Reshaping the path of mild cognitive impairment by refining exercise prescription: a study protocol of a randomized controlled trial to understand the "what," "for whom," and "how" of exercise to promote cognitive function

Cindy K Barha, Ryan S Falck, John R Best, Lindsay S Nagamatsu, Ging-Yuek Robin Hsiung, A William Sheel, Chun Liang Hsu, Arthur F Kramer, Michelle W Voss, Kirk I Erickson, Jennifer C Davis, J Kevin Shoemaker, Lara Boyd, Rachel A Crockett, Lisanne Ten Brinke, Louis Bherer, Joel Singer, Liisa A M Galea, Claudia Jacova, Alexis Bullock, Sofia Grant, Teresa Liu-Ambrose, Cindy K Barha, Ryan S Falck, John R Best, Lindsay S Nagamatsu, Ging-Yuek Robin Hsiung, A William Sheel, Chun Liang Hsu, Arthur F Kramer, Michelle W Voss, Kirk I Erickson, Jennifer C Davis, J Kevin Shoemaker, Lara Boyd, Rachel A Crockett, Lisanne Ten Brinke, Louis Bherer, Joel Singer, Liisa A M Galea, Claudia Jacova, Alexis Bullock, Sofia Grant, Teresa Liu-Ambrose

Abstract

Background: Targeted exercise training is a promising strategy for promoting cognitive function and preventing dementia in older age. Despite the utility of exercise as an intervention, variation still exists in exercise-induced cognitive gains and questions remain regarding the type of training (i.e., what), as well as moderators (i.e., for whom) and mechanisms (i.e., how) of benefit. Both aerobic training (AT) and resistance training (RT) enhance cognitive function in older adults without cognitive impairment; however, the vast majority of trials have focused exclusively on AT. Thus, more research is needed on RT, as well as on the combination of AT and RT, in older adults with mild cognitive impairment (MCI), a prodromal stage of dementia. Therefore, we aim to conduct a 6-month, 2 × 2 factorial randomized controlled trial in older adults with MCI to assess the individual effects of AT and RT, and the combined effect of AT and RT on cognitive function and to determine the possible underlying biological mechanisms.

Methods: Two hundred and sixteen community-dwelling adults, aged 65 to 85 years, with MCI from metropolitan Vancouver will be recruited to participate in this study. Randomization will be stratified by biological sex and participants will be randomly allocated to one of the four experimental groups: (1) 4×/week balance and tone (BAT; i.e., active control); (2) combined 2×/week AT + 2×/week RT; (3) 2×/week AT + 2×/week BAT; or (4) 2×/week RT + 2×/week BAT. The primary outcome is cognitive function as measured by the Alzheimer's Disease Assessment Scale-Cognitive-Plus. Secondary outcomes include cognitive function, health-related quality of life, physical function, actigraphy measures, questionnaires, and falls. Outcomes will be measured at baseline, 6 months (i.e., trial completion), and 18 months (i.e., 12-month follow-up).

Discussion: Establishing the efficacy of different types and combinations of exercise training to minimize cognitive decline will advance our ability to prescribe exercise as "medicine" to treat MCI and delay the onset and progression of dementia. This trial is extremely timely as cognitive impairment and dementia pose a growing threat to global public health.

Trial registration: ClinicalTrials.gov NCT02737878 . Registered on April 14, 2016.

Keywords: Aerobic training; Biomarkers, Exercise; Cognition; Mild cognitive impairment; Mobility; Randomized controlled trial; Resistance training.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Overview of study design from recruitment to follow-up
Fig. 2
Fig. 2
Schematic representation of the three primary comparisons in the factorial randomized controlled trial design
Fig 3
Fig 3
Schedule of enrolment, interventions, and assessments according to the SPIRIT Checklist

References

    1. Barrios H, Narciso S, Guerreiro M, Maroco J, Logsdon R, de Mendonca A. Quality of life in patients with mild cognitive impairment. Aging Ment Health. 2013;17(3):287–292. doi: 10.1080/13607863.2012.747083.
    1. Wimo A, Guerchet M, Ali GC, Wu YT, Prina AM, Winblad B, et al. The worldwide costs of dementia 2015 and comparisons with 2010. Alzheimers Dement. 2017;13(1):1–7. doi: 10.1016/j.jalz.2016.07.150.
    1. Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi H. Forecasting the global burden of Alzheimer's disease. Alzheimer's Dement. 2007;3:186–191. doi: 10.1016/j.jalz.2007.04.381.
    1. Raschetti R, Albanese E, Vanacore N, Maggini M. Cholinesterase inhibitors in mild cognitive impairment: a systematic review of randomised trials. PLoS Med. 2007;4(11):e338. doi: 10.1371/journal.pmed.0040338.
    1. Erickson K, Kramer AF. Aerobic exercise effects on cognitive and neural plasticity in older adults. Br J Sports Med. 2009;43(1):22–24.
    1. Khan KM, Thompson AM, Blair SN, Sallis JF, Powell KE, Bull FC, et al. Sport and exercise as contributors to the health of nations. Lancet. 2012;380(9836):59–64. doi: 10.1016/S0140-6736(12)60865-4.
    1. Barnes DE, Yaffe K. The projected effect of risk factor reduction on Alzheimer's disease prevalence. Lancet Neurol. 2011;10(9):819–28.
    1. Wanderley FAC, Moreira A, Sokhatska O, Palmares C, Moreira P, Sandercock G, et al. Differential responses of adiposity, inflammation and autonomic function to aerobic versus resistance training in older adults. Exp Gerontol. 2013;48(3):326–33.
    1. Northey JM, Cherbuin N, Pumpa KL, Smee DJ, Rattray B. Exercise interventions for cognitive function in adults older than 50: a systematic review with meta-analysis. Br J Sports Med. 2018;52(3):154–160. doi: 10.1136/bjsports-2016-096587.
    1. Barha CK, Davis JC, Falck RS, Nagamatsu LS, Liu-Ambrose T. Sex differences in exercise efficacy to improve cognition: a systematic review and meta-analysis of randomized controlled trials in older humans. Front Neuroendocrinol. 2017;46:71–85. doi: 10.1016/j.yfrne.2017.04.002.
    1. Barha CK, Falck RS, Skou ST, Liu-Ambrose T. Personalising exercise recommendations for healthy cognition and mobility in ageing: time to consider one's pre-existing function and genotype (Part 2) Br J Sports Med. 2021;55(6):301–303. doi: 10.1136/bjsports-2020-102865.
    1. Barha CK, Falck RS, Skou ST, Liu-Ambrose T. Personalising exercise recommendations for healthy cognition and mobility in aging: time to address sex and gender (Part 1) Br J Sports Med. 2021;55(6):300–301. doi: 10.1136/bjsports-2020-102864.
    1. Colcombe S, Kramer AF. Fitness effects on the cognitive function of older adults: a meta-analytic study. Psychol Sci. 2003;14(2):125–130. doi: 10.1111/1467-9280.t01-1-01430.
    1. Sanders LMJ, Hortobagyi T, la Bastide-van GS, van der Zee EA, van Heuvelen MJG. Dose-response relationship between exercise and cognitive function in older adults with and without cognitive impairment: a systematic review and meta-analysis. PLoS One. 2019;14(1):e0210036. doi: 10.1371/journal.pone.0210036.
    1. Coelho-Junior H, Marzetti E, Calvani R, Picca A, Arai H, Uchida M. Resistance training improves cognitive function in older adults with different cognitive status: a systematic review and Meta-analysis. Aging Ment Health. 2022;26(2):213–224. doi: 10.1080/13607863.2020.1857691.
    1. Xiong J, Ye M, Wang L, Zheng G. Effects of physical exercise on executive function in cognitively healthy older adults: a systematic review and meta-analysis of randomized controlled trials: Physical exercise for executive function. Int J Nurs Stud. 2021;114:103810. doi: 10.1016/j.ijnurstu.2020.103810.
    1. Gates N, Fiatarone Singh MA, Sachdev PS, Valenzuela M. The effect of exercise training on cognitive function in older adults with mild cognitive impairment: a meta-analysis of randomized controlled trials. Am J Geriatr Psychiatry. 2013;21(11):1086–97.
    1. van Uffelen JG, Chin APMJ, Hopman-Rock M, van Mechelen W. The effects of exercise on cognition in older adults with and without cognitive decline: a systematic review. Clin J Sport Med. 2008;18(6):486–500. doi: 10.1097/JSM.0b013e3181845f0b.
    1. Ohman H, Savikko N, Strandberg TE, Pitkala KH. Effect of physical exercise on cognitive performance in older adults with mild cognitive impairment or dementia: a systematic review. Dement Geriatr Cogn Disord. 2014;38(5-6):347–365. doi: 10.1159/000365388.
    1. Demurtas J, Schoene D, Torbahn G, Marengoni A, Grande G, Zou L, et al. Physical activity and exercise in mild cognitive impairment and dementia: an umbrella review of intervention and observational studies. J Am Med Dir Assoc. 2020;21(10):1415–22 e6. doi: 10.1016/j.jamda.2020.08.031.
    1. Huang X, Zhao X, Li B, Cai Y, Zhang S, Wan Q, et al. Comparative efficacy of various exercise interventions on cognitive function in patients with mild cognitive impairment or dementia: a systematic review and network meta-analysis. J Sport Health Sci. 2022;11(2):212–223. doi: 10.1016/j.jshs.2021.05.003.
    1. Feldman HH, Jacova C. Mild cognitive impairment. Am J Geriatr Psychiatry. 2005;13(8):645–655. doi: 10.1097/00019442-200508000-00003.
    1. Burns A, Zaudig M. Mild cognitive impairment in older people. Lancet. 2002;360(9349):1963–1965. doi: 10.1016/S0140-6736(02)11920-9.
    1. Yaffe K, Petersen RC, Lindquist K, Kramer J, Miller B. Subtype of mild cognitive impairment and progression to dementia and death. Dement Geriatr Cogn Disord. 2006;22(4):312–319. doi: 10.1159/000095427.
    1. Jungwirth S, Zehetmayer S, Hinterberger M, Tragl KH, Fischer P. The validity of amnestic MCI and non-amnestic MCI at age 75 in the prediction of Alzheimer's dementia and vascular dementia. Int Psychogeriatrics. 2012;24(6):959–66.
    1. Petersen RC. Mild cognitive impairment. Lancet. 2006;367(9527):1979. doi: 10.1016/S0140-6736(06)68881-8.
    1. Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol. 1999;56(3):303–308. doi: 10.1001/archneur.56.3.303.
    1. Busse A, Bischkopf J, Riedel-Heller SG, Angermeyer MC. Mild cognitive impairment: prevalence and incidence according to different diagnostic criteria. Results of the Leipzig Longitudinal Study of the Aged (LEILA75+) Br J Psychiatry. 2003;182:449–454. doi: 10.1192/bjp.182.5.449.
    1. Teng E, Tassniyom K, Lu PH. Reduced quality-of-life ratings in mild cognitive impairment: analyses of subject and informant responses. Am J Geriatr Psychiatry. 2012;20(12):1016–1025. doi: 10.1097/JGP.0b013e31826ce640.
    1. Barha CK, Hsiung GR, Best JR, Davis JC, Eng JJ, Jacova C, et al. Sex difference in aerobic exercise efficacy to improve cognition in older adults with vascular cognitive impairment: secondary analysis of a randomized controlled trial. J Alzheimer's Dis. 2017;60(4):1397–1410. doi: 10.3233/JAD-170221.
    1. van Uffelen JG, Chinapaw MJ, van Mechelen W, Hopman-Rock M. Walking or vitamin B for cognition in older adults with mild cognitive impairment? A randomised controlled trial. Br J Sports Med. 2008;42(5):344–351. doi: 10.1136/bjsm.2007.044735.
    1. Baker LD, Frank LL, Foster-Schubert K, Green PS, Wilkinson CW, McTiernan A, et al. Effects of aerobic exercise on mild cognitive impairment: a controlled trial. Arch Neurol. 2010;67(1):71–79. doi: 10.1001/archneurol.2009.307.
    1. Barha CK, Davis JC, Falck RS, Nagamatsu LS, Liu-Ambrose T. Sex differences in exercise efficacy to improve cognition: a systematic review and meta-analysis of randomized controlled trials in older humans. Front Neuroendocrinol. 2017;46:71–78. doi: 10.1016/j.yfrne.2017.04.002.
    1. Cassilhas RC, Lee KS, Fernandes J, Oliveira MG, Tufik S, Meeusen R, et al. Spatial memory is improved by aerobic and resistance exercise through divergent molecular mechanisms. Neuroscience. 2012;202:309–317. doi: 10.1016/j.neuroscience.2011.11.029.
    1. Huang H, Li W, Qin Z, Shen H, Li X, Wang W. Physical exercise increases peripheral brain-derived neurotrophic factors in patients with cognitive impairment: a meta-analysis. Restor Neurol Neurosci. 2021;39(3):159–171.
    1. Ruiz-Gonzalez D, Hernandez-Martinez A, Valenzuela PL, Morales JS, Soriano-Maldonado A. Effects of physical exercise on plasma brain-derived neurotrophic factor in neurodegenerative disorders: a systematic review and meta-analysis of randomized controlled trials. Neurosci Biobehav Rev. 2021;128:394–405. doi: 10.1016/j.neubiorev.2021.05.025.
    1. Cassilhas RC, Viana VA, Grassmann V, Santos RT, Santos RF, Tufik S, et al. The impact of resistance exercise on the cognitive function of the elderly. Med Sci Sports Exerc. 2007;39(8):1401–1407. doi: 10.1249/mss.0b013e318060111f.
    1. Marinus N, Hansen D, Feys P, Meesen R, Timmermans A, Spildooren J. The impact of different types of exercise training on peripheral blood brain-derived neurotrophic factor concentrations in older adults: a meta-analysis. Sports Med. 2019;49(10):1529–1546. doi: 10.1007/s40279-019-01148-z.
    1. Shen XN, Niu LD, Wang YJ, Cao XP, Liu Q, Tan L, et al. Inflammatory markers in Alzheimer's disease and mild cognitive impairment: a meta-analysis and systematic review of 170 studies. J Neurol Neurosurg Psychiatry. 2019;90(5):590–598. doi: 10.1136/jnnp-2018-319148.
    1. Ma C, Lin M, Gao J, Xu S, Huang L, Zhu J, et al. The impact of physical activity on blood inflammatory cytokines and neuroprotective factors in individuals with mild cognitive impairment: a systematic review and meta-analysis of randomized-controlled trials. Aging Clin Exp Res. 2022;34(7):1471–84.
    1. Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, et al. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell. 2003;112(2):257–269. doi: 10.1016/S0092-8674(03)00035-7.
    1. Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7(3):270–279. doi: 10.1016/j.jalz.2011.03.008.
    1. Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology. 1993;43(11):2412–2414. doi: 10.1212/WNL.43.11.2412-a.
    1. Warburton DE, Gledhill N, Jamnik VK, Bredin SS, McKenzie DC, Stone J, et al. The Physical Activity Readiness Questionnaire for Everyone (PAR-Q+) and electronic Physical Activity Readiness Medical Examination (ePARmed-X+): Summary of Consensus Panel recommendations. Health Fitness J Canada. 2011;4(2):26–37.
    1. Gifford KA, Liu D, Lu Z, Tripodis Y, Cantwell NG, Palmisano J, et al. The source of cognitive complaints predicts diagnostic conversion differentially among nondemented older adults. Alzheimers Dement. 2014;10(3):319–327. doi: 10.1016/j.jalz.2013.02.007.
    1. Nasreddine ZS, Phillips NA, Bedirian 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. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–198. doi: 10.1016/0022-3956(75)90026-6.
    1. Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist. 1969;9(3):179–186. doi: 10.1093/geront/9.3_Part_1.179.
    1. Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, et al. 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. Skinner J, Carvalho JO, Potter GG, Thames A, Zelinski E, Crane PK, et al. The Alzheimer's Disease Assessment Scale-Cognitive-Plus (ADAS-Cog-Plus): an expansion of the ADAS-Cog to improve responsiveness in MCI. Brain Imaging Behav. 2012;6(4):489–501. doi: 10.1007/s11682-012-9166-3.
    1. Falck RS, Davis JC, Best JR, Chan PCY, Li LC, Wyrough AB, et al. Effect of a multimodal lifestyle intervention on sleep and cognitive function in older adults with probable mild cognitive impairment and poor sleep: a randomized clinical trial. J Alzheimer's Dis. 2020;76(1):179–193. doi: 10.3233/JAD-200383.
    1. Falck RS, Davis JC, Best JR, Crockett RA, Liu-Ambrose T. Impact of exercise training on physical and cognitive function among older adults: a systematic review and meta-analysis. Neurobiol Aging. 2019;79:119–130. doi: 10.1016/j.neurobiolaging.2019.03.007.
    1. Ludyga S, Gerber M, Puhse U, Looser VN, Kamijo K. Systematic review and meta-analysis investigating moderators of long-term effects of exercise on cognition in healthy individuals. Nat Hum Behav. 2020;4(6):603–612. doi: 10.1038/s41562-020-0851-8.
    1. Oldfield RC. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia. 1971;9(1):97–113. doi: 10.1016/0028-3932(71)90067-4.
    1. Groll DL, To T, Bombardier C, Wright JG. The development of a comorbidity index with physical function as the outcome. J Clin Epidemiol. 2005;58(6):595–602. doi: 10.1016/j.jclinepi.2004.10.018.
    1. Day N, Oakes S, Luben R, Khaw KT, Bingham S, Welch A, et al. EPIC-Norfolk: study design and characteristics of the cohort. European Prospective Investigation of Cancer. Br J Cancer. 1999;80(Suppl 1):95–103.
    1. Schinka JA, McBride A, Vanderploeg RD, Tennyson K, Borenstein AR, Mortimer JA. Florida Cognitive Activities Scale: initial development and validation. J Int Neuropsychol Soc. 2005;11(1):108–116. doi: 10.1017/S1355617705050125.
    1. Wilson R, Barnes L, Bennett D. Assessment of lifetime participation in cognitively stimulating activities. J Clin Exp Neuropsychol. 2003;25(5):634–642. doi: 10.1076/jcen.25.5.634.14572.
    1. Grober E, Sliwinski M. Development and validation of a model for estimating premorbid verbal intelligence in the elderly. J Clin Exp Neuropsychol. 1991;13(6):933–949. doi: 10.1080/01688639108405109.
    1. Lord C, Duchesne A, Pruessner JC, Lupien SJ. Measuring indices of lifelong estrogen exposure: self-report reliability. Climacteric. 2009;12(5):387–394. doi: 10.1080/13697130802664660.
    1. Beydoun MA, Boueiz A, Abougergi MS, Kitner-Triolo MH, Beydoun HA, Resnick SM, et al. Sex differences in the association of the apolipoprotein E epsilon 4 allele with incidence of dementia, cognitive impairment, and decline. Neurobiol Aging. 2012;33(4):720–31 e4. doi: 10.1016/j.neurobiolaging.2010.05.017.
    1. Mohs RC, Knopman D, Petersen RC, Ferris SH, Ernesto C, Grundman M, et al. Development of cognitive instruments for use in clinical trials of antidementia drugs: additions to the Alzheimer's Disease Assessment Scale that broaden its scope. Alzheimer Dis Assoc Disord. 1997;11:13–21. doi: 10.1097/00002093-199700112-00003.
    1. Mungas D, Crane P, Dowling M, Gershon R, Gibbons LE, Jones R. Optimizing cognitive outcome measures in AD clinical trials: Technical Summary. 2013.
    1. Heaton RK, Akshoomoff N, Tulsky D, Mungas D, Weintraub S, Dikmen S, et al. Reliability and validity of composite scores from the NIH Toolbox Cognition Battery in adults. J Int Neuropsychol Soc. 2014;20(6):588–598. doi: 10.1017/S1355617714000241.
    1. Mungas D, Heaton R, Tulsky D, Zelazo PD, Slotkin J, Blitz D, et al. Factor structure, convergent validity, and discriminant validity of the NIH Toolbox Cognitive Health Battery (NIHTB-CHB) in adults. J Int Neuropsychol Soc. 2014;20(6):579–587. doi: 10.1017/S1355617714000307.
    1. Nagamatsu LS, Chan A, Davis JC, Beattie BL, Graf P, Voss MW, et al. Physical activity improves verbal and spatial memory in older adults with probable mild cognitive impairment: a 6-month randomized controlled trial. J Aging Res. 2013;2013:861893. doi: 10.1155/2013/861893.
    1. Schrag A, Schott JM. What is the clinically relevant change on the ADAS-Cog? J Neurol Neurosurg Psychiatry. 2012;83(2):171–3.
    1. Trenerry M, Crosson B, DeBoe J, Leber W. Stroop Neuropsychological Screening Test. Lutz: Psychological Assessment Resources; 1988.
    1. Shin MS, Park SY, Park SR, Seol SH, Kwon JS. Clinical and empirical applications of the Rey-Osterrieth Complex Figure Test. Nat Protoc. 2006;1(2):892–899. doi: 10.1038/nprot.2006.115.
    1. Tuokko H, Griffith LE, Simard M, Taler V. Cognitive measures in the Canadian Longitudinal Study on Aging. Clin Neuropsychol. 2017;31(1):233–250. doi: 10.1080/13854046.2016.1254279.
    1. Benton AL, Hamsher K, Varney N, Spreen O. Contributions to neuropsychological assessment: a clinical manual. New York: Oxford University Press; 1983.
    1. Dolan P. Modeling valuations for EuroQol health states. Med Care. 1997;35(11):1095–1108. doi: 10.1097/00005650-199711000-00002.
    1. Neumann PJ, Goldie SJ, Weinstein MC. Preference-based measures in economic evaluation in health care. Annu Rev Public Health. 2000;21:587–611. doi: 10.1146/annurev.publhealth.21.1.587.
    1. Al-Janabi H, Flynn TN, Coast J. Development of a self-report measure of capability wellbeing for adults: the ICECAP-A. Qual Life Res. 2012;21(1):167–176. doi: 10.1007/s11136-011-9927-2.
    1. Al-Janabi H, Peters TJ, Brazier J, Bryan S, Flynn TN, Clemens S, et al. An investigation of the construct validity of the ICECAP-A capability measure. Qual Life Res. 2013;22(7):1831–1840. doi: 10.1007/s11136-012-0293-5.
    1. Balke B. A Simple Field Test for the Assessment of Physical Fitness. Rep 63-6. Rep Civ Aeromed Res Inst US. 1963:1–8.
    1. Guralnik JM, Ferrucci L, Simonsick EM, Salive ME, Wallace RB. Lower-extremity function in persons over the age of 70 years as a predictor of subsequent disability. N Engl J Med. 1995;332(9):556–561. doi: 10.1056/NEJM199503023320902.
    1. Buchner DM. One lap around the track: the standard for mobility disability? J Gerontol A Biol Sci Med Sci. 2008;63(6):586–587. doi: 10.1093/gerona/63.6.586.
    1. Jones CJ, Rikli RE, Beam WC. A 30-s chair-stand test as a measure of lower body strength in community-residing older adults. Res Q Exerc Sport. 1999;70(2):113–119. doi: 10.1080/02701367.1999.10608028.
    1. Carney CE, Buysse DJ, Ancoli-Israel S, Edinger JD, Krystal AD, Lichstein KL, et al. The consensus sleep diary: standardizing prospective sleep self-monitoring. Sleep. 2012;35(2):287–302. doi: 10.5665/sleep.1642.
    1. Falck RS, Landry GJ, Brazendale K, Liu-Ambrose T. Measuring physical activity in older adults using MotionWatch 8 actigraphy: how many days are needed? J Aging Phys Act. 2017;25(1):51–57. doi: 10.1123/japa.2015-0256.
    1. Spielberger C. Manual for the state-trait anxiety inventory. Palo Alto: Consulting Psychologists Press; 1983.
    1. Radloff L. The CES-D Scale: a self-reported depression scale for research in the general population. Appl Psychol Measur. 1977;1:385. doi: 10.1177/014662167700100306.
    1. Buysse DJ, Reynolds CF, 3rd, 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. Chung F, Subramanyam R, Liao P, Sasaki E, Shapiro C, Sun Y. High STOP-Bang score indicates a high probability of obstructive sleep apnoea. Br J Anaesth. 2012;108(5):768–775. doi: 10.1093/bja/aes022.
    1. Peel C, Sawyer Baker P, Roth DL, Brown CJ, Brodner EV, Allman RM. Assessing mobility in older adults: the UAB Study of Aging Life-Space Assessment. Phys Ther. 2005;85(10):1008–1119. doi: 10.1093/ptj/85.10.1008.
    1. Sunderland A, Harris JE, Gleave J. Memory failures in everyday life following severe head injury. J Clin Neuropsychol. 1984;6(2):127–142. doi: 10.1080/01688638408401204.
    1. Brown KW, Ryan RM. The benefits of being present: mindfulness and its role in psychological well-being. J Pers Soc Psychol. 2003;84(4):822–848. doi: 10.1037/0022-3514.84.4.822.
    1. Stewart AL, Mills KM, King AC, Haskell WL, Gillis D, Ritter PL. CHAMPS physical activity questionnaire for older adults: outcomes for interventions. Med Sci Sports Exerc. 2001;33(7):1126–1141. doi: 10.1097/00005768-200107000-00010.
    1. Rosenberg DE, Norman GJ, Wagner N, Patrick K, Calfas KJ, Sallis JF. Reliability and validity of the Sedentary Behavior Questionnaire (SBQ) for adults. J Phys Act Health. 2010;7(6):697–705. doi: 10.1123/jpah.7.6.697.
    1. Lubben J, Blozik E, Gillmann G, Iliffe S, von Renteln KW, 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. Cutrona CE, Russell DW. The provisions of social relationships and adaptation to stress. Adv Personal Relationships. 1987;1:37–67.
    1. Russell D, Peplau LA, Cutrona CE. The revised UCLA Loneliness Scale: concurrent and discriminant validity evidence. J Pers Soc Psychol. 1980;39(3):472–480. doi: 10.1037/0022-3514.39.3.472.
    1. Maetzel A, Li LC, Pencharz J, Tomlinson G, Bombardier C, Community H, et al. The economic burden associated with osteoarthritis, rheumatoid arthritis, and hypertension: a comparative study. Ann Rheum Dis. 2004;63(4):395–401. doi: 10.1136/ard.2003.006031.
    1. Wu M, Rosano C, Butters M, Whyte E, Nable M, Crooks R, et al. A fully automated method for quantifying and localizing white matter hyperintensities on MR images. Psychiatry Res. 2006;148(2-3):133–142. doi: 10.1016/j.pscychresns.2006.09.003.
    1. Borich MR, Wadden KP, Boyd LA. Establishing the reproducibility of two approaches to quantify white matter tract integrity in stroke. NeuroImage. 2012;59(3):2393–2400. doi: 10.1016/j.neuroimage.2011.09.009.
    1. Birn RM, Molloy EK, Patriat R, Parker T, Meier TB, Kirk GR, et al. The effect of scan length on the reliability of resting-state fMRI connectivity estimates. NeuroImage. 2013;83:550–558. doi: 10.1016/j.neuroimage.2013.05.099.
    1. Ragland JD, Ranganath C, Harms MP, Barch DM, Gold JM, Layher E, et al. Functional and neuroanatomic specificity of episodic memory dysfunction in schizophrenia: a functional magnetic resonance imaging study of the relational and item-specific encoding task. JAMA Psychiat. 2015;72(9):909–916. doi: 10.1001/jamapsychiatry.2015.0276.
    1. Yeo BT, Krienen FM, Sepulcre J, Sabuncu MR, Lashkari D, Hollinshead M, et al. The organization of the human cerebral cortex estimated by intrinsic functional connectivity. J Neurophysiol. 2011;106(3):1125–1165. doi: 10.1152/jn.00338.2011.
    1. Borg G. Ratings of perceived exertion and heart rates during short-term cycle exercise and their use in a new cycling strength test. Int J Sports Med. 1982;3(3):153–158. doi: 10.1055/s-2008-1026080.
    1. Liu-Ambrose T, Best JR, Davis JC, Eng JJ, Lee PE, Jacova C, et al. Aerobic exercise and vascular cognitive impairment: a randomized controlled trial. Neurology. 2016;87(20):2082–2090. doi: 10.1212/WNL.0000000000003332.
    1. Nagamatsu LS, Handy TC, Hsu CL, Voss M, Liu-Ambrose T. Resistance training promotes cognitive and functional brain plasticity in seniors with probable mild cognitive impairment. Arch Intern Med. 2012;172(8):666–668. doi: 10.1001/archinternmed.2012.379.
    1. Liu-Ambrose T, Nagamatsu LS, Graf P, Beattie BL, Ashe MC, Handy TC. Resistance training and executive functions: a 12-month randomized controlled trial. Arch Intern Med. 2010;170(2):170–178. doi: 10.1001/archinternmed.2009.494.
    1. Montero-Odasso M, Almeida QJ, Burhan AM, Camicioli R, Doyon J, Fraser S, et al. SYNERGIC TRIAL (SYNchronizing Exercises, Remedies in Gait and Cognition) a multi-Centre randomized controlled double blind trial to improve gait and cognition in mild cognitive impairment. BMC Geriatr. 2018;18(1):93. doi: 10.1186/s12877-018-0782-7.
    1. van Buuren S, Groothuis-Oudshoorn K. Mice: multivariate imputation by chained equations in R. J Stat Softw. 2011;45(3):1–67. doi: 10.18637/jss.v045.i03.
    1. Preacher KJ, Hayes AF. Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models. Behav Res Methods. 2008;40(3):879–891. doi: 10.3758/BRM.40.3.879.
    1. Glick HA, Doshi J, Sonnad SS, Polsky D. Economic evaluation in clinical trials. 1. New York: Oxford University Press; 2007.
    1. Drummond MF, Sculpher MJ, Claxton K, Stoddart GL, Torrance GW. Methods for the economic evaluation of health care programmes. 4. New York: Oxford University Press; 2015.

Source: PubMed

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