The International HIV Dementia Scale: a new rapid

screening test for HIV dementia

Ned C. Sacktora, Matthew Wongb, Noeline Nakasujjac, Richard L.
Skolaskya, Ola A. Selnesa, Seggane Musisic, Kevin Robertsond,
Justin C. McArthura, Allan Ronalde and Elly Katabirac

Objective: HIV dementia is an important neurological complication of advanced HIV

infection. The use of a cross-cultural screening test to detect HIV dementia within the
international community is critical for diagnosing this condition. The objective of this
study was to evaluate the sensitivity and specificity of a new screening test for HIV
dementia, the International HIV Dementia Scale (IHDS) in cohorts from the US and
Uganda.
Design: Two cross-sectional cohort studies designed to evaluate for the presence of
HIV dementia.
Methods: Sixty-six HIV-positive individuals in the US and 81 HIV-positive individuals
in Uganda received the IHDS and full standardized neurological and neuropsycholo-
gical assessments. The sensitivity and specificity of varying cut-off scores of the IHDS
were evaluated in the two cohorts.
Results: In the US cohort, the mean IHDS score for HIV-positive individuals without
dementia and with dementia were 10.6 and 9.3 respectively (P < 0.001). Using the cut-
off of
10, the sensitivity and specificity for HIV dementia with the IHDS were 80% and
57% respectively in the US cohort, and 80% and 55% respectively in the Uganda
cohort.
Conclusions: The IHDS may be a useful screening test to identify individuals at risk for
HIV dementia in both the industrialized world and the developing world. Full neu-
ropsychological testing should then be performed to confirm a diagnosis of HIV
dementia. ß 2005 Lippincott Williams & Wilkins

AIDS 2005, 19:1367–1374

Keywords: HIV, dementia, screening test, Uganda, international, scale

Introduction plex (HIV dementia), a dementia affecting cognitive and

The HIV/AIDS epidemic is a major global public health
crisis with an estimated 40 million adults and children
living with HIV infection [1]. The vast majority of HIV
cases globally, an estimated 26.6 million people, are in
Sub-Saharan Africa [1]. The frequency of neurological
complications such as HIV-1-associated dementia com-
motor abilities, is largely unknown in resource-limited
countries, although preliminary surveys in Uganda
suggest a relatively high frequency of cognitive dysfunc-
tion [2].
In the US, HIV dementia is characterized by cognitive,
behavioral, and motor dysfunction and occurs in 10–15%

From the aDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA, the bDepartment
of Medicine, University of Calgary, Calgary, Alberta, Canada, the cDepartment of Medicine, Makerere University, Kampala,
Uganda, the dDepartment of Neurology, University of North Carolina, Chapel Hill, North Carolina, USA, and the eDepartment of
Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Correspondence to N. Sacktor, Johns Hopkins Bayview Medical Center, Department of Neurology, B Building, Room 122, 4940
Eastern Avenue, Baltimore, MD 21224, USA.
Tel: +1 410 550 0978; fax: +1 410 550 0539; e-mail: sacktor@jhmi.edu
Received: 10 April 2005; revised: 7 June 2005; accepted: 27 June 2005.

ISSN 0269-9370 Q 2005 Lippincott Williams & Wilkins 1367

1368 AIDS 2005, Vol 19 No 13
of HIV-seropositive (HIVþ) individuals with advanced
infection [3]. If a similar proportion were to be seen on a
global scale, then HIV dementia would be the most
common cause of dementia worldwide in patients under
the age of 40 years. The diagnosis of HIV dementia is
dependent upon a clinical history and neurological
examination consistent with criteria developed by the
American Academy of Neurology (AAN) [4]. Neurop-
sychological testing is a critical component of the
diagnosis, but it is time consuming, language and
education dependent, and often not available in devel-
oping countries.
Screening tests are essential for directing limited resources
for the diagnosis of dementia to those most at risk for the
development of this complication. Brief instruments have
been developed to screen for specific dementia syn-
dromes, for example the Mini Mental State Exam
(MMSE) [5,6]. However, the MMSE was designed to
screen for cortical dementia such as Alzheimer’s disease,
and it is therefore less sensitive for detecting subcortical
dementia such as HIV dementia [7]. The HIV Dementia
Scale (HDS) was designed as a brief but sensitive
screening instrument to identify HIVþ patients at risk
for dementia [8]. The HDS includes subtests that evaluate
motor speed (timed written alphabet), memory (recall of
four words at 5 min), constructional praxis (cube copy
time), and executive functions (antisaccadic errors
subtest). The HDS has been validated as a sensitive and
well-tolerated screening instrument for dementia in
patients with HIV disease [9] and in patients with
subcortical vascular ischemic disease [10]. The anti-
saccadic error subtest, however, has proven difficult for
non-neurologists to administer [11]. The HDS also
includes subtests (alphabet writing and cube-copying
tests) which may be difficult for individuals with a non-
Western educational background. Thus, the objective of
this study was to evaluate a new practical cross-cultural
screening instrument, the International HIV Dementia
Scale (IHDS). The IHDS eliminates the antisaccades
subtest and replaces the timed written alphabet and cube
copy time subtests with tests of motor speed and
psychomotor speed which can easily be performed across
different cultures. The IHDS was initially evaluated in a
US clinic, and then was applied in an Infectious Disease
clinic in Kampala, Uganda. Results from both studies are
described below.
Methods
Study population
US study
Sixty-six HIVþ participants over a period of 5 months
from July 2002 to November 2002 underwent the IHDS
and standardized neurological, neuropsychological, and
functional assessments as part of a longitudinal cohort at
Johns Hopkins Hospital [12] (the NorthEastern AIDS
Dementia–NEAD–cohort). The NEAD cohort
includes HIVþ individuals at high risk for HIV dementia
with either a CD4 cell count < 200  106 cells/l or a
CD4 cell count < 300  106 cells/l and demonstrating
cognitive impairment defined as performance on
neuropsychological testing that was 2 SD below the
appropriate mean on one test or 1 SD below the mean on
two tests [12]. Exclusion criteria for the US study were
current or past opportunistic central nervous system
(CNS) infection at study entry, or history of severe
medical, psychiatric, or neurologic disorder believed to
interfere with the ability to perform the study evaluations.
Uganda study
Eighty-one HIVþ individuals also received standardized
neurological, neuropsychological, and functional assess-
ments at an Infectious Disease Clinic in Kampala, Uganda
over a period of 8 months from August 2003 to March
2004. This clinic is part of the Academic Alliance for
AIDS Care and Prevention in Africa, a collaboration
between HIV-AIDS care experts from North America
and Makerere University Medical School in Uganda [13].
Exclusion criteria for the Uganda study included HIVþ
individuals less than 18 years of age, HIVþ individuals
with an active or known past CNS opportunistic
infection, fever > 37.58C, a history of a chronic
neurological disorder, active psychiatric disorder, alco-
holism, physical deficit (e.g., amputation), severe func-
tional impairment (Karnofsky < 50), or severe medical
illness that would interfere with the ability to perform the
study evaluations. Fluency in English was not a
requirement for the study. All evaluations were translated
into the local language, Luganda.
Normative data were also collected on 100 HIV-
seronegative (HIV) individuals recruited at an AIDS
Information Center (AIC) in Kampala, Uganda. The
AIC is a voluntary counseling and testing center.
Inclusion and exclusion criteria were identical to the
Uganda HIVþ cohort except that the HIV individuals
had documentation of a negative HIV test within 1 year
preceding the evaluation.
International HIV Dementia Scale
The IHDS consists of three subtests: timed fingertapping,
timed alternating hand sequence test, and recall of four
items at 2 min (Fig. 1), and is administered as follows. The
timed fingertapping test from the Unified Parkinson’s
Disease Rating Scale (UPDRS) was used [14]. The
number of fingertaps of the first two fingers of the non-
dominant hand was measured by instructing the
participant to open and close the fingers as widely and
as quickly as possible over a 5-s period. The scale from the
UPDRS was used with 4 points assigned for normal
performance (i.e. 15 taps/5 s). The alternating hand
sequence test was adapted from the Luria Motor test
[15]. Individuals were asked to perform the following
 The International HIV Dementia Scale Sacktor et al. 1369

International HIV Dementia Scale (IHDS)

Memory-Registration – Give four words to recall (dog, hat, bean, red) – 1 second to
say each. Then ask the patient all four words after you have said them. Repeat words
if the patient does not recall them all immediately. Tell the patient you will ask for
recall of the words again a bit later.

1. Motor Speed: Have the patient tap the first two fingers of the non-dominant hand
as widely and as quickly as possible.
4 = 15 in 5 seconds
3 = 11-14 in 5 seconds
2 = 7-10 in 5 seconds
1 = 3-6 in 5 seconds
0 = 0-2 in 5 seconds
____

2. Psychomotor Speed: Have the patient perform the following movements with the
non-dominant hand as quickly as possible: 1) Clench hand in fist on flat surface. 2)
Put hand flat on surface with palm down. 3) Put hand perpendicular to flat surface on
th
the side of the 5 digit. Demonstrate and have patient perform twice for practice.
4 = 4 sequences in 10 seconds
3 = 3 sequences in 10 seconds
2 = 2 sequences in 10 seconds
1 = 1 sequence in 10 seconds
0 = unable to perform
____

3. Memory-Recall: Ask the patient to recall the four words. For words not recalled,
prompt with a semantic clue as follows: animal (dog); piece of clothing (hat);
vegetable (bean); color (red).
Give 1 point for each word spontaneously recalled.
Give 0.5 points for each correct answer after prompting
Maximum – 4 points.
____

Total International HIV Dementia Scale Score: This is the sum of the scores on
items 1-3. The maximum possible score is 12 points. A patient with a score of ≤ 10
should be evaluated further for possible dementia.

____

N. Sacktor, et.al.
Department of Neurology
Johns Hopkins University
Baltimore, Maryland

Fig. 1. International HIV Dementia Scale.

movement with the non-dominant hand as quickly as
possible over a 10s period: (i) clench the hand in a fist on a
flat surface; (ii) put the hand flat on the surface with the
palm down; and (iii) put the hand perpendicular to the flat
surface on the side of the fifth digit. The three hand
positions were demonstrated to the participant by the
examiner, and the participant would then perform the
sequence correctly twice for practice before the 10-s
subtest was performed. The number of sequences
correctly performed within 10s up to a maximum
number of 4 was scored. A participant unable to perform
the alternating hand sequence was assigned a score of 0.
The verbal recall subset of the IHDS was similar to the
verbal recall subtest of the HDS. Registration (new
learning) was measured by reciting four words to the
subject and then asking him/her to repeat them
immediately. The words were repeated by the examiner
until the subject could repeat all four words correctly. The
subject was then asked to recall the four words after the
timed fingertapping and alternating hand sequence tests
were performed. The number of items recalled was
scored out of 4. For words not recalled, the subject was
prompted with a ‘semantic’ clue as follows: animal (dog),
piece of clothing (hat), vegetable (bean), and color (red).
A half-point was assigned for each correct word recalled
after prompting. A total score out of 12 was calculated for
each participant, with each of the three subtests
contributing 4 points to the total score.
Neurological, neuropsychological, and
functional assessments
The neurological, neuropsychological, and functional
assessments in the US study have been described in detail
previously [12]. In brief, all HIVþ individuals received a
structured demographic assessment, medical history, and
neurological examination. The neuropsychological test-
ing battery covered six domains including verbal memory
(Rey Auditory Verbal Learning test), constructional
praxis (Rey Complex Figure Copy test), psychomotor
performance (Digit Symbol test, Trail Making test),
motor speed (Grooved Pegboard test), frontal systems
(Verbal Fluency, Odd Man Out tests), and reaction time
1370 AIDS 2005, Vol 19 No 13

[California Computerized Assessment Package (CAL-
CAP)] [16–22]. An age and education adjusted z score
was used to quantify performance for each of the
neuropsychological tests [12,23,24]. Functional perform-
ance and depression symptomatology also were assessed
[20,25–27]. These assessments were used to assign a
Memorial Sloan Kettering (MSK) dementia stage [28], by
a consensus conference including a neurologist (N.S.) and
neuropsychologist (O.S.).
For the Uganda study, HIVþ and HIV individuals
received clinical assessments using standardized ques-
tionnaires assessing demographic information including
primary language used and reading abilities, medical
history, psychiatric history, neurological symptoms
assessments, and a neurological examination. The
neuropsychological testing battery included the World
Health Organization (WHO) University of California
Los Angeles (UCLA) Verbal Learning test for verbal
memory [29]. This test is similar to the Rey Auditory
Verbal Learning test (RAVLT) in that it uses a list-learning
task. However, all of its items have been carefully selected
(from categories such as parts of the body, tools,
household objects, and common transportation vehicles)
to be familiar in a variety of cultures. The Timed Gait and
Grooved Pegboard tests were used to assess motor
performance. The Digit Symbol test [17] and the Color
Trails test [29] were used to assess psychomotor speed
performance. The Color Trails 1 and 2 are similar to the
Trail Making test except that to minimize cultural bias, no
letters or written instructions are used. Both Color Trails
1 and 2 consist of several numbered circles colored in pink
or yellow; in Color Trails 1, each number is represented
by only one color, whereas in Color Trails 2, each number
is printed twice, once in pink and once in yellow. In
Color Trails 1, the participant is instructed to draw a line
between the numbered circles one after the other,
following the number sequence. In Color Trails 2, the
participant must maintain the sequence of numbers and
alternate between pink and yellow. Digit span forward
and backward was used to assess attention. The functional
assessment included the Karnofsky Performance Scale
[25]. These assessments were used to assign a MSK
dementia stage of 0, 0.5, or  1 by a consensus conference
including the primary examiners (M.W. and N.N.), a
neurologist (N.S.), a neuropsychologist (K.R.), and a
psychiatrist (N.N.).
Data analysis
US study
HIVþ individuals were classified by MSK stage, and
mean values for demographic and laboratory variables
were compared using t tests. Chi-square tests were used to
compare proportions among the groups. IHDS results
and performance on the Grooved Pegboard test with the
non-dominant hand, a test frequently used to screen for
HIV dementia, were each evaluated as a screening
instrument in HIVþ individuals stratified by MSK
dementia stage using a t test. The IHDS and Grooved
Pegboard results also were correlated with a correlation
coefficient. A receiver–operator characteristic (ROC)
curve was performed to determine the cut-off which
maximizes sensitivity and specificity for the diagnosis of
HIV dementia in the US study [30]. This same cut-off
was then evaluated in the Uganda study.
Uganda study
HIVþand HIV individuals were compared with respect
to demographic, neuropsychological test, functional, and
IHDS performance. Using the entire battery of assess-
ments to assign the MSK dementia stage, the IHDS score
was then compared to the MSK dementia stage to define
the sensitivity and specificity of the IHDS in the Uganda
study using the cut-off determined by the US study.
Results
IHDS Performance in the US
The mean demographic and clinical characteristics of the
HIVþ individuals stratified by MSK stage in the US study
are shown in Table 1. There were no differences between
the MSK stages for age, education, or CD4 cell count.
The IHDS scores and the Grooved Pegboard non-
dominant hand test score are also shown in Table 1.
Individuals with HIV dementia (MSK stage 1–3)
performed worse on both the IHDS (t, 5.1;
P < 0.001) and the Grooved Pegboard non-dominant
hand test (t, 3.6, P < 0.001), compared to those HIVþ
individuals without dementia (MSK stage 0–0.5). With

Table 1. Demographic Characteristics and International HIV Dementia Scale (IHDS) and Grooved Pegboard (GP) non-dominant hand
performance stratified by the (MSK) dementia severity rating.

No dementia Dementia

No impairment Equivocal/subclinical Mild Moderate Severe

MSK score 0 (n ¼ 5) 0.5 (n ¼ 36) 1 (n ¼ 15) 2 (n ¼ 9) 3 (n ¼ 1)

Age (years) [mean (SD)] 43.4 (7.5) 43.7 (6.6) 47.1 (5.8) 43.9 (8.2) 48.9
Education (years) [mean (SD)] 13.8 (2.9) 13.1 (2.6) 12.8 (1.7) 11.8 (1.9) 13.0
CD4 cell count ( 106 cells/l) [mean (SD)] 262 (181) 186 (166) 146 (120) 167 (194) 817
IHDS score [mean (SD)] 10.6 (1.3) 10.6 (1.1) 9.3 (1.4) 8.6 (1.8) 7.0
GP Nondom z score [mean (SD)] 0.35 (0.5) 1.1 (1.2) 2.2 (2.8) 3.8 (3.1) 18.1
 The International HIV Dementia Scale Sacktor et al. 1371

specificities for HIV dementia. The cut-off value of

(age-and education-adjusted score)
r = 0.45, p < .001
0 9.5 for the IHDS maximized the sensitivity (71%) and
GP non-dominant hand

specificity (79%) for HIV dementia. However, the cut-off

-5 value of 10.0 for the IHDS improved the sensitivity (80%)
with fewer false negative results. Because a screening test
-10 should have a high sensitivity of at least 80% to minimize
false negative results, the cut-off of
10 for HIV
-15 dementia was used in the Uganda study.

-20 IHDS Performance in Uganda

4 6 8 10 12
The clinical characteristics of the HIVþ individuals and
I-HDS total score HIV individuals in Uganda are described in Table 3.
HIVþ individuals were older (mean age  SD,
Fig. 2. Correslation of the IHDS and Grooved Pegboard 37.0  9.4 years) compared to HIV individuals
Non-dominant hand test performance. (31.4  7.3 years) (P < 0.001).

The IHDS total score and each of its three subscores, as

advancing MSK dementia stage severity, both the IHDS well as each neuropsychological test and the Karnofsky
score and the Grooved Pegboard non-dominant hand test functional performance scores are summarized in Table 3
score became progressively more impaired. The mean for both HIVþ individuals and HIV individuals. HIVþ
IHDS score for both the MSK 0 (no impairment) and individuals performed worse on the IHDS total score and
MSK 0.5 (equivocal/subclinical dementia) groups was each of the three IHDS subscores (the fingertapping,
10.6 whereas the mean IHDS score for the MSK 1 (mild alternating hand position, and verbal recall subtests)
dementia) group was 9.3, suggesting that 10.0 may be a compared to HIV individuals. In the full neuropsy-
useful cutoff to distinguish HIVþ individuals with and chological test battery, HIVþ individuals performed
without dementia. The correlation of the IHDS score and worse on the AVLT Total score test, AVLT Delayed
the Grooved Pegboard non-dominant hand test score is Recall score, the Color Trails 1 and 2 tests, and the
shown in Fig. 2. Performance on the IHDS correlated Symbol Digit Modalities test. In the functional (Kar-
well with performance on the Grooved Pegboard non- nofsky) assessment, HIVþ individuals self-reported more
dominant hand test (r, 0.42; P < 0.001). functional impairment.

To determine the optimal cut-off value for the IHDS to Using normative data from HIV individuals in Uganda,
maximize sensitivity and specificity, a receiver–operator 31% of the HIVþ individuals in this study were diagnosed
characteristic (ROC) curve analysis was performed. Cut- with dementia. The mean IHDS total score among
off values in 0.5 increments from 8.0 to 12.0 are shown in HIVþ individuals with an MSK score of 0 was 10.8,
Table 2 with the corresponding sensitivities and whereas the mean IHDS total score among HIVþ
individuals with an MSK score of 0.5 was 10.1. The mean
Table 2. Characterization of varying cut-offs for HIV dementia on IHDS total score among HIVþ individuals with an MSK
the International HIV Dementia Scale (IHDS). score of 1 was 8.9, which was decreased compared to the
Cut-off value Sensitivity Specificity other two MSK stages, P < 0.05. The sensitivity of the
IHDS for HIV dementia in this cohort was 80%, and the
US cohort specificity for HIV dementia was 55% using a cut-off of
12.0 100% 0%
11.5 92% 22%

10 for abnormal performance (see Table 2). If the cut-
11.0 92% 31% off of
10.5 for abnormal performance is used, the
10.5 83% 52% sensitivity of the IHDS for HIV dementia in the Uganda
10.0 80% 57% cohort is increased to 88% with a mild decrease in the
9.5 71% 79%
9.0 63% 88% specificity to 48%.
8.5 46% 95%
8.0 46% 100%
Uganda cohort
12.0 100% 0%
11.5 100% 20% Discussion
11.0 96% 23%
10.5 88% 48% A sensitive and rapid screening test for HIV dementia is
10.0 80% 55%
9.5 64% 71% essential for future international studies in developing
9.0 60% 79% countries. The IHDS does not require knowledge of the
8.5 40% 89% English language, can be performed briefly in 2–3 min by
8.0 36% 89% non-neurologists in an outpatient setting, and requires no
7.5 20% 95%
special instrumentation other than a watch with a second
1372 AIDS 2005, Vol 19 No 13

Table 3. Demographic characteristics and neuropsychological testing performance among HIVS and HIVR individuals in Uganda. Values are
mean (W SD).

HIV cohort (n ¼ 100) HIVþ cohort (n ¼ 81) P

Age (years) 31.4 (7.3) 37.0 (9.4) < 0.0001

Education (years) 9.7 (3.8) 8.7 (4.9) 0.12
Karnofsky Score 97.4 74.8 < 0.00001
IHDS total Score 11.0 (1.0) 9.9 (1.6) < 0.0000001
IHDS fingertapping subscore 3.8 (0.4) 3.5 (0.6) < 0.00001
IHDS alternating hand sequence subscore 3.5 (0.6) 3.1 (0.9) < 0.001
IHDS 4-word recall subscore 3.6 (0.6) 3.3 (0.8) < 0.001
VLT 5 Trial Total 43.6 (7.4) 39.1 (7.7) < 0.001
VLT Recall After Interference 9.1 (2.0) 7.9 (2.4) < 0.001
VLT Delayed Recall 9.2 (2.3) 7.5 (2.5) < 0.00001
VLT Correct Recognition 14.1 (1.5) 13.1 (2.0) < 0.001
Symbol Digit (seconds) 31.1 (11.3) 25.8 (12.1) < 0.01
Grooved Pegboard-dominant hand (seconds) 86.5 (21.3) 90.8 (27.0) 0.23
Grooved Pegboard-nondominant hand (seconds) 102.7 (25.2) 101.1 (40.4) 0.74
Timed Gait Total (seconds) 20.9 (2.5) 21.1 (3.01) 0.61
Color Trails 1 (seconds) 74.1 (22.2) 87.8 (45.9) < 0.01
Color Trails 2 (seconds) 124.5 (37.2) 165.4 (60.3) < 0.000001
Digit Span Forward 5.3 (0.9) 5.0 (0.9) < 0.05
Digit Span Backward 3.5 (0.9) 3.1 (1.1) < 0.05

IHDS, International HIV Dementia Scale; VLT, WHO/UCLA Verbal Learning Test.

P < 0.05.

hand. Thus, it is ideally suited for an international setting
where resources may be limited.
Our results suggest that the IHDS is a useful screening test
for HIV dementia in both the industrialized world and
the developing world. The sensitivity and specificity of
the IHDS are comparable to the sensitivity (71%) and
specificity (46%) of the Grooved Pegboard non-dominant
hand test, an established test for HIV dementia (using a
cut-off of 1.5 SD below the age- and education-adjusted
mean) [11,31,32]. The IHDS has a major advantage in
that the IHDS requires no special instrumentation. The
IHDS is useful for HIVþ individuals with and without a
complete high school education (US cohort mean
education, 13 years; Uganda cohort mean education,
9 years).
rate of the IHDS for the diagnosis of HIV dementia is
relatively low. A cut-off of
10.5 provides even greater
sensitivity with a minimal loss of specificity. Thus, most
HIVþ individuals with HIV dementia will be identified
and can be referred for subsequent full neuropsycholo-
gical testing. However, using the cut-off of
10, the false
positive rate is notable, and HIVþ individuals with an
abnormal IHDS score may upon further testing have
normal neurocognitive functioning. Thus, a full neu-
ropsychological test battery is essential before a diagnosis
of dementia is made. The IHDS is useful to screen for
HIV dementia in a resource-limited environment, but it
should not be used in place of a full neuropsychological
test battery. In settings where full neuropsychological
testing cannot be performed, the IHDS would be useful
to identify those individuals at high risk for dementia.

The IHDS though does have several limitations. It is not
useful for detecting mild cognitive impairment associated
with HIV infection, as there was no difference between
HIVþ individuals with normal neuropsychological
testing (MSK stage 0) and HIVþ individuals with mild
impairment on neuropsychological testing but not severe
enough to meet criteria for dementia (MSK stage 0.5).
The IHDS cannot be used to distinguish between
different stages of HIV dementia, although progressively
lower mean IHDS scores did correspond to greater
dementia severity in the US study. The role that
depression may have on IHDS performance also requires
further evaluation. The practice effects of the IHDS have
not been determined.
The IHDS should not be used as a replacement for a full
neuropsychological test battery in the clinical diagnosis of
HIV dementia. Using a cut-off of
10, the false negative
The area under the curve analysis suggests a cut-off of

9.5 maximizes the sensitivity and specificity of the
IHDS. However, the sensitivity of the IHDS would only
be 71% with a cut-off of
9.5, and there would be a
significant false negative rate. For clinical purposes, a
screening test should have a low false negative rate, and
the sensitivity of the test should be at least 80%. Thus,
despite the overall lower combined sensitivity and
specificity of the
10 cut-off, this value was chosen
for use on a practical basis, because it achieves a sensitivity
of 80%, and thus is within acceptable limits as a screening
tool.
The study in Uganda has separate limitations. The HIVþ
cohort is older than the HIV cohort. Because many of
the differences between the HIVþ cohort and HIV
cohort were in motor performance tests, and age is
associated with motor performance decline, one cannot

rule out the possibility that the differences between the
two groups are due to age and not HIV infection.
However, age-associated motor slowing is more promi-
nent in the fifth and sixth decades of life rather than the
third and fourth decades of life. Individuals in the HIV
cohort may have had undetected etiologies of potential
cognitive impairment such as tuberculosis, malaria,
syphilis, alcohol use, or depression. The diagnosis of
dementia in the HIVþ cohort is limited by the lack of
neuroimaging to rule out a CNS opportunistic infection,
malignancy, or cerebrovascular disease and the lack of a
cerebrospinal fluid examination to rule out a CNS
opportunistic meningoencephalitis. Given the frequency
of cryptococcal or tuberculous meningitis in this
population, this is a significant concern. However, none
of the HIVþ subjects in this study had either a fever or a
focal neurological examination to suggest a focal CNS
lesion or meningoencephalitis.
HIV dementia is an important complication to diagnose
in patients with AIDS for several reasons: (i) it is associated
with an increased risk of mortality [31,33]; (ii) the
presence of dementia can affect antiretroviral medication
adherence which is essential for suppression of virological
replication [34]; and (iii) HIV dementia is a potentially
treatable condition with highly active antiretroviral
therapy [35,36]. The IHDS may have great value as a
screening test for HIV dementia in the industrialized
world and the developing world. The diagnosis of HIV
dementia may then be an indication for initiation of
antiretroviral therapy which could have enormous benefit
for the individuals themselves, their families, and their
communities.
Acknowledgements
Amanda Barnes, Jason Creighton, Alice Namudde and
Fred Sebuma assisted in the evaluations of subjects. The
studies of HIVþ subjects were conducted in the
Infectious Disease Institute of Makerere University.
Sponsorship: Supported by NS044807, NS049465,
NS036519, MH71150, RR00052, the Bill and Melinda
Gates Foundation, and the Academic Alliance Founda-
tion (which has received support from Pfizer Pharma-
ceuticals).
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