Journal of NeuroVirology

, Volume 23, Issue 2, pp 239–249 | Cite as

Association of midlife smoking status with change in processing speed and mental flexibility among HIV-seropositive and HIV-seronegative older men: the Multicenter AIDS Cohort Study

  • Wajiha Z. Akhtar-Khaleel
  • Robert L. Cook
  • Steve Shoptaw
  • Eric N. Miller
  • Ned Sacktor
  • Pamela J. Surkan
  • Jim Becker
  • Linda A. Teplin
  • Rebecca J. Beyth
  • Catherine Price
  • Michael Plankey


Smoking is a potential risk factor for age-related cognitive decline. To date, no study has examined the association between smoking and cognitive decline in men living with human immunodeficiency virus (HIV). The aim of this present study is to examine whether smoking status and severity in midlife is associated with a rate of decline in cognitive processing speed among older HIV-seropositive and HIV-seronegative men who have sex with men. Data from 591 older HIV-seropositive and HIV-seronegative men who have sex with men from the Multicenter AIDS Cohort Study were examined. All participants had information on smoking history collected before age 50 years and at least 5 years of follow-up after age 50. Smoking history was categorized as never smoker, former smoker, and current smoker and cumulative pack years was calculated. The raw scores of three neuropsychological tests (Trail Making A, Trail Making B, and Symbol Digit Modalities tests) were log transformed (Trail Making A and B) and used in linear mixed models to determine associations between smoking history and at least subsequent 5-year decline in cognitive processing speed. There were no significant differences in the rates of neurological decline among never smokers, former smokers, and current smokers. Findings were similar among HIV-seropositive participants. However, an increase of 5 pack-years was statistically significantly associated with a greater rate of decline in the Trail Making Test B score and Composite Score (β −0.0250 [95% CI, −0.0095 to −0.0006] and −0.0077 [95% CI, −0.0153 to −0.0002], respectively). We found no significant association between smoking treated as a categorical variable (never smoked, former smoker, or current smoker) and a small change in every increase of 5 pack-years on measures of psychomotor speed and cognitive flexibility. To optimize healthy aging, interventions for smoking cessation should be tailored to men who have sex with men.


HIV Neuropsychological test Smoking Neurocognition 



The data in this manuscript were collected by the Multicenter AIDS Cohort Study (MACS) with centers at Baltimore (U01-AI35042): The Johns Hopkins University Bloomberg School of Public Health: Joseph B. Margolick (PI), Barbara Crain, Adrian Dobs, Homayoon Farzadegan, Joel Gallant, Lisette Johnson-Hill, Cynthia Munro, Michael W. Plankey, Ned Sacktor, James Shepard, and Chloe Thio; Chicago (U01-AI35039): Feinberg School of Medicine, Northwestern University, and Cook County Bureau of Health Services: Steven M. Wolinsky (PI), John P. Phair, Sheila Badri, Maurice O’Gorman, David Ostrow, Frank Palella, and Ann Ragin; Los Angeles (U01-AI35040): University of California, UCLA Schools of Public Health and Medicine: Roger Detels (PI), Otoniel Martínez-Maza (Co-PI), Aaron Aronow, Robert Bolan, Elizabeth Breen, Anthony Butch, Beth Jamieson, Eric N. Miller, John Oishi, Harry Vinters, Dorothy Wiley, Mallory Witt, Otto Yang, Stephen Young, Zuo Feng Zhang; Pittsburgh (U01-AI35041): University of Pittsburgh, Graduate School of Public Health: Charles R. Rinaldo (PI), Lawrence A. Kingsley (Co-PI), James T. Becker, Ross D. Cranston, Jeremy J. Martinson, John W. Mellors, Anthony J. Silvestre, and Ronald D. Stall; and the Data Coordinating Center (UM1-AI35043): The Johns Hopkins University Bloomberg School of Public Health: Lisa P. Jacobson (PI), Alvaro Munoz (Co-PI), Alison, Abraham, Keri Althoff, Christopher Cox, Jennifer Deal, Gypsyamber D’Souza, Priya Duggal, Janet Schollenberger, Eric C. Seaberg, Sol Su, and Pamela Surkan. The MACS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional co-funding from the National Cancer Institute (NCI). Targeted supplemental funding for specific projects was also provided by the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute on Deafness and Communication Disorders (NIDCD). MACS data collection is also supported by UL1-TR000424 (JHU CTSA). Website located at The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH).

Compliance with ethical standards

Conflict of Interests

The authors declare that they have no conflict of interest.


  1. Akhtar-Khaleel WZ, Cook RL, Shoptaw S et al (2016) Trends and predictors of cigarette smoking among HIV seropositive and seronegative men: the Multicenter AIDS Cohort Study. AIDS Behav 20(3):622–632CrossRefPubMedPubMedCentralGoogle Scholar
  2. Becker JT, Kingsley KA, Molsberry S et al (2015) Cohort profile: recruitment cohorts in the neuropsychological substudy of the Multicenter AIDS Cohort Study. Int J Epidemiol 44(5):1506–1516CrossRefPubMedGoogle Scholar
  3. Bryant VE, Kahler CW, Devlin KN et al (2013) The effects of cigarette smoking on learning and memory performance among people living with HIV/AIDS. AIDS Care 25:1308–1316CrossRefPubMedPubMedCentralGoogle Scholar
  4. Canizares S, Cherner M, Ellis R (2014) HIV and aging: effects on the central nervous system. Semin Neurol 34(1):27–34CrossRefPubMedPubMedCentralGoogle Scholar
  5. Centers for Disease Control and Prevention (2016) HIV/AIDS among persons aged 50 and older. Available at: Accessed on June 28, 2016.
  6. Collins N, Sachs-Ericsson N, Preacher KJ et al (2009 Nov) Smoking increases risk for cognitive decline among community-dwelling older Mexican Americans. Am J Geriatr Psychiatry 17(11):934–942CrossRefPubMedPubMedCentralGoogle Scholar
  7. Dudley J, Jin S, Hoover D, Metz S, Thackeray R, Chmiel J (1995) The Multicenter AIDS Cohort Study: retention after 9 1/2 years. Am J Epidemiol 142(3):323–330CrossRefPubMedGoogle Scholar
  8. Durazzo TC, Rothlind JC, Cardenas V et al (2007) Chronic cigarette smoking and heavy drinking in human immunodeficiency virus: consequences for neurocognition and brain morphology. Alcohol 41(7):489–501CrossRefPubMedPubMedCentralGoogle Scholar
  9. Durazzo TC, Meyerhoff DJ, Nixon SJ (2010) Chronic cigarette smoking: implications for neurocognition and brain neurobiology. Int J Environ Res Pub Health 7(10):3760–3791CrossRefGoogle Scholar
  10. Durazzo TC, Mattson N, Weiner MW (2014) Smoking and increased Alzheimer’s disease risk: a review of potential mechanisms. Alzheimers Dement 10:S122–S145CrossRefPubMedPubMedCentralGoogle Scholar
  11. Gabrieli J (1995) Contribution of the basal ganglia to skill learning and working memory in humans. In: Houk JC, Davis JL, Beiser DG (eds) Models of information processing in the basal ganglia. MIT Press, Cambridge, MAGoogle Scholar
  12. Giorgi JV, Cheng H, Margolick JB et al (1990) Quality controls in the flow cytometric measurement of T-lymphocyte subsets: the Multicenter AIDS Cohort Study experience. Clin Immunol Immunopathol 55(2):173–186CrossRefPubMedGoogle Scholar
  13. Gray F, Adle-Biassette H, Chretien F et al (2001) Neuropathology and neurodegeneration in human immunodeficiency virus infection. Pathogenesis of HIV-induced lesions of the brain, correlations with HIV-associated disorders and modifications according to treatments. Neuropathol 20:146–155Google Scholar
  14. High KP, Brennan-Ing M, Clifford DB et al (2012) HIV and aging: state of knowledge and areas of critical need for research: a report to the NIH Office of AIDS Research by the HIV and Aging Working Group. J Acquir Immune Defic Syndr 60(Suppl 1):S1–18CrossRefPubMedGoogle Scholar
  15. Ho AJ, Raji CA, Becker JT, Lopez OL, Kuller LH, Hua X et al (2010 Aug) Obesity is linked with lower brain volume in 700 AD and MCI patients. Neurobiol Aging 31(8):1326–1339CrossRefPubMedPubMedCentralGoogle Scholar
  16. Ho AJ, Raji CA, Saharan P, DeGiorgio A, Madsen SK, Hibar DP et al (2011 Jan 5) Hippocampal volume is related to body mass index in Alzheimer’s disease. Neuroreport 22(1):10–14CrossRefPubMedPubMedCentralGoogle Scholar
  17. Justice AC (2009) HIV and aging: time for a new paradigm. Curr HIV/AIDS Rep 7:69–76CrossRefGoogle Scholar
  18. Kaslow RA, Ostrow DG, Detels R et al (1987) The Multicenter AIDS Cohort Study: rationale, organization, and selected characteristics of the participants. Am J Epidemiol 126:310–318CrossRefPubMedGoogle Scholar
  19. Knopman DS, Mosley TH, Catellier DJ et al (2009) Fourteen-year longitudinal study of vascular risk factors, APOE genotype, and cognition: the ARIC MRI Study. Alzheimers Dement 5(3):207–214CrossRefPubMedGoogle Scholar
  20. Lewinsohn PM, Seeley JR, Roberts RE, Allen NB (1997) Center for Epidemiologic Studies Depression Scale (CES-D) as a screening instrument for depression among community-residing older adults. Psychol Aging 12(2):277–287CrossRefPubMedGoogle Scholar
  21. Lindl KA, Marks D, Kolson DL et al (2010) HIV-associated neurocognitive disorder: pathogenesis and therapeutic opportunities. J NeuroImmune Pharmacol 5(3):294–309CrossRefPubMedPubMedCentralGoogle Scholar
  22. Miller EN, Selnes OA, McArthur JC et al (1990) Neuropsychological performance in HIV-1-infected homosexual men: the Multicenter AIDS Cohort Study (MACS). Neurology 40:197–203CrossRefPubMedGoogle Scholar
  23. Monnig MA, Kahler CW, Lee H et al (2016) Effects of smoking and alcohol use on neurocognitive functioning in heavy drinking, HIV-positive men who have sex with men. AIDS Care 28(3):300–305CrossRefPubMedGoogle Scholar
  24. Nabha L, Duong L, Timpone J (2013) HIV-associated neurocognitive disorders: perspective on management strategies. Drugs 73(9):893–905CrossRefPubMedPubMedCentralGoogle Scholar
  25. Nooyens AC, van Gelder BM, Verschuren WM (2008) Smoking and cognitive decline among middle-aged men and women: the Doetinchem Cohort Study. Am J Public Health 98(12):2244–2250CrossRefPubMedPubMedCentralGoogle Scholar
  26. North TL, Palmer TM, Lewis SJ et al (2015) Effect of smoking on physical and cognitive capability in later life: a multicohort study using observational and genetic approaches. BMJ Open 5(12):e008393CrossRefPubMedPubMedCentralGoogle Scholar
  27. Peters R, Poulter R, Warner J et al (2008) Smoking, dementia and cognitive decline in the elderly, a systematic review. BMC Geriatr 8:36CrossRefPubMedPubMedCentralGoogle Scholar
  28. Raji CA, Ho AJ, Parikshak NN, Becker JT, Lopez OL, Kuller LH et al (2010 Mar) Brain structure and obesity. Hum Brain Mapp 31(3):353–364PubMedPubMedCentralGoogle Scholar
  29. Reitz C, Mayeux R (2014) Alzheimer disease: epidemiology, diagnostic criteria, risk factors and biomarkers. Biochem Pharmacol 88(4):640–651CrossRefPubMedPubMedCentralGoogle Scholar
  30. Sabia S, Marmot M, Dufouil C et al (2008) Smoking history and cognitive function in middle age from the Whitehall II study. Arch Intern Med 168(11):1165–1173CrossRefPubMedPubMedCentralGoogle Scholar
  31. Sabia S, Elbaz A, Dugravot A et al (2012) Impact of smoking on cognitive decline in early old age: the Whitehall II cohort study. Arch Gen Psychiatry 69:627–635CrossRefPubMedPubMedCentralGoogle Scholar
  32. Sacktor N, Tarwater PM, Skolasky RL et al (2001) CSF antiretroviral drug penetrance and the treatment of HIV-associated psychomotor slowing. Neurology 57:542–544CrossRefPubMedGoogle Scholar
  33. Sacktor N, Skolasky RL, Cox C et al (2010) Longitudinal psychomotor speed performance in human immunodeficiency virus–seropositive individuals: impact of age and serostatus. J Neurovirol. 16:335–341CrossRefPubMedPubMedCentralGoogle Scholar
  34. Satz P, Morgenstern H, Miller EN, Selnes OA, McArthur JC, Cohen BA et al (1993) Low education as a possible risk factor for early cognitive abnormalities in HIV1: new findings from the Multicenter AIDS Cohort Study (MACS). JAIDS 6(5):503–511Google Scholar
  35. Schenker E, Hultin L, Bauer K et al (1993) Evaluation of a dual-color flow cytometry immuphenotyping panel in a multicenter quality assurance program. Cytometry 14(3):307–317CrossRefPubMedGoogle Scholar
  36. Stern RA, Silva SG, Chaisson N, Evans DL (1996) Influence of cognitive reserve on neuropsychological functioning in asymptomatic human immunodeficiency virus-1 infection. Arch Neurol 53(2):148–153CrossRefPubMedGoogle Scholar
  37. Substance Abuse and Mental Health Services Administration. Binge drinking: terminology and patterns of use. Available from: Accessed February 15, 2014
  38. Valcour VG, Shikuma CM, Watters MR, Sacktor NC (2004) Cognitive impairment in older HIV-1-seropositive individuals: prevalence and potential mechanisms. AIDS 18(Suppl 1):S79–S86CrossRefPubMedPubMedCentralGoogle Scholar
  39. Valcour VG, Paul R, Chiao S et al (2011) Screening for cognitive impairment in human immunodeficiency virus. Clin Infect Dis 53(8):836–842CrossRefPubMedPubMedCentralGoogle Scholar
  40. Weuve J, Tchetgen EJ, Glymour MM et al (2012) Accounting for bias due to selective attrition: the example of smoking and cognitive decline. Epidemiology 23(1):119–128CrossRefPubMedPubMedCentralGoogle Scholar
  41. Woods SP, Moore DJ, Weber E et al (2009) Cognitive neuropsychology of HIV-associated neurocognitive disorders. Neuropsychol Rev 19:152–168CrossRefPubMedPubMedCentralGoogle Scholar
  42. Wojna V, Robles L, Skolasky RL (2007) Associations of cigarette smoking with viral immune and cognitive function in human immunodeficiency virus–seropositive women. J Neurovirol 13:561–568CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2016

Authors and Affiliations

  • Wajiha Z. Akhtar-Khaleel
    • 1
  • Robert L. Cook
    • 1
  • Steve Shoptaw
    • 2
  • Eric N. Miller
    • 3
  • Ned Sacktor
    • 4
  • Pamela J. Surkan
    • 5
  • Jim Becker
    • 6
  • Linda A. Teplin
    • 7
  • Rebecca J. Beyth
    • 8
  • Catherine Price
    • 9
  • Michael Plankey
    • 10
  1. 1.Department of Epidemiology, College of Public Health and Health Professions and College of MedicineUniversity of FloridaGainesvilleUSA
  2. 2.David Geffen School of Medicine, Departments of Family Medicine and PsychiatryUniversity of CaliforniaLos AngelesUSA
  3. 3.Semel Institute for NeuroscienceUniversity of CaliforniaLos AngelesUSA
  4. 4.Department of NeurologyThe Johns Hopkins University School of MedicineBaltimoreUSA
  5. 5.Department of International Health, Johns Hopkins Bloomberg School of Public HealthBaltimoreUSA
  6. 6.Department of Psychiatry, Neurology, and PsychologyUniversity of PittsburghPittsburghUSA
  7. 7.Departments of Psychiatry and Behavioral Sciences, Feinberg School of MedicineNorthwestern UniversityChicagoUSA
  8. 8.Malcom Randall VA Medical CenterGainesvilleUSA
  9. 9.Department of Clinical and Health PsychologyUniversity of FloridaGainesvilleUSA
  10. 10.Department of Medicine, Division of Infectious DiseasesGeorgetown University Medical CenterWashingtonUSA

Personalised recommendations