Bull MJ. Down syndrome. N Engl J Med. 2020;382(24):2344–52.

Article  PubMed  Google Scholar 

De Graaf G, Buckley F, Skotko BG. Estimation of the number of people with Down syndrome in the United States. Genet Med. 2017;19(4):439.

Article  PubMed  Google Scholar 

Englund A, Jonsson B, Zander CS, Gustafsson J, Annerén G. Changes in mortality and causes of death in the Swedish Down syndrome population. Am J Med Genet A. 2013;161(4):642–9.

Article  Google Scholar 

Fortea J, Vilaplana E, Carmona-Iragui M, Benejam B, Videla L, Barroeta I, et al. Clinical and biomarker changes of Alzheimer’s disease in adults with Down syndrome: a cross-sectional study. Lancet. 2020;395(10242):1988–97.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fortea J, Zaman SH, Hartley S, Rafii MS, Head E, Carmona-Iragui M. Alzheimer’s disease associated with Down syndrome: a genetic form of dementia. Lancet Neurology. 2021;20(11):930–42.

Article  CAS  PubMed  Google Scholar 

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.

Article  CAS  PubMed  Google Scholar 

Bherer L, Erickson KI, Liu-Ambrose T. A review of the effects of physical activity and exercise on cognitive and brain functions in older adults. J Aging Res. 2013;2013.

España-Irla G, Gomes-Osman J, Cattaneo G, Albu S, Cabello-Toscano M, Solana-Sanchéz J, et al. Associations between cardiorespiratory fitness, cardiovascular risk, and cognition are mediated by structural brain health in midlife. J Am Heart Assoc. 2021;10(18):e020688.

Article  PubMed  PubMed Central  Google Scholar 

Nianogo RA, Rosenwohl-Mack A, Yaffe K, Carrasco A, Hoffmann CM, Barnes DE. Risk factors associated with Alzheimer disease and related dementias by sex and race and ethnicity in the US. JAMA Neurol. 2022;79(6):584–91.

Article  PubMed  PubMed Central  Google Scholar 

DeFina LF, Willis BL, Radford NB, Gao A, Leonard D, Haskell WL, et al. The association between midlife cardiorespiratory fitness levels and later-life dementia: a cohort study. Ann Intern Med. 2013;158(3):162–8.

Article  PubMed  PubMed Central  Google Scholar 

Ou Y-N, Tan C-C, Shen X-N, Xu W, Hou X-H, Dong Q, et al. Blood pressure and risks of cognitive impairment and dementia: a systematic review and meta-analysis of 209 prospective studies. Hypertension. 2020;76(1):217–25.

Article  CAS  PubMed  Google Scholar 

Whalley LJ, Deary IJ, Appleton CL, Starr JM. Cognitive reserve and the neurobiology of cognitive aging. Ageing Res Rev. 2004;3(4):369–82.

Article  PubMed  Google Scholar 

Fleming V, Piro-Gambetti B, Patrick A, Zammit M, Alexander A, Christian BT, et al. Physical activity and cognitive and imaging biomarkers of Alzheimer’s disease in down syndrome. Neurobiol Aging. 2021;107:118–27.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pape SE, Baksh RA, Startin C, Hamburg S, Hithersay R, Strydom A. The association between physical activity and CAMDEX-DS changes prior to the onset of Alzheimer’s disease in Down Syndrome. J Clin Med. 2021;10(9):1882.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ptomey LT, Szabo-Reed AN, Martin LE, Mayo MS, Washburn RA, Gorczyca AM, et al. The promotion of physical activity for the prevention of Alzheimer’s disease in adults with Down syndrome: rationale and design for a 12 month randomized trial. Contemp Clin Trials Commun. 2020;19:100607.

Article  PubMed  PubMed Central  Google Scholar 

Deb S, Hare M, Prior L, Bhaumik S. Dementia screening questionnaire for individuals with intellectual disabilities. Br J Psychiatry. 2007;190:440–4.

Article  PubMed  Google Scholar 

Flint AC, Conell C, Ren X, Banki NM, Chan SL, Rao VA, et al. Effect of systolic and diastolic blood pressure on cardiovascular outcomes. N Engl J Med. 2019;381(3):243–51.

Article  PubMed  Google Scholar 

Kannel W, Dawber T, McGee D. Perspectives on systolic hypertension The Framingham study. Circulation. 1980;61(6):1179–82.

Article  CAS  PubMed  Google Scholar 

Fernhall B, McCubbin JA, Pitetti KH, Rintala P, Rimmer JH, Millar AL, et al. Prediction of maximal heart rate in individuals with mental retardation. Med Sci Sports Exerc. 2001;33(10):1655–60.

Article  CAS  PubMed  Google Scholar 

Choi L, Liu Z, Matthews CE, Buchowski MS. Validation of accelerometer wear and nonwear time classification algorithm. Med Sci Sports Exerc. 2011;43(2):357.

Article  PubMed  PubMed Central  Google Scholar 

Masse LC, Fuemmeler BF, Anderson CB, Matthews CE, Trost SG, Catellier DJ, et al. Accelerometer data reduction: a comparison of four reduction algorithms on select outcome variables. Medicine & Science in Sports & Exercise. 2005;37(11 (Suppl)):S544-S54.

Troiano RP, Berrigan D, Dodd KW, Masse LC, Tilert T, McDowell M. Physical activity in the United States measured by accelerometer. Med Sci Sports Exerc. 2008;40(1):181–8.

Article  PubMed  Google Scholar 

Matthews CE, Chen KY, Freedson PS, Buchowski MS, Beech BM, Pate RR, et al. Amount of time spent in sedentary behaviors in the United States, 2003–2004. American Journal of Epidemiology. 2008;167:875–81.

Falconer DW, Cleland J, Fielding S, Reid IC. Using the Cambridge Neuropsychological Test Automated Battery (CANTAB) to assess the cognitive impact of electroconvulsive therapy on visual and visuospatial memory. Psychol Med. 2010;40(6):1017–25.

Article  CAS  PubMed  Google Scholar 

Soares FC, de Oliveira TC, de Macedo LD, Tomas AM, Picanco-Diniz DL, Bento-Torres J, et al. CANTAB object recognition and language tests to detect aging cognitive decline: an exploratory comparative study. Clin Interv Aging. 2015;10:37–48.

PubMed  Google Scholar 

Cooper S-A, Caslake M, Evans J, Hassiotis A, Jahoda A, McConnachie A, et al. Toward onset prevention of cognitive decline in adults with Down syndrome (the TOP-COG study): study protocol for a randomized controlled trial. Trials. 2014;15(1):202-.

Vicari S, Pontillo M, Armando M. Neurodevelopmental and psychiatric issues in Down’s syndrome: assessment and intervention. Psychiatr Genet. 2013;23(3):95–107.

Article  CAS  PubMed  Google Scholar 

Égerházi A, Berecz R, Bartók E, Degrell I. Automated Neuropsychological Test Battery (CANTAB) in mild cognitive impairment and in Alzheimer’s disease. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31(3):746–51.

Article  PubMed  Google Scholar 

Jakobsen LH, Sorensen JM, Rask IK, Jensen BS, Kondrup J. Validation of reaction time as a measure of cognitive function and quality of life in healthy subjects and patients. Nutrition. 2011;27(5):561–70.

Article  PubMed  Google Scholar 

Deary IJ, Der G. Reaction time, age, and cognitive ability: longitudinal findings from age 16 to 63 years in representative population samples. Aging Neuropsychol Cogn. 2005;12(2):187–215.

Article  Google Scholar 

Prabu Kumar A, Omprakash A, Kuppusamy M, K.N M, B.W.C S, P.V V, et al. How does cognitive function measured by the reaction time and critical flicker fusion frequency correlate with the academic performance of students? BMC Medical Education. 2020;20(1):507.

R Core Team. R: a language and environment for statistical computing [R Foundation for Statistical Computing]. Vienna, Austria; [cited 2022. Available from: https://www.R-project.org/.

Beck VDY, Baynard T, Lefferts EC, Hibner BA, Fernhall B, Hilgenkamp TIM. Anthropometry does not fully explain low fitness among adults with Down syndrome. J Intellect Disabil Res. 2021;65(4):373–9.

Article  CAS  PubMed  Google Scholar 

Fernhall B, Mendonca GV, Baynard T. Reduced work capacity in individuals with Down syndrome: a consequence of autonomic dysfunction? Exerc Sport Sci Rev. 2013;41(3):138–47.

Article  PubMed  Google Scholar 

Hilgenkamp TI, Wee SO, Schroeder EC, Baynard T, Fernhall B. Peripheral blood flow regulation in response to sympathetic stimulation in individuals with Down syndrome. Artery research. 2018;24:16–21.

Article  PubMed  PubMed Central  Google Scholar 

Rodrigues AN, Coelho LC, Goncalves WL, Gouvea SA, Vasconcellos MJ, Cunha RS, et al. Stiffness of the large arteries in individuals with and without Down syndrome. Vasc Health Risk Manag. 2011;7:375–81.

Article  PubMed  PubMed Central  Google Scholar 

Wang C-Y, Haskell WL, Farrell SW, LaMonte MJ, Blair SN, Curtin LR, et al. Cardiorespiratory fitness levels among US adults 20–49 years of age: findings from the 1999–2004 National Health and Nutrition Examination Survey. Am J Epidemiol. 2010;171(4):426–35.

Article  PubMed  Google Scholar 

Hilgenkamp TIM, Wee SO, Schroeder EC, Baynard T, Fernhall B. Peripheral blood flow regulation in response to sympathetic stimulation in individuals with Down syndrome. Artery Res. 2018;24:16–21.

Article  PubMed  PubMed Central  Google Scholar 

Wee SO, Pitetti KH, Goulopoulou S, Collier SR, Guerra M, Baynard T. Impact of obesity and Down syndrome on peak heart rate and aerobic capacity in youth and adults. Res Dev Disabil. 2015;36c:198–206.

Palta P, Albert MS, Gottesman RF. Heart health meets cognitive health: evidence on the role of blood pressure. Lancet Neurol. 2021;20(10):854–67.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Iadecola C, Gottesman RF. Neurovascular and cognitive dysfunction in hypertension. Circ Res. 2019;124(7):1025–44.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zigman WB. Atypical aging in Down syndrome. Dev Disabil Res Rev. 2013;18(1):51–67.

Article  PubMed  Google Scholar 

Lott IT, Head E. Dementia in Down syndrome: unique insights for Alzheimer disease research. Nat Rev Neurol. 2019;15(3):135–47.