand published widelyon the topic.

Drs. Zeifert, Leary,and Boccellari are co-authors of AIDS andthe Impact ofCognitive Impairment,the first in the AHPMonograph Series(UCSF AIDS HealthProject, 1995).

also overly responsive to stimulation.They can become easily distracted oragitated, and they have little tolerance forfrustration. Emotions can be quick andintense, manifesting as sudden moodchanges or as angry outbursts that resolvequickly. This changeability in emotionscan be easily misunderstood bycaregivers, who may see this behavior asvolitional, and who may respond in kindwith frustration or annoyance.

These changes cannot be addresseddirectly: confronting clients by challeng-ing their reasoning or proposed course ofaction is likely to lead to outbursts and amore entrenched position. Redirecting ordistracting clients from dangerous orinappropriate behaviors is likely to bemore effective.

Psychopharmacological InterventionsPsychopharmacologic agents can pro-

vide valuable treatment of psychiatric andbehavioral symptoms seen in clients withHIV-related cognitive impairment, particu-larly in response to psychosis, anxiety,and the affective disorders. Patients withHIV-related cognitive impairment, whatev-er the cause, are likely to be more sensi-tive than usual to the effects—includingundesirable ones—of psychotropic medi-cations. For this reason it is prudent tobegin treatment with lower than usualdosages, to make changes gradually, tomonitor for side effects regularly andcarefully, and to limit the number of psy-chopharmacologic agents used.

Organic psychosis may develop duringthe course of HIV-associated dementia,often manifesting as organic mania, butalso including auditory or visual hallucina-tions, paranoia, delusions, and confusion.

Treatment of psychosis consists of pre-scribing moderate potency antipsychoticmedications in low dosages, providing aroutine and structured environment, andmonitoring levels of stimulation.

Organic mania usually occurs withadvanced HIV disease and is frequentlyassociated with motor abnormalities andmemory problems. Symptoms includehyperactivity, impulsivity, grandiose think-ing, agitation, and delusions. Treatmentconsists of education, medication (lithiumand Depakote), a structured environmentto ensure safety and medication compli-ance, and in severe cases, hospitalization.

Cognitive symptoms associated withdepression include generalized mentalslowing and impaired attention and concen-tration, both resulting in apparent memoryproblems. Psychotherapy with depressedpatients with mild cognitive impairmentmay include supportive individual therapy,as well as couples or group therapy. Forpatients with more serious cognitiveimpairment, depression is likely to beorganic, and antidepressants or psychos-timulants may be useful. Psychostimulantsare particularly well-tolerated by clientswith advanced HIV disease.

ConclusionHIV-related cognitive impairment is

manageable using a combination of mea-sures. The fundamental tenets of treat-ment—accurate diagnosis, coordinatedcare, psychopharmacological intervention,matching psychotherapeutic approachwith degree of impairment, and applyingcompensatory and environmental engi-neering strategies—place providers in apowerful position to mitigate cognitiveimpairment and to improve quality of life.

FOCUS4 February 1996

ReferencesBoccellari A, Zeifert P. Management ofneurobehavioral impairment in HIV-1infection. Psychiatric Clinics of NorthAmerica. 1994; 17(1): 183-203.

Bornstein RA, Nasrallah HA, Para MF, et al. Duration of illness and neuropsy-chological performance in asymptomaticHIV infection. Journal of Neuropsychiatryand Clinical Neurosciences. 1994; 6(2):160-164.

Everall IP. Neuropsychiatric aspects ofHIV infection. Journal of Neurology,

Neurosurgery & Psychiatry. 1995; 58(4):399-402.

Grunseit AC, Perdices M, Dunbar N, et al. Neuropsychological function inasymptomatic HIV-1 infection: Methodo-logical issues. Journal of Clinical andExperimental Neuropsychology. 1994;16(6): 898-910.

Harvath TA, Patsdaughter CA, BumbaloJA, et al. Dementia-related behaviors inAlzheimer’s disease and AIDS. Journalof Psychosocial Nursing and MentalHealth Services. 1995; 33(1): 35-39.

Heaton RK, Grant I, Butters N, et al. TheHNRC 500: Neuropsychology of HIVinfection at different disease stages.Journal of the InternationalNeuropsychological Society. 1995; 1(3):231-251.

Karlsen NR, Reinvang I, Froland SS. Afollow-up study of neuropsychologicalfunctioning in AIDS-patients: Prognosticsignificance and effect of zidovudinetherapy. Acta Neurologica Scandinavica.1995; 91(3): 215-221.

Maruff P, Currie J, Malone V, et al.Neuropsychological characterization ofthe AIDS dementia complex and ration-alization of a test battery. Archives ofNeurology. 1994; 51(7): 689-695.

Clearinghouse: Cognitive Impairment

References1. Navia BA, JordanBD, Price RW. The AIDSdementia complex: I.Clinical features.Annals of Neurology.1986b; 19(6): 517-524.

2. Working Group ofthe AmericanAcademy ofNeurology AIDS TaskForce. Nomenclatureand research casedefinitions for neuro-logic manifestationsof human immunode-ficiency virus-type 1(HIV-1) infection.Neurology. 1991;41(6): 778-785.

3. Kieburtz K,Zettelmaier AE,Ketonen L, et al.Manic syndrome in AIDS. AmericanJournal of Psychiatry.1991; 148(8): 1068-1070.

FOCUS5 February 1996

HIV-related cognitive impairment iscomplicated because symptoms may varyonly minimally across the many conditionsthat cause it. Treatment, however, variesdramatically, and so accurate diagnosis iscrucial. This article delineates the causesof cognitive impairment and outlines thetools necessary to differentiate them.

Direct Infection of the BrainMost HIV-related cognitive impairment is

caused by direct infection of the brain. HIVappears to damage the “myelin” and reduceelectrochemical conduction of nerve impuls-es. Two conditions result from infection:“HIV-associated minor cognitive/motordisorder” at the mild end, and “HIV-associat-ed dementia,” which is an AIDS-definingcondition, at the severe end. Dysfunctioncaused by direct infection is neither pro-gressive, orderly, nor predictable.1 Peoplewith HIV-associated minor cognitive/motordisorder do not necessarily develop demen-tia,2 and it is the degree of impairment inactivities of daily living that distinguishesbetween the two conditions.

Among the functions affected by directHIV infection of the brain are: concentra-tion, memory, emotion, behavior, ability toperform complex tasks, coordination andbalance, and muscle strength. Diagnosis isachieved by confirming the presence ofHIV and symptoms of impairment, andexcluding other causes through testing.

Opportunistic DiseasesFour HIV-related opportunistic conditions

commonly cause cognitive impairment:

toxoplasmosis, cryptococcal meningitis,progressive multifocal leukoencephalopa-thy, and lymphoma. Toxoplasmosis iscaused by a parasite, which when active,typically produces lesions in various partsof the brain. This results in symptomsranging from motor weakness to seizures tochanges in mental status including confu-sion and memory loss. Common presentingsymptoms of toxoplasmosis include feverand constant headache. Ongoing antibiotictreatment can suppress the symptoms oftoxoplasmosis but not cure it. Toxoplas-mosis is diagnosed in three ways: bloodtests, magnetic resonance imaging (MRI),and lumbar puncture (“spinal tap”).

Cryptococcal meningitis, a fungal infec-tion of the outer covering of the brain,typically presents with fever and severeheadache. Mental status changes rangefrom mild behavioral and personalitychanges to severe memory loss and confu-sion. Antifungal drugs can clear infection.For an accurate diagnosis, clients mustundergo lumbar puncture.

Progressive multifocal leukoencepha-lopathy (PML) is a neuropsychiatric diseasecaused by the JC virus. It usually results insevere dementia and death within severalmonths. However, small but encouragingreports suggest that experimental treat-ments may stabilize progression. Definitivediagnosis of PML requires a brain biopsy. Itis most frequently diagnosed on the basisof MRI scans and marked neurologicalsymptoms (for example, one-sided weak-ness), which are not present in HIV-associ-ated dementia.

Lymphoma, a cancer originating in thelymphatic system, can invade the brain andcause impairment. Some clients with brainlymphoma present similarly to those with

Portegies P. Review of antiretroviraltherapy in the prevention of HIV-relatedAIDS dementia complex (ADC). Drugs.1995; 49 (Supp 1): 25-31.

Power C, Johnson RT. HIV-1 associateddementia: Clinical features and patho-genesis. Canadian Journal of NeurologicalSciences. 1995; 22(2): 92-100.

Pugh K, Riccio M, Jadresic D, et al. Alongitudinal study of the neuropsychi-atric consequences of HIV-1 infectionin gay men. Psychological Medicine.1994; 24(4): 897-904.

Stern Y. Neuropsychological evaluationof the HIV patient. Psychiatric Clinics ofNorth America. 1994; 17(1): 125-134.

Stern Y, Liu X, Marder K, et al.Neuropsychological changes in aprospectively followed cohort ofhomosexual and bisexual men with andwithout HIV infection. Neurology. 1995;45(3, Part 1): 467-472.

White DA, Heaton RK, Monsch AU, et al.Neuropsychological studies of asymp-tomatic human immunodeficiency virus-type 1 infected individuals. Journal ofthe International NeuropsychologicalSociety. 1995; 1(3): 304-315.

ContactsDebra Ann Brodie, PhD, Detroit MedicalCenter-Harper Hospital, Harper-CanfieldOutpatient Services, 50 East Canfield,Detroit, MI 48201, 313-745-8901.

James W. Dilley, MD, UCSF AIDS HealthProject, Box 0884, San Francisco, CA94143-0884, 415-476-6430.

Mark Leary, MD, University of CaliforniaSan Francisco, Box 0852, San Francisco,CA 94143-0852, 415-206-5216.

Donely Meris, NYU AIDS/SIDA MentalHealth Project, 35 West Fourth Street,Suite 1200, New York, NY 10012-1172,212-998-5614.

Penelope Zeifert, PhD, 1947 Divisadero,Suite 5, San Francisco, CA 94115, 510-273-9445.

See also references cited in articles in this issue.

Diagnosis of Cognitive ImpairmentPenelope Zeifert, PhD, Mark Leary, MD and Alicia Boccellari, PhD

AuthorsPenelope Zeifert, PhDis an Assistant ClinicalProfessor of Psychiatryat the University ofCalifornia SanFrancisco and aclinical neuropsycholo-gist at StanfordUniversity and LagunaHonda Hospital in SanFrancisco.

Mark Leary, MD isDeputy Chief ofPsychiatry at SanFrancisco GeneralHospital (SFGH) and anAssistant ClinicalProfessor of Psychiatryat UCSF. He is Co-Chairof the SFGH PsychiatryHIV Task Force.

Alicia Boccellari, PhDis Director of theNeuropsychologyService and theDivision ofPsychosocial Medicineat SFGH and anAssociate ClinicalProfessor ofPsychology at UCSF.She has worked withHIV disease since1985 and has lecturedand published widelyon the topic.

dementia, but significant neurologic symp-toms often differentiate the two condi-tions. While CT or MRI scans are critical fordiagnosis, at times a brain biopsy may benecessary to distinguish lymphoma fromtoxoplasmosis. Radiation therapy is themost effective form of treatment.

Other Causes“Organic affective disorders” are distur-

bances of mood that result from specificbiological causes. HIV-related organicaffective disorders emerge late in thecourse of HIV disease as immunosuppres-sion increases. Organic mania, similar tothe mania of bipolar disorder in symptomsand treatment, occurs four times moreoften in people with HIV disease whencompared to the general population.3

Organic depression, best identified usingneuropsychological assessment, is treatedwith antidepressants or psychostimulants.

Some cognitive impairment is “tran-sient,” that is, short-lived and reversible.Delirium is a common medical syndromewith a variety of symptoms and underly-ing causes, including opportunistic infec-tions and some HIV-related medications. Itis signaled by abrupt changes in mentalstatus, and clients may present as highlyaroused or withdrawn. To accuratelyassess delirium, it is necessary to conduct“serial” mental status examinations (sever-al times daily and over consecutive days).

While chronic and heavy substanceabuse may cause permanent impairment,drug use generally causes transient prob-lems with attention, memory, orientation,agitation, and confusion. Substance abusemay also result in secondary psychiatricdisorders such as depression.

Diagnostic ToolsThere are five procedures used in the

diagnosis of cognitive impairment: mentalstatus examination, neuropsychiatricinterview, neurologic examination, labora-tory and radiologic testing, and neuropsy-chological testing. The diagnostic processbegins with a mental status examinationand neuropsychiatric interview to assessoverall level of neuropsychiatric function-ing. These procedures may be conductedby a psychotherapist or primary healthcare provider.

The mental status examination aims atdetecting deficits in basic cognitive func-tions by looking at a variety of indicatorsincluding: general appearance, coordination,memory, language, affect, orientation, andconcentration. The neuropsychiatric inter-view expands upon the mental status exami-

nation, adding a comprehensive medicaland psychological history and assessing theclient’s current ability to function at workand in activities of daily living.

Neurologic examination and laboratoryand radiologic testing are critical to clarifythe cause of impairment and are best per-formed by health practitioners familiar withHIV disease. A neurologic examinationfocuses on indicators that may signifycentral nervous system disease such asneurological functioning, including walking,coordination, and muscle tone. Laboratorytests include: routine blood tests, whichindicate the general functioning of organsystems and immunity; more specializedtests, which indicate conditions that cancause cognitive impairment; brain scans;electroencephalograms (EEG), which identi-fy seizure disorders; and lumbar puncture,which assesses acute brain infection.

If the diagnostic picture remainsunclear, for example, if there are no bio-logical indicators of cognitive impairment,it may be necessary for a neuropsycholo-gist to undertake neuropsychologicaltesting. Neuropsychological testing usesstandardized measures, primarily paper-and-pencil tests, to assess suspected cog-nitive and emotional dysfunction that maynot be evident through other procedures.*

ConclusionThe complexity of diagnosing cognitive

impairment may be daunting, but it isimportant to remember that diagnosticapproaches are tools. No single providerneed understand the intricacies of all ofthese tools, and psychiatrists, neurolo-gists, and neuropsychologists can beuseful resources in negotiating this pro-cess. Most significantly, accurate diagno-sis is the gateway to the effectivetreatment of many of the conditions thatcause cognitive impairment.

FOCUS6 February 1996

Comments and Submissions We invite readers to send letters

responding to articles published inFOCUS or dealing with current AIDSresearch and counseling issues. Wealso encourage readers to submit arti-cle proposals, including a summary ofthe idea and a detailed outline of thearticle. Send correspondence to:

Editor, FOCUSUCSF AIDS Health Project, Box 0884San Francisco, CA 94143-0884

*It is important tonote that brief neuropsychiatricscreening measuressuch as the Mini-Mental Status Examare relatively insensi-tive to the cognitivedeficits in HIV-infectedclients and thus arenot clinically useful.

FOCUS7 February 1996

Mapping Brain Infection in Dementia PatientsBrew BJ, Rosenblum M, Cronin K, et al. AIDSdementia complex and HIV-1 brain infection:Clinical-virological correlations. Annals ofNeurology. 1995; 38(4): 563-570. (National Centrein HIV Epidemiology and Clinical Research,Sydney; Memorial Sloan-Kettering Cancer Center,New York; and University of Minnesota.)

Autopsies of 55 AIDS patients revealedthat HIV infection of the brain was morelimited than expected in patients withlate-stage AIDS Dementia Complex (ADC)and absent in some cases of mild to mod-erate ADC. Researchers theorized that thisevidence suggests that brain infectionmay be a late event in the course of HIVprogression, and that brain infectionalone cannot explain the clinical symp-toms of ADC.

Researchers mapped HIV infection bothpathologically and virologically in thebrains of 54 men and one woman. The

subjects ranged from 21 years oldto 60 years old. Autopsy includedan evaluation that mapped thefrequency and regional distribu-tion of the p24 antigen amongsections of the brain.

Twenty-one brains containeddetectable HIV p24 antigen.Instead of a homogeneous orrandom distribution, the antigentended to concentrate in certainsections of each brain. Althoughdifferent sections were infected indifferent brains, HIV infected theglobus pallidus in almost two-thirds of the subjects and thecorpus callosum (deep white mat-ter) in more than half, suggestingthat these two subcortical areasmay be particularly susceptible toactive infection.

Overall, p24 antigen was detect-ed more often in late-stage ADCpatients than in early-stage ADCpatients. But the amount ofdetectable brain infection wassurprisingly small, even non-existent, in several cases ofsevere clinical ADC. Two of the six

cases of stage 3 ADC (the second highestseverity level) had no brain infection atall; researchers noted that in these cases,ADC diagnosis had been made based onimpaired ambulation rather than cognitivedysfunction. But there was no explanationfor one of the six cases of end-stage ADCin which there was cognitive impairment

but no detectable brain infection. Inmilder stages of ADC, p24 antigen wasalso undetectable or disproportionatelyminor in relation to the symptoms ofinfection. It is notable, however, that therewere no cases of productive brain infec-tion without symptomatic ADC.

Neurological Impairment in ChildrenBrouwers P, Tudor-Williams G, DeCarli C, et al.Relation between stage of disease and neurobehav-ioral measures in children with symptomatic HIVdisease. AIDS. 1995; 9(7): 713. (National CancerInstitute; National Institute of NeurologicalDisorders and Stroke; Medical Illness CounselingCenter, Chevy Chase, Maryland; and Children’sNational Medical Center.)

A small but comprehensive study foundthat children with severe symptomatic HIVdisease also experience severe cognitivedysfunction and high levels of neurologi-cal abnormalities. Unlike adults, who maydevelop cognitive impairment as a resultof opportunistic infections, children seemto develop neurologic deficits as a resultof direct HIV infection of the brain.

The study comprised 44 boys and 31girls with moderate to severe symptomaticHIV disease. Ages ranged from less than ayear old to almost 14 years old. Evaluationincluded brain scans, psychological mea-surement of cognitive function, and T-helper cell and p24 antigen testing.

Significant correlations were foundbetween high T-helper cell levels andsevere brain atrophy and white matterabnormalities. Brain lesions were associat-ed with both cognitive and social-emo-tional dysfunction. Since opportunisticinfections and lymphoma of the CNS areuncommon in children, these findingssuggest that both neurological abnormali-ties and the resulting dysfunction aresymptoms of direct infection.Researchers concluded that the progres-sion of HIV-infection continuously com-promises CNS functions, placingseropositive children at increased risk fordevelopmental impairment.

No Evidence for Continuum of ImpairmentSelnes OA, Galai N, Bacellar H, et al. Cognitiveperformance after progression to AIDS: A longitudi-nal study from the Multicenter AIDS Cohort Study.Neurology. 1995; 45(2): 267-275. (Johns HopkinsUniversity; University of California, Los Angeles;University of Pittsburgh; and NorthwesternUniversity.)

A national study found that an AIDSdiagnosis predicts only a modest declinein fine motor skills, providing no evidencefor a continuum of cognitive decline inpeople with AIDS.

Recent Reports

A small studyfound that

the decline ofcognitivefunction

among HIV-infected drug

users is dueto the chronic

use of toxicsubstancesrather than

HIV infection.

FOCUS8 February 1996

Researchers studied 138 HIV-infectedindividuals, including 52 with T-helpercell counts of less than 200 but no AIDS-defining illness, 57 with AIDS-definingillnesses but no central nervous systeminvolvement, and 29 with a clinical diag-nosis of HIV-associated dementia. Themean age of diagnosis was approximately40 years, and the mean number of yearsof education was 16. The groups receivedtwo neuropsychological evaluationsbefore and after AIDS diagnosis, and theCenter for Epidemiological StudiesDepression (CES-D) scale at each visit.

Following an AIDS diagnosis, the onlycognitive impairment that researchersobserved was a slight decline inpsychomotor speed. As expected, thegroup with dementia showed the mostsignificant decline after an AIDS diagno-sis, with a less pronounced decline in theAIDS group, and a barely perceptibledecline in the immunosuppressed group.These results suggest that dementia maybe a discrete diagnosis with a specificpathogenesis rather than the end to acontinuum of cognitive decline.

Disability and Neuropsychologic ImpairmentAlbert SM, Marder K, Dooneief G, et al. Neuro-psychologic impairment in early HIV infection: Arisk factor for work disability. Archives of Neurology.1995; 52(5): 525-530. (Columbia University; andthe New York State Psychiatric Institute.)

Among people with HIV disease, defec-tive neuropsychological performance is achronic condition that leads to increasedincidence of work disability, according toa prospective study of 185 gay and bisex-ual men.

Researchers evaluated 44 asymptomaticseropositive men and 72 seronegativemen for HIV-related symptoms, neuropsy-chological performance (NP), and workdisability (defined as having worked lessthan half-time for two or more years).

Over a period of 4.5 years, work disabili-ty was consistently predicted by cognitivedeficit. The incidence of disability was 70percent among eight seropositive men with“defective” NP scores, 30 percent among 36seropositive men with normal scores, 25percent for 12 seronegative men with“defective” NP scores, and 15 percent for 60seronegative men with normal NP scores.About the same proportion of seronegativeand asymptomatic seropositive subjectsscored in the defective range of neuropsy-chologic performance. But the 17 percent ofseronegatives who scored in the defectiverange did so sporadically, while the 18percent of asymptomatic seropositive sub-

jects were more likely to do so consistentlyover a period of several visits.

Chronic Drug Use and Cognitive Decline Grassi MP, Clerici F, Perin C, et al. HIV infection anddrug use: Influence on cognitive function. AIDS.1995; 9(2): 165-170. (L. Sacco Hospital, Milan.)

The decline of cognitive function amongHIV-infected drug users is due to thechronic use of toxic substances rather thanHIV infection, according to a small Italianstudy. An evaluation of cognitive functionfound that slower reaction time and poormemory occurred more often among thedrug users regardless of serostatus.

The sample consisted of 56 seropositivedrug users, 19 seronegative drug users,and 27 seronegative non-drug users.Researchers employed 13 neuropsycho-logical tests.

Seronegative non-drug users scoredhighest, with statistically significant betterscores in visual-spatial orientation, atten-tive capacity and psychomotor speed,story recall, and abstract thinking.However, there were no significant differ-ences in test results between the two drug-using groups. In addition, active drug usersscored significantly worse than ex-drugusers, also regardless of serostatus, whichmay suggest that cognitive deficit isreversible when drug use is discontinued.

Next MonthSeveral studies in the past few years

have heralded the growth of HIV dis-ease in rural areas that had been freeof large caseloads. It is not news thatrural social service systems are notable to meet the increasing and thecomplex mental health needs of peo-ple with HIV disease and their fami-lies. The March 1996 issue of FOCUSlooks at two approaches to deliveringcare to these underserved areas.

Michael Shernoff, LCSW, one of thepioneers in HIV-related mental healthcare, describes the psychosocial issuesfaced in rural areas and an innovativestrategy to providing support to peoplewith HIV disease who are moving backfrom adult lives in urban areas to theirrural families of origin. AlexanderTartaglia, DMin, a therapist at a SouthCarolina pastoral counseling center,looks at the role of rural clergy andcongregations in supporting the fami-lies of people with HIV disease.

Executive Editor; Director,AIDS Health ProjectJames W. Dilley, MD

EditorRobert Marks

Staff WriterJohn Tighe

Founding Editor; AdvisorMichael Helquist

Medical AdvisorStephen Follansbee, MD

MarketingMichal Longfelder

DesignSaul Rosenfield

ProductionJennifer CohenKelly Van Noord

CirculationSandra Kriletich

InternsJulie BalovichShirley GibsonMark Kuhnle

FOCUS is a monthly pub-lication of the AIDSHealth Project, affiliatedwith the University ofCalifornia San Francisco.

Twelve issues of FOCUSare $36 for U.S. residents,$24 for those with limitedincomes, $48 for individu-als in other countries, $90for U.S. institutions, and$110 for institutions inother countries. Makechecks payable to “UCRegents.” Address sub-scription requests and cor-respondence to: FOCUS,UCSF AIDS HealthProject, Box 0884, SanFrancisco, CA 94143-0884. Back issues are $3each: for a list, write to theabove address or call(415) 476-6430.

To ensure uninterrupteddelivery, send your newaddress four weeks beforeyou move.

Printed on recycled paper.

©1996 UC Regents: All rights reserved.

ISSN 1047-0719

FOCUSA Guide toAIDSResearch and Counseling

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