A case-control pilot study on cognitive functioning,symptom validity and psychological wellbeing in HIV-1-infected patients in the Netherlands

Abstract

Summary

The objective of this study was to examine and relate both cognitive functioning and psychological wellbeing in Dutch HIV-1-infected patients (n = 30) in comparison with a matched healthy control group (n = 30), taking symptom validity into account. Significant differences in performance between patients and controls were found in the domain Working memory (P = 0.036), but not in the other cognitive domains. There was a significant difference in all dimensions of the psychological wellbeing scale, measured with the SCL-90-R (P values between 0.002 and 0.023), except for agoraphobia, cognitive performance difficulty and sleep disturbances. No correlations were found between the performance on the Working memory domain and wellbeing. Future research should focus on unravelling the underlying mechanisms of neurocognitive dysfunction further using neuropsychological tests, including a symptom validity test in combination with neuroimaging techniques in larger samples.

Keywords

HIV cognitive functioning symptom validity psychological wellbeing working memory

INTRODUCTION

Combination antiretroviral therapy (cART) has improved the course of HIV infection dramatically. Nevertheless, several studies have shown that 30–60% of these patients develop at least mild cognitive impairments.¹ Deficits in Memory, Psychomotor speed, Attention and Executive functioning are most prominent.² Cognitive deficits, even in mild or moderate forms, may potentially hamper everyday activities and may cause problems in achieving life goals, which in turn might result in diminished psychological wellbeing and quality of life.^3,4 Psychiatric symptoms are present in almost 50% of HIV-1-infected individuals, of which depressive symptoms, anxiety, mania, psychosis and substance abuse are the most common.⁵

Several studies report a relation between psychological wellbeing and cognitive functioning.^6,7 Carter et al.⁸ examined the relation between cognitive impairments and psychological complaints in HIV-1-infected patients, using structural equation modelling. Here, they found that increased cognitive complaints were associated with worse neuropsychological performance and that depressed mood and physical symptoms also affected the self-reported cognitive complaints. However, other results did not reveal correlations between depressive symptoms and cognitive functioning.⁹

Very few studies on cognitive functioning in HIV-1-infected patients have taken symptom validity into account. Woods et al.¹⁰ pointed out that it is possible that a small subset of HIV-1-infected patients feign or exaggerate their neuropsychological deficits in order to obtain monetary compensation and/or service benefits. The detection of invalid neuropsychological test performance due to insufficient mental effort in possible disability or compensation-seeking individuals is important in both clinical and research settings. Symptom validity tests are useful tools in the detection of suboptimal mental effort in that they are designed to be passable for all but the most severely impaired patients, given that the participant has provided adequate effort in the test. Furthermore, a substantial amount of studies on cognitive functioning and wellbeing lack a non-HIV-1 infected control group.

Considering the lack of consensus about the existence of a relationship between cognition and wellbeing, the present study aimed to assess the nature and extent of changes in cognitive performance and to explore the relationship with psychological wellbeing in a randomly selected sample of HIV-1-infected patients in comparison with a matched HIV-negative control group. A symptom validity test is included to take suboptimal mental effort into account.

METHODS

Participants

Thirty HIV-1-infected patients and 30 controls were included between 16 March 2009 and 19 December 2011. Consecutive patients were recruited through their treating physicians via the outpatient clinic for infectious diseases at the Department of General Internal Medicine in the Radboud University Nijmegen Medical Centre if they met the following inclusion criteria: aged between 18 and 70 years, fluent in the Dutch language, no current drug or alcohol addiction and no history of psychiatric or neurological disorder (unrelated to HIV-1 infection in the patients). Inclusion criteria for the patients were HIV-1 infection and absence of active opportunistic infections, pregnancy, malignancy and neurosyphilis. Patients were selected regardless of the presence of signs or symptoms of suspected cognitive impairment or subjective cognitive complaints. Controls were recruited among spouses and acquaintances of the HIV-1-infected patients and the network of the researchers and were matched for age, gender and education level. For measuring the amount of drug and alcohol use, a subscale of the European Addiction Severity Index (EuropASI) was administered.¹¹ Medical ethical approval was obtained for this study and written informed consent was obtained from all participants.

Neuropsychological assessment

Participants completed an extensive neuropsychological test battery measuring six major cognitive domains. Abstract reasoning was assessed by Raven Advanced Progressive Matrices (12-item short form).¹² Memory was divided into two subdomains, Working memory and Episodic memory. Working memory was assessed by the Letter-Number Sequencing of the Wechsler Adult Intelligence Scale, third edition (WAIS-III).¹³ Episodic memory was assessed verbally and non-verbally with the Dutch version of the Rey Auditory Verbal Learning Task¹⁴ and the Location Learning Task – Revised,¹⁵ respectively. Both Episodic memory tasks consisted of immediate memory (total score on trials 1–5) and delayed recall. The domain Psychomotor speed included Digit symbol Substitution subtest from the WAIS-III¹³ and the Grooved Pegboard Test¹⁶ (administered for the dominant and non-dominant hand). Visuoconstruction was measured with the copy trial of the Rey-Osterrieth Complex Figure Test.¹⁷ Executive functioning consisted of four subdomains: Concept shifting, Response generation, Planning and Response inhibition. Concept shifting was measured with de Brixton Spatial Anticipation Test.¹⁸ Response generation was assessed with a letter fluency tasks (K-O-M; 1 minute per letter).¹⁹ Planning was assessed with the Zoo Map test from the Behavioural Assessment of the Dysexecutive Syndrome (BADS).²⁰ Response inhibition was assessed by the Stroop Color-Word Test.²¹ Here, the Stroop interference score was computed, using the following formula: (time needed for card III − time needed for card II)/time needed for card II.²² Finally, Attention was measured with the 2.0 and 1.6 Inter stimulus interval (ISI) trials of the Paced Auditory Serial Addition Test (PASAT) (60-items per ISI).²³

Tests were chosen to be sensitive to small or moderate differences in ability and were administered by trained neuropsychologists. The allocation of tests to the domains was made a priori, according to standard neuropsychological practice and cognitive theory.²⁴ The assessment took 90–120 minutes and all tests were administered in a fixed order.

Psychological wellbeing was assessed with the 90-item revised Dutch version of the Symptom Checklist (SCL-90-R).²⁵ The SCL-90-R is a multidimensional self-report questionnaire designed to screen for a broad range of psychological problems by asking subjects to reflect on the previous seven days. The questionnaire contains 90 items subdivided in eight symptom dimensions: agoraphobia, anxiety, depression, somatization, cognitive performance difficulty, interpersonal sensitivity, anger–hostility and sleep disturbance. Responses are given on a scale of 1–5 and a score for each of the dimensions is calculated, in addition to one global score: the total score. Symptom validity was measured with the short version of the Amsterdam Short Term Memory Test (ASTM) (cut-off score <85).²⁶ Education level was recorded using seven categories in agreement with the Dutch educational system (1 = less than primary school; 7 = academic degree). Premorbid intellectual level was estimated with the Dutch version of the National Adult Reading Test.²⁷

Clinical ratings of neuropsychological test performance were computed for each of the HIV-1-infected patients. Neuropsychological impairments were classified per cognitive domain using age- and education-adjusted normative data in patients and controls (i.e. using 1.65 SD below the normative mean as cut-off, reflecting the lowest 5% of the normative population).^24,28 Impairments had to be present in at least two domains for a participant to be classified as ‘cognitively impaired’. At least one of the ability deficits had to be outside the motor and sensory perceptual domain, in agreement with the updated nosology for HIV-associated neurocognitive disorders by Antinori et al.²⁹

Statistical analysis

To compare the different cognitive domains, raw test scores were transformed into z-scores. Positive test scores for the Location Learning Test, the Grooved Pegboard Test and the Stroop Color-Word Test were converted into negative z-scores and negative test scores, for these tests, into positive z-scores to make sure that higher scores indicated a better performance for all tests. Subsequently, domain scores were calculated by averaging the z-scores of the tests that contributed to the six cognitive domains. Between-group differences in cognitive functioning were examined with a general linear model multivariate analysis of variance (MANOVA) with group as independent variable and the cognitive domains as dependent variables. General linear model univariate ANOVAs were performed for between-group differences in the subscales of the SCL-90-R, with group as independent variable and each subscale as dependent variable. Effect sizes (partial eta-squared [η_p²]) were computed for all analyses.

In agreement with Woods et al.,¹⁰ a performance below the cut-off of a symptom validity test is likely not the result of HIV-associated cognitive impairment and must therefore be regarded as an indication of under-performance. Participants performing below this cut-off were removed from the statistical analyses.

RESULTS

Table 1 shows the characteristics of the two groups. No significant differences were found in gender distribution (χ²(1) = 0.111, P = 0.739), level of education (U = 433.5, Z = −0.255, P = 0.799) and estimated IQ (t(58) = −1.715, P = 0.092) between patients and controls, indicating that the groups were well matched on these variables. Five patients and one control performed below the cut-off indicative for under-performance on the ASTM. However, this difference between the groups was not statistically significant (x²(1) = 0.963, p = 0.085). With respect to participants performing in the ‘impaired’ range (excluding all participants who performed suboptimally on the symptom validity test), 12% of the patients were classified as neuropsychologically impaired compared with 3.5% of the controls. Magnetic resonance imaging (MRI) data were available for 26 of the patients and cerebrospinal fluid (CSF) viral load was obtained in 25 patients.

Table 1

Participant characteristics

Characteristics	HIV-1-infectedpatients (n = 30)	Controls(n = 30)
Age in years (mean ± SD)	46.67 (10.67)	48.47 (9.90)
Gender (male:female)	25:5	24:6
Estimated IQ (mean ± SD)	96.37 (15.17)	102.13 (10.44)
Education level (mode, range)	6 (6)	5 (3)
Receiving cART (%)	73.3%	–
CSF viral load* ≤ undetectable^† (%)	56%	–
CSF viral load* > undetectable^† – 10000 c/mL (%)	44%	–
Nadir CD4 (median, IQR)	280 (115–360)	–
Nadir CD4 <200 (%)	30%
Nadir CD4 ≥200 (%)	70%
MRI^‡ White matter abnormalities	19.2%	–
MRI^‡ Grey matter abnormalities	7.7%	–
Regular alcohol use^§	43.3%	93.3%
Regular cannabis use^§	20%	0%
Regular drug use^§ other than cannabis	3.3%	0%

cART = combination antiretroviral therapy; IQR = interquartile range; MRI = magnetic resonance imaging; CSF = cerebrospinal fluid

*In 25 patients HIV RNA viral load was measured in the CSF

^†Undetectable CSF = ≤20 c/mL

^‡In 26 patients MRI of the brain was performed (T2-weighted MRI, 1.5 T)

^§Regular use is use of a substance for three or more times a week

Six of the participants scored below the cut-off (<85) of the symptom validity test (ASTM); these participants were excluded from all further analyses. Scores on the cognitive domains and each individual test (mean z-scores ± standard deviation for the cognitive domains and raw test scores ± standard deviation for tests) of the two groups are shown in Table 2. Overall, results of the MANOVA showed a significant difference between the groups on cognitive function (F(1,52) = 2.83, P = 0.015, η_p² = 0.30). Subsequent analyses of the individual domains showed a significantly worse performance in the patients on the domain Working memory compared with controls (F(1,52) = 4.63, P = 0.036, η_p² = 0.082). The patients performed statistically significantly better than controls on the domain Visuoconstruction (F(1,52) = 10.12, P = 0.002, η_p² = 0.163). None of the other domains showed significant group differences (all F values <1.64).

Table 2

Neuropsychological performance on the different cognitive domains and on each test for the HIV-1-infected patients and the control group

Cognitive domains	HIV-1-infectedpatients (n = 25)	Controls(n = 29)
Abstract reasoning	0.10 (±0.83)	−0.08 (±1.14)
Raven Advanced Progressive Matrices (mean total score)	9.20 (±1.58)	8.86 (±2.17
Working memory	−0.31 (±1.07)*	0.26 (±0.87)
WAIS-III Letter-Number Sequencing (mean total score)	9.80 (±2.20)	10.97 (±1.78)
Episodic memory	−0.00 (±0.69)	0.00 (±0.94)
Rey Auditory Verbal Learning Test (mean total score on trials 1–5)	39.16 (±7.66)	40.69 (±8.98)
Rey Auditory Verbal Learning Test (mean delayed recall score)	7.40 (±2.80)	7.72 (±3.60)
Location Learning Test-R (mean total score on trials 1–5)	23.36 (±17.91)	22.38 (±20.34)
Location Learning Test-R (mean delayed recall score)	1.48 (±2.69)	2.72 (±4.93)
Psychomotor speed	0.04 (±0.85)	−0.04 (±0.68)
Grooved Pegboard Test dominant hand (mean score)	73.48 (±13.01)	75.03 (±9.30)
Grooved Pegboard Test non-dominant hand (mean score)	82.32 (±19.42)	85.10 (±15.09)
WAIS-III Digit Symbol substitution (mean score)	71.60 (±17.18)	72.45 (±14.53)
Visuoconstruction	0.43 (±0.57)*	−0.37 (±1.14)
Rey Complex Figure-copy (mean score)	35.58 (±0.86)	34.36 (±1.74)
Executive functioning	−0.08 (±0.50)	0.07 (±0.38)
Brixton Spatial Anticipation Test (mean score)	39.88 (±6.67)	40.55 (±4.96)
Letter Fluency Test (mean trials K-O-M)	36.00 (±10.99)	39.31 (±8.92)
BADS Zoo Map Test (mean score condition 1–2)	12.24 (±3.66)	11.72 (±3.39)
Stroop Color Word Test (interference score)	0.64 (±0.26)	0.57 (±0.16)
Attention	−0.04 (±1.02)	0.04 (±0.87)
Paced Auditory Serial Addition Test 2.0 ISI (mean score)	33.32 (±13.46)	35.10 (±11.18)
Paced Auditory Serial Addition Test 1.6 ISI (mean score)	30.68 (±11.34)	30.83 (±10.28)

Domain scores are presented as mean z-scores ± standard deviation. Negative z-values indicate worse performance. Test scores are presented as mean raw test scores ± standard deviation

*P < 0.05

With respect to psychological wellbeing (Table 3), significantly higher levels of complaints in patients were found on the subscales anxiety, depression, somatic complaints, interpersonal sensitivity, hostility and on the total score (P values between 0.002 and 0.023). No significant difference between the groups was found on the subscales agoraphobia, cognitive performance difficulty and sleep disturbances. A correlational analysis was conducted taking all participants together (n = 54) in order to establish whether or not psychological wellbeing was correlated with cognitive functioning for the impaired domain Working memory. None of the wellbeing subscales were significantly correlated with cognitive performance on the domain Working memory (Pearson's r between −0.24 and −0.04). Furthermore, no difference was found with respect to the performance on Working memory between patients with a nadir CD4 <200 and patients with a nadir CD4 ≥200 (t(23) = 0.85, P = 0.402). Also, the lower performance on the domain Working memory remained significant when the untreated HIV-1-infected patients were excluded from the analysis (F(1,44) = 6.93, P = 0.012, η_p² = 0.14).

Table 3

Mean scores on the different dimensions of the SCL-90-R for the HIV-1-infected patients and controls

Dimension	HIV-1-infectedpatients (n = 25)	Controls(n = 29)	P
Agoraphobia	7.92 (±1.38)	7.48 (±1.35))	0.026
Anxiety	15.16 (±4.81)	12.17 (±2.16)	0.004**
Depression	25.44 (±7.58)	20.28 (±3.87)	0.002**
Somatization	19.48 (±7.11)	15.69 (±4.69)	0.023*
Cognitive performance difficulty	16.36 (±6.60)	14.10 (±3.38)	0.113
Interpersonal sensitivity	25.68 (±5.27)	21.93 (±3.93)	0.004**
Anger–hostility	8.12 (±2.09)	6.79 (±0.90)	0.003**
Sleep disturbance	6.20 (±3.01)	4.93 (±2.63)	0.105
Total score	136.08 (±30.68)	113.52 (±18.55)	S0.002**

Dimension scores are presented as mean scores ± standard deviation.

*P < 0.05; **P < 0.01

DISCUSSION

The results of this study showed a worse performance on cognitive functioning in our sample of HIV-1-infected patients compared with uninfected controls when combining all tests in one overall analysis. This effect is mainly due to a worse performance of the patient group on Working memory, with a medium-to-large effect size.³⁰ This worse performance in patients compared with controls was also reflected in the clinical evaluation of the neuropsychological assessment, where 12% of the patients were classified as cognitively impaired compared with 3.5% of the controls. This finding is in line with previous results showing that deficits in Working memory are among the strongest predictors of cognitive complaints in HIV patients.³¹ In contrast with several previous studies,^1,32 no impairments in other cognitive domains were found in the present study. A possible explanation for this discrepancy may be found in differences in disease stages or number of patients on cART across studies. That is, the severity of the neuropsychological dysfunctions may be associated with the disease stage of HIV-1.² Moreover, neuroimaging data of a subgroup of our sample demonstrated grey and white matter abnormalities in approximately 25% of the patients that may underlie the cognitive decrements that we observed.

Furthermore, our results showed that patients report more psychological complaints than controls. Specifically, they reported higher levels of anxiety, depressive symptoms, somatic complaints, lowered self-esteem and heightened irritability. Interestingly, patients did not report higher levels of cognitive complaints. The finding that patients showed high levels of psychological complaints might be due to the chronic nature of HIV-1, as in chronic illness depression- and anxiety-related complaints are frequently reported.³³ While psychological complaints may affect cognitive functioning,⁷ we did not find any significant correlations between the dimensions of psychological wellbeing and Working memory. This may indicate that psychological complaints do not fully explain the lower performance on Working memory in our sample of HIV-1-infected patients.

One of the strengths of the current study is that it is one of the few to examine cognitive functioning in HIV-1-infected patients that assessed symptom validity, which is important to be taken into account in HIV-1-infected patients.¹⁰ In our study, five out of 30 HIV-1-infected patients obtained a score under the cut-off on the symptom validity test and one of the 30 controls performed below the cut-off. These participants were removed from the analyses. However, this difference on the symptom validity test between patients and controls was not statistically significant. In contrast, the slightly better performance of the patients on the domain Visuoconstruction compared with controls has previously been linked to optimal mental effort during cognitive testing.³⁴ Another strength is that both cognitive performance and psychological wellbeing were compared with a matched healthy control group in a single study. Previous studies either lacked a matched control group or examined cognition or wellbeing in isolation. Next to a healthy control group, future studies could include controls with other chronic diseases to take non-HIV-specific emotional consequences into account. Also, studies in European samples of HIV-1-infected patients are scarce. A limitation of this study is that cART treatment may have influenced cognitive performance, partly due to differences in penetration into the CSF.³⁵ Another limitation was that data about viral load and MRI were not available for all patients, and that MRI abnormalities could not be quantitatively analysed using, e.g. volumetry. Finally, in this study both treated and untreated patients participated, but the lower performance on Working memory remained significant when the untreated patients were excluded from the analysis.

In all, this cross-sectional pilot study showed decrements in cognitive functioning, specifically in Working memory even in a small, randomly-selected sample of HIV-1-infected patients, as well as lower levels of psychological wellbeing. The findings of the current study indicate that future research should focus on unravelling the underlying mechanisms of neurocognitive dysfunction further, using neuropsychological tests, including a symptom validity test in combination with neuroimaging techniques and taking other aspects of quality of life into account than psychological wellbeing in larger samples. Finally, longitudinal studies examining the course and clinical significance of cognitive functioning in large cohorts of patients are warranted.

Footnotes

ACKNOWLEDGEMENTS

The authors acknowledge the participation of the study participants. Marjolein Bosch, HIV research nurse, was very helpful with the recruitment and data collection. Further, the authors thank Dr Sieberen van der Werf for his help with selection of the neuropsychological tests and start of the study. This research was partially supported by Abbott International, North suburban Chicago, Illinois, USA and by MSD (Merck Sharp & Dohme) B.V., Haarlem, The Netherlands.

Conflict of interest: None declared.

References

Grant

. Neurocognitive disturbances in HIV. Int Rev Psychiatr 2008;20:33–47

Reger

Welsh

Razani

Martin

Boone

. A meta-analysis of the neuropsychological sequelae of HIV infection. J Int Neuropsychol Soc 2002;8:410–24

Tozzi

Balestra

Murri

Neurocognitive impairment influences quality of life in HIV-infected patients receiving HAART. Int J STD AIDS 2004;15:254–9

Doyle

Weber

Atkinson

Grant

Woods

. Aging, prospective memory, and health-related quality of life in HIV infection. AIDS Behav 2012;16:2309–18

Owe-Larsson

Sall

Salamon

Allgulander

. HIV infection and psychiatric illness. Afr J Psychiatry 2009;12:115–28

Sadek

Vigil

Grant

Heaton

, the HNRC group. The impact of neuropsychological functioning and depressed mood on functional complaints in HIV-1 infection and methamphetamine dependence. J Clin Exp Neuropsychol 2007;29:266–76

Hasler

Drevets

Manji

Charney

. Discovering endophenotypes for major depression. Neuropsychopharmacology 2004;29:1765–81

Carter

Murji

Rourke

Shore

Rourke

. Cognitive complaints, depression, medical symptoms, and their association with neuropsychological functioning in HIV infection: a structural equation model analysis. Neuropsychology 2003;17:410–9

Heaton

Marcotte

Mindt

The impact of HIV-associated neuropsychological impairment on everyday functioning. J Int Neuropsych Soc 2004;10:317–31

10.

Woods

Conover

Weinborn

Base Rate of Hiscock Digit Memory Test Failure in HIV-associated neurocognitive disorders. Clin Neuropsychol 2003;17:383–9

11.

Hartgers

. Manual ‘De Sleutel’. European Addiction Severity Index. EuropASI. Follow-upASI. Merelbeke: De Sleutel, 2004

12.

Raven

Court

. Manual for Raven's Progressive Matrices and Vocabulary Scales. Oxford: Oxford University Press, 1993

13.

Wechsler

. Wechsler Adult Intelligence Scale Manual. New York: The Psychological Cooperation, 1955

14.

Rey

. L'Examen Clinique en Psychologie. Paris: Presses Universitaires de France, 1964

15.

Bucks

Willison

Byrne

LMT

Kessels

RPC

. Location Learning Test – Revised Edition (Dutch Version). Amsterdam: Hogrefe, 2011

16.

Heaton

Grant

Matthews

. Comprehensive Norms for an Expanded Halstead-Reitan Battery. Odessa, FL: Psychological Assessment Resources, 1992

17.

Rey

. L'examen psychologique dans les cas d'encephalopathie traumatique. Arch Psychol 1941;28:286–340

18.

Burgess

Shallice

. The Hayling and Brixton Tests. Burry St Edmunds, U.K: Thames Valley Test Company, 1997

19.

Schmand

Groenink

van den Dungen

. Letter fluency: psychometric properties and Dutch normative data. Tijdschr Gerontol Geriatr 2008;39:64–76

20.

Wilson

Alderman

Burgess

Emslie

Evans

. Behavioral assessment of the dysexecutive syndrome (BADS). J Occup Psychol Employ Disabil 2003;5:33–7

21.

Stroop

. Studies of interference in serial verbal reactions. J Exp Psychol 1935;18:643–62

22.

Stuss

Floden

Alexander

Levine

Katz

. Stroop performance in focal lesion patients: dissociation of processes and frontal lobe lesion location. Neuropsychologia 2001;39:771–86

23.

Aarnoudse

van den

Saan

. De Paced Auditory Serial Addition Task (PASAT) in een steekproef van gezonde proefpersonen: Betrouwbaarheden en normeringen. Groningen: Academisch Ziekenhuis Groningen, Afdeling Neuropsychologie, 1995

24.

Lezak

Howieson

Loring

. Neuropsychological Assessment. Oxford: Oxford University Press, 2004

25.

Arrindell

Ettema

JHM

. SCL-90 Symptom checklist: Handleiding bij een multidimensionele psychopathologie. Lisse: Swets Test Publishers, 2003

26.

Schmand

De Sterke

Lindeboom

. De Amsterdamse Korte Termijn Geheugentest: Handleiding. Lisse: Swets & Zeitlinger, 1999

27.

Schmand

Lindeboom

Van Harskamp

. The NLV: Dutch Adult Reading Test. Lisse: the Netherlands, Swets & Zeitlinger, 1992 (in Dutch)

28.

Van den Berg

Kessels

RPC

De Haan

Kappelle

Biessels

. Mild impairments in cognition in patients with type 2 diabetes mellitus: the use of the concepts MCI and CIND. J Neurol Neurosurg Psychiatry 2005;76:1466–7

29.

Antinori

Arendt

Becker

Updated research nosology for HIV-associated neurocognitive disorders. Neurology 2007;69:1789–99

30.

Cohen

. Statistical Power Analysis for the Behavioral Sciences. New York: Erlbaum, 1988

31.

Hinkin

Hardy

Mason

Verbal and spatial working memory performance among HIV-infected adults. J Int Neuropsychol Soc 2002;8:532–8

32.

Woods

Moore

Weber

Grant

. Cognitive neuropsychology of HIV-associated neurocognitive disorders. Neuropsychol Rev 2009;19:152–68

33.

Morisson

Bennet

. An Introduction to Health Psychology. London: Pearson Education Limited, 2006

34.

Brands

AMA

Kessels

RPC

Hoogma

RPLM

Cognitive performance, psychological well-being, and brain magnetic resonance imaging in older patients with type 1 diabetes. Diabetes 2006;55:1800–6

35.

Cysique

Brew

. Neuropsychological functioning and antiretroviral treatment in HIV/AIDS: a review. Neuropsychol Rev 2009;19:169–85