Skip to main content

Advertisement

Log in

Cognitive reserve and neuropsychological functioning in older HIV-infected people

  • Published:
Journal of NeuroVirology Aims and scope Submit manuscript

Abstract

Progress in treatments has led to HIV+ patients getting older. Age and HIV are risk factors for neurocognitive impairment (NCI). We explored the role of cognitive reserve (CR) on cognition in a group of virologically suppressed older HIV+ people. We performed a multicenter study, consecutively enrolling asymptomatic HIV+ subjects ≥60 years old during routine outpatient visits. A comprehensive neuropsychological battery was administered. Raw test scores were adjusted based on Italian normative data and transformed into z-scores; NCI was defined according to Frascati criteria. All participants underwent the Brief Intelligence Test (TIB) and the Cognitive Reserve Index (CRI) questionnaire as proxies for CR. Relationships between TIB, CRI, and NCI were investigated by logistic or linear regression analyses. Sixty patients (85 % males, median age 66, median education 12, 10 % HCV co-infected, 25 % with past acquired immunodeficiency syndrome (AIDS)-defining events, median CD4 cells count 581 cells/μL, median nadir CD4 cells count 109 cells/μL) were enrolled. Twenty-four patients (40 %) showed Asymptomatic Neurocognitive Impairment. At logistic regression analysis, only CRI (OR 0.94; 95 % CI 0.91–0.97; P = 0.001) and TIB (OR 0.80; 95 % CI 0.71–0.90; P < 0.001) were associated with a lower risk of NCI. Higher CRI and TIB were significantly correlated with a better performance (composite z-score) both globally and at individual cognitive domains. Our findings highlight the role of CR over clinical variables in maintaining cognitive integrity in a virologically suppressed older HIV-infected population. A lifestyle characterized by experiences of mental stimulation may help to cope aging and HIV-related neurodegeneration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, Clifford DB, Cinque P, Epstein LG, Goodkin K, Gisslen M, Grant I, Heaton RK, Joseph J, Marder K, Marra CM, McArthur JC, Nunn M, Price RW, Pulliam L, Robertson KR, Sacktor N, Valcour V, Wojna VEJT (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69:1789–1799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barnett JH, Salmond CH, Jones PB, Sahakian BJ (2006) Cognitive reserve in neuropsychiatry. Psychol Med 36:1053–1064

    Article  CAS  PubMed  Google Scholar 

  • Basso MR, Bornstein RA (2000) Estimated premorbid intelligence mediates neurobehavioral change in individuals infected with HIV across 12 months. J Clin Exp Neuropsychol 22:208–218

    Article  CAS  PubMed  Google Scholar 

  • Capitani E, Laiacona M (1997) Composite neuropsychological batteries and demographic correction: standardization based on equivalent scores, with a review of published data. The Italian group for the neuropsychological study of ageing. J Clin Exp Neuropsychol 19:795–809

    Article  CAS  PubMed  Google Scholar 

  • Carlesimo GA, Caltagirone C, Gainotti G (1996) The mental deterioration battery: normative data, diagnostic reliability and qualitative analyses of cognitive impairment. The group for the standardization of the mental deterioration battery. Eur Neurol 36:378–384

    Article  CAS  PubMed  Google Scholar 

  • Castellon SA, Hardy DJ, Hinkin CH, Satz P, Stenquist PK, van Gorp WG, Myers HF, Moore L (2006) Components of depression in HIV-1 infection: their differential relationship to neurocognitive performance. J Clin Exp Neuropsychol 28:420–437

    Article  PubMed  PubMed Central  Google Scholar 

  • Chang L, Holt JL, Yakupov R, Jiang CS, Ernst T (2013) Lower cognitive reserve in the aging human immunodeficiency virus-infected brain. Neurobiol Aging 34:1240–1253. doi:10.1016/j.neurobiolaging.2012.10.012

    Article  PubMed  Google Scholar 

  • Ciccarelli N, Fabbiani M, Colafigli M, Trecarichi EM, Silveri MC, Cauda R, Murri R, De Luca A, Di Giambenedetto S (2013) Revised central nervous system neuropenetration-effectiveness score is associated with cognitive disorders in HIV-infected patients with controlled plasma viraemia. Antivir Ther 18:153–160. doi:10.3851/IMP2560

    Article  PubMed  Google Scholar 

  • Cole MA, Castellon SA, Perkins AC, Ureno OS, Robinet MB, Reinhard MJ, Barclay TR, Hinkin CH (2007) Relationship between psychiatric status and frontal-subcortical systems in HIV-infected individuals. J Int Neuropsychol Soc 13:549–554

    Article  PubMed  PubMed Central  Google Scholar 

  • Colombo L, Sartori G, Brivio C (2002) Stima del quoziente intellettivo tramite l’applicazione del TIB (Test Breve di Intelligenza). G Ital Psicol 613–638

  • Dufouil C, Alperovitch A, Tzourio C (2003) Influence of education on the relationship between white matter lesions and cognition. Neurology 60:831–836

    Article  CAS  PubMed  Google Scholar 

  • Elkins JS, Longstreth WT Jr, Manolio TA, Newman AB, Bhadella RA, Johnston SC (2006) Education and the cognitive decline associated with MRI-defined brain infarct. Neurology 67:435–440

    Article  CAS  PubMed  Google Scholar 

  • Fabbiani M, Ciccarelli N, Tana M, Farina S, Baldonero E, Di Cristo V, Colafigli M, Tamburrini E, Cauda R, Silveri MC, Grima P, Di Giambenedetto S (2013) Cardiovascular risk factors and carotid intima-media thickness are associated with lower cognitive performance in HIV-infected patients. HIV Med 14:136–144. doi:10.1111/j.1468-1293.2012.01044.x

    Article  CAS  PubMed  Google Scholar 

  • Fabbiani M, Grima P, Milanini B, Mondi A, Baldonero E, Ciccarelli N, Cauda R, Silveri MC, De Luca A, Di Giambenedetto S (2014) Antiretroviral neuropenetration scores better correlate with cognitive performance of HIV-infected patients after accounting for drug susceptibility. Antivir Ther. doi:10.3851/IMP2926

    Google Scholar 

  • Foley JM, Ettenhofer ML, Kim MS, Behdin N, Castellon SA, Hinkin CH (2012) Cognitive reserve as a protective factor in older HIV-positive patients at risk for cognitive decline. Appl Neuropsychol Adult 19:16–25. doi:10.1080/09084282.2011.595601

    Article  PubMed  PubMed Central  Google Scholar 

  • Glatt SL, Hubble JP, Lyons K, Paolo A, Tröster AI, Hassanein RE, Koller WC (1996) Risk factors for dementia in Parkinson’s disease: effect of education. Neuroepidemiology 15:20–25

    Article  CAS  PubMed  Google Scholar 

  • Gunning-Dixon FM, Brickman AM, Cheng JC, Alexopoulos GS (2009) Aging of cerebral white matter: a review of MRI findings. Int J Geriatr Psychiatry 24:109–117. doi:10.1002/gps.2087

    Article  PubMed  PubMed Central  Google Scholar 

  • Hammond ER, Crum RM, Treisman GJ, Mehta SH, Marra CM, Clifford DB, Morgello S, Simpson DM, Gelman BB, Ellis RJ, Grant I, Letendre SL, McArthur JC, CHARTER Group (2014) The cerebrospinal fluid HIV risk score for assessing central nervous system activity in persons with HIV. Am J Epidemiol 180:297–307. doi:10.1093/aje/kwu098

    Article  PubMed  PubMed Central  Google Scholar 

  • Heaton RK, Clifford DB, Franklin DR Jr, Woods SP, Ake C, Vaida F, Ellis RJ, Letendre SL, Marcotte TD, Atkinson JH, Rivera-Mindt M, Vigil OR, Taylor MJ, Collier AC, Marra CM, Gelman BB, McArthur JC, Morgello S, Simpson DM, McCutchan JA, Abramson I, Gamst A, Fennema-Notestine C, Jernigan TL, Wong J, Grant I, CHARTER Group (2010) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology 75:2087–2096. doi:10.1212/WNL.0b013e318200d727

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kesler SR, Adams HF, Blasey CM, Bigler ED (2003) Premorbid intellectual functioning, education, and brain size in traumatic brain injury: an investigation of the cognitive reserve hypothesis. Appl Neuropsychol 10:153–162

    Article  PubMed  Google Scholar 

  • Letendre S, Fitzsimons C, Ellis RJ, Clifford D, Collier AC, Gelman B, Marra C, McArthur J, McCutchan JA, Morgello S, Simpson D, Vaida F, Heaton R, Grant I and the CHARTER Group (2010) Correlates of CSF viral loads in 1,221 volunteers of the CHARTER cohort. 17th Conference on Retroviruses and Opportunistic Infections, 16–19 February, San Francisco, CA, USA, Abstract 172

  • Malaspina L, Woods SP, Moore DJ, Deep C, Letendre SL, Jeste D, Grant I, HIV Neurobehavioral Research Programs (HNRP) Group (2011) Successful cognitive aging in persons living with HIV infection. J Neurovirol 17:110–119. doi:10.1007/s13365-010-0008-z

    Article  PubMed  Google Scholar 

  • Morgan EE, Woods SP, Smith C, Weber E, Scott JC, Grant I, HIV Neurobehavioral Research Program (HNRP) Group (2012) Lower cognitive reserve among individuals with syndromic HIV-associated neurocognitive disorders (HAND). AIDS Behav 16:2279–2285. doi:10.1007/s10461-012-0229-7

    Article  PubMed  PubMed Central  Google Scholar 

  • National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (2002) Third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) final report. Circulation 106:3143–3421

    Google Scholar 

  • Nucci M, Mapelli D, Mondini S (2011) Cognitive Reserve Index questionnaire (CRIq): a new instrument for measuring cognitive reserve. Aging Clin Exp Res 24:218–226. doi:10.3275/800

    PubMed  Google Scholar 

  • Patel SM, Thames AD, Arbid N, Panos SE, Catellon S, Hinkin CH (2013) The aggregate effects of multiple comorbid risk factors on cognition among HIV-infected individuals. J Clin Exp Neuropsychol 35:421–434. doi:10.1080/13803395.2013.783000

    Article  PubMed  PubMed Central  Google Scholar 

  • Pereda M, Ayuso-Mateos JL, Gomez Del Barrio A, Echevarria S, Farinas MC, Garcia Palomo D, Gonzáles Macias J, Vázquez-Barquero JL (2000) Factors associated with neuropsychological performance in HIV-seropositive subjects without AIDS. Psychol Med 30:205–217

    Article  CAS  PubMed  Google Scholar 

  • Robertson IH (2013) A noradrenergic theory of cognitive reserve: implications for Alzheimer’s disease. Neurobiol Aging 34:298–308. doi:10.1016/j.neurobiolaging.2012.05.019

    Article  CAS  PubMed  Google Scholar 

  • Robertson IH (2014) Right hemisphere role in cognitive reserve. Neurobiol Aging 35:1375–1385. doi:10.1016/j.neurobiolaging.2013.11.028

    Article  PubMed  Google Scholar 

  • Sacktor N, Lyles RH, Skolasky R, Kleeberger C, Selnes OA, Miller EN, Becker JT, Cohen B, McArthur JC, Multicenter AIDS Cohrt Study (2001) HIV-associated neurologic disease incidence changes: multicenter AIDS cohort study, 1990–1998. Neurology 56:257–260

    Article  CAS  PubMed  Google Scholar 

  • Sacktor N, Skolasky R, Selnes OA, Watters M, Poff P, Shiramizu B, Shikuma C, Valcour V (2007) Neuropsychological test profile differences between young and old human immunodeficiency virus-positive individuals. J Neurovirol 13:203–209

    Article  PubMed  Google Scholar 

  • Satz P, Morgenstern H, Miller EN, Selnes OA, McArthur JC, Cohen BA, Wesch J, Becker JT, Jacobson L, D’Elia LF, van Gorp W, Visscher B (1993) Low education as a possible risk factor for cognitive abnormalities in HIV-1: findings from the multicenter AIDS Cohort Study (MACS). J Acquir Immune Defic Syndr 6:503–511

    Article  CAS  PubMed  Google Scholar 

  • 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 53:148–153

    Article  CAS  PubMed  Google Scholar 

  • Stern Y (2002) What is cognitive reserve? theory and research application of the reserve concept. J Int Neuropsychol Soc 8:448–460

    Article  PubMed  Google Scholar 

  • Stern Y (2013) Cognitive reserve: implications for assessment and intervention. Folia Phoniatr Logop 65:49–54. doi:10.1159/000353443

    Article  PubMed  PubMed Central  Google Scholar 

  • Sumowski JF, Wylie GR, Deluca J, Chiaravalloti N (2010) Intellectual enrichment is linked to cerebral efficiency in multiple sclerosis: functional magnetic resonance imaging evidence for cognitive reserve. Brain 133:362–374. doi:10.1093/brain/awp307

    Article  PubMed  Google Scholar 

  • Tozzi V, Balestra P, Bellagamba R, Corpolongo A, Salvatori MF, Visco-Comandini U, Vlassi C, Giulianelli M, Galgani S, Antinori A, Narciso P (2007) Persistence of neuropsychologic deficits despite long-term highly active antiretroviral therapy in patients with HIV-related neurocognitive impairment: prevalence and risk factors. J Acquir Immune Defic Syndr 45:174–182

    Article  PubMed  Google Scholar 

  • Valcour V, Paul R, Chiao S, Wendelken LA, Miller B (2011) Screening for cognitive impairment in human immunodeficiency virus. Clin Infect Dis 53:836–842. doi:10.1093/cid/cir524

    Article  PubMed  PubMed Central  Google Scholar 

  • Valcour V, Shikuma C, Shiramizu B, Poff P, Watters M, Selnes O, Holck P, Grove J, Sacktor N (2004) Higher frequency of dementia in older HIV-1 individuals: the Hawaii aging with HIV-1 cohort. Neurology 63:822–827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wendelken LA, Valcour V (2012) Impact of HIV and aging on neuropsychological function. J Neurovirol 18:256–263. doi:10.1007/s13365-012-0094-1

    Article  PubMed  PubMed Central  Google Scholar 

  • Wilson RS, Nag S, Boyle PA, Hizel LP, Yu L, Buchman AS, Schneider JA, Bennett DA (2013) Neural reserve, neuronal density in the locus ceruleus, and cognitive decline. Neurology 80:1202–1208. doi:10.1212/WNL.0b013e3182897103

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors want to thank all the study’s participants.

Preliminary results of this work were previously presented as poster at the Conference on Retroviruses and Opportunistic Infections (CROI), Seattle, Washington, USA, February 23–26, 2015.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Benedetta Milanini.

Ethics declarations

Conflict of interest

No specific funding was received for this study. MF received speakers’ honoraria from Abbott Virology, Merck Sharp & Dohme, and Janssen-Cilag. RC has been advisor for Gilead, Janssen-Cilag, and Basel Pharmaceutical, received speakers’ honoraria from ViiV, Bristol-Myers Squibb, Merck Sharp and Dohme, Abbott, Gilead, and Janssen-Cilag, and research support from “Fondazione Roma.” SDG received speakers’ honoraria and support for travel meetings from Gilead, Bristol-Myers Squibb, Abbott, Boehringer Ingelheim, Janssen-Cilag, and GlaxoSmithKline. All the other authors declare that they have not conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(DOC 87.5 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Milanini, B., Ciccarelli, N., Fabbiani, M. et al. Cognitive reserve and neuropsychological functioning in older HIV-infected people. J. Neurovirol. 22, 575–583 (2016). https://doi.org/10.1007/s13365-016-0426-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13365-016-0426-7

Keywords

Navigation