How the Brain can be Affected by HIV-Infection:
A Neuropsychological Primer
PHASE, Canadian Psychological Association and Health Canada
Module developed by Sean B. Rourke, Ph.D., C.Psych.
Assistant Professor of Psychiatry, University of Toronto
Director of Research, St. Michael’s Hospital Mental Health Service, Toronto, Ontario
Overview
• Clinical case vignettes to highlight differential diagnoses• What psychologists need to know about HIV-related
brain impairments when treating clients with HIV/AIDS• How well do subjective cognitive complaints correspond
with HIV-related brain impairments?• Impact of neuropsychological impairments on everyday
functioning and instrumental activities of daily living• What can psychologists do to help clients with HIV-
related brain impairments?• Clinical resources.
2
Three Clinical Case Vignettes
• Peter is a 38-year-old gay man who has been infected with HIV for eight years.
• Paul is a 44-year-old man with hemophilia who first tested positive for HIV in 1986.
• Mary is a 35-year-old married woman who contracted HIV four years ago
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Peter
Peter is a 38-year-old gay man who has been HIV+ for eight years and on disability for the past three years since having PCP. He is medically stable and is on HAART. His CD4 count is 176 and his viral load is < 500. Lately, Peter has been complaining of depression, low energy, and difficulty with memory, word-finding, and concentration. Peter’s primary- care physician makes a referral to you for psychological assessment to determine the nature and clinical significance of Peter’s complaints.
How do you proceed ?4
General Assessment Issues to Address
• Developmental and academic history• Neuromedical history• HIV-related conditions and symptoms• Psychiatric and substance use history• Subjective cognitive complaints• Neuropsychological test performance.
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Determine Differential Diagnosisfor Peter
What Peter’s complaints might reflect:
(1) learning disability or developmental problem
(2) pre-existing neurological condition or brain injury
(3) long-standing characterological features
(4) a mood disorder (pre-existing or new onset)
(5) HIV-related neuropsychological (brain) impairments
(6) physical problems
(7) psychoactive prescription (e.g., Percodan, Diazepam)
(8) excessive drinking or illicit drug use.6
Peter’s Neuropsychological Profile
202530354045505560
T-S
core
Attention andworkingmemory
Learningefficiency
Memory(retention)
Psychomotorskills
Executiveskills
CLINICAL IMPRESSION: Neuropsychological impairment in psychomotor efficiency;possible reduced efficiency with attention / working memory and executive skills.(Neuropsychological ability is considered to be in the “impaired” range if T-Score < 40.) 7
Paul
Paul is a 44-year-old man with hemophilia who first tested positive for HIV in 1986. He has esophageal thrush and has had PCP twice. His CD4 count is 20; his viral load has increased over the past month from 45,000 to 150,000. Paul is currently on HAART.
Referral Question: Paul does not appear to be able to manage his ADLs well and I am not sure whether he is adhering to his medication regimen. While Paul reports only the occasional problem with memory, he appears to be quite disorganized, forgetful and somewhat apathetic.
Please assess and offer treatment suggestions8
Determine Differential Diagnosisfor Paul
What Paul’s behaviour might reflect:
(1) learning disability or developmental problem
(2) pre-existing neurological condition or brain injury
(3) long-standing characterological features
(4) a mood disorder (pre-existing or new onset)
(5) HIV-related neuropsychological (brain) impairments
(6) physical problems
(7) use of psychoactive medications
(8) excessive drinking or illicit drug use.9
Paul’s NeuropsychologicalProfile
20
25
30
35
40
45
50
55
60
T-S
core
Attention andworkingmemory
Learningefficiency
Memory(retention)
Psychomotorskills
Executiveskills
CLINICAL IMPRESSION: Neuropsychological impairments in all ability areas.(Neuropsychological ability is considered to be in the “impaired” range if T-Score < 40.) 10
Mary
Mary is a 35-year-old married woman who contracted HIV four years ago. She has had only minor opportunistic infections (e.g., oral thrush) but her CD4 count is low and her viral load is 89,000. She has had a recent medication breakthrough. For the past four months, she has been complaining of reduced efficiency at work. Although she continues to work full-time, she is feeling overwhelmed and exhausted when she comes home.
Referral Question: Is Mary’s reduced efficiency at work due to systemic HIV-infection, stress, HIV-related brain problems, or a combination of these ? Please advise.
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Determine Differential Diagnosis for Mary
What Mary’s complaints might reflect:
(1) learning disability or developmental problem
(2) pre-existing neurological condition or brain injury
(3) long-standing characterological features
(4) a mood disorder (pre-existing or new onset)
(5) HIV-related neuropsychological (brain) impairments
(6) physical problems (persistent fatigue, low energy)
(7) use of psychoactive medications
(8) excessive drinking or illicit drug use. 12
Mary’s Neuropsychological Profile
20
25
30
35
40
45
50
55
60
T-S
core
Attention andworkingmemory
Learningefficiency
Memory(retention)
Psychomotorskills
Executiveskills
CLINICAL IMPRESSION: Neuropsychological impairments in attention, learning and psychomotor skills. (Neuropsychological ability is considered to be in the “impaired” range if T-Score < 40.)
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Mood Disorders and HIV-Infection
1. Is the assessment of a mood disorder different when client is HIV-infected?
2. If there is mood disorder, is it common for clients to report problems with memory or concentration?
3. Is the mood disorder directly caused by HIV?
4. Is the treatment of choice for a mood disorder different for a client who is HIV-infected?
5. Do clients with symptomatic HIV-infection respond as well to treatment as those who have no symptoms?
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Assessing for HIV-related brain impairments
1. What tools can psychologists use to assess for HIV-related neuropsychological (brain) impairments, and does the selection of instruments depend on the stage of HIV disease?
2. What is the difference between a neuropsychological impairment and a neuropsychological disorder, and why is this distinction important in working with clients with HIV-infection ?
3. What is meant by the term “HIV dementia” ?
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Assessing for HIV-Related Brain Impairments
1. What is the concordance between client’s subjective cognitive complaints and neuropsychological testing?
2. Does the type and/or severity of cognitive complaint reported by the client predict which clients will show progression of brain impairments?
3. Are there specific neuropsychological test scores that predict whether a client may progress ?
4. What are the available treatments for HIV-related neuropsychological (brain) impairments ?
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What is the impact ofsystemic medical problems?
1. Are there guidelines to help discern when somatic or vegetative symptoms (e.g., fatigue, sleep and appetite disturbance, loss of libido) are related to a mood disorder and when they may be HIV-related?
2. How much do fatigue and other medical problems contribute to concentration and memory problems?
3. Should psychological assessments be conducted when clients are medically unstable ?
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Neuropsychological Impairments in HIV:What Psychologists Need to Know When
Treating Clients with HIV-Infection
Terminology and nosology Prevalence and type of neuropsychological
impairments associated with HIV-infection Understanding the nature of memory impairment in
HIV is important for clinical management When to refer for neuropsychological assessment What neuropsychological tests should be
administered? Are neuropsychological “screening” tests available ?
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Classification of HIV-Related Brain
Impairments
Delirium (acute)Secondary (CNS infection)
NPINo apparent impact on ADLs
HIV-1 MCMDMild to moderate NPIImpaired ADLs (mild)
HIV-1 HADCModerate to severe NPIImpaired ADLs (severe)
"Dementia" ("chronic")Primary
HIV-Associated Neurological Disease
NPI = Neuropsychological Impairment; ADL = Activities of Daily LivingHIV-1-associated cognitive/motor complex (includes MCMD and HADC)(MCMD: minor cognitive/motor disorder; HADC: HIV-associated dementia complex) 19
“Cortical” vs. “Subcortical”Brain Disorders
“Cortical” (e.g., AD)• Aphasia• Apraxia• Agnosia• Acalculia• Executive deficits• Memory deficits
(rapid forgetting)
AD = Alzheimer’s disease
“Subcortical” (e.g., HIV)• Bradyphrenia (slowing)• Complex attentional deficits• Retrieval problems• Mood disturbance• Executive deficits• Memory deficits (learning
efficiency and retrieval)
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Prevalence of Neurocognitive Deficits in Non-demented
HIV-1 Individuals
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0
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40
50
60
% w
ith im
pairm
ent
HIV-Controls
CDC-A CDC-B CDC-C
Heaton et al., 1995 21
Neuropsychological impairment in asymptomatic HIV-infection:
Why so much variability ?
• White et al. (1995) examined 57 studies that compared HIV-positive asymptomatics to HIV-negative controls.
• Overall, median rate of NP impairment was 35% for asymptomatics with HIV-infection.
• Test battery size was important determinant (larger batteries found more impairments).
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Pattern of Deficits Associated with HIV-Infection
6157
4441
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3228
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0
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70
% w
ith
imp
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Attention Learning Verbal Motor Memory Psychomot Sensory Abstract
Heaton et al., 1995 23
Verbal Memory Characteristics
0
2
4
6
8
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Num
ber o
f wor
ds re
calle
d
Trial 1 Trial 2 Trial 3 Delayed Recall Recognition
ADHIVNormal
AD = Alzheimer’s disease (example of “cortical” memory profile)HIV (characteristic of “subcortical” memory profile)
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Factors That Can Affect Memory Processing in HIV-infection
• Increasing age or lower education• Reduced attention skills• Reduced speed of information processing• Frontal lobe executive system impairments• Mood disorder ??
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Diagnostic Issues• Peter ??• Paul ??• Mary ??
Therapeutic and Management Issues
• How will the condition diagnosed affect the diagnosis client’s ability to carry out basic and instrumental ADLs (e.g., job, managing finances or medication regimen), and will there be change over time?• What other referrals or consultations are needed (e.g., OT)?• Discuss psychological interventions.
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Diagnostic Summary: Peter
• Diagnosis: Mood disorder (recurrent)• Psychomotor slowing detected but otherwise relatively
normal in other neuropsychological abilities• Does not meet criteria for HIV-associated
cognitive/motor complex• Subjective cognitive complaints due to depression;
complaints will be expected to improve (i.e., lessen) with treatment for depression
• For treatment-related issues, see the PHASE module Anxiety, Depression and HIV.
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Diagnostic Summary: Paul
• Diagnosis: HIV-associated dementia complex• Impairment in all neuropsychological abilities• Minimization of subjective cognitive complaints likely
due to disruption in frontal executive brain systems• Issues for discussion: ability to live independently;
ability to manage finances, drive a motor vehicle, and adhere to medication regimen; power of attorney; likelihood of neurological progression
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Diagnostic Summary: Mary
• Diagnosis: Minor cognitive/motor disorder (MCMD)• Neuropsychological impairments detected in
attention, learning efficiency and psychomotor skills• Discuss sparing of executive skills and memory and
importance to everyday functioning and ADLs• Complaints correspond well with neuropsychological
test findings• Mood symptoms secondary to life events and
physical/neurological changes• Client will likely need psychological support to deal
with changes (e.g., going on disability)29
Neuropsychological Testing: When to Refer (or Administer Tests)
• Patient reports cognitive complaints and it is not clear whether these are related to mood, medical complications, alcohol or drug use, or HIV-related brain changes
• Partners, caregivers or significant others notice functional cognitive changes
• To establish a baseline for later comparison• To monitor progress with antiretroviral
treatment• Functional or everyday activities are at issue
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Neuropsychological Battery:Which Tests to Use
Attention and Concentration• Digit Span* (look at forward vs.
backwards)• Spatial Span* (WMS-R)• Letter-Number Sequencing (WAIS-III)• Digit Vigilance (time and errors)• Simple, choice, and sequential reaction
time31
Neuropsychological Battery:Which Tests to Use
Language and Premorbid IQ Estimation• WAIS-R Vocabulary* & Information • ANART*• Boston Naming Test*• Phonemic (FAS) and category fluency*• Thurstone Written Fluency
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Neuropsychological Battery:Which Tests to Use
Verbal and Visual Learning and Memory• California Verbal Learning Test*• Rey Auditory Verbal Learning Test• Story Learning and Memory• Figure Learning and Memory*• Rey Osterrieth Complex Figure Test
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Neuropsychological Battery:Which Tests to Use
Speed of Processing and Psychomotor Skills• WAIS-R Digit Symbol*• Symbol Digit Modalities Test• Trail Making Test: Parts A and B*• Reaction time (simple and complex)*• Rey Osterrieth Complex Figure Test• Sternberg Search Task*• Grooved Pegboard*
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Neuropsychological Battery:Which Tests to Use
Executive Processing Skills• Trail Making Test: Part B*• Working memory tasks*• Category Test*• Wisconsin Card Sorting Test• Stroop
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Concordance Between Subjective Cognitive Complaints and Neuropsychological Test
Performance
• Research studies
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Do subjective cognitive complaints by patients correspond to
neuropsychological test performance ?
Yes:• Stern et al., 1991• Mapou et al., 1993• Beason-Hazen et al.,
1994• Poutiainen et al., 1996• Rourke et al., 1999a
No Relationship:• van Gorp et al., 1991• Wilkins et al., 1991• Burgess et al., 1993• Hinkin et al., 1996• Moore et al., 1997• Rourke et al., 1999b
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What Clients Might Say About Their Problems With Cognition
• I’m forgetful; I walk into a room and forget what I went to get; I keep on losing my keys or the remote; I check the stove several times.
• I have trouble remembering people’s names; it’s on the tip of my tongue; I have word-finding problems.
• I am easily distracted; I have trouble focusing my attention; I can’t do several things at once anymore.
• I am a lot slower; I tend to drop things more often.
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Relationship Between Cognitive Complaints, Mood and
Neuropsychological Performance
Cognitive complaints
Depression (Beck) + 0.67*
Attention (Digit Span-B) - 0.25*
Speed (Trails B) - 0.30*
Memory (CVLT total) - 0.19*
Executive (WCST errors) + 0.02
N=100; All Pearson Correlation Coefficients; * p < 0.05; Rourke et al., 1999a 39
4 Clinical Memory SubtypesComplaints CVLT
Accurate
“Accurate-Impaired” High Impaired
“Accurate-Normal” Low Normal
Inaccurate
“Under-Reporters” Low Impaired
“Over-Reporters” High Normal
Memory complaints (PAOF): “Low” 1-19; “High” > 20
California Verbal Learning Test (CVLT) Trials 1-5 T-Score:“Normal” = 40+; “Impaired” < 40From Rourke S.B. et al. (1999b). Journal of Clinical and Experimental Neuropsychology, pp. 737-756 © Swets & Zeitlinger; used with permission. 40
Clinical Subtypes
ACCURATE INACCURATE
(n=29) (n=20) (n=16) (n=26)
Normal NP-Impaired Under-Report Over-Report
Beck Depression Mild Moderate Mild Moderate
Memory Complaints Low High Low High
Executive (WCST) Normal Normal Impaired Normal
Speed (SDMT) Normal Impaired Low Normal Normal
Memory (CVLT) Normal Impaired Impaired Normal
NP = Neuropsychological; WCST= Wisconsin Card Sorting Test; SDMT= Symbol Digit Modalities Test; CVLT= California Verbal Learning Test
(N=91)
From Rourke S.B. et al. (1999b). Journal of Clinical and Experimental Neuropsychology, pp. 737-756 © Swets & Zeitlinger; used with permission.
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HIV-Related Brain Impairments and Everyday Functioning
• Research studies and issues for discussion
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Effects of “Mild” Neuropsychological Impairment on Job Functioning
108
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18
0
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30
% U
nem
ploy
ed
NP Normal NP Impaired
All HIV+ subjects
HIV+ subjectswithout medicalsymptoms
(Heaton et al., 1994; “non-demented” sample (N= 289); NP = neuropsychologically)43
Percentage of HIV+ Subjects (Still Working) Reporting a Decrease
in Job Functioning
6
30
4
30
0
5
10
15
20
25
30
35
% U
nem
ploy
ed
All HIV+ subjects HIV+ subjectswithout medical
symptoms
NP Normal
NP Impaired
(Heaton et al., 1994; “non-demented” sample (N= 289); NP = neuropsychologically)44
Impact of Neurological Disease on Life Quality
Kaplan and colleagues (1995) demonstrated that quality of life in patients with HIV infection can be independently affected by:
Mood (as measured by Beck Depression) Medical status (as reflected by CD4 count) Neurologist’s rating of brain abnormalities Neuropsychological impairment.
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Guidelines for Neuropsychological Feedback
Discuss reason(s) for referral or assessment (e.g., establish baseline, concerns of “dementia,” new work difficulties, or difficulty managing ADLs).
Describe abilities assessed (e.g., concentration, memory, psychomotor, and problem-solving skills).
Focus only on 2-4 of the most important findings (can be helpful to write these down on paper for client).
Clarify terms (e.g., “dementia,” “encephalitis,” “neuropsychological impairment,” “MCMD,” “HADC”).
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Neuropsychological Feedback Issues
Discuss with client how impairments may be expected to interfere with everyday functioning (use examples of problem areas from client whenever possible).
Discuss compensatory strategies that may be used to overcome everyday problems (capitalize on neuropsychological strengths whenever possible).
Clarify terms used in the report, if it is given to client. Discuss timing for retest and appropriate referrals.
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Internet Resources
http://www.ama-assn.org/(J of American Med. Assoc. HIV/AIDS Info Centre)
http://www.smartlink.net/~martinjh/#top(extensive collection of AIDS information and links)
http://www.teleport.com/~celinec/aids.shtml(AIDS Resource List with links to AIDS-related resources)
http://medstat.med.utah.edu/WebPath/TUTORIAL/AIDS/(Internet Pathology Laboratory from Univ. of Utah)
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