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Journal of Adolescent Health 44 (2009) 133–135
Journal of Adolescent Health 44 (2009) 133–135

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. D’Angelo, M.D., M.P.H.

Division of Adolescent and Young Adult Medicine, Children’s National Medical Center and Children’s Research Institute, Washington, DC Manuscript received November 18, 2007; manuscript accepted June 27, 2008

Abstract

Keywords:

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 ¼ 71) from 1999 to 2006, extracting data from psy- chological testing, disease classification, and demographic variables. HDS and MMSE scores were in- dependent. 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.

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), de- creased prevalence of all encephalopathy was found for those born before 1996 (29.6%, n ¼ 113), compared with those born after 1996 (18.2%, n ¼ 33) [2]. Incidence rates for HIV encephalopathy [5] in children with HIV, aged 0–12 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 Ad- olescent and Young Adult Medicine, Children’s 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 previ- ous examinations using the American Academy of Neurol- ogy (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 deter- mine 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 hospital- based 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

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M.E. Lyon et al. / Journal of Adolescent Health 44 (2009) 133–135

approved by our institutional review board. In accordance with the Code of Federal Regulations for Protection of Hu- man Subjects Section 46.116(d), informed consent/assent was not required. The HDS is a 10-minute, standardized measure of HIV- dementia (HIV-D) in adults [7], measuring four domains: At- tention (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 g iven these four

points, creating a bias to underestimate positive screens for encephalopathy. The MMSE [8] is a 30-point questionnaire that is com- monly used to screen for dementia and that requires about

10 minutes to administer. It samples various cognitive func-

tions, 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 Dis- ease 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 c 2 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 encepha- lopathy were examined. Receiver operating characteristic curves were plotted pairing sensitivities and specificities.

Table 1 Associations between independent variables and covariates with outcome variable (N¼71)

Characteristic

Dementia Diagnosis

p Value

 

Yes (n ¼6, 8%) No (n¼65, 92%)

n(%)

n(%)

Gender

 

0.022

Male

5 (83)

29 (45)

Female

0 (0)

34 (52)

M

>F

1 (17)

2 (3)

Age (y)

 

0.72 (NS)

Median

17.0

16.0

Mean (SD)

16.8 (2.2)

16.5 (2.2)

Range Mode of HIV transmission

13-21

14-20

0.127 (NS)

Perinatal

6 (100)

36 (55)

Sexual

0 (0)

27 (41)

Other/unknown

0 (0)

2 (3)

CDC classification

 

0.011

A

0 (0)

29 (44)

B

2 (33)

24 (46)

C

4 (66)

12(18)

Wechsler Intelligence Index Perceptual

 

organization

n¼66

n¼5

 

Median

74

91

Mean (SD)

69.6 (12.2)

91.9 (14.1)

0.001*

Range

55-84

51-130

Working memory

n¼63

n ¼5

 

Median

75

89

Mean (SD)

77 (4.9)

88.8 (15.1)

0.0876 (NS)

Range

72-84

55-128

Processing speed

n¼59

n ¼4

 

Median

68

86

Mean (SD)

64.8(10.1)

88.0 (15.1)

0.0039*

Range

50-73

54-131

M

>F¼transgender.

CDC¼Centers for Disease Control and Prevention; HlV ¼human immu- nodeficiency virus. NS ¼not statistically significant.

* Two-tailed t tests, statistically significant.

Results

All patients were African-American. Patients with CDC classifications B and C were prescribed antiretroviral medica- tions. 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, encephalopa- thy, 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 neuro- logical 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.

The HDS and MMSE scores were correlated (r ¼ .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) 133–135

135

1.00 0.75 0.50 0.25 0.00 0.00 0.25 0.50 0.75 1.00 Sensitivity
1.00
0.75
0.50
0.25
0.00
0.00
0.25
0.50
0.75
1.00
Sensitivity

1-Specificity

hivdemsc ROC area: 0.8932

mmsesc ROC area: 0.7109

Reference

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.

Acknowledgments

The authors thank Lucy Civitello, M.D. who provided guidance with the initial study design and who was the neu- rologist 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

who were responsible for the chart review and administrative support. Screening Instrument Sensitivity Specificity

support.who were responsible for the chart review and administrative Screening Instrument Sensitivity Specificity Estimate (95

Screening Instrument Sensitivity Specificity Estimate (95 CI) Estimate (95 CI) HDS1 83.3 (35.9 - 99.6
Screening Instrument
Sensitivity
Specificity
Estimate (95
CI)
Estimate (95
CI)
HDS1
83.3
(35.9
- 99.6
(66.5
78.5
- 87.7
)
Mini Mental (MMSE)2
50.0
(11.8
- 88.2
(82.7
92.2
- 97.4
)

1 Cutpoint (HDS) 10

2 Cutpoint (MMSE) < 24

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

three of the six; nonetheless the HDS was not found to be sta- tistically 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 post- HAART 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.

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