The Impact of Depressive Symptoms on Neuropsychological Performance Tests in HIV-Infected Individuals: A Study of the Hawaii Aging with HIV Cohort

doi:10.4236/wja.2011.14020

Paper Menu >>

Journal Menu >>

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.

E-mail: *[email protected]

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

0.5

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.

REFERENCES

[1] F. K. Judd and A. M. Mijch, “Depressive Symptoms in

Patients with HIV Infection,” The Australian and New

Zealand Journal of Psychiatry, Vol. 30, No. 1, 1996, pp.

104-109. doi:10.3109/00048679609076077

[2] R. H. McAllister-Williams, I. N. Ferrier and A. H. Young,

“Mood and Neuropsychological Function in Depression:

The Role of Corticosteroids and Serotonin,” Psychologi-

cal Medicine, Vol. 28, No. 3, 1998, pp. 573-584.

doi:10.1017/S0033291798006680

[3] T. D. Marcotte, R. K. Heaton, T. Wolfson, et al., “The

Impact of HIV-Related Neuropsychological Dysfunction

on Driving Behavior. The HNRC Group,” Journal of the

International Neuropsychological Society, Vol. 5, No. 7,

1999, pp. 579-592. doi:10.1017/S1355617799577011

[4] A. Ammassari, A. Antinori, M. S. Aloisi, et al., “Depres-

sive Symptoms, Neurocognitive Impairment, and Adher-

ence to Highly Active Antiretroviral Therapy among

HIV-Infected Persons,” Psychosomatics, Vol. 45, No. 5,

2004, pp. 394-402. doi:10.1176/appi.psy.45.5.394

[5] S. A. Castellon, D. J. Hardy, C. H. Hinkin, et al., “Com-

ponents of Depression in HIV-1 Infection: Their Differ-

ential Relationship to Neurocognitive Performance,” Jour-

nal of Clinical and Experimental Neuropsychology, Vol.

28, No. 3, 2006, pp. 420-437.

doi:10.1080/13803390590935444

[6] J. D. Hartzell, I. E. Janke and A. C. Weintrob, “Impact of

Depression on HIV Outcomes in the HAART Era,” Jour-

nal of Antimicrobial Chemotherapy, Vol. 62, No. 2, 2008,

pp. 246-255. doi:10.1093/jac/dkn193

[7] M. A. Cole, S. A. Castellon, A. C. Perkins, et al., “Rela-

tionship between Psychiatric Status and Frontal-Subco-

rtical Systems in HIV-Infected Individuals,” Journal of

the International Neuropsychological Society, Vol. 13,

No. 3, 2007, pp. 549-554.

doi:10.1017/S135561770707066X

[8] R. A. Bornstein, H. A. Nasrallah, M. F. Para, C. C. Whi-

tacre, P. Rosenberger and R. J. Fass, “Neuropsychological

Performance in Symptomatic and Asymptomatic HIV In-

fection,” AIDS, Vol. 7, No. 4, 1993, pp. 519-524.

doi:10.1097/00002030-199304000-00011

[9] R. L. Mapou, W. A. Law, A. Martin, D. Kampen, A. M.

Salazar and J. R. Rundell, “Neuropsychological Per-

formance, Mood, and Complaints of Cognitive and Motor

Difficulties in Individuals Infected with the Human Im-

munodeficiency Virus,” Journal of Neuropsychiatry &

Clinical Neurosciences, Vol. 5, 1993, pp. 86-93.

[10] B. C. Bix, G. Glosser, W. Holmes, et al., “Relationship

between Psychiatric Disease and Neuropsychological Im-

pairment in HIV Seropositive Individuals,” Journal of the

International Neuropsychological Society, Vol. 1, No. 6,

1995, pp. 581-588. doi:10.1017/S1355617700000722

[11] K. J. Goggin, S. Zisook, R. K. Heaton, et al., “Neuropsy-

chological Performance of HIV-1 Infected Men with Ma-

jor Depression. HNRC Group. HIV Neurobehavioral Re-

search Center,” Journal of the International Neuropsy-

chological Society, Vol. 3, 1997, pp. 457-464.

[12] S. B. Rourke, M. H. Halman and C. Bassel, “Neurocogni-

tive Complaints in HIV-Infection and Their Relationship

to Depressive Symptoms and Neuropsychological Func-

tioning,” Journal of Clinical and Experimental Neuro-

psychology, Vol. 21, No. 6, 1999, pp. 737-756.

doi:10.1076/jcen.21.6.737.863

[13] E. G. Bing, M. A. Burnam, D. Longshore, et al., “Psychi-

atric Disorders and Drug Use among Human Immunode-

ficiency Virus-Infected Adults in the United States,” Ar-

chives of General Psychiatry, Vol. 58, No. 8, 2001, pp.

721-728. doi:10.1001/archpsyc.58.8.721

[14] C. Grov, S. A. Golub, J. T. Parsons, M. Brennan and S. E.

Karpiak, “Loneliness and HIV-Related Stigma Explain

Depression among Older HIV-Positive Adults,” AIDS

Care, Vol. 22, No. 5, pp. 630-639.

doi:10.1080/09540120903280901

[15] Centers for Disease Control and Prevention, “CDC Sur-

veillance Report Notes Slowdown in New HIV/AIDS

Rates,” AIDS Policy Law, Vol. 17, No. 5, 2002, p. 8.

[16] V. Valcour, C. Shikuma, B. Shiramizu, et al., “Higher

Frequency of Dementia in Older HIV-1 Individuals: The

Hawaii Aging with HIV-1 Cohort,” Neurology, Vol. 63,

2004, pp. 822-827.

[17] M. Cherner, R. J. Ellis, D. Lazzaretto, et al., “Effects of

HIV-1 Infection and Aging on Neurobehavioral Func-

tioning: Preliminary Findings,” AIDS, Vol. 18, Suppl. 1,

2004, pp. S27-S34.

doi:10.1097/00002030-200401001-00005

[18] American Academy of Neurology AIDS Task Force,

“Nomenclature and Research Case Definitions for Neu-

rologic Manifestations of Human Immunodeficiency Vi-

rus-Type 1 (HIV-1) Infection,” Neurology, Vol. 41, 1991,

pp. 778-785.

[19] F. A. Schmitt, J. W. Bigley, R. McKinnis, P. E. Logue, R.

W. Evans and J. L. Drucker, “Neuropsychological Out-

come of Zidovudine (AZT) Treatment of Patients with

AIDS and AIDS-Related Complex,” The New England

Journal of Medicine, Vol. 319, 1988, pp. 1573-1578.

doi:10.1056/NEJM198812153192404

[20] A. T. Beck and R. A. Steer, “Internal Consistencies of the

Original and Revised Beck Depression Inventory,” Jour-

nal of Clinical Psychology 1984, Vol. 40, No. 6, pp.

The Impact of Depressive Symptoms on Neuropsychological Performance Tests in HIV-Infected Individuals:

A Study of the Hawaii Aging with HIV Cohort

145

1365-1367.

doi:10.1002/1097-4679(198411)40:6<1365::AID-JCLP22

70400615>3.0.CO;2-D

[21] F. K. Judd and A. M. Mijch, “Depressive Symptoms in

Patients with HIV Infection,” The Australian and New

Zealand Journal of Psychiatry, Vol. 30, No. 1, 1996, pp.

104-109. doi:10.3109/00048679609076077

[22] T. Gibbie, A. Mijch, S. Ellen, et al., “Depression and

Neurocognitive Performance in Individuals with HIV/

AIDS: 2-Year Follow-Up,” HIV Medicine, Vol. 7, No. 2,

2006, pp. 112-121.

doi:10.1111/j.1468-1293.2006.00350.x

[23] F. K. Judd, A. M. Cockram, A. Komiti, A. M. Mijch, J.

Hoy and R. Bell, “Depressive Symptoms Reduced in In-

dividuals with HIV/AIDS Treated with Highly Active

Antiretroviral Therapy: A Longitudinal Study,” The Aus-

tralian and New Zealand Journal of Psychiatry, Vol. 34,

No. 6, 2000, pp. 1015-1021. doi:10.1080/000486700278

[24] C. H. Hinkin, S. A. Castellon, R. S. Durvasula, et al.,

“Medication Adherence among HIV+ Adults: Effects of

Cognitive Dysfunction and Regimen Complexity,” Neu-

rology, Vol. 59, 2002, pp. 1944-1950.

[25] R. C. Kessler, P. Berglund, O. Demler, R. Jin, K. R.

Merikangas and E. E. Walters, “Lifetime Prevalence and

Age-of-Onset Distributions of DSM-IV Disorders in the

National Comorbidity Survey Replication,” Archives of

General Psychiatry, Vol. 62, No. 6, 2005, pp. 593-602.

doi:10.1001/archpsyc.62.6.593

[26] L. Boisse, M. J. Gill and C. Power, “HIV Infection of the

Central Nervous System: Clinical Features and Neuropa-

thogenesis,” Neurologic Clinics, Vol. 26, No. 3, 2008, pp.

799-819. doi:10.1016/j.ncl.2008.04.002

[27] B. M. Ances and R. J. Ellis, “Dementia and Neurocogni-

tive Disorders Due to HIV-1 Infection,” Seminars in

Neurology, Vol. 27, No. 1, 2007, pp. 86-92.

doi:10.1055/s-2006-956759

[28] D. B. Miller, J. P. O’Callaghan and S. F. Ali, “Age as a

Susceptibility Factor in the Striatal Dopaminergic Neuro-

toxicity Observed in the Mouse Following Substituted

Amphetamine Exposure,” Annals of the New York Aca-

demy of Sciences, Vol. 914, 2000, pp. 194-207.

doi:10.1111/j.1749-6632.2000.tb05196.x

[29] V. A. Bohr, “Repair of Oxidative DNA Damage in Nu-

clear and Mitochondrial DNA, and Some Changes with

Aging in Mammalian Cells,” Free Radical Biology and

Medicine, Vol. 32, No. 9, 2002, pp. 804-812.

doi:10.1016/S0891-5849(02)00787-6

[30] J. B. Lohr, “Oxygen Radicals and Neuropsychiatric Ill-

ness. Some Speculations,” Archives of General Psychia-

try, Vol. 48, No. 12, 1991, pp. 1097-1106.

[31] J. R. Berger and G. Arendt, “HIV Dementia: The Role of

the Basal Ganglia and Dopaminergic Systems,” Journal

of Psychopharmacology, Vol. 14, No. 3, 2000, pp. 214-

221. doi:10.1177/026988110001400304

[32] T. Yamaguchi, I. Katoh and S. Kurata, “Azidothymidine

Causes Functional and Structural Destruction of Mito-

chondria, Glutathione Deficiency and HIV-1 Promoter

Sensitization,” European Journal of Biochemistry, Vol.

269, No. 11, 2002, pp. 2782-2788.

doi:10.1046/j.1432-1033.2002.02954.x

[33] F. L. Wilkie, K. Goodkin, I. Khamis, et al., “Cognitive

Functioning in Younger and Older HIV-1-Infected Adults,”

Journal of Acquired Immune Deficiency Syndromes, Vol.

33, Suppl. 2, 2003, pp. S93-S105.

doi:10.1097/00126334-200306012-00006

[34] C. K. Schotte, M. Maes, R. Cluydts, D. De Doncker and P.

Cosyns, “Construct Validity of the Beck Depression In-

ventory in a Depressive Population,” Journal of Affective

Disorders, Vol. 46, No. 2, 1997, pp. 115-125.

doi:10.1016/S0165-0327(97)00094-3

[35] A. Komiti, F. Judd, P. Grech, et al., “Depression in Peo-

ple Living with HIV/AIDS Attending Primary Care and

Outpatient Clinics,” The Australian and New Zealand

Journal of Psychiatry, Vol. 37, 2003, pp. 70-77.

doi:10.1046/j.1440-1614.2003.01118.x