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Journal of Adolescent Health 44 (2009) 133135

Original article

Detecting HIV Associated Neurocognitive Disorders in Adolescents:


What Is the Best Screening Tool?
Maureen E. Lyon, Ph.D.*, Robert McCarter, D.Sc., and Lawrence J. DAngelo, M.D., M.P.H.
Division of Adolescent and Young Adult Medicine, Childrens National Medical Center and Childrens Research Institute, Washington, DC
Manuscript received November 18, 2007; manuscript accepted June 27, 2008

Abstract

Purpose: To examine the ability of the HIV-Dementia Scale (HDS) and Mini Mental State Exam
(MMSE) to detect encephalopathy in adolescents living with human immunodeficiency virus (HIV)
and/or acquired immunodeficency syndrome (AIDS).
Method: The study was based on chart review (N 71) from 1999 to 2006, extracting data from psychological testing, disease classification, and demographic variables. HDS and MMSE scores were independent. Diagnosis of encephalopathy used American Academy of Neurology Criteria. Receiver
Operating Characteristic Curves were plotted.
Results: Six patients had encephalopathy. The HDS identified five of these cases (83% sensitivity,
76% specificity). The MMSE identified three cases (50% sensitivity, 92% specificity).
Conclusion: Based on the study results, the HDS appears to be clinically useful. 2009 Society for
Adolescent Medicine. All rights reserved.

Keywords:

HIV-associated neurocognitive disorders (HAND); HIV-Dementia Scale; Mini-Mental State Exam; Adolescent HIV

With the advent of highly active antiretroviral therapy


(HAART) the incidence of human immunodeficiency virus
(HIV)related dementia (HIV-D) has decreased, although
the prevalence of HIV-associated nuerocognitive disorders
(HAND) has persisted [1,2]. Biomarkers linked to HAND
[3] are not clinically available, so diagnosis for treatment of
associated psychiatric comorbidity, cognitive decline and
poor survival is critical [2,4].
There are no data available on the prevalence, incidence,
or screening for encephalopathy in adolescents with HIV.
Among HIV-positive children (median age, 8.1 years), decreased prevalence of all encephalopathy was found for those
born before 1996 (29.6%, n 113), compared with those
born after 1996 (18.2%, n 33) [2]. Incidence rates for HIV
encephalopathy [5] in children with HIV, aged 012 years,
from 1985 to 2004 was 2% (2/84). At the time of this study,
the diagnostic gold standard for adolescents consisted of
neuropsychological testing, neurological examinations, and

*Address correspondence to: Maureen E. Lyon, Ph.D., Division of Adolescent and Young Adult Medicine, Childrens National Medical Center,
111 Michigan Avenue, N.W., Washington, DC 20010-2970.
E-mail address: mlyon@cnmc.org

neuroimaging comparison of the results with those of previous examinations using the American Academy of Neurology (AAN) criteria [6].
This study compared the validity of the HIV Dementia
Scale (HDS) [7] with the Mini-Mental State Exam
(MMSE) [8] as a screening tool in detecting encephalopathy
in adolescents living with HIV/AIDS (ALWHA) to determine whether the HDS is a more sensitive and specific
measure.
Methods
Psychological and medical charts of 71 patients, who
completed psychological assessments between April 1999
and July 2006, were reviewed independently. Neurology
consultation was based on psychological testing results (not
HDS scores) or clinical symptoms upon exam in a hospitalbased Adolescent Clinic. The neurologist, blinded to the
results of the HIV dementia scale, MMSE and IQ results,
determined the presence of encephalopathy using AAN
criteria [6].
Data were de-identified and coded in compliance with the
Health Insurance Portability and Accountability Act and

1054-139X/09/$ see front matter 2009 Society for Adolescent Medicine. All rights reserved.
doi:10.1016/j.jadohealth.2008.06.023

134

M.E. Lyon et al. / Journal of Adolescent Health 44 (2009) 133135

approved by our institutional review board. In accordance


with the Code of Federal Regulations for Protection of Human Subjects Section 46.116(d), informed consent/assent
was not required.
The HDS is a 10-minute, standardized measure of HIVdementia (HIV-D) in adults [7], measuring four domains: Attention (antisaccadic errors), Psychomotor Speed (timed
written alphabet), Memory Recall (recall of four items at 5
minutes), and Construction (cube copy time). Total score is
16 points. Scores 10 points suggest HIV-D in adults with
established reliablity, 80% sensitivity, and 91% specificity
[7]. The administration of the HDS was modified to exclude
the test of antisaccadic eye movements, which requires
training to administer. All patients were given these four
points, creating a bias to underestimate positive screens for
encephalopathy.
The MMSE [8] is a 30-point questionnaire that is commonly used to screen for dementia and that requires about
10 minutes to administer. It samples various cognitive functions, including arithmetic ability, memory, and orientation.
The Beck Depression Inventories I and II [9] are 21-item,
self-report questionnaires with well-established reliablity and
validity. The full WISC-III, WISC-IV, or WAIS III was
completed [10,11]. Three index scores measured constructs
of interest: Perceptual Reasoning Index (PRI), Working
Memory Index (WMI), and Processing Speed Index (PSI).
Age, gender, and illness data based on the Centers for Disease Control and Prevention (CDC) criteria for HIV illness
severity [12] were also collected.
Data were analyzed using STATA 9 [13]. Two-tailed
t tests for continuous variables and c2 analyses for categorical
variables were used to test for differences between patients
with and without encephalopathy. Sensitivity and specificity
of the MMSE and HDS in identifying patients with encephalopathy were examined. Receiver operating characteristic
curves were plotted pairing sensitivities and specificities.

Results
All patients were African-American. Patients with CDC
classifications B and C were prescribed antiretroviral medications. Adherence data were not available. Six patients (Table
1), 8% of sample (all male, all six perinatally infected) had
a diagnosis of encephalopathy (three patients, encephalopathy, NOS; one patient, herpes encephalitis; one patient,
encephalitis history and toxoplasmosis of brain; and one
patient, HIV encephalopathy). One patient had lymphoma
of the brain and was excluded. No other patient had a neurological condition.
Perceptual Organization and Processing Speed on the
Wechsler Indices were correlated with dementia diagnosis
(p < .004). A CDC classification of B (symptomatic) or C
(AIDS) was significantly correlated with dementia (p <
.011). Depression and age were not correlated with clinical
dementia diagnoses.

Table 1
Associations between independent variables and covariates with outcome
variable (N71)
Characteristic

Dementia Diagnosis

p Value

Yes (n6, 8%) No (n65, 92%)


n(%)
n(%)
Gender
Male
5 (83)
Female
0 (0)
M>F
1 (17)
Age (y)
Median
17.0
Mean (SD)
16.8 (2.2)
Range
13-21
Mode of HIV transmission
Perinatal
6 (100)
Sexual
0 (0)
Other/unknown
0 (0)
CDC classification
A
0 (0)
B
2 (33)
C
4 (66)
Wechsler Intelligence Index
Perceptual
organization
n66
Median
74
Mean (SD)
69.6 (12.2)
Range
55-84
Working memory
n63
Median
75
Mean (SD)
77 (4.9)
Range
72-84
Processing speed
n59
Median
68
Mean (SD)
64.8(10.1)
Range
50-73

0.022
29 (45)
34 (52)
2 (3)
0.72 (NS)
16.0
16.5 (2.2)
14-20
0.127 (NS)
36 (55)
27 (41)
2 (3)
0.011
29 (44)
24 (46)
12(18)

n5
91
91.9 (14.1)
51-130
n5
89
88.8 (15.1)
55-128
n4
86
88.0 (15.1)
54-131

0.001*

0.0876 (NS)

0.0039*

M>Ftransgender.
CDCCenters for Disease Control and Prevention; HlVhuman immunodeficiency virus.
NSnot statistically significant.
* Two-tailed t tests, statistically significant.

The HDS and MMSE scores were correlated (r .5215,


p < .0001). With a cut-off score of 10, the HDS alone
screened for five of the six patients, missing one. With
a cut-off score of <24, the MMSE screened for three of the
patients and missed three.
Receiver operating characteristic curve analysis (Figure 1)
indicated no statistically significant differences in sensitivity
and specificity between the HDS and MMSE. Using standard
cut-offs, HDS had 83% sensitivity, 79% specificity, although
MMSE had 50% sensitivity, 92% specificity. The optimal
cut-off score for the HDS, producing the highest sensitivity
and specificity, was 9, providing 88% sensitivity and
83% specificity (87% correct classification).
Discussion
The HDS correctly classified five of six adolescents with
encephalopathy, in comparison to the MMSE identifying

M.E. Lyon et al. / Journal of Adolescent Health 44 (2009) 133135

In conclusion, until biomarkers of HAND are clinically


available, the HDS may be clinically useful, providing early
identification of patients at risk and preserving resources.

1.00

0.75

Sensitivity

135

Acknowledgments

0.50

0.25

0.00
0.00

0.25

0.50

0.75

1.00

1-Specificity
hivdemsc ROC area: 0.8932
Reference

mmsesc ROC area: 0.7109

The authors thank Lucy Civitello, M.D. who provided


guidance with the initial study design and who was the neurologist to whom we referred our patients for assessment. We
also express our appreciation to Jennifer Marsh, J.D., Ph.D.
who conducted the initial data analysis and was responsible
for the integrity of the data. We thank Constance L. Trexler,
B.S.N., R.N., C.P.N., and Stephanie Crane, B.A., Ph.D., who
were responsible for the chart review and administrative
support.
References

Screening Instrument
HDS1
Mini Mental (MMSE)2

Sensitivity
Estimate (95 CI)
83.3 (35.9 - 99.6
50.0 (11.8 - 88.2

)
)

Specificity
Estimate (95 CI)
78.5 (66.5 - 87.7
92.2 (82.7 - 97.4

)
)

1 Cutpoint (HDS) 10
2 Cutpoint (MMSE) < 24

Figure 1. Comparison of the HIV-Dementia Scale (HDS) and the Mini-Mental State Exam (MMSE) against clinical diagnosis of HIV dementia.

three of the six; nonetheless the HDS was not found to be statistically significantly superior to the MMSE. Small sample
size, lack of a base rate for encephalopathy in ALWHA, as
well as earlier studies suggesting that the HDS is lacking in
sensitivity but is highly specific [14] may account for this
finding. Consistent with findings by Morgan et al [14], in
our sample, which was close in age and education, the
HDS demonstrated good sensitivity and specificity using
a cut-off of 9.
The finding of a prevalence of encephalopathy in our postHAART sample of 8% is similar to the 18.2% prevalence
found in children [2]. Two adolescents with encephalopathy
were asymptomatic, consistent with findings that individuals
with virologic suppression continue to experience cognitive
decline. These findings support the new term asymptomatic
neurocognitive impairment (ANI) for individuals with
subclinical impairment [1].
In contrast to earlier studies, male gender was a high risk
factor for encephalopathy, whereas depression was not [2,4].
This study was conducted prior to the refinement of AAN
criteria [1]. The small sample size probably limited the ability
to detect a significant relationship between encephalopathy
and Working Memory. Findings with African-American
ALWHA may not generalize.

[1] Antinori A, Arendt G, Becker JT, et al. Updated research nosology for
HIV-associated neurocognitive disorders. Neurology 2007;69:178999.
[2] Shanbhag MC, Rutstein RM, Zaoutis T, et al. Neurocognitive functioning in pediatric human immunodeficiency virus infection: Effects of
combined therapy. Arch Pediatr Adolesc Med 2005;159:6516.
[3] Price R, Epstein L, Becker J, et al. Biomarkers of HIV-1 CNS infection
and injury [Review]. Neurology 2007;69:17818.
[4] Kopinisky KL, Bao J, Lin YW. Neurobiology of HIV, psychiatric and
substance abuse comorbidity research; Workshop report. Brain,
Behavior, and Immunity 2007;21:42841.
[5] Stromme P, Kanavin OJ, Abdelnoor M, et al. Incidence rates of
progressive childhood encephalopahty in Oslo, Norway: A population
based study. BMC Pediatr 2007;7:25.
[6] Janssen RS, Cornblath DR, Epstein LG, et al. Nomenclature and
research case definitions for neurologic manifestations of human immunodeficiency virus-type 1 (HIV-1) infection. Report of a Working
Group of the American Academy of Neurology AIDS Task Force.
Neurology 1991;41:77885.
[7] Power C, Selnes OA, Grim JA, McArthur JC. HIV-D Scale: A rapid
screening test. J AIDS Hum Retrovirol 1995;8:2738.
[8] Folstein MF, Folstein SE, McHugh PR. Mini-Mental State: A practical
method for grading the cognitive states of patients for the clinician.
J Psychiatr Res 1975;12:18998.
[9] Beck AT, Steer RA, Brown GK. Beck Depression Inventory Manual.
2nd Edition. San Antonio, Texas: Psychological Corporation, Harcourt
Brace & Company, 1996.
[10] Wechsler D. Wechsler Intelligence Scale for Children. Fourth Edition.
Psychological Corporation, Harcourt Brace & Company, 2003.
[11] Wechsler D. Wechsler Adult Intelligence Scale. Third Edition. The
Psychological Corporation, Harcourt Brace & Company, 1997.
[12] Centers for Disease Control. 1993 Revised classification system for
HIV infection and expanded surveillance case definition for AIDS
among adolescents and adults. Morbid Mortal Wkly Rep 1992;
41:117.
[13] StataCorp. Stata Statistical Software: Release 9. College Station, TX:
StataCorp LP, 2005.
[14] Morgan EE, Woods SP, Scott JC, et al. Predictive validity of demographically adjusted normative standards for the HIV Dementia Scale.
J Clin Exp Neuropsychol 2008;30:8390.