Depression, lifestyle factors and cognitive function in people living with HIV and comparable HIV-negative controls

D De Francesco, J Underwood, E Bagkeris, M Boffito, F A Post, Pwg Mallon, J H Vera, I Williams, J Anderson, M Johnson, C A Sabin, A Winston, Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) study, Daphne Babalis, Laura Burgess, Paddy Mallon, Memory Sachikonye, David Asboe, Lucy Garvey, Anton Pozniak, Amanda Clarke, Andrew Bexley, Celia Richardson, Sarah Kirk, Rebecca Gleig, Margherita Bracchi, Nicole Pagani, Maddalena Cerrone, Daniel Bradshaw, Francesca Ferretti, Chris Higgs, Elisha Seah, Stephen Fletcher, Michelle Anthonipillai, Ashley Moyes, Katie Deats, Irtiza Syed, Clive Matthews, Peter Fernando, Chido Chiwome, Shane Hardwick, Sifiso Mguni, Rebecca Clark, Rhiannon Nevin-Dolan, Sambasivarao Pelluri, Lucy Campbell, Selin Yurdakul, Sara Okumu, Louise Pollard, Beatriz Santana-Suarez, Alan Macken, Bijan Ghavani-Kia, Joanne Maher, Maria Byrne, Ailbhe Flaherty, Sumesh Babu, Damilola Otiko, Laura Phillips, Rosanna Laverick, Michelle Beynon, Anna-Lena Salz, Abigail Severn, Lavender Tembo, Matthew Stott, Linda McDonald, Felix Dransfield, Andrew Whitehouse, Nnenna Ngwu, Nargis Hemat, Martin Jones, Anne Carroll, Sabine Kinloch, Mike Youle, Sara Madge, D De Francesco, J Underwood, E Bagkeris, M Boffito, F A Post, Pwg Mallon, J H Vera, I Williams, J Anderson, M Johnson, C A Sabin, A Winston, Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) study, Daphne Babalis, Laura Burgess, Paddy Mallon, Memory Sachikonye, David Asboe, Lucy Garvey, Anton Pozniak, Amanda Clarke, Andrew Bexley, Celia Richardson, Sarah Kirk, Rebecca Gleig, Margherita Bracchi, Nicole Pagani, Maddalena Cerrone, Daniel Bradshaw, Francesca Ferretti, Chris Higgs, Elisha Seah, Stephen Fletcher, Michelle Anthonipillai, Ashley Moyes, Katie Deats, Irtiza Syed, Clive Matthews, Peter Fernando, Chido Chiwome, Shane Hardwick, Sifiso Mguni, Rebecca Clark, Rhiannon Nevin-Dolan, Sambasivarao Pelluri, Lucy Campbell, Selin Yurdakul, Sara Okumu, Louise Pollard, Beatriz Santana-Suarez, Alan Macken, Bijan Ghavani-Kia, Joanne Maher, Maria Byrne, Ailbhe Flaherty, Sumesh Babu, Damilola Otiko, Laura Phillips, Rosanna Laverick, Michelle Beynon, Anna-Lena Salz, Abigail Severn, Lavender Tembo, Matthew Stott, Linda McDonald, Felix Dransfield, Andrew Whitehouse, Nnenna Ngwu, Nargis Hemat, Martin Jones, Anne Carroll, Sabine Kinloch, Mike Youle, Sara Madge

Abstract

Objectives: We investigated whether differences in cognitive performance between people living with HIV (PLWH) and comparable HIV-negative people were mediated or moderated by depressive symptoms and lifestyle factors.

Methods: A cross-sectional study of 637 'older' PLWH aged ≥ 50 years, 340 'younger' PLWH aged < 50 years and 276 demographically matched HIV-negative controls aged ≥ 50 years enrolled in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) study was performed. Cognitive function was assessed using a computerized battery (CogState). Scores were standardized into Z-scores [mean = 0; standard deviation (SD) = 1] and averaged to obtain a global Z-score. Depressive symptoms were evaluated via the Patient Health Questionnaire (PHQ-9). Differences between the three groups and the effects of depression, sociodemographic factors and lifestyle factors on cognitive performance were evaluated using median regression. All analyses accounted for age, gender, ethnicity and level of education.

Results: After adjustment for sociodemographic factors, older and younger PLWH had poorer overall cognitive scores than older HIV-negative controls (P < 0.001 and P = 0.006, respectively). Moderate or severe depressive symptoms were more prevalent in both older (27%; P < 0.001) and younger (21%; P < 0.001) PLWH compared with controls (8%). Depressive symptoms (P < 0.001) and use of hashish (P = 0.01) were associated with lower cognitive function; alcohol consumption (P = 0.02) was associated with better cognitive scores. After further adjustment for these factors, the difference between older PLWH and HIV-negative controls was no longer significant (P = 0.08), while that between younger PLWH and older HIV-negative controls remained significant (P = 0.01).

Conclusions: Poorer cognitive performances in PLWH compared with HIV-negative individuals were, in part, mediated by the greater prevalence of depressive symptoms and recreational drug use reported by PLWH.

Keywords: HIV; HIV-associated neurocognitive disorders; cognitive disorder; cognitive function; depression; people living with HIV.

© 2019 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.

Figures

Figure 1
Figure 1
Domain and global Z‐scores in people living with HIV (PLWH) ≥ 50 years old, PLWH < 50 years old and HIV‐negative participants ≥ 50 years old adjusted for age, gender, ethnicity and level of education.
Figure 2
Figure 2
Difference (95% confidence interval) in the median global Z‐score by severity of depressive symptoms and group. The median (interquartile range) global Z‐score for HIV‐negative controls ≥ 50 years old with no depressive symptoms was 0.20 (−0.15, 0.46).

References

    1. Schouten J, Su T, Wit FW et al Determinants of reduced cognitive performance in HIV‐1‐infected middle‐aged men on combination antiretroviral therapy. AIDS 2016; 30: 1027–1038.
    1. Simioni S, Cavassini M, Annoni J‐M et al Cognitive dysfunction in HIV patients despite long‐standing suppression of viremia. AIDS 2010; 24: 1243–1250.
    1. Winston A, Arenas‐Pinto A, Stöhr W et al Neurocognitive function in HIV infected patients on antiretroviral therapy. PLoS ONE 2013; 8: e61949.
    1. De Francesco D, Underwood J, Post FA et al Defining cognitive impairment in people‐living‐with‐HIV: the POPPY study. BMC Infect Dis 2016; 16: 617.
    1. Zanjani F, Saboe K, Oslin D. Age difference in rates of mental health/substance abuse and behavioral care in HIV‐positive adults. AIDS Patient Care STDS 2007; 21: 347–355.
    1. Ciesla JA, Roberts JE. Meta‐analysis of the relationship between HIV infection and risk for depressive disorders. Am J Psychiatry 2001; 158: 725–730.
    1. Nanni MG, Caruso R, Mitchell AJ, Meggiolaro E, Grassi L. Depression in HIV infected patients: a review. Curr Psychiatry Rep 2014; 17: 530.
    1. Lee RS, Hermens DF, Porter MA, Redoblado‐Hodge MA. A meta‐analysis of cognitive deficits in first‐episode major depressive disorder. J Affect Disord 2012; 140: 113–124.
    1. Fellows RP, Byrd DA, Morgello S. Major depressive disorder, cognitive symptoms, and neuropsychological performance among ethnically diverse HIV+ men and women. J Int Neuropsychol Soc 2013; 19: 216–225.
    1. Heaton RK, Franklin DR Jr, Deutsch R et al Neurocognitive change in the era of HIV combination antiretroviral therapy: the longitudinal CHARTER study. Clin Infect Dis 2014; 60: 473–480.
    1. Cysique LA, Dermody N, Carr A, Brew BJ, Teesson M. The role of depression chronicity and recurrence on neurocognitive dysfunctions in HIV‐infected adults. J Neurovirol 2016; 22: 56–65.
    1. Cysique LA, Deutsch R, Atkinson JH et al Incident major depression does not affect neuropsychological functioning in HIV‐infected men. J Int Neuropsychol Soc 2007; 13: 1–11.
    1. Garin N, Velasco C, De Pourcq JT et al Recreational drug use among individuals living with HIV in Europe: review of the prevalence, comparison with the general population and HIV guidelines recommendations. Front Microbiol 2015; 6: 690.
    1. Garin N, Zurita B, Velasco C et al Prevalence and clinical impact of recreational drug consumption in people living with HIV on treatment: a cross‐sectional study. BMJ Open 2017; 7: e014105.
    1. Galvan FH, Bing EG, Fleishman JA et al The prevalence of alcohol consumption and heavy drinking among people with HIV in the United States: results from the HIV Cost and Services Utilization Study. J Stud Alcohol 2002; 63: 179–186.
    1. Klugman A, Gruzelier J. Chronic cognitive impairment in users of ’ecstasy’ and cannabis. World Psychiatry 2003; 2: 184.
    1. Bagkeris E, Burgess L, Mallon PW et al Cohort profile: the pharmacokinetic and clinical observations in PeoPle over fiftY (POPPY) study. Int J Epidemiol 2018; 47: 1391e–1392e.
    1. Kirwan PD, Chau C, Brown AE, Gill ON, Delpech VC. HIV in the UK ‐ 2016 report. London: Public Health England; 2016. December 2016.
    1. Cogstate website 2017. Available at (accessed 19 May, 2017).
    1. Darby DG, Pietrzak RH, Fredrickson J et al Intraindividual cognitive decline using a brief computerized cognitive screening test. Alzheimers Dement 2012; 8: 95–104.
    1. Steinberg SI, Sammel MD, Harel BT et al Exercise, sedentary pastimes, and cognitive performance in healthy older adults. Am J Alzheimers Dis Other Demen 2014; 30: 290–298.
    1. Maruff P, Thomas E, Cysique L et al Validity of the CogState brief battery: relationship to standardized tests and sensitivity to cognitive impairment in mild traumatic brain injury, schizophrenia, and AIDS dementia complex. Arch Clin Neuropsychol 2009; 24: 165–178.
    1. Cysique LA, Maruff P, Darby D, Brew BJ. The assessment of cognitive function in advanced HIV‐1 infection and AIDS dementia complex using a new computerised cognitive test battery. Arch Clin Neuropsychol 2006; 21: 185–194.
    1. Overton ET, Kauwe JS, Paul R et al Performances on the CogState and standard neuropsychological batteries among HIV patients without dementia. AIDS Behav 2011; 15: 1902–1909.
    1. Woods SP, Moore DJ, Weber E, Grant I. Cognitive neuropsychology of HIV‐associated neurocognitive disorders. Neuropsychol Rev 2009; 19: 152–168.
    1. DrugRehab website 2018. Available at (accessed 17 August, 2018).
    1. Kroenke K, Spitzer RL, Williams JB. The phq‐9. J Gen Intern Med 2001; 16: 606–613.
    1. Su T, Schouten J, Geurtsen GJ et al Multivariate normative comparison, a novel method for more reliably detecting cognitive impairment in HIV infection. AIDS 2015; 29: 547–557.
    1. Stern Y, McDermott MP, Albert S et al Factors associated with incident human immunodeficiency virus–dementia. Arch Neurol 2001; 58: 473–479.
    1. Valcour V, Paul R, Neuhaus J, Shikuma C. The effects of age and HIV on neuropsychological performance. J Int Neuropsychol Soc 2011; 17: 190–195.
    1. Crum‐Cianflone NF, Moore DJ, Letendre S et al Low prevalence of neurocognitive impairment in early diagnosed and managed HIV‐infected persons. Neurology 2013; 80: 371–379.
    1. Underwood J, Cole JH, Caan M et al Grey and white matter abnormalities in treated HIV‐disease and their relationship to cognitive function. Clin Infect Dis 2017; 65: 422–432.
    1. Cole JH, Caan MW, Underwood J et al No evidence for accelerated ageing‐related brain pathology in treated HIV: longitudinal neuroimaging results from the Comorbidity in Relation to AIDS (COBRA) project. Clin Infect Dis 2018; 66: 1899–1909.
    1. Drevets WC. Neuroimaging studies of mood disorders. Biol Psychiat 2000; 48: 813–829.
    1. Ma N, Li L, Shu N et al White matter abnormalities in first‐episode, treatment‐naive young adults with major depressive disorder. Am J Psychiatry 2007; 164: 823–826.
    1. Everall I, Salaria S, Atkinson J et al Diminished somatostatin gene expression in individuals with HIV and major depressive disorder. Neurology 2006; 67: 1867–1869.
    1. Schroecksnadel K, Sarcletti M, Winkler C et al Quality of life and immune activation in patients with HIV‐infection. Brain Behav Immun 2008; 22: 881–889.
    1. Maes M, Bosmans E, Suy E, Vandervorst C, De Jonckheere C, Raus J. Immune disturbances during major depression: upregulated expression of interleukin‐2 receptors. Neuropsychobiology 1990; 24: 115–120.
    1. Maes M, Lambrechts J, Bosmans E et al Evidence for a systemic immune activation during depression: results of leukocyte enumeration by flow cytometry in conjunction with monoclonal antibody staining. Psychol Med 1992; 22: 45–53.
    1. UK Chief Medical Officers . UK Chief Medical Officers’ Low Risk Drinking Guidelines. In: Department of Health and Social Care, editor. London 2016.
    1. Elwood P, Gallacher J, Hopkinson CA et al Smoking, drinking, and other life style factors and cognitive function in men in the Caerphilly cohort. J Epidemiol Community Health 1999; 53: 9–14.
    1. Cervilla J, Prince M, Mann A. Smoking, drinking, and incident cognitive impairment: a cohort community based study included in the Gospel Oak project. J Neurol Neurosurg Psychiatry 2000; 68: 622–626.
    1. Edelstein SL, Kritz‐Silverstein D, Barrett‐Connor E. Prospective association of smoking and alcohol use with cognitive function in an elderly cohort. J Womens Health 1998; 7: 1271–1281.
    1. Britton A, Singh‐Manoux A, Marmot M. Alcohol consumption and cognitive function in the Whitehall II Study. Am J Epidemiol 2004; 160: 240–247.
    1. Rimm EB, Williams P, Fosher K, Criqui M, Stampfer MJ. Moderate alcohol intake and lower risk of coronary heart disease: meta‐analysis of effects on lipids and haemostatic factors. BMJ 1999; 319: 1523–1528.
    1. Becker J, Kingsley L, Mullen J et al Vascular risk factors, HIV serostatus, and cognitive dysfunction in gay and bisexual men. Neurology 2009; 73: 1292–1299.
    1. Crean RD, Crane NA, Mason BJ. An evidence based review of acute and long‐term effects of cannabis use on executive cognitive functions. J Addict Med 2011; 5: 1.
    1. Attonito JM, Dévieux JG, Lerner BD, Hospital MM, Rosenberg R. Exploring substance use and HIV treatment factors associated with neurocognitive impairment among people living with HIV/AIDS. Front Public Health 2014; 2: 105.

Source: PubMed

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