How the Brain can be Affected by HIV-Infection: A Neuropsychological Primer PHASE, Canadian...

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

3

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.

5

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:






(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


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.

11

Determine Differential Diagnosis for Mary

What Mary’s complaints might reflect:






(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


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.)

13

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?

14

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” ?

15

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 ?

16

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 ?

17

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 ?

18

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)

20

Prevalence of Neurocognitive Deficits in Non-demented

HIV-1 Individuals

17

31

44

56

0

10

20

30

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).

22

Pattern of Deficits Associated with HIV-Infection

6157

4441

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3228

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0

10

20

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40

50

60

70

% w

ith

imp

airm

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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

10

12

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)

24

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 ??

25

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.

26

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.

27

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

28

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

30

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


Language and Premorbid IQ Estimation• WAIS-R Vocabulary* & Information • ANART*• Boston Naming Test*• Phonemic (FAS) and category fluency*• Thurstone Written Fluency

32


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

33


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*

34


Executive Processing Skills• Trail Making Test: Part B*• Working memory tasks*• Category Test*• Wisconsin Card Sorting Test• Stroop

35

Concordance Between Subjective Cognitive Complaints and Neuropsychological Test

Performance

• Research studies

36

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

37

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.

38

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.

41

HIV-Related Brain Impairments and Everyday Functioning

• Research studies and issues for discussion

42

Effects of “Mild” Neuropsychological Impairment on Job Functioning

108

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18

0

5

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15

20

25

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.

45

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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