The Brain in Motion II Study: study protocol for a randomized controlled trial of an aerobic exercise intervention for older adults at increased risk of dementia

Renata L Krüger, Cameron M Clark, Adrienna M Dyck, Todd J Anderson, Fiona Clement, Patrick J Hanly, Heather M Hanson, Michael D Hill, David B Hogan, Jayna Holroyd-Leduc, R Stewart Longman, Meghan McDonough, G Bruce Pike, Jean M Rawling, Tolulope Sajobi, Marc J Poulin, Renata L Krüger, Cameron M Clark, Adrienna M Dyck, Todd J Anderson, Fiona Clement, Patrick J Hanly, Heather M Hanson, Michael D Hill, David B Hogan, Jayna Holroyd-Leduc, R Stewart Longman, Meghan McDonough, G Bruce Pike, Jean M Rawling, Tolulope Sajobi, Marc J Poulin

Abstract

Background: There remains no effective intervention capable of reversing most cases of dementia. Current research is focused on prevention by addressing risk factors that are shared between cardiovascular disease and dementia (e.g., hypertension) before the cognitive, functional, and behavioural symptoms of dementia manifest. A promising preventive treatment is exercise. This study describes the methods of a randomized controlled trial (RCT) that assesses the effects of aerobic exercise and behavioural support interventions in older adults at increased risk of dementia due to genetic and/or cardiovascular risk factors. The specific aims are to determine the effect of aerobic exercise on cognitive performance, explore the biological mechanisms that influence cognitive performance after exercise training, and determine if changes in cerebrovascular physiology and function persist 1 year after a 6-month aerobic exercise intervention followed by a 1-year behavioural support programme (at 18 months).

Methods: We will recruit 264 participants (aged 50-80 years) at elevated risk of dementia. Participants will be randomly allocated into one of four treatment arms: (1) aerobic exercise and health behaviour support, (2) aerobic exercise and no health behaviour support, (3) stretching-toning and health behaviour support, and (4) stretching-toning and no health behaviour support. The aerobic exercise intervention will consist of three supervised walking/jogging sessions per week for 6 months, whereas the stretching-toning control intervention will consist of three supervised stretching-toning sessions per week also for 6 months. Following the exercise interventions, participants will receive either 1 year of ongoing telephone behavioural support or no telephone support. The primary aim is to determine the independent effect of aerobic exercise on a cognitive composite score in participants allocated to this intervention compared to participants allocated to the stretching-toning group. The secondary aims are to examine the effects of aerobic exercise on a number of secondary outcomes and determine whether aerobic exercise-related changes persist after a 1-year behavioural support programme (at 18 months).

Discussion: This study will address knowledge gaps regarding the underlying mechanisms of the pro-cognitive effects of exercise by examining the potential mediating factors, including cerebrovascular/physiological, neuroimaging, sleep, and genetic factors that will provide novel biologic evidence on how aerobic exercise can prevent declines in cognition with ageing.

Trial registration: ClinicalTrials.gov NCT03035851 . Registered on 30 January 2017.

Keywords: Alzheimer’s disease; Behavioural support; Brain health; Cognitive function; Dementia; Physical activity; Sleep quality.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Overview of study design and participant flow through the trial

References

    1. Kontis V, Bennett JE, Mathers CD, Li G, Foreman K, Ezzati M. Future life expectancy in 35 industrialised countries: projections with a Bayesian model ensemble. Lancet. 2017;389(10076):1323–1335. doi: 10.1016/S0140-6736(16)32381-9.
    1. WHO. No title [Internet]. 2021. Available from: . Accessed on Feb 27, 2021.
    1. Bushnik T, Tjepkema M, Martel L. Health-adjusted life expectancy in Canada. Health Reports. 2018;29:14–22.
    1. WHO . WHO | 10 facts on dementia. Who; 2018.
    1. Alzheimer’s Society of Canada. 2017-2018 Impact report. [Internet]. 2019 [cited 2019 Dec 5]. Available from:
    1. Snowden M, Steinman L, Mochan K, Grodstein F, Prohaska TR, Thurman DJ, Brown DR, Laditka JN, Soares J, Zweiback DJ, Little D, Anderson LA. Effect of exercise on cognitive performance in community-dwelling older adults: review of intervention trials and recommendations for public health practice and research. J Am Geriatr Soc. 2011;59(4):704–716. doi: 10.1111/j.1532-5415.2011.03323.x.
    1. Imtiaz B, Tolppanen AM, Kivipelto M, Soininen H. Future directions in Alzheimer’s disease from risk factors to prevention. Biochem Pharmacol. 2014;88(4):661–670. doi: 10.1016/j.bcp.2014.01.003.
    1. de Asteasu MLS, Martínez-Velilla N, Zambom-Ferraresi F, Casas-Herrero Á, Izquierdo M. Role of physical exercise on cognitive function in healthy older adults: a systematic review of randomized clinical trials. Ageing Res Rev. 2017;37:117–134. doi: 10.1016/j.arr.2017.05.007.
    1. Karssemeijer EGA, Bossers WJR, Aaronson JA, Sanders LMJ, Kessels RPC, Olde Rikkert MGM. Exergaming as a physical exercise strategy reduces frailty in people with dementia: a randomized controlled trial. J Am Med Dir Assoc. 2019;20(12):1502–1508. doi: 10.1016/j.jamda.2019.06.026.
    1. Buchman AS, Yu L, Wilson RS, Lim A, Dawe RJ, Gaiteri C, Leurgans SE, Schneider JA, Bennett DA. Physical activity, common brain pathologies, and cognition in community-dwelling older adults. Neurology. 2019;92(8):e811–e822. doi: 10.1212/WNL.0000000000006954.
    1. Tari AR, Nauman J, Zisko N, Skjellegrind HK, Bosnes I, Bergh S, Stensvold D, Selbæk G, Wisløff U. Temporal changes in cardiorespiratory fitness and risk of dementia incidence and mortality: a population-based prospective cohort study. Lancet Public Heal. 2019;4(11):e565–e574. doi: 10.1016/S2468-2667(19)30183-5.
    1. Young J, Angevaren M, Rusted J, Tabet N. Aerobic exercise to improve cognitive function in older people without known cognitive impairment. Cochrane Database Syst Rev. 2015;4:CD005381.
    1. Barnes JN, Corkery AT. Exercise improves vascular function, but does this translate to the brain? Brain Plast. 2018;4(1):65–79. doi: 10.3233/BPL-180075.
    1. Mattsson N, Tosun D, Insel PS, Simonson A, Jack CR, Beckett LA, et al. Association of brain amyloid-β with cerebral perfusion and structure in Alzheimer’s disease and mild cognitive impairment. Brain. 2014;137(Pt 5):1550–1561. doi: 10.1093/brain/awu043.
    1. Katz PP, Pate R. Exercise as medicine. Ann Intern Med. 2016;165(12):880–881. doi: 10.7326/M16-2086.
    1. Tarumi T, Zhang R. Cerebral blood flow in normal aging adults: cardiovascular determinants, clinical implications, and aerobic fitness. J Neurochem. 2018;144(5):595–608. doi: 10.1111/jnc.14234.
    1. Chen Z, Zhong C. Decoding Alzheimer’s disease from perturbed cerebral glucose metabolism: implications for diagnostic and therapeutic strategies. Prog Neurobiol. 2013;108:21–43. doi: 10.1016/j.pneurobio.2013.06.004.
    1. Larson EB, Wang L, Bowen JD, McCormick WC, Teri L, Crane P, et al. Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older. Ann Intern Med. 2006;144(2):73–81. doi: 10.7326/0003-4819-144-2-200601170-00004.
    1. Lin S, Yang Y, Qi Q, Wei L, Jing N, Jie Z, Xia L, Shifu X. The beneficial effect of physical exercise on cognitive function in a non-dementia aging Chinese population. Front Aging Neurosci. 2019;11:238. doi: 10.3389/fnagi.2019.00238.
    1. Chen FT, Chen YP, Schneider S, Kao SC, Huang CM, Chang YK. Effects of exercise modes on neural processing of working memory in late middle-aged adults: an fMRI study. Front Aging Neurosci. 2019;11:224. doi: 10.3389/fnagi.2019.00224.
    1. Kramer AF, Colcombe S. Fitness effects on the cognitive function of older adults: a meta-analytic study—revisited. Perspect Psychol Sci. 2018;13(2):213–217. doi: 10.1177/1745691617707316.
    1. Sofi F, Valecchi D, Bacci D, Abbate R, Gensini GF, Casini A, Macchi C. Physical activity and risk of cognitive decline: a meta-analysis of prospective studies. J Intern Med [Internet]. 2011;269(1):107–117. doi: 10.1111/j.1365-2796.2010.02281.x.
    1. Guiney H, Machado L. Benefits of regular aerobic exercise for executive functioning in healthy populations. Psychon Bull Rev. 2013;20(1):73–86. doi: 10.3758/s13423-012-0345-4.
    1. Middleton LE, Barnes DE, Lui LY, Yaffe K. Physical activity over the life course and its association with cognitive performance and impairment in old age. J Am Geriatr Soc. 2010;58(7):1322–1326. doi: 10.1111/j.1532-5415.2010.02903.x.
    1. Falck RS, Best JR, Davis JC, Liu-Ambrose T. The independent associations of physical activity and sleep with cognitive function in older adults. J Alzheimer’s Dis. 2018;63(4):1469–1484. doi: 10.3233/JAD-170936.
    1. Colcombe SJ, Erickson KI, Raz N, Webb AG, Cohen NJ, McAuley E, et al. Aerobic fitness reduces brain tissue loss in aging humans. J Gerontol Ser A Biol Sci Med Sci. 2003;58:176–180. doi: 10.1093/gerona/58.2.M176.
    1. Colcombe SJ, Erickson KI, Scalf PE, Kim JS, Prakash R, McAuley E, Elavsky S, Marquez DX, Hu L, Kramer AF. Aerobic exercise training increases brain volume in aging humans. J Gerontol - Ser A Biol Sci Med Sci. 2006;61(11):1166–1170. doi: 10.1093/gerona/61.11.1166.
    1. Erickson KI, Prakash RS, Voss MW, Chaddock L, Hu L, Morris KS, White SM, Wójcicki TR, McAuley E, Kramer AF. Aerobic fitness is associated with hippocampal volume in elderly humans. Hippocampus. 2009;19(10):1030–1039. doi: 10.1002/hipo.20547.
    1. Johnson NF, Kim C, Clasey JL, Bailey A, Gold BT. Cardiorespiratory fitness is positively correlated with cerebral white matter integrity in healthy seniors. Neuroimage. 2012;59(2):1514–1523. doi: 10.1016/j.neuroimage.2011.08.032.
    1. Sexton CE, Betts JF, Demnitz N, Dawes H, Ebmeier KP, Johansen-Berg H. A systematic review of MRI studies examining the relationship between physical fitness and activity and the white matter of the ageing brain. Neuroimage. 2016;131:81–90. doi: 10.1016/j.neuroimage.2015.09.071.
    1. Cotman CW, Berchtold NC. Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci. 2002;25(6):295–301. doi: 10.1016/S0166-2236(02)02143-4.
    1. Kelly ME, Loughrey D, Lawlor BA, Robertson IH, Walsh C, Brennan S. The impact of exercise on the cognitive functioning of healthy older adults: a systematic review and meta-analysis. Ageing Res Rev. 2014;16:12–31. doi: 10.1016/j.arr.2014.05.002.
    1. Gorelick PB, Furie KL, Iadecola C, Smith EE, Waddy SP, Lloyd-Jones DM, et al. Defining optimal brain health in adults: a presidential advisory from the American Heart Association/American Stroke Association Stroke. Stroke. 2017;48(10):e284–303.
    1. Colcombe S, Kramer AF. Fitness effects on the cognitive function of older adults: a meta-analytic study. Psychol Sci. 2003;13(2):213–217.
    1. Sink KM, Espeland MA, Castro CM, Church T, Cohen R, Dodson JA, Guralnik J, Hendrie HC, Jennings J, Katula J, Lopez OL, McDermott MM, Pahor M, Reid KF, Rushing J, Verghese J, Rapp S, Williamson JD. Effect of a 24-month physical activity intervention vs health education on cognitive outcomes in sedentary older adults: the LIFE randomized trial. JAMA. 2015;314(8):781–790. doi: 10.1001/jama.2015.9617.
    1. Stefanidis KB, Askew CD, Greaves K, Summers MJ. The effect of non-stroke cardiovascular disease states on risk for cognitive decline and dementia: a systematic and meta-analytic review. Neuropsychol Rev. 2018;28(1):1–15. doi: 10.1007/s11065-017-9359-z.
    1. Lim ASP, Yu L, Kowgier M, Schneider JA, Buchman AS, Bennett DA. Sleep modifies the relation of APOE to the risk of Alzheimer disease and neurofibrillary tangle pathology. JAMA Neurol. 2013;70(12):1544–1551. doi: 10.1001/jamaneurol.2013.4215.
    1. Hansson L, Hedner T, Dahlöf B. Prospective randomized open blinded end-point (PROBE) study. A novel design for intervention trials. Blood Press. 1992;1(2):113–119. doi: 10.3109/08037059209077502.
    1. Friedenreich CM, Courneya KS, Neilson HK, Matthews CE, Willis G, Irwin M, Troiano R, Ballard-Barbash R. Reliability and validity of the past year total physical activity questionnaire. Am J Epidemiol. 2006;163(10):959–970. doi: 10.1093/aje/kwj112.
    1. Nelson ME, Rejeski WJ, Blair SN, Duncan PW, Judge JO, King AC, et al. Physical activity and public health in older adults: recommendation from the American College of Sports Medicine and the American Heart Association. Circulation. 2007;39:1423–1434.
    1. Lautenschlager NT, Cox KL, Flicker L, Foster JK, Van Bockxmeer FM, Xiao J, et al. Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial. JAMA. 2008;300(9):1027–1037. doi: 10.1001/jama.300.9.1027.
    1. Bauman AE, Reis RS, Sallis JF, Wells JC, Loos RJF, Martin BW, et al. Correlates of physical activity: why are some people physically active and others not? Lancet. 2012;380(9838):258–271. doi: 10.1016/S0140-6736(12)60735-1.
    1. O’Bryant SE, Lacritz LH, Hall J, Waring SC, Chan W, Khodr ZG, et al. Validation of the new interpretive guidelines for the clinical dementia rating scale sum of boxes score in the National Alzheimer’s Coordinating Center database. Arch Neurol. 2010;67(6):746–749. doi: 10.1001/archneurol.2010.115.
    1. De Jager CA, Budge MM, Clarke R. Utility of TICS-M for the assessment of cognitive function in older adults. Int J Geriatr Psychiatry. 2003;18(4):318–324. doi: 10.1002/gps.830.
    1. Go RCP, Duke LW, Harrell LE, Cody H, Bassett SS, Folstein MF, Albert MS, Foster JL, Sharrow NA, Blacker D. Development and validation of a structured telephone interview for dementia assessment (STIDA): the NIMH Genetics Initiative. J Geriatr Psychiatry Neurol. 1997;10(4):161–167. doi: 10.1177/089198879701000407.
    1. Dams-O’Connor K, Cantor JB, Brown M, Dijkers MP, Spielman LA, Gordon WA. Screening for traumatic brain injury: findings and public health implications. J Head Trauma Rehabil. 2014;29(6):479–489. doi: 10.1097/HTR.0000000000000099.
    1. Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53(4):695–699. doi: 10.1111/j.1532-5415.2005.53221.x.
    1. Crook TH, Feher EP, Larrabee GJ. Assessment of memory complaint in age-associated memory impairment: the MAC-Q. Int Psychogeriatrics. 1992;4(2):165–176. doi: 10.1017/S1041610292000991.
    1. Jamnik VK, Warburton DER, Makarski J, McKenzie DC, Shephard RJ, Stone JA, et al. Enhancing the effectiveness of clearance for physical activity participation: background and overall process. Appl Physiol Nutr Metab. 2011;36(1):3–13. doi: 10.1139/h11-044.
    1. Warburton DER, Gledhill N, Jamnik VK, Bredin SSD, McKenzie DC, Stone J, et al. Evidence-based risk assessment and recommendations for physical activity clearance: an introduction. Appl Physiol Nutr Metab. 2011;36:266–298. doi: 10.1139/h11-062.
    1. Buckley R, Saling MM, Ames D, Rowe CC, Lautenschlager NT, MacAulay SL, et al. Factors affecting subjective memory complaints in the AIBL aging study: biomarkers, memory, affect, and age. Int Psychogeriatrics. 2013;25(8):1307–1315. doi: 10.1017/S1041610213000665.
    1. Tyndall AV, Davenport MH, Wilson BJ, Burek GM, Arsenault-Lapierre G, Haley E, Eskes GA, Friedenreich CM, Hill MD, Hogan DB, Longman RS, Anderson TJ, Leigh R, Smith EE, Poulin MJ. The brain-in-motion study: effect of a 6-month aerobic exercise intervention on cerebrovascular regulation and cognitive function in older adults. BMC Geriatr. 2013;13(1):21. doi: 10.1186/1471-2318-13-21.
    1. Lu K, Luo X, Chen PY. Sample size estimation for repeated measures analysis in randomized clinical trials with missing data. Int J Biostat. 2008;4(1):Article 9. doi: 10.2202/1557-4679.1098.
    1. Hagger MS, Chatzisarantis NLD. An integrated behavior change model for physical activity. Exerc Sport Sci Rev. 2014;42(2):62–69. doi: 10.1249/JES.0000000000000008.
    1. Kahn EB, Ramsey LT, Brownson RC, Heath GW, Howze EH, Powell KE, et al. The effectiveness of interventions to increase physical activity: a systematic review. Am J Prev Med. 2002;22(4 Suppl):73–107. doi: 10.1016/S0749-3797(02)00434-8.
    1. Allen K, Morey MC. Physical activity and Adherence. New York: Springer; 2010. Improving patient treatment adherence; pp. 9–38.
    1. Michie S, Ashford S, Sniehotta FF, Dombrowski SU, Bishop A, French DP. A refined taxonomy of behaviour change techniques to help people change their physical activity and healthy eating behaviours: the CALO-RE taxonomy. Psychol Heal. 2011;26(11):1479–1498. doi: 10.1080/08870446.2010.540664.
    1. Lally P, Van Jaarsveld CHM, Potts HWW, Wardle J. How are habits formed: modelling habit formation in the real world. Eur J Soc Psychol. 2010;40(6):998–1009. doi: 10.1002/ejsp.674.
    1. Stud HR. Constructing composites to optimise cognitive outcomes. J Clin Stud [Internet]. 2017;9:40–45.
    1. Brown AD, McMorris CA, Longman RS, Leigh R, Hill MD, Friedenreich CM, et al. Effects of cardiorespiratory fitness and cerebral blood flow on cognitive outcomes in older women. Neurobiol Aging. 2010;31(12):2047–2057. doi: 10.1016/j.neurobiolaging.2008.11.002.
    1. Churchill JD, Galvez R, Colcombe S, Swain RA, Kramer AF, Greenough WT. Exercise, experience and the aging brain. Neurobiol Aging. 2002;23(5):941–955. doi: 10.1016/S0197-4580(02)00028-3.
    1. Eskes GA, Longman S, Brown AD, McMorris CA, Langdon KD, Hogan DB, et al. Contribution of physical fitness, cerebrovascular reserve and cognitive stimulation to cognitive function in post-menopausal women. Front Aging Neurosci. 2010;2:137. doi: 10.3389/fnagi.2010.00137.
    1. Smith PJ, Blumenthal JA, Hoffman BM, Cooper H, Strauman TA, Welsh-Bohmer K, Browndyke JN, Sherwood A. Aerobic exercise and neurocognitive performance: a meta-analytic review of randomized controlled trials. Psychosom Med. 2010;72(3):239–252. doi: 10.1097/PSY.0b013e3181d14633.
    1. ACSM’s guidelines for exercise testing and prescription 9th Ed. 2014. J Can Chiropr Assoc. 2014;58(3):328.
    1. Clark CM, Guadagni V, Mazerolle EL, Hill M, Hogan DB, Pike GB, Poulin MJ. Effect of aerobic exercise on white matter microstructure in the aging brain. Behav Brain Res. 2019;373:112042. doi: 10.1016/j.bbr.2019.112042.
    1. Shatenstein B, Payette H. Evaluation of the relative validity of the short diet questionnaire for assessing usual consumption frequencies of selected nutrients and foods. Nutrients. 2015;7(8):6362–6374. doi: 10.3390/nu7085282.
    1. Armstrong T, Bull F. Development of the World Health Organization Global Physical Activity Questionnaire (GPAQ) J Public Health (Bangkok). 2006;14(2):66–70. doi: 10.1007/s10389-006-0024-x.
    1. Bull FC, Maslin TS, Armstrong T. Global physical activity questionnaire (GPAQ): nine country reliability and validity study. J Phys Act Heal. 2009;6(6):790–804. doi: 10.1123/jpah.6.6.790.
    1. Markland D, Tobin V. A modification to the behavioural regulation in exercise questionnaire to include an assessment of amotivation. J Sport Exerc Psychol. 2004;26(2):191–196. doi: 10.1123/jsep.26.2.191.
    1. Zigmond AS, Snaith RP. The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand. 1983;67(6):361–370. doi: 10.1111/j.1600-0447.1983.tb09716.x.
    1. Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, Leirer VO. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res. 1982;17(1):37–49. doi: 10.1016/0022-3956(82)90033-4.
    1. Lubben J, Blozik E, Gillmann G, Iliffe S, Von Kruse WR, Beck JC, et al. Performance of an abbreviated version of the Lubben Social Network Scale among three European community-dwelling older adult populations. Gerontologist. 2006;46(4):503–513. doi: 10.1093/geront/46.4.503.
    1. Sallis JF, Grossman RM, Pinski RB, Patterson TL, Nader PR. The development of scales to measure social support for diet and exercise behaviors. Prev Med (Baltim). 1987;16(6):825–836. doi: 10.1016/0091-7435(87)90022-3.
    1. Martire LM, Stephens MAP, Mogle J, Schulz R, Brach J, Keefe FJ. Daily spousal influence on physical activity in knee osteoarthritis. Ann Behav Med. 2013;45(2):213–223. doi: 10.1007/s12160-012-9442-x.
    1. Kremen WS, Lachman ME, Pruessner JC, Sliwinski M, Wilson RS. Mechanisms of age-related cognitive change and targets for intervention: social interactions and stress. J Gerontol - Ser A Biol Sci Med Sci. 2012;67(7):760–765. doi: 10.1093/gerona/gls125.
    1. Anstey KJ, Cherbuin N, Herath PM. Development of a new method for assessing global risk of Alzheimer’s disease for use in population health approaches to prevention. Prev Sci. 2013;14(4):411–421. doi: 10.1007/s11121-012-0313-2.
    1. Kessler RC, Adler L, Ames M, Demler O, Faraone S, Hiripi E, et al. The World Health Organization Adult ADHD Self-Report scale (ASRS): a short screening scale for use in the general population. Psychol Med. 2005;35(2):245–256. doi: 10.1017/S0033291704002892.
    1. Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, Kim JS, Heo S, Alves H, White SM, Wojcicki TR, Mailey E, Vieira VJ, Martin SA, Pence BD, Woods JA, McAuley E, Kramer AF. Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci U S A. 2011;108(7):3017–3022. doi: 10.1073/pnas.1015950108.
    1. Burdette JH, Laurienti PJ, Espeland MA, Morgan A, Telesford Q, Vechlekar CD, et al. Using network science to evaluate exercise-associated brain changes in older adults. Front Aging Neurosci. 2010;2:23.
    1. Voss MW, Prakash RS, Erickson KI, Basak C, Chaddock L, Kim JS, et al. Plasticity of brain networks in a randomized intervention trial of exercise training in older adults. Front Aging Neurosci. 2010;2:32.
    1. Jack CR, Bernstein MA, Fox NC, Thompson P, Alexander G, Harvey D, Borowski B, Britson PJ, L. Whitwell J, Ward C, Dale AM, Felmlee JP, Gunter JL, Hill DLG, Killiany R, Schuff N, Fox-Bosetti S, Lin C, Studholme C, DeCarli CS, Gunnar Krueger, Ward HA, Metzger GJ, Scott KT, Mallozzi R, Blezek D, Levy J, Debbins JP, Fleisher AS, Albert M, Green R, Bartzokis G, Glover G, Mugler J, Weiner MW, ADNI Study The Alzheimer’s Disease Neuroimaging Initiative (ADNI): MRI methods. J J Magn Reson Imaging. 2008;27(4):685–691. doi: 10.1002/jmri.21049.
    1. Hoge RD, Atkinson J, Gill B, Crelier GR, Marrett S, Pike GB. Linear coupling between cerebral blood flow and oxygen consumption in activated human cortex. Proc Natl Acad Sci U S A. 1999;96(16):9403–9408. doi: 10.1073/pnas.96.16.9403.
    1. Hoge RD, Atkinson J, Gill B, Crelier GR, Marrett S, Pike GB. Investigation of BOLD signal dependence on cerebral blood flow and oxygen consumption: the deoxyhemoglobin dilution model. Magn Reson Med. 1999;42(5):849–63. 10.1002/(SICI)1522-2594(199911)42:5<849::AID-MRM4>;2-Z.
    1. Hamer M, Kivimaki M, Steptoe A. Longitudinal patterns in physical activity and sedentary behaviour from mid-life to early old age: a substudy of the Whitehall II cohort. J Epidemiol Community Health. 2012;66(12):1110–1115. doi: 10.1136/jech-2011-200505.
    1. Mark CI, Fisher JA, Pike GB. Improved fMRI calibration: precisely controlled hyperoxic versus hypercapnic stimuli. Neuroimage. 2011;54(2):1102–1111. doi: 10.1016/j.neuroimage.2010.08.070.
    1. Mazerolle EL, Ma Y, Sinclair D, Pike GB. Impact of abnormal cerebrovascular reactivity on BOLD fMRI: a preliminary investigation of moyamoya disease. Clin Physiol Funct Imaging. 2018;38(1):87–92. doi: 10.1111/cpf.12387.
    1. Downar J, Crawley AP, Mikulis DJ, Davis KD. The effect of task relevance on the cortical response to changes in visual and auditory stimuli: an event-related fMRI study. Neuroimage. 2001;14(6):1256–1267. doi: 10.1006/nimg.2001.0946.
    1. Buysse DJ, Reynolds CF, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28(2):193–213. doi: 10.1016/0165-1781(89)90047-4.
    1. Ancoli-Israel S, Cole R, Alessi C, Chambers M, Moorcroft W, Pollak CP. The role of actigraphy in the study of sleep and circadian rhythms. Sleep. 2003;26(3):342–392. doi: 10.1093/sleep/26.3.342.
    1. Anderson RT, Aaronson NK, Wilkin D. Critical review of the international assessments of health-related quality of life. Qual Life Res. 1993;2(6):369–395. doi: 10.1007/BF00422215.
    1. EuroQol Group. EuroQol - a new facility for the measurement of health-related quality of life. Health Policy (New York). 1990;16(3):199–208.
    1. Herdman M, Gudex C, Lloyd A, Janssen M, Kind P, Parkin D, Bonsel G, Badia X. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L) Qual Life Res. 2011;20(10):1727–1736. doi: 10.1007/s11136-011-9903-x.
    1. Xie F, Pullenayegum E, Gaebel K, Bansback N, Bryan S, Ohinmaa A, Poissant L, Johnson JA. A time trade-off-derived value set of the EQ-5D-5L for Canada. Med Care. 2016;54(1):98–105. doi: 10.1097/MLR.0000000000000447.
    1. Hecksteden A, Faude O, Meyer T, Donath L. How to construct, conduct and analyze an exercise training study? Front. Physiol. 2018;9:1007. doi: 10.3389/fphys.2018.01007.
    1. Stern Y, Lee S, Predovan D, Sloan RP. Sex moderates the effect of aerobic exercise on some aspects of cognition in cognitively intact younger and middle-age adults. J Clin Med. 2019;8(6):886. doi: 10.3390/jcm8060886.
    1. Stern Y, Mackay-Brandt A, Lee S, McKinley P, McIntyre K, Razlighi Q, et al. Effect of aerobic exercise on cognition in younger adults: a randomized clinical trial. Neurology. 2019;93(4):185. doi: 10.1212/WNL.0000000000007292.
    1. Stothart CR, Simons DJ, Boot WR, Kramer AF. Is the effect of aerobic exercise on cognition a placebo effect? PLoS One. 2014;9(10):e109557. doi: 10.1371/journal.pone.0109557.

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