Skip to main content
SpringerLink
Log in

Apolipoprotein E ε4 Allele Modulates the Immediate Impact of Acute Exercise on Prefrontal Function

  • Published:
Behavior Genetics Aims and scope Submit manuscript

Abstract

The difference between Apolipoprotein E ε4 carriers and non-carriers in response to single exercise sessions was tested. Stroop and Posner tasks were administered to young untrained women immediately after walking sessions or moderately heavy exercise. Exercise had a significantly more profound impact on the Stroop effect than on the Posner effect, suggesting selective involvement of prefrontal function. A significant genotype-by-exercise interaction indicated differences in response to exercise between ε4 carriers and non-carriers. Carriers showed facilitation triggered by exercise. The transient executive down-regulation was construed as due to exercise-dependent hypofrontality. The facilitation observed in carriers was interpreted as better management of prefrontal metabolic resources, and explained within the antagonistic pleiotropy hypothesis framework. The findings have implications for the interpretation of differences between ε4 carriers and non-carriers in the benefits triggered by long-term exercise that might depend, at least partially, on mechanisms of metabolic response to physical activity.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Ahlskog JE, Geda YE, Graff-Radford NR, Petersen RC (2011) Physical exercise as a preventive or disease-modifying treatment of dementia and brain aging. Mayo Clin Proc 86(9):876–884

    Article  PubMed Central  PubMed  Google Scholar 

  • Alexopoulos P, Richter-Schmidinger T, Horn M, Maus S, Reichel M, Sidiropoulos C, Rhein C, Lewczuk P, Doerfler A, Kornhuber J (2011) Hippocampal volume differences between healthy young apolipoprotein E ε2 and ε4 carriers. J Alzheimers Dis 26:207–210

  • Audiffren M, Tomporowski PD, Zagrodnik J (2009) Acute aerobic exercise and information processing: modulation of executive control in a Random Number Generation task. Acta Psychol (Amst) 132(1):85–95

    Article  Google Scholar 

  • Borg GAV (1982) Psychophysical bases of perceived exertion. Med Sci Sports Exerc 14(5):377–381

    Article  PubMed  Google Scholar 

  • Colcombe SJ, Erickson KI, Scalf PE, Kim JS, Prakash RS, McAuley E, Elavsky S, Marquez DX, Hu L, Kramer AF (2006) Aerobic exercise training increases brain volume in aging humans. J Gerontol A Biol Sci Med Sci 61(11):1166–1170

    Article  PubMed  Google Scholar 

  • Corbo RM, Scacchi R (1999) Apolipoprotein E (APOE) allele distribution in the world. Is APOE*4 a ‘thrifty’ allele? Ann Hum Genet 63(Pt 4):301–310

    Article  PubMed  Google Scholar 

  • Davranche K, McMorris T (2009) Specific effects of acute moderate exercise on cognitive control. Brain Cogn 69(3):565–570

    Article  PubMed  Google Scholar 

  • Deeny SP, Poeppel D, Zimmerman JB, Roth SM, Brandauer J, Witkowski S, Hearn JW, Ludlow AT, Contreras-Vidal JL, Brandt J, Hatfield BD (2008) Exercise, APOE, and working memory: MEG and behavioral evidence for benefit of exercise in epsilon4 carriers. Biol Psychol 78(2):179–187

    Article  PubMed Central  PubMed  Google Scholar 

  • Deeny SP, Winchester J, Nichol K, Roth SM, Wu JC, Dick M, Cotman CW (2012) Cardiovascular fitness is associated with altered cortical glucose metabolism during working memory in ε4 carriers. Alzheimers Dement 8(4):352–356

    Article  PubMed Central  PubMed  Google Scholar 

  • Del Giorno JM, Hall EE, O’Leary KC, Bixby WR, Miller PC (2010) Cognitive function during acute exercise: a test of the transient hypofrontality theory. J Sport Exerc Psychol 32(3):312–323

    PubMed  Google Scholar 

  • Dietrich A, Audiffren M (2011) The reticular-activating hypofrontality (RAH) model of acute exercise. Neurosci Biobehav Rev 35(6):1305–1325

    Article  PubMed  Google Scholar 

  • Dietrich A, Sparling PB (2004) Endurance exercise selectively impairs prefrontal-dependent cognition. Brain Cogn 55(3):516–524

    Article  PubMed  Google Scholar 

  • Du N, Bai S, Oguri K, Kato Y, Matsumoto I, Kawase H, Matsuoka T (2005) Heart rate recovery after exercise and neural regulation of heart rate variability in 30–40 year old female marathon runners. J Sports Sci Med 4(1):9–17

    PubMed Central  PubMed  Google Scholar 

  • Erickson KI, Weinstein AM, Lopez OL (2012a) Physical activity, brain plasticity, and Alzheimer’s disease. Arch Med Res 43(8):615–621

    Article  PubMed Central  PubMed  Google Scholar 

  • Erickson KI, Miller DL, Weinstein AM, Akl SL, Banducci SE (2012b) Physical activity and brain plasticity in late adulthood: a conceptual review. Ageing Res 4(6):34–47

    Google Scholar 

  • Eston R (2012) Use of ratings of perceived exertion in sports. Int J Sports Physiol Perform 7(2):175–182

    PubMed  Google Scholar 

  • Etnier JL, Caselli RJ, Reiman EM, Alexander GE, Sibley BA, Tessier D, McLemore EC (2007) Cognitive performance in older women relative to ApoE-epsilon4 genotype and aerobic fitness. Med Sci Sports Exerc 39(1):199–207

    Article  PubMed  Google Scholar 

  • Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, Myers RH, Pericak-Vance MA, Risch N, van Duijn CM (1997) Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA 278(16):1349–1356

    Article  PubMed  Google Scholar 

  • Garber CE, Blissmer B, Deschenes MR, Franklin BA, LaMonte MJ, Lee IM, Nieman DC, Swain DP (2011) American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Med Sci Sports Exerc 43(7):1334–1359

    Article  PubMed  Google Scholar 

  • Han SD, Bondi MW (2008) Revision of the Apolipoprotein E compensatory mechanism recruitment hypothesis. Alzheimers Dement 4(4):251–254

    Article  PubMed  Google Scholar 

  • Head D, Bugg JM, Goate AM, Fagan AM, Mintun MA, Benzinger T, Holtzman DM, Morris JC (2012) Exercise engagement as a moderator of the effects of APOE genotype on amyloid deposition. Arch Neurol 69(5):636–643

    Article  PubMed Central  PubMed  Google Scholar 

  • Hecksteden A, Grütters T, Meyer T (2013) Associations between acute and chronic effects of exercise on indicators of metabolic health: a pilot training trial. PLoS ONE. doi:10.1371/journal.pone.0081181

    PubMed Central  PubMed  Google Scholar 

  • Herdy AH, Uhlendorf D (2011) Reference values for cardiopulmonary exercise testing for sedentary and active men and women. Arq Bras Cardiol 96(1):54–59

    Article  PubMed  Google Scholar 

  • Huang YD, Liu XQ, Wyss-Coray T, Brecht WJ, Sanan DA, Mahley RW (2001) Apolipoprotein E fragments present in Alzheimer’s disease brains induce neurofibrillary tangle-like intracellular inclusions in neurons. Proc Natl Acad Sci USA 98(15):8838–8843

    Article  PubMed Central  PubMed  Google Scholar 

  • Ihle A, Bunce D, Kliegel M (2012) APOE epsilon4 and cognitive function in early life: a meta-analysis. Neuropsychology 26(3):267–277

    Article  PubMed  Google Scholar 

  • Kivipelto M, Rovio S, Ngandu T, Kåreholt I, Eskelinen M, Winblad B, Hachinski V, Cedazo-Minguez A, Soininen H, Tuomilehto J, Nissinen A (2008) Apolipoprotein E epsilon4 magnifies lifestyle risks for dementia: a population-based study. J Cell Mol Med 12(6B):2762–2771

    Article  PubMed  Google Scholar 

  • Labelle V, Bosquet L, Mekary S, Bherer L (2013) Decline in executive control during acute bouts of exercise as a function of exercise intensity and fitness level. Brain Cogn 81(1):10–17

    Article  PubMed  Google Scholar 

  • Lautenschlager NT, Cox K, Kurz AF (2010) Physical activity and mild cognitive impairment and Alzheimer’s disease. Curr Neurol Neurosci Rep 10(5):352–358

    Article  PubMed  Google Scholar 

  • Mahley RW, Rall SC Jr (2000) Apolipoprotein E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet 1:507–537

    Article  PubMed  Google Scholar 

  • Mahley RW, Weisgraber KH, Huang Y (2006) Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer’s disease. Proc Natl Acad Sci USA 103(15):5644–5651

    Article  PubMed Central  PubMed  Google Scholar 

  • Milne E, van Bockxmeer FM, Robertson L, Brisbane JM, Ashton LJ, Scott RJ, Armstrong BK (2006) Buccal DNA collection: comparison of buccal swabs with FTA cards. Cancer Epidemiol Biomarkers Prev 15(4):816–819

    Article  PubMed  Google Scholar 

  • Netz Y, Argov E, Inbar O (2009) Fitness’s moderation of the facilitative effect of acute exercise on cognitive flexibility in older women. J Aging Phys Act 17(2):154–166

    PubMed  Google Scholar 

  • Niti M, Yap KB, Kua EH, Tan CH, Ng TP (2008) Physical, social and productive leisure activities, cognitive decline and interaction with APOE-ε4 genotype in Chinese older adults. Int Psychogeriatr 20(2):237–251

    Article  PubMed  Google Scholar 

  • Obisesan TO, Umar N, Paluvoi N, Gillum RF (2012) Association of leisure-time physical activity with cognition by apolipoprotein-E genotype in persons aged 60 years and over: the National Health and Nutrition Examination Survey (NHANES-III). Clin Interv Aging 7:35–43

    Article  PubMed Central  PubMed  Google Scholar 

  • Ossendorf M, Prellwitz W (2000) Rapid and easy apolipoprotein E genotyping using an improved PCR-RFLP technique. Qiagen News 1:11–13

    Google Scholar 

  • Pearson-Fuhrhop KM, Kleim JA, Cramer SC (2009) Brain plasticity and genetic factors. Top Stroke Rehabil 16(4):282–299

    Article  PubMed  Google Scholar 

  • Peelen MV, Heslenfeld DJ, Theeuwes J (2004) Endogenous and exogenous attention shifts are mediated by the same large-scale neural network. Neuroimage 22(2):822–830

    Article  PubMed  Google Scholar 

  • Pesce C (2009) An integrated approach to the effect of acute and chronic exercise on cognition: the linked role of individual and task constraints. In: McMorris T, Tomporowski PD, Audiffren M (eds) Exercise and cognitive function. Wiley-Blackwell, Hoboken, pp 213–226

    Google Scholar 

  • Peterson BS, Kane MJ, Alexander GM, Lacadie C, Skudlarski P, Leung HC, May J, Gore JC (2002) An event-related functional MRI study comparing interference effects in the Simon and Stroop tasks. Cogn Brain Res 13(3):427–440

    Article  Google Scholar 

  • Petruzzello SJ, Landers DM, Hatfield BD, Kubitz KA, Salazar W (1991) A meta-analysis on the anxiety-reducing effects of acute and chronic exercise. Outcomes and mechanisms. Sports Med 11(3):143–182

    Article  PubMed  Google Scholar 

  • Podewils LJ, Guallar E, Kuller LH, Fried LP, Lopez OL, Carlson M, Lyketsos CG (2005) Physical activity, APOE genotype, and dementia risk: findings from the Cardiovascular Health Cognition Study. Am J Epidemiol 161(7):639–651

    Article  PubMed  Google Scholar 

  • Posner MI, Cohen Y (1984) Components of visual orienting. In: Bouma H, Bowhuis D (eds) Attention and performance X. Erlbaum, Hillsdale, NJ, pp 531–556

    Google Scholar 

  • Predovan D, Fraser SA, Renaud M, Bherer L (2012) The effect of three months of aerobic training on Stroop performance in older adults. J Aging Res. Article ID 269815

  • Ravaglia G, Forti P, Lucicesare A, Pisacane N, Rietti E, Bianchin M, Dalmonte E (2008) Physical activity and dementia risk in the elderly: findings from a prospective Italian study. Neurology 70(19, Part 2):1786–1794

    PubMed  Google Scholar 

  • Robergs RA, Landwehr R (2002) The surprising history of the “HRmax = 220-age” equation. J Exerc Physiol Online 5(2):1–10

    Google Scholar 

  • Rovio S, Kåreholt I, Helkala EL, Viitanen M, Winblad B, Tuomilehto J, Soininen H, Nissinen A, Kivipelto M (2005) Leisure-time physical activity at midlife and the risk of dementia and Alzheimer’s disease. Lancet Neurol 4(11):705–711

    Article  PubMed  Google Scholar 

  • Sabbagh MN, Malek-Ahmadi M, Dugger BN, Lee K, Sue LI, Serrano G, Walker DG, Davis K, Jacobson SA, Beach TG (2013) The influence of Apolipoprotein E genotype on regional pathology in Alzheimer’s disease. BMC Neurol 13(44):1–8

    Google Scholar 

  • Sanabria D, Morales E, Luque A, Gálvez G, Huertas F, Lupiañez J (2011) Effects of acute aerobic exercise on exogenous spatial attention. Psychol Sport Exerc 12(5):570–574

    Article  Google Scholar 

  • Sando SB, Melquist S, Cannon A, Hutton ML, Sletvold O, Saltvedt I, White LR, Lydersen S, Aasly JO (2008) APOE ε4 lowers age at onset and is a high risk factor for Alzheimer’s disease: a case control study from central Norway. BMC Neurol 8(9):1–7

    Google Scholar 

  • Scherr J, Wolfarth B, Christie JW, Pressler A, Wagenpfeil S, Halle M (2013) Associations between Borg’s rating of perceived exertion and physiological measures of exercise intensity. Eur J Appl Physiol 113(1):147–155

    Article  PubMed  Google Scholar 

  • Schuit AJ, Feskens EJ, Launer LJ, Kromhout D (2001) Physical activity and cognitive decline, the role of the apolipoprotein e4 allele. Med Sci Sports Exerc 33(5):772–777

    Article  PubMed  Google Scholar 

  • Smith JC, Nielson KA, Woodard JL, Seidenberg M, Durgerian S, Antuono P, Butts AM, Hantke NC, Lancaster MA, Rao SM (2011) Interactive effects of physical activity and APOE- ε4 on BOLD semantic memory activation in healthy elders. Neuroimage 54(1):635–644

    Article  PubMed Central  PubMed  Google Scholar 

  • Strittmatter WJ, Weisgraber KH, Huang DY, Dong LM, Salvesen GS, Pericak-Vance M, Schmechel D, Saunders AM, Goldgaber D, Roses AD (1993) Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset Alzheimer disease. Proc Natl Acad Sci USA 90(17):8098–8102

    Article  PubMed Central  PubMed  Google Scholar 

  • Stroop JR (1935) Studies of Interference in Serial Verbal Reactions. J Exp Psychol 18(6):643–662

  • Taaffe DR, Irie F, Masaki KH, Abbott RD, Petrovitch H, Ross GW, White LR (2008) Physical activity, physical function, and incident dementia in elderly men: the Honolulu-Asia Aging Study. J Gerontol A Biol Sci Med Sci 63(5):529–535

    Article  PubMed  Google Scholar 

  • Tuminello ER, Han SD (2011) The apolipoprotein E antagonistic pleiotropy hypothesis: Review and recommendations. Int J Alzheimers Dis. Article ID 726197

  • Vossel S, Weidner R, Thiel CM, Fink GR (2009) What is “Odd’’ in Posner’s location-cueing paradigm? Neural responses to unexpected location and feature changes compared. J Cogn Neurosci 21(1):30–41

    Article  PubMed  Google Scholar 

  • Yanagisawa H, Dan I, Tsuzuki D, Kato M, Okamoto M, Kyutoku Y, Soya H (2010) Acute moderate exercise elicits dorsolateral prefrontal activation and improves cognitive performance with Stroop test. Neuroimage 50(4):1702–1710

    Article  PubMed  Google Scholar 

  • Zivelin A, Rosenberg N, Peretz H, Amit Y, Kornbrot N, Seligsohn U (1997) Improved method for genotyping Apolipoprotein E polymorphisms by a PCR-based assay simultaneously utilizing two distinct restriction enzymes. Clin Chem 43(9):1657–1659

    PubMed  Google Scholar 

  • Zysset S, Schroeter ML, Neumann J, von Cramon DY (2007) Stroop interference, hemodynamic response and aging: an event-related fMRI study. Neurobiol Aging 28(6):937–946

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was partially supported by a University of Hull Faculty of Science scholarship to MDM and by funding from MIUR and FP7 VPH-DARE to AV.

Conflict of interest

Matteo De Marco, Peter J. Clough, Charlotte E. Dyer, Rebecca V. Vince, Jennifer S. Waby, Adrian W. Midgley and Annalena Venneri declare that they have no conflict of interest.

Human and Animal Rights

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5).

Informed Consent

Informed consent for being included in the study was obtained from all participants.

Author information

Authors and Affiliations

  1. IRCCS San Camillo Hospital Foundation, Venice, Italy

    Matteo De Marco & Annalena Venneri

  2. Department of Neuroscience, Medical School, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK

    Matteo De Marco & Annalena Venneri

  3. Department of Psychology, Manchester Metropolitan University, Manchester, UK

    Peter J. Clough

  4. School of Biological, Biomedical and Environmental Sciences, University of Hull, Kingston-Upon-Hull, UK

    Charlotte E. Dyer & Jennifer S. Waby

  5. Department of Sport, Health, and Exercise Science, University of Hull, Kingston-Upon-Hull, UK

    Rebecca V. Vince

  6. Department of Sport and Physical Activity, Edge Hill University, Ormskirk, UK

    Adrian W. Midgley

Authors
  1. Matteo De Marco
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter J. Clough
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Charlotte E. Dyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rebecca V. Vince
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jennifer S. Waby
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Adrian W. Midgley
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Annalena Venneri
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Annalena Venneri.

Additional information

Edited by Chandra Reynolds.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

De Marco, M., Clough, P.J., Dyer, C.E. et al. Apolipoprotein E ε4 Allele Modulates the Immediate Impact of Acute Exercise on Prefrontal Function. Behav Genet 45, 106–116 (2015). https://doi.org/10.1007/s10519-014-9675-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10519-014-9675-5

Keywords

Search

Navigation