World Journal of AIDS, 2011, 1, 139-145
doi:10.4236/wja.2011.14020 Published Online December 2011 (http://www.SciRP.org/journal/wja)
139
The Impact of Depressive Symptoms on
Neuropsychological Performance Tests in
HIV-Infected Individuals: A Study of the
Hawaii Aging with HIV Cohort
Sheri M. Shimizu1, Dominic C. Chow1*, Victor Valcour1,2, Kamal Masaki3, Beau Nakam o to1,4,
Kalpana J. Kallianpur1, Cecil i a Sh i k u m a 1
1Hawaii Center for AIDS, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, USA; 2Department of Neu-
rology and Division of Geriatric Medicine, Memory and Aging Center, Department of Medicine, University of California at San
Francisco, San Francisco, USA; 3Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, USA;
4Department of Neurology, Straub Clinic and Hospital, Honolulu, USA.
Received August 19th, 2011; revised October 8th, 2011; accepted October 24th, 2011.
ABSTRACT
Background: The frequency of neurocognitive impairment (NCI) in human immunodeficiency virus (HIV)-infected in-
dividuals remains high despite the availability of potent antiretroviral therapy (ART). The concurrence of depression
among HIV-infected patients with NCI is common, especially among older individuals. Depression has been implicated
as a risk factor for impaired neuropsychological performance (NP). This study explored the relationship between de-
pressive symptoms and NP testing in HIV-infected individuals. Methods: A cross-sectional analysis was performed
within the Hawaii Aging with HIV Cohort, a large prospective study of cognition of older (50 or more years old) com-
pared to younger (20 to 39 years old) HIV-infected individuals. Results: Two hundred and eighty-five HIV infected par-
ticipants (157 older and 128 younger) were administered a battery of NP tests to measure performance in major cogni-
tive domains. Depressive symptoms were measured using the Beck Depression Inventory (BDI). The rates of depressive
symptoms and neuropsychological impairment were similar in older and younger groups. Multivariate analyses re-
vealed depressive symptoms were associated with NP test impairment in the younger group. In the older group, depres-
sive symptoms were not associated with NP. Conclusion: This study suggests that depressive symptoms are associated
with NP test impairment in younger HIV-infected individuals, but not in older individuals.
Keywords: Depression, HIV, Neurocognitive Function, Aging
1. Background
The frequency of neurocognitive impairment (NCI) in
human immunodeficiency virus (HIV)-infected individu-
als remains high despite the availability of potent anti-
retroviral therapy (ART). Neuropsychological perform-
ance (NP) testing provides diagnostic clarification and
grading of clinical severity for patients with subtle or
obvious cognitive disorders. This testing provides clini-
cal classification as to whether a HIV-infected patient
may have HIV associated neurocognitive disorder
(HAND) and dementia. Depression has been implicated
as a risk factor for impaired NP in HIV individuals and
has been shown to cause poor concentration, lack of in-
terest and apathy towards NP testing [1-6]. Studies have
found an association between subtypes of depressive
symptoms and cognitive deficits [5,7]. However, incon-
sistencies are present with some studies demonstrating
that depressive symptoms do not influence NP testing
[8-12]. Few studies in the era of highly active antiretro-
viral therapy (HAART) have looked at depression in
aging HIV populations.
Depression is commonly observed in HIV-infected in-
dividuals, where the prevalence is estimated to be over
36% [1,13]. Among older HIV-infected patients, depres-
sion is the second most prevalent behavioral health issues
[14]. Aging is a potential risk factor for depression and

The Impact of Depressive Symptoms on Neuropsychological Performance Tests in HIV-Infected Individuals: 140
A Study of the Hawaii Aging with HIV Cohort
neuropsychological impairment. Individuals with HIV
today have a longer life expectancy with more than
114,951 individuals with AIDS over the age of 50 cur-
rently living in the United States [15]. There is limited
data on neuropsychological functioning in older HIV
infected individuals. Previous studies have found a
higher frequency of dementia in older HIV infected indi-
viduals and that older adults may be at greater risk of
NCI [16,17]. The importance of furthering our under-
standing of the impact of aging and depression on NP
testing is necessitated by the growing population of older
HIV infected individuals.
The changing nature of HIV treatment and longer pa-
tient survival highlight the need to re-evaluate these rela-
tionships in aging cohorts. This study evaluated the rela-
tionship between depressive symptoms using the Beck
Depression Inventory (BDI) and NP tests in a well-
characterized cohort of older and younger HIV-infected
individuals.
2. Methods
2.1. Study Population—Hawaii Aging with HIV
Cohort
The analyses utilized baseline (entry) data from the Ha-
waii Aging with HIV Cohort study (HAHC), a longitudi-
nal cohort study assessing cognitive and neurologic out-
comes in older compared to younger HIV-infected indi-
viduals [16]. Briefly, 158 older (50 years of age or older)
and 128 younger (20 - 39 years of age) HIV-infected
individuals were recruited between October 2001 to Oc-
tober 2005. Major exclusion criteria were the following:
1) head injury with loss of consciousness greater than 1
hour, 2) opportunistic brain infection, 3) learning disabil-
ity, 4) major neurologic disease such as multiple sclerosis,
major stroke, or current delirium, and 5) diagnosed major
psychiatric disorder including bipolar illness, schizo-
phrenia, or active major depression at baseline based on
DSM-IV criteria. All individuals identified English as
their primary language of communication. Most partici-
pants were Caucasian, and all were living in Hawaii at
the time of enrollment and were recruited from all major
islands of Hawaii.
2.2. Neuropsychological Performance Tests
Participant evaluations included the macro-neurologic
examination, neuropsychological testing, medical intake
with record of co-morbid illnesses, demographic data,
risk behavior inventory, HIV laboratory parameters, and
medication histories. The 80-minute neuropsychological
battery designed to assess multiple cognitive domains
most affected by HIV was administered and included the
following: Choice and Sequential Reaction Time (Cal-
Cap), Rey Auditory Verbal Learning Test (RAVLT),
Rey-Osterreith Complex Figure Test (RCF), Trail Mak-
ing Tests A and B, WAIS-R Digit Symbol, Grooved
Pegboard, Timed Gait, Odd Man Out, FAS, Animal
Naming, Boston Naming Test (BNT), and WAIS-R Digit
Span. The Human Subjects Review Committee of the
University of Hawaii approved the study protocol, and all
subjects signed a written informed consent prior to entry.
Raw scores from the neuropsychological tests were
transformed to standardized z-scores using published
age- and education-matched normative datasets, as pre-
viously described [16]. Four composite neuropsycholo-
gical indices were examined in the present study, includ-
ing 1) Psychomotor (Grooved Pegboard Non-Dominant
hand, Digit Symbol subtest from the WAIS-R, and Trail
Making Test Trial B), 2) Memory (RAVLT Trial De-
layed Recall Trial, Rey Complex Figure Test Delayed
Recall, and the RAVLT Trial 5 minus Immediate Recall)
3) and a global NPZ-8 score. We used the NPZ8 score, a
summary measure of neuropsychological testing per-
formance and cognitive diagnostic categorizations for
NCI and HIV-associated dementia as determined by a
consensus conference with neurologists and neuropsy-
chologists based on the American Academy of Neurol-
ogy 1991 criteria [18]. The NPZ-8 score is defined as the
average of z-scores for Timed Gait, Grooved Pegboard
Dominant hand, Grooved Pegboard Non-Dominant hand,
Trail Making Tests Parts A and B, the Digit Symbol
subtest from the WAIS-R, and the Choice and Sequential
Reaction Time trials from the CalCap test battery. This
common composite score was first reported to relate to
cognitive improvement following AZT treatment [19].
Our version substitutes the Choice and Sequential reac-
tion times from the CalCap test for the Finger Tapping
tests. For participants over the age of 60, the NPZ-8
score did not include the CalCap tests due to limited
normative data for this age group (n = 18).
2.3. Beck Depression Inventory
The Beck Depression Inventory (BDI) was used to assess
the presence and severity of depressive symptoms. The
BDI has high validity and reliability in measuring de-
pressive symptoms and takes approximately [20]. In this
self-completed questionnaire, participants are asked to
rate 21 items from zero to three according to how they
have felt during the past week.
2.4. Statistical Considerations
All statistical analyses were carried out on SAS v9.1
(SAS Institute Inc., Cary, NC). Group differences in con-
tinuous outcome variables were analyzed using two-

The Impact of Depressive Symptoms on Neuropsychological Performance Tests in HIV-Infected Individuals:
A Study of the Hawaii Aging with HIV Cohort
141
tailed t-tests. For discrete variables we used chi-square
tests. We employed both simple correlation and regres-
sion analyses to assess the relationship between demo-
graphic factors and the cognitive endpoints. First, demo-
graphic predictors were tested by themselves using cor-
relation analyses to determine whether they were associ-
ated with the cognitive endpoints. When significant as-
sociations were noted, the predictor was entered into the
multiple regression analyses. BDI score was entered into
all models. Associations were considered statistically
significant if the p-value was less than 0.05.
3. Results
There were 285 (157 older and 128 younger) HIV-in-
fected participants enrolled. The study sample generally
reflected the epidemiology of HIV infection in Hawaii
exclusive of individuals in their forties, by study design,
with the predominant risk factor for HIV being men who
have sex with men, and a mean age of 54.5 years in the
older group and 35.2 years in the younger group (Table
1). Caucasians comprised the majority of the participants
in both the older group (69.6%) and the younger group
(42.2%). There were no significant group differences
between the younger and older participants in regards to
CD4 count and percent on HAART therapy. The older
group had a higher percentage of patients with undetect-
able viral loads. Differences were noted in self- reported
duration of infection (p ≤ 0.01), with a longer duration
noted among older subjects. The older group also had a
higher intelligence quotient (IQ) (p ≤ 0.01) and self-re-
ported years of maximal educational attainment (p ≤
0.01). The younger group had a higher rate of self-re-
ported substance abuse (p ≤ 0.01). The mean total BDI
score did not differ by age group, noted to be 8.6 in the
older group and 9.1 in the younger group (p = 0.42). A
summary of all demographic characteristics is presented
in Table 1.
We completed a series of univariate analyses to deter-
mine if demographic characteristics correlated with the
cognitive endpoints. The BDI, ethnicity, gender, IQ, and
current CD4 count were associated with poor NP test and
were included in the multivariate analyses. Viral load,
antiretroviral therapy, years of HIV infection, and sub-
stance abuse were not associated with lower NP testing.
Results of multiple regression analyses testing the
relative contribution of significant covariates and cogni-
tive endpoints in the younger and older groups are sum-
marized in Tables 2 and 3 respectively. In the younger
group, the BDI score was significantly associated with
lower NP performance in psychomotor speed (p = 0.04)
and the NPZ-8 score (p = 0.03). In the older group BDI
scores were not associated with cognitive endpoints,
Table 1. Baseline demographic and medical characteristics.
Characteristics Young Old p
Sample Size 128 157
Age (years), Mean ± SD 35.2 ± 4.9 54.5 ± 5.3 <0.01
% Male 76.6 89.9 <0.01
Education (years), Mean ± SD 13.2 ± 1.9 14.6 ± 2.5 <0.01
Ethnicity
% Asian Pacific Islanders 20.3 8.9
% Caucasian 42.2 69.6
% Other 37.5 21.5
Intelligence Quotient score, Mean ± SD 103.6 ± 6.2 110.8 ± 7.5 <0.01
Current CD4 Count cells/mm3, Mean ± SD 435 ± 228 478 ± 257 0.14
% Undetectable Viral Load 42.2 54.4 0.04
% on antiretroviral therapy 76.8 68.5 0.13
Years Infected, Mean ± SD 7.18 (5.6) 11.8 (5.31) <0.01
% Substance Abuse—Current* 22.6 8.8 <0.01
Beck Depression Index (total score), Mean ± SD 9.1 ± 7.2 8.6 ± 7.2 0.42
*Current substance abuse within last month including marijuana, cocaine, amphetamines, and heroin.

The Impact of Depressive Symptoms on Neuropsychological Performance Tests in HIV-Infected Individuals: 142
A Study of the Hawaii Aging with HIV Cohort
Table 2. Multivariate analysis of neuropsychological performance tests to characteristics in young er HIV-infected individuals*.
Memory Psychomotor Speeda NPZ8 b
β p β p β p
Gender −0.141 0.72
IQ 0.028 0.06 0.027 0.02
Ethnicity 0.031 0.75 −0.08 0.53 −0.095 0.31
CD4 count 0.001 0.07 0.001 0.39 0.001 0.32
BDI −0.001 0.5 −0.054 0.04 −0.053 0.03
*All models included Beck Depression Index score (BDI), ethnicity, and CD4 count. Additional models included: aIQ; bgender and IQ.
Table 3. Multivariate analysis of neuropsychological performance tests to characteristics in older HIV-infected individuals*.
Memory Psychomotor Speeda NPZ8b
Gender −0.22 0.08
IQ 0.078 <0.01 0.023 <0.01
Ethnicity −0.122 0.25 −0.41 <0.01 −0.32 <0.01
CD4 count 0.001 0.04 0.023 <0.01 0.025 0.31
BDI 0.031 0.18 −0.023 0.451 −0.041 0.09
*All models included Beck Depression Index score (BDI), ethnicity, and CD4 count. Additional models included: aIQ; bgender and IQ.
however lower CD4 counts were associated with lower
performance in psychomotor speed (p =< 0.01) and
memory (p = 0.04). In both groups, IQ was associated
with NP tests.
When standardized clinical cut off points were applied
to determine the severity of depressive symptoms (BDI <
10 = minimal symptoms, BDI 10 - 16 = mild symptoms,
BDI 17 - 29 = moderate symptoms, BDI ≥ 30 = severe
symptoms) on all subjects, significant trends were found
with poorer cognitive performance on psychomotor and
NPZ-8 scores (Figure 1). These trends were not seen in
the memory score.
4. Discussion
The results of this study designed to determine the effects
of depressive symptoms on neuropsychological per-
formance in older and younger HIV infected individuals
suggest that depressive symptoms are associated with
neuropsychological impairment in younger HIV infected
individuals. Neuropsychological impairment as evi-
denced by standardized composite z-scores of psycho-
motor speed and the previously defined NPZ-8 score was
associated with depressive symptoms, however measures
of disease progression such as CD4 count and viral load
are not indicative of neuropsychological impairment in
younger HIV infected individuals. This may be explained
by the fact that the younger group had a shorter length of
time to infection than the older group, resulting in less
advanced disease progression and central nervous system
(CNS) involvement than the older group. Depressive
symptoms were associated neuropsychological impair-
ment, especially in tests of psychomotor speed. This is
consistent with previous studies in which depression has
been implicated as a risk factor for impaired NP testingin
HIV-infected individuals [2-6,21]. Depression remains
predictive of poor treatment outcomes, decreased medi-
cation adherence, and increased mortality [22-24]. The
younger group displayed higher rates of substance abuse,
which when coupled with depressive symptoms may
compound neuropsychological impairment in younger
HIV infected individuals. Our findings highlight the need
to identify depression early in young HIV infected indi-
viduals who exhibit neuropsychological impairment.
Similar to the findings from the National Comorbidity
Survey Replication Interventions on the general popula-
tion, young adults are at high risk for anxiety and depres-
sion. Additionally, young adults with mental disorders
are more likely to suffer disability compared to older
individuals. This suggests that interventions aimed at
prevention or early treatment of mental illness need to

The Impact of Depressive Symptoms on Neuropsychological Performance Tests in HIV-Infected Individuals: 143
A Study of the Hawaii Aging with HIV Cohort
-1.5
-1
-0.5
0
0.5
1
1.5
minimal BDI symptoms
mild BDI symptoms
moder ate BDI symptoms
severe BDI symptoms
Psychomotor Memory NPZ8 Score
*
*
Figure 1. Neurocognitive impairment according to severity of depressive symptoms (units are in z-scores). *Significant trend,
p < 0.05.
focus on youth and young adults [25].
The effect of depressive symptoms on neuropsycho-
logical impairment was not seen in the older group. In-
stead, our study suggests that neuropsychological decline
may be a sequela of direct HIV related CNS involvement,
as CD4 count was most predictive of neuropsychological
impairment in the older group. It is known that HIV en-
ters the CNS early in the course of infection and has been
shown to produce detrimental effects on NP performance
as the disease progresses. Impairment can range from
mild cognitive and motor difficulties to AIDS related
dementia and is consistent with frontal-subcortical pa-
thology with evidence of decreased psychomotor proc-
essing speed, executive function, and memory [26,27]. In
addition, aging has been associated with decreases in
dopaminergic transmission as well as mitochondrial
function and increases in oxidative free radicals [28-30].
These changes have also been seen in HIV infection
[31,32]. It has been suggested that a more prominent re-
lationship in each of these processes would be evidenced
among older HIV-infected individuals [33].
There are several limitations of this study, primarily
depressive symptoms were self-reported and measured at
a single point in time. However, the BDI has previously
shown construct validity in depressive populations [34].
Although individuals who were on antidepressant medi-
cations were included in this study, participants’ were
examined by a physician and determined that their symp-
toms were stable and without recent exacerbation. Al-
though this was a cross-sectional study without controls,
there was a significant trend in NCI and degree of de-
pressive symptoms. There were differences between the
racial groups between the young and old groups. How-
ever, there were no differences between BDI and NPZ-8
scores in regards to racial groups. This study may not
have been powered to detect these differences. Addition-
ally, the difference in the duration of HIV infection be-
tween age groups was significant, although there was no
association between duration of HIV infection and
NPZ-8 scores. No interaction between age groups and
duration of HIV infection was noted. Our findings are
consistent with a previous study that concluded that the
duration of HIV illness and use of antiretroviral medica-
tion regimen were not related to depression [35].
The findings of this study emphasize the need for early
evaluation of depressive symptoms particularly in
younger HIV infected individuals. In older HIV infected
individuals, cognitive status was related to CD4 count
and attention to more aggressive antiretroviral treatment
may be warranted.
5. Acknowledgements
This study was supported by the Hawaii Medical Student
Aging Research National Training Center (National In-

The Impact of Depressive Symptoms on Neuropsychological Performance Tests in HIV-Infected Individuals: 144
A Study of the Hawaii Aging with HIV Cohort
stitute on Aging, John A. Hartford Foundation and
American Federation for Aging Research grant T35
AG-026722-02), National Institute of Neurological Dis-
orders and Stroke (1U54NS43049). Additionally, D
Chow received funding from the National Institutes of
Health NHLBI 1 K23 HL088981, P20RR011091and
NCRR 1 R25 RR019321. The content is solely the re-
sponsibility of the authors and does not necessarily rep-
resent the official views of the National Institute of Neu-
rological Diseases and Stroke or the National Institutes
of Health.
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