World Health Organization. Dementia. 2017; Available at: http://www.who.int/news-room/fact-sheets/detail/dementia. Accessed 17 April 2019.
Cummings J, Aisen PS, DuBois B, Frolich L, Jack CR,Jr, Jones RW, et al. Drug development in Alzheimer’s disease: the path to 2025. Alzheimers Res Ther 2016;8:39-016-0207-9.
Liu-Ambrose T, Donaldson MG, Ahamed Y, Graf P, Cook WL, Close J, et al. Otago home-based strength and balance retraining improves executive functioning in older fallers: a randomized controlled trial. J Am Geriatr Soc. 2008;56(10):1821–30.
Forte R, Boreham CA, Leite JC, De Vito G, Brennan L, Gibney ER, et al. Enhancing cognitive functioning in the elderly: multicomponent vs resistance training. Clin Interv Aging. 2013;8:19–27.
Sanders LMJ, Hortobagyi T, la Bastide-van Gemert S, 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.
Granacher U, Gruber M, Gollhofer A. Resistance training and neuromuscular performance in seniors. Int J Sports Med. 2009;30(9):652–7.
Layne AS, Hsu FC, Blair SN, Chen SH, Dungan J, Fielding RA, et al. Predictors of change in physical function in older adults in response to long-term, structured physical activity: the LIFE Study. Arch Phys Med Rehabil. 2017;98(1):11–24 e3.
Stenholm S, Koster A, Valkeinen H, Patel KV, Bandinelli S, Guralnik JM, et al. Association of physical activity history with physical function and mortality in old age. J Gerontol A Biol Sci Med Sci. 2016;71(4):496–501.
Tsuzuku S, Kajioka T, Sakakibara H, Shimaoka K. Slow movement resistance training using body weight improves muscle mass in the elderly: a randomized controlled trial. Scand J Med Sci Sports. 2018;28(4):1339–44.
Eggermont LHP, Swaab DF, Hol EM, Scherder EJA. Walking the line: a randomised trial on the effects of a short term walking programme on cognition in dementia. J Neurol Neurosurg Psychiatry. 2009;80(7):802–4.
Bossers WJ, van der Woude LH, Boersma F, Hortobagyi T, Scherder EJ, van Heuvelen MJ. A 9-week aerobic and strength training program improves cognitive and motor function in patients with dementia: a randomized. Controlled Trial Am J Geriatr Psychiatry. 2015;23(11):1106–16.
Sobol NA, Hoffmann K, Frederiksen KS, Vogel A, Vestergaard K, Braendgaard H, et al. Effect of aerobic exercise on physical performance in patients with Alzheimer’s disease. Alzheimers Dement. 2016;12(12):1207–15.
Toots A, Littbrand H, Bostrom G, Hornsten C, Holmberg H, Lundin-Olsson L, et al. Effects of exercise on cognitive function in older people with dementia: a randomized controlled trial. J Alzheimers Dis. 2017;60(1):323–32.
Lamb SE, Sheehan B, Atherton N, Nichols V, Collins H, Mistry D, et al. Dementia and physical activity (DAPA) trial of moderate to high intensity exercise training for people with dementia: randomised controlled trial. BMJ. 2018;361:k1675.
Vincent KR, Braith RW, Bottiglieri T, Vincent HK, Lowenthal DT. Homocysteine and lipoprotein levels following resistance training in older adults. Prev Cardiol. 2003;6(4):197–203.
Vaynman S, Gomez-Pinilla F. Revenge of the “Sit”: how lifestyle impacts neuronal and cognitive health through molecular systems that interface energy metabolism with neuronal plasticity. J Neurosci Res. 2006;84(4):699–715.
Ding Q, Vaynman S, Akhavan M, Ying Z, Gomez-Pinilla F. Insulin-like growth factor I interfaces with brain-derived neurotrophic factor-mediated synaptic plasticity to modulate aspects of exercise-induced cognitive function. Neuroscience. 2006;140(3):823–33.
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):1401–7.
Cotman CW, Berchtold NC, Christie LA. Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends Neurosci. 2007;30(9):464–72.
Rasmussen P, Brassard P, Adser H, Pedersen MV, Leick L, Hart E, et al. Evidence for a release of brain-derived neurotrophic factor from the brain during exercise. Exp Physiol. 2009;94(10):1062–9.
Whiteman AS, Young DE, He X, Chen TC, Wagenaar RC, Stern CE, et al. Interaction between serum BDNF and aerobic fitness predicts recognition memory in healthy young adults. Behav Brain Res. 2014;259:302–12.
Leckie RL, Oberlin LE, Voss MW, Prakash RS, Szabo-Reed A, Chaddock-Heyman L, et al. BDNF mediates improvements in executive function following a 1-year exercise intervention. Frontiers in human neuroscience 2014;8(DEC).
Vanzella C, Neves JD, Vizuete AF, Aristimunha D, Kolling J, Longoni A, et al. Treadmill running prevents age-related memory deficit and alters neurotrophic factors and oxidative damage in the hippocampus of Wistar rats. Behav Brain Res. 2017;334:78–85.
Voss MW, Erickson KI, Prakash RS, Chaddock L, Kim JS, Alves H, et al. Neurobiological markers of exercise-related brain plasticity in older adults. Brain Behav Immun. 2013;28:90–9.
Maass A, Duzel S, Goerke M, Becke A, Sobieray U, Neumann K, et al. Vascular hippocampal plasticity after aerobic exercise in older adults. Mol Psychiatry. 2015;20(5):585–93.
Maass A, Duzel S, Brigadski T, Goerke M, Becke A, Sobieray U, et al. Relationships of peripheral IGF-1, VEGF and BDNF levels to exercise-related changes in memory, hippocampal perfusion and volumes in older adults. Neuroimage. 2016;131:142–54.
Duzel E, van Praag H, Sendtner M. Can physical exercise in old age improve memory and hippocampal function? BRAIN} 2016} MAR 1};139}(3}):662–673}.
Leckie RL, Weinstein AM, Hodzic JC, Erickson KI. Potential moderators of physical activity on brain health. J Aging Res. 2012;2012:948981.
Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science. 1993;261(5123):921–3.
Podewils LJ, Guallar E, Kuller LH, Fried LP, Lopez OL, Carlson M, et al. Physical activity, APOE genotype, and dementia risk: findings from the Cardiovascular Health Cognition Study. Am J Epidemiol. 2005;161(7):639–51.
Fenesi B, Fang H, Kovacevic A, Oremus M, Raina P, Heisz JJ. Physical exercise moderates the relationship of apolipoprotein E (APOE) genotype and dementia risk: a population-based study. J Alzheimers Dis. 2017;56(1):297–303.
Smith JC, Lancaster MA, Nielson KA, Woodard JL, Seidenberg M, Durgerian S, et al. Interactive effects of physical activity and APOE-epsilon4 on white matter tract diffusivity in healthy elders. Neuroimage. 2016;131:102–12.
Farlow MR, He Y, Tekin S, Xu J, Lane R, Charles HC. Impact of APOE in mild cognitive impairment. Neurology. 2004;63(10):1898–901.
Brown PJ, Devanand DP, Liu X, Caccappolo E. Alzheimer’s disease neuroimaging initiative. Functional impairment in elderly patients with mild cognitive impairment and mild Alzheimer disease. Arch Gen Psychiatry. 2011;68(6):617–26.
Doi T, Shimada H, Makizako H, Tsutsumimoto K, Uemura K, Suzuki T. Apolipoprotein E genotype and physical function among older people with mild cognitive impairment. Geriatr Gerontol Int. 2015;15(4):422–7.
Mou C, Han T, Wang M, Jiang M, Liu B, Hu J. Correlation of polymorphism of APOE and LRP genes to cognitive impairment and behavioral and psychological symptoms of dementia in Alzheimer’s disease and vascular dementia. Int J Clin Exp Med. 2015;8(11):21679–83.
Neeper SA, Gomez-Pinilla F, Choi J, Cotman CW. Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain. Brain Res. 1996;726(1–2):49–56.
Dalise S, Cavalli L, Ghuman H, Wahlberg B, Gerwig M, Chisari C, et al. Biological effects of dosing aerobic exercise and neuromuscular electrical stimulation in rats. Sci Rep. 2017;7(1):10830 -017-11260-7.
Schwarz AJ, Brasel JA, Hintz RL, Mohan S, Cooper DM. Acute effect of brief low- and high-intensity exercise on circulating insulin-like growth factor (IGF) I, II, and IGF-binding protein-3 and its proteolysis in young healthy men. J Clin Endocrinol Metab. 1996;81(10):3492–7.
Rojas Vega S, Knicker A, Hollmann W, Bloch W, Struder HK. Effect of resistance exercise on serum levels of growth factors in humans. Horm Metab Res. 2010;42(13):982–6.
Garber CE, Blissmer B, Deschenes MR, Franklin BA, Lamonte MJ, Lee IM, et al. 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. 2011;43(7):1334–59.
Moll van Charante E, Perry M, Vernooij-Dassen MJFJ, Boswijk DFR, Stoffels J, Achthoven L, Luning-Koster MN. NHG-Standaard Dementie (derde herziening). Huisarts Wet. 2012;55(7):306–17.
Podsiadlo D, Richardson S. The timed “Up & Go”: a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc. 1991;39(2):142–8.
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):189–98.
Blankevoort CG, van Heuvelen MJ, Boersma F, Luning H, de Jong J, Scherder EJ. Review of effects of physical activity on strength, balance, mobility and ADL performance in elderly subjects with dementia. Dement Geriatr Cogn Disord. 2010;30(5):392–402.
American College of Sports Medicine. ACSM’s guidelines for exercise testing and prescription. Philadelphia: Lippincott Williams & Wilkins; 2013.
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.
Hilmer SN, Mager DE, Simonsick EM, Cao Y, Ling SM, Windham BG, et al. A drug burden index to define the functional burden of medications in older people. Arch Intern Med. 2007;167(8):781–7.
Koch W, Ehrenhaft A, Griesser K, Pfeufer A, Muller J, Schomig A, et al. TaqMan systems for genotyping of disease-related polymorphisms present in the gene encoding apolipoprotein E. Clin Chem Lab Med. 2002;40(11):1123–31.
Bossers WJ, van der Woude LH, Boersma F, Scherder EJ, van Heuvelen MJ. Recommended measures for the assessment of cognitive and physical performance in older patients with dementia: a systematic review. Dement Geriatr Cogn Dis Extra. 2012;2(1):589–609.
Tappen RM, Roach KE, Buchner D, Barry C, Edelstein J. Reliability of physical performance measures in nursing home residents with Alzheimer’s disease. J Gerontol A Biol Sci Med Sci. 1997;52(1):M52–5.
Hoeymans N, Wouters ER, Feskens EJ, van den Bos GA, Kromhout D. Reproducibility of performance-based and self-reported measures of functional status. J Gerontol A Biol Sci Med Sci. 1997;52(6):M363–8.
Rossiter-Fornoff JE, Wolf SL, Wolfson LI, Buchner DM. A cross-sectional validation study of the FICSIT common data base static balance measures. Frailty and Injuries: Cooperative Studies of Intervention Techniques. J Gerontol A Biol Sci Med Sci. 1995;50(6):M291–7.
Verkerke GJ, Lemmink KA, Slagers AJ, Westhoff MH, van Riet GA, Rakhorst G. Precision, comfort and mechanical performance of the Quadriso-tester, a quadriceps force measuring device. Med Biol Eng Computing. 2003;41:283–9.
Reitan RM. Validity of the trail making test as an indicator of organic brain damage. Percept Mot Skills. 1958;8(3):271–6.
Wechsler D. Wechsler Adult Intelligence Scale – third edition: administration and scoring manual; 1997.
Stroop JR. Studies of interference in serial verbal reactions. J Exp Psychol Gen. 1992;121(1):15–23.
Luteijn F, Vanderploeg FAE. Groninger intelligence test manual; 1983.
Cohen J. Statistical power analysis for the behavioral sciences. 2nd ed. Hillsdale: Lawrence Erlbaum Associates; 1988.
Nakagawa S, Cuthill IC. Effect size, confidence interval and statistical significance: a practical guide for biologists. Biol Rev Camb Philos Soc. 2007;82(4):591–605.
da Silva VP, Ramalho Oliveira BR, Tavares Mello RG, Moraes H, Deslandes AC, Laks J. Heart rate variability indexes in dementia: a systematic review with a quantitative analysis. Curr Alzheimer Res. 2018;15(1):80–8.
Dumurgier J, Artaud F, Touraine C, Rouaud O, Tavernier B, Dufouil C, et al. Gait speed and decline in gait speed as predictors of incident dementia. J Gerontol A Biol Sci Med Sci. 2017;72(5):655–61.
Abellan van Kan G, Rolland Y, Andrieu S, Bauer J, Beauchet O, Bonnefoy M, et al. Gait speed at usual pace as a predictor of adverse outcomes in community-dwelling older people an International Academy on Nutrition and Aging (IANA) Task Force. J Nutr Health Aging. 2009;13(10):881–9.
Studenski S, Perera S, Patel K, Rosano C, Faulkner K, Inzitari M, et al. Gait speed and survival in older adults. JAMA. 2011;305(1):50–8.
Perera S, Mody SH, Woodman RC, Studenski SA. Meaningful change and responsiveness in common physical performance measures in older adults. J Am Geriatr Soc. 2006;54(5):743–9.
Van Abbema R, De Greef M, Craje C, Krijnen W, Hobbelen H, Van Der Schans C. What type, or combination of exercise can improve preferred gait speed in older adults? A meta-analysis. BMC Geriatr 2015;15:72-015-0061-9.
Schwenk M, Zieschang T, Englert S, Grewal G, Najafi B, Hauer K. Improvements in gait characteristics after intensive resistance and functional training in people with dementia: a randomised controlled trial. BMC Geriatr 2014;14:73-2318-14-73.
Esain I, Gil SM, Bidaurrazaga-Letona I, Rodriguez-Larrad A. Effects of 3 months of detraining on functional fitness and quality of life in older adults who regularly exercise. Aging Clin Exp Res. 2019;31(4):503–10.
Geirsdottir OG, Arnarson A, Ramel A, Briem K, Jonsson PV, Thorsdottir I. Muscular strength and physical function in elderly adults 6-18 months after a 12-week resistance exercise program. Scand J Public Health. 2015;43(1):76–82.
Telenius EW, Engedal K, Bergland A. Long-term effects of a 12 weeks high-intensity functional exercise program on physical function and mental health in nursing home residents with dementia: a single blinded randomized controlled trial. BMC Geriatr 2015;15:158-015-0151-8.
Kemoun G, Thibaud M, Roumagne N, Carette P, Albinet C, Toussaint L, et al. Effects of a physical training programme on cognitive function and walking efficiency in elderly persons with dementia. Dement Geriatr Cogn Disord. 2010;29(2):109–14.
Kuiack SL, Campbell WW, Evans WJ. A structured resistive training program improves muscle dstrength and power in elderly persons with dementia. Act Adapt Aging. 2004;28(1):35–47.
Thomas VS, Hageman PA. Can neuromuscular strength and function in people with dementia be rehabilitated using resistance-exercise training? Results from a preliminary intervention study. J Gerontol A Biol Sci Med Sci. 2003;58(8):746–51.
Hageman PA, Thomas VS. Gait performance in dementia: the effects of a 6-week resistance training program in an adult day-care setting. Int J Geriatr Psychiatry. 2002;17(4):329–34.
Cott CA, Dawson P, Sidani S, Wells D. The effects of a walking/talking program on communication, ambulation, and functional status in residents with Alzheimer disease. Alzheimer Dis Assoc Disord. 2002;16(2):81–7.
Morris R, Lord S, Bunce J, Burn D, Rochester L. Gait and cognition: mapping the global and discrete relationships in ageing and neurodegenerative disease. Neurosci Biobehav Rev. 2016;64:326–45.
de Souto BP, Cesari M, Denormandie P, Armaingaud D, Vellas B, Rolland Y. Exercise or social intervention for nursing home residents with dementia: a pilot randomized, controlled trial. J Am Geriatr Soc. 2017;19:E123–E129.
Vreugdenhil A, Cannell J, Davies A, Razay G. A community-based exercise programme to improve functional ability in people with Alzheimer’s disease: a randomized controlled trial. Scand J Caring Sci. 2012;26(1):12–9.
Steinberg M, Leoutsakos JM, Podewils LJ, Lyketsos CG. Evaluation of a home-based exercise program in the treatment of Alzheimer’s disease: the Maximizing Independence in Dementia (MIND) study. Int J Geriatr Psychiatry. 2009;24(7):680–5.
Holthoff VA, Marschner K, Scharf M, Steding J, Meyer S, Koch R, et al. Effects of physical activity training in patients with Alzheimer’s dementia: results of a pilot RCT study. PLoS One. 2015;10(4):e0121478.
Kwak YS, Um SY, Son TG, Kim DJ. Effect of regular exercise on senile dementia patients. Int J Sports Med. 2008;29(6):471–4.
Karssemeijer EGA, Aaronson JA, Bossers WJR, Donders R, Olde Rikkert MGM, Kessels RPC. The quest for synergy between physical exercise and cognitive stimulation via exergaming in people with dementia: a randomized controlled trial. Alzheimers Res Ther 2019;11(1):3-018-0454-z.
Venturelli M, Scarsini R, Schena F. Six-month walking program changes cognitive and ADL performance in patients with Alzheimer. Am J Alzheimers Dis Other Dement. 2011;26(5):381–8.
Arcoverde C, Deslandes A, Moraes H, Almeida C, Araujo NB, Vasques PE, et al. Treadmill training as an augmentation treatment for Alzheimer’s disease: a pilot randomized controlled study. Arq Neuropsiquiatr. 2014;72(3):190–6.
de Andrade LP, Gobbi LT, Coelho FG, Christofoletti G, Costa JL, Stella F. Benefits of multimodal exercise intervention for postural control and frontal cognitive functions in individuals with Alzheimer’s disease: a controlled trial. J Am Geriatr Soc. 2013;61(11):1919–26.
Hokkanen L, Rantala L, Remes AM, Harkonen B, Viramo P, Winblad I. Dance and movement therapeutic methods in management of dementia: a randomized, controlled study. J Am Geriatr Soc. 2008;56(4):771–2.
Stevens J, Killeen M. A randomised controlled trial testing the impact of exercise on cognitive symptoms and disability of residents with dementia. Contemp Nurse. 2006;21(1):32–40.
Van de Winckel A, Feys H, De Weerdt W, Dom R. Cognitive and behavioural effects of music-based exercises in patients with dementia. Clin Rehabil. 2004;18(3):253–60.
Button KS, Ioannidis JP, Mokrysz C, Nosek BA, Flint J, Robinson ES, et al. Power failure: why small sample size undermines the reliability of neuroscience. Nat Rev Neurosci. 2013;14(5):365–76.
Blankevoort CG, van Heuvelen MJ, Scherder EJ. Reliability of six physical performance tests in older people with dementia. Phys Ther. 2013;93(1):69–78.
Chalfont G, Milligan C, Simpson J. A mixed methods systematic review of multimodal non-pharmacological interventions to improve cognition for people with dementia. Dementia (London). 2018;7:1471301218795289.
Ngandu T, Lehtisalo J, Solomon A, Levalahti E, Ahtiluoto S, Antikainen R, et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015;385(9984):2255–63.
Tait JL, Duckham RL, Milte CM, Main LC, Daly RM. Influence of sequential vs. simultaneous dual-task exercise training on cognitive function in older adults. Front Aging Neurosci. 2017;9:368.
Amieva H, Robert PH, Grandoulier AS, Meillon C, De Rotrou J, Andrieu S, et al. Group and individual cognitive therapies in Alzheimer’s disease: the ETNA3 randomized trial. Int Psychogeriatr. 2016;28(5):707–17.
Woods B, Aguirre E, Spector AE, Orrell M. Cognitive stimulation to improve cognitive functioning in people with dementia. Cochrane Database Syst Rev. 2012;(2):CD005562 doi(2):CD005562.
Doody RS, Massman P, Dunn JK. A method for estimating progression rates in Alzheimer disease. Arch Neurol. 2001;58(3):449–54.
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):1027–37.
Holland D, Desikan RS, Dale AM, McEvoy LK, Alzheimer’s Disease Neuroimaging Initiative. Higher rates of decline for women and apolipoprotein E epsilon4 carriers. AJNR Am J Neuroradiol. 2013;34(12):2287–93.
Gronwald T, Budde H. Commentary: physical exercise as personalized medicine for dementia prevention? Front Physiol. 2019;10:1358.
Nes BM, Janszky I, Wisloff U, Stoylen A, Karlsen T. Age-predicted maximal heart rate in healthy subjects: the HUNT fitness study. Scand J Med Sci Sports. 2013;23(6):697–704.
Westwood AJ, Beiser A, Decarli C, Harris TB, Chen TC, He XM, et al. Insulin-like growth factor-1 and risk of Alzheimer dementia and brain atrophy. Neurology. 2014;82(18):1613–9.
Weinstein G, Beiser AS, Choi SH, Preis SR, Chen TC, Vorgas D, et al. Serum brain-derived neurotrophic factor and the risk for dementia: the Framingham Heart Study. JAMA Neurol. 2014;71(1):55–61.
Moloney AM, Griffin RJ, Timmons S, O’Connor R, Ravid R, O’Neill C. Defects in IGF-1 receptor, insulin receptor and IRS-1/2 in Alzheimer’s disease indicate possible resistance to IGF-1 and insulin signalling. Neurobiol Aging. 2010;31(2):224–43.
Rivera EJ, Goldin A, Fulmer N, Tavares R, Wands JR, de la Monte SM. Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer’s disease: link to brain reductions in acetylcholine. J Alzheimers Dis. 2005;8(3):247–68.