Physical Activity as a Moderator of Alzheimer Pathology: A Systematic Review of Observational Studies

Author(s): Kristian Steen Frederiksen*, Le Gjerum, Gunhild Waldemar, Steen Gregers Hasselbalch.

Journal Name: Current Alzheimer Research

Volume 16 , Issue 4 , 2019

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer

Abstract:

Introduction: Observational studies have found that physical activity is associated with a reduced risk of cognitive decline and dementia. Whether physical activity may also reduce the level of AD pathology, remains undetermined.

Objective: To examine the relationship between physical activity and AD biomarkers (beta-amyloid1- 42, total tau and phosphorylated tau in CSF, amyloid PET, hippocampal atrophy on MRI and parietotemporal hypometabolism on brain 18F-FDG-PET).

Methods: We carried out a systematic review of the observational studies of physical activity and AD biomarkers in healthy subjects, subjective cognitive complaints, mild cognitive impairment (MCI) and AD dementia.

Results: We identified a total of 40 papers, which were eligible for inclusion. Thirty-four studies were conducted on healthy subjects, 3 on MCI and healthy subjects, 1 on MCI, and 2 on AD and healthy controls. Six studies reported on CSF biomarkers, 9 on amyloid PET, 29 on MRI and 4 on brain 18FFDG- PET. The majority of studies did not find a significant association between physical activity and AD biomarkers.

Conclusion: The quality of included studies with only a few longitudinal studies, limits the conclusions which may be drawn from the present findings especially regarding the biomarkers other than hippocampal volume. However, the majority of the identified studies did not find a significant association.

Keywords: Dementia, Alzheimer’s disease, physical activity, exercise, amyloid, hippocampus, tau, MRI.

[1]
Association A. 2017 Alzheimer’s disease facts and figures. Alzheimers Dement 13(4): 325-73. (2017).
[2]
Miech RA, Breitner JCS, Zandi PP, Khachaturian AS, Anthony JC. Incidence of AD may decline in the early 90s for men, later for women. Neurology 58: 209-18. (2002).
[3]
Kukull WA, Higdon R, Bowen JD, McCormick WC, Teri L, Schellenberg GD, et al. Dementia and Alzheimer disease incidence: a prospective cohort study. Arch Neurol 59(11): 1737-46. (2002).
[4]
Prince M, Wimo A, Guerchet M, Gemma-Claire A, Wu Y-T, Prina M. World Alzheimer Report 2015: The global impact of dementia - an analysis of prevalence, incidence, cost and trends. Alzheimer’s Dis Int 84: (2015).
[5]
Bateman RJ, Benzinger TL, Berry S, Clifford DB, Duggan C, Fagan AM, et al. The DIAN-TU next generation Alzheimer’s prevention trial: adaptive design and disease progression model. Alzheimers Dement 13(1): 8-19. (2017).
[6]
Sperling RA, Rentz DM, Johnson KA, Karlawish J, Donohue M, Salmon DP, et al. The A4 study: stopping ad before symptoms begin? Sci Transl Med 6(228): 228fs13-228fs13 (2014).
[7]
Marengoni A, Rizzuto D, Fratiglioni L, Antikainen R, Laatikainen T, Lehtisalo J, et al. The Effect of a 2-year intervention consisting of diet, physical exercise, cognitive training, and monitoring of vascular risk on chronic morbidity-the finger randomized controlled trial. J Am Med Dir Assoc 19(4): 355-360.e1. (2018).
[8]
Köbe T, Witte AV, Schnelle A, Lesemann A, Fabian S, Tesky VA, et al. Combined omega-3 fatty acids, aerobic exercise and cognitive stimulation prevents decline in gray matter volume of the frontal, parietal and cingulate cortex in patients with mild cognitive impairment. Neuroimage 131: 22638. (2016).
[9]
Tay L, Lim WS, Chan M, Ali N, Chong MS. A combined cognitive stimulation and physical exercise programme (mindvital) in early dementia: differential effects on single- and dual-task gait performance. Gerontology 62(6): 604-10. (2016).
[10]
Baker LD, Frank LL, Foster-Schubert K, Green PS, Wilkinson CW, McTiernan A, et al. Effects of aerobic exercise on mild cognitive impairment. Arch Neurol 67(1): 71-9. (2010).
[11]
Nguyen J, Suarez A, Le Saout E, Meignier M, Nizard J, Lefaucheur J. Brain Stimulation Combining cognitive training and multi-site rTMS to improve cognitive functions in Alzheimer ’ s disease. Brain Stimul 12. (2018).
[12]
Bayer-Carter JL, Green PS, Montine TJ, VanFossen B, Baker LD, Watson GS, et al. Diet intervention and cerebrospinal fluid biomarkers in amnestic mild cognitive impairment. Arch Neurol 68(6): 743-52. (2011).
[13]
Scheltens P, Kamphuis PJGH, Verhey FRJ, Olde Rikkert MGM, Wurtman RJ, Wilkinson D, et al. Efficacy of a medical food in mild Alzheimer’s disease: a randomized, controlled trial. Alzheimers Dement 6(1): 1-10.e1. (2010).
[14]
Krikorian R, Shidler MD. Nash T a, Kalt W, Vinqvist-Tymchuk MR, Shukitt-Hale B, et al. Blueberry supplementation improves memory in older adults. J Agric Food Chem 58(7): 3996-4000. (2010).
[15]
Sofi F, Valecchi D, Bacci D, Abbate R, Gensini GF. Casini a, et al. Physical activity and risk of cognitive decline: a meta-analysis of prospective studies. J Intern Med 269(1): 107-17. (2011).
[16]
Xu W, Wang HF, Wan Y, Tan C-C, Yu J-T, Tan L. Leisure time physical activity and dementia risk: a dose-response meta-analysis of prospective studies. BMJ Open 7(10): e014706. (2017).
[17]
Barnes D, Yaffe K. The projected impact of risk factor reduction on Alzheimer’s disease prevalence. Lancet Neurol 10(9): 819-28. (2013).
[18]
Livingston G, Sommerlad A, Orgeta V, Costafreda SG, Huntley J, Ames D, et al. Dementia prevention, intervention, and care. Lancet 390(10113): 2673-34. (2017).
[19]
Yuede CM, Zimmerman SD, Dong H, Kling MJ, Bero AW, Holtzman DM, et al. Effects of voluntary and forced exercise on plaque deposition, hippocampal volume, and behavior in the Tg2576 mouse model of Alzheimer’s disease. Neurobiol Dis 35(3): 426-32. (2009).
[20]
Um HS, Kang EB, Leem YH, Cho IH, Yang CH, Chae KR, et al. Exercise training acts as a therapeutic strategy for reduction of the pathogenic phonetypes for Alzheimer’s disease in an NSE/APPSw-transgenic model. Int J Mol Med 22(4): 529-39. (2008).
[21]
Adlard P, Perreau VM, Pop V, Cotman CW. Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer’s disease. J Neurosci 25(17): 4217-21. (2005).
[22]
Kang E, Cho J. Effect of treadmill exercise on PI3K/AKT/mTOR, autophagy, and Tau hyperphosphorylation in the cerebral cortex of NSE/htau23 transgenic mice. J Exerc Nutrition Biochem 19(3): 199-209. (2015).
[23]
Jack CR, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, et al. Updated hypothetical model of dynamic biomarkers. Lancet Neurol 12(2): 207-16. (2013).
[24]
Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, et al. Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. Lancet Neurol 6(8): 734-46. (2007).
[25]
Dubois B, Feldman HH, Jacova C, Cummings JL, Dekosky ST, Barberger-Gateau P, et al. Revising the definition of Alzheimer’s disease: a new lexicon. Lancet Neurol 9(11): 1118-27. (2010).
[26]
Cummings JL, Dubois B, Molinuevo JL, Scheltens P. International Work Group criteria for the diagnosis of Alzheimer disease. Med Clin North Am 97(3): 363-8. (2013).
[27]
Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, et al. Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol 13(6): 614-29. (2014).
[28]
Bateman RJ, Xiong C, Benzinger TLS, Fagan AM, Goate A, Fox NC, et al. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med 367(9): 795-804. (2012).
[29]
Cabral D, Beach TG, Vedders L, Sue LI, Jacobson S, Myers K, et al. Frequency of Alzheimer’s disease pathology at autopsy in patients with clinical normal pressure hydrocephalus. Alzheimers Dement 7(5): 509-13. (2011).
[30]
Frederiksen KS, Gjerum L, Waldemar G, Hasselbalch SG. Effects of physical exercise on Alzheimer’s disease biomarkers: a systematic review of intervention studies. J Alzheimers Dis 61(1): 359-72. (2017).
[31]
Groot C, Hooghiemstra AM, Raijmakers PGHM, van Berckel BNM, Scheltens P, Scherder EJA, et al. The effect of physical activity on cognitive function in patients with dementia: a meta-analysis of randomized control trials (2016).
[32]
Forbes D, Forbes S, Morgan DG, Markle-Reid M, Wood J, Culum I. Physical activity programs for persons with dementia. Cochrane Database Syst Rev (3): CD006489. (2008).
[33]
Forbes D, Forbes SC, Blake CM, Thiessen EJ, Forbes S. Exercise programs for people with dementia. Cochrane Database Syst Rev 4: CD006489. (2015).
[34]
Jensen CS, Hasselbalch SG, Waldemar G, Simonsen AH. Biochemical markers of physical exercise on mild cognitive impairment and dementia: systematic review and perspectives. Front Neurol 6(Aug): 1-10. (2015).
[35]
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 62(10): 1006-12. (2009).
[36]
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 7(3): 270-9. (2011).
[37]
Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7(3): 280-92. (2011).
[38]
Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 56(3): 303-8. (1999).
[39]
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group* under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 34(7): 939-39. (1984).
[40]
McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR, Kawas CH, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging and the Alzheimer’s Association workgroup. Alzheimers Dement 7(3): 263-9. (2011).
[41]
Available from: https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools last on the 27th of March 2018).
[42]
Schlaffke L, Lissek S, Lenz M, Brüne M, Juckel G, Hinrichs T, et al. Sports and brain morphology - A voxel-based morphometry study with endurance athletes and martial artists. Neuroscience 259(2014): 35-42 (2014).
[43]
Rottensteiner M, Leskinen T, Niskanen E, Aaltonen S, Mutikainen S, Wikgren J, et al. Physical activity, fitness, glucose homeostasis, and brain morphology in twins. Med Sci Sports Exerc 47(3): 509-18. (2014).
[44]
Tseng BY, Uh J, Rossetti HC, Cullum CM, Diaz-Arrastia RF, Levine BD, et al. Masters athletes exhibit larger regional brain volume and better cognitive performance than sedentary older adults. J Magn Reson Imaging 38(5): 1169-76. (2013).
[45]
Erickson KI, Raji CA, Lopez OL, Becker JT, Rosano C, Newman AB, et al. Physical activity predicts gray matter volume in late adulthood: The cardiovascular health study. Neurology 75(16): 141522. (2010).
[46]
Vidoni ED, Honea R, Billinger S, Swerdlow RH, Burns JM. Cardiorespiratory fitness is associated with atrophy in Alzheimer’s and aging over 2 years. Neurobiol Aging 33(8): 1624-32. (2012).
[47]
Smith JC, Nielson KA, Woodard JL, Seidenberg M, Durgerian S, Hazlett KE, et al. Physical activity reduces hippocampal atrophy in elders at genetic risk for Alzheimer’s disease. Front Aging Neurosci 6(APR): 1-7. (2014).
[48]
Vemuri P, Lesnick TG. Przybelski S a., Knopman DS, Roberts RO, Lowe VJ, et al. Effect of lifestyle activities on AD biomarkers and cognition. Ann Neurol (2012).
[49]
Brown BM, Sohrabi HR, Taddei K, Gardener SL, Rainey-Smith SR, Peiffer JJ, et al. Habitual exercise levels are associated with cerebral amyloid load in presymptomatic autosomal dominant Alzheimer’s disease. Alzheimers Dement 1-10. (2017).
[50]
Yamamoto M, Wada-Isoe K, Yamashita F, Nakashita S, Kishi M, Tanaka K, et al. Association between exercise habits and subcortical gray matter volumes in healthy elderly people: A population-based study in Japan. Neurological Sci 7: 1-6. (2017).
[51]
Killgore WDS, Olson EA, Weber M. Physical exercise habits correlate with gray matter volume of the hippocampus in healthy adult humans. Sci Rep 3(1): 3457. (2013).
[52]
Head D, Bugg JM, Goate AM, Fagan AM, Mintun MA, Benzinger T, et al. Exercise engagement as a moderator of the effects of apoe genotype on amyloid deposition. Arch Neurol E1-8. (2012).
[53]
Schultz SA, Boots EA, Almeida RP, Oh JM, Einerson J, Korcarz CE, et al. Cardiorespiratory fitness attenuates the influence of amyloid on cognition. J Int Neuropsychol Soc 21(10): 841-50. (2015).
[54]
Liang KY. Mintun M a, Fagan AM, Goate AM, Bugg JM, Holtzman DM, et al. Exercise and Alzheimer’s disease biomarkers in cognitively normal older adults. Ann Neurol 68(3): 311-8. (2010).
[55]
Baker LD, Bayer-Carter JL, Skinner J, Montine TJ, Cholerton BA, Callaghan M, et al. High-intensity physical activity modulates diet effects on cerebrospinal amyloid-β levels in normal aging and mild cognitive impairment. J Alzheimers Dis 28(1): 137-46. (2012).
[56]
Schultz SA, Boots EA, Darst BF, Zetterberg H, Blennow K, Edwards DF, et al. Cardiorespiratory fitness alters the influence of a polygenic risk score on biomarkers of AD. Neurology 88(17): 1650-8. (2017).
[57]
De Souto Barreto P, Andrieu S, Payoux P, Demougeot L, Rolland Y, Vellas B. Physical activity and amyloid-beta brain levels in elderly adults with intact cognition and mild cognitive impairment. J Am Geriatr Soc 63(8): 1634-9. (2015).
[58]
Brown BM, Peiffer JJ, Taddei K, Lui JK, Laws SM, Gupta VB, et al. Physical activity and amyloid-β plasma and brain levels: results from the Australian imaging, biomarkers and lifestyle study of ageing. Mol Psychiatry 18(8): 875-81. (2013).
[59]
Okonkwo OC, Schultz S, Oh JM, Larson J, Edwards D, Cook D, et al. Physical activity attenuates age-related biomarker alterations in preclinical AD. Neurology 83(19): 1753-60. (2014).
[60]
Wirth M, Haase CM, Villeneuve S, Vogel J, Jagust WJ. Neuroprotective pathways: lifestyle activity, brain pathology, and cognition in cognitively normal older adults. Neurobiol Aging 35(8): 1873-82. (2014).
[61]
Varma VR, Chuang Y, Harris GC, Tan EJ, Carlson MC. Low-intensity daily walking activity is associated with hippocampal volume in older adults. Hippocampus 25(5): 605-5. (2015).
[62]
Demirakca T, Brusniak W, Tunc-Skarka N, Wolf I, Meier S, Matthäus F, et al. Does body shaping influence brain shape? Habitual physical activity is linked to brain morphology independent of age. World J Biol Psychiatry 2975: 1-10. (2014).
[63]
Szabo AN, McAuley E, Erickson KI, Voss M, Prakash RS, Mailey EL, et al. Cardiorespiratory fitness, hippocampal volume, and frequency of forgetting in older adults. Neuropsychology 25(5): 545-53. (2011).
[64]
Boots EA, Schultz SA, Oh JM, Larson J, Edwards D, Cook D, et al. Cardiorespiratory fitness is associated with brain structure, cognition, and mood in a middle-aged cohort at risk for Alzheimer’s disease. Brain Imaging Behav 9(3): 639-49. (2015).
[65]
Doi T, Makizako H, Shimada H, Tsutsumimoto K, Hotta R, Nakakubo S, et al. Objectively measured physical activity, brain atrophy, and white matter lesions in older adults with mild cognitive impairment. Exp Gerontol 62: 1-6. (2015).
[66]
Honea RA, Thomas GP, Harsha A, Anderson HS, Donnelly JE, Brooks WM, et al. Cardiorespiratory fitness and preserved medial temporal lobe volume in Alzheimer disease. Alzheimer Dis Assoc Disord 23(3): 188-97. (2009).
[67]
Makizako H, Liu-Ambrose T, Shimada H, Doi T, Park H, Tsutsumimoto K, et al. Moderate-intensity physical activity, hippocampal volume, and memory in older adults with mild cognitive impairment. Journals Gerontol Ser A Biol Sci. Med Sci 70(4): 480-6. (2015).
[68]
Tan ZS, Spartano NL, Beiser AS, DeCarli C, Auerbach SH, Vasan RS, et al. Physical Activity, brain volume, and dementia risk: the framingham study. J Gerontol Ser A Biol Sci Med Sci 17(3): glw130. (2016).
[69]
Tian Q, Studenski SA, Resnick SM, Davatzikos C, Ferrucci L. midlife and late-life cardiorespiratory fitness and brain volume changes in late adulthood: results from the baltimore longitudinal study of aging. J Gerontol Ser A Biol Sci Med Sci 71(1): 124-30. (2016).
[70]
Lamont AJ, Mortby ME, Anstey KJ, Sachdev PS, Cherbuin N. Using sulcal and gyral measures of brain structure to investigate benefits of an active lifestyle. Neuroimage 91: 353-9. (2014).
[71]
Brown BM, Bourgeat P, Peiffer JJ, Burnham S, Laws SM, Rainey-Smith SR, et al. Influence of BDNF Val66Met on the relationship between physical activity and brain volume. Neurology 83(15): 1345-52. (2014).
[72]
Benedict C, Brooks SJ, Kullberg J, Nordenskjöld R, Burgos J, Le Grevès M, et al. Association between physical activity and brain health in older adults. Neurobiol Aging 34(1): 83-90. (2013).
[73]
Head D, Singh T, Bugg JM. The moderating role of exercise on stress-related effects on the hippocampus and memory in later adulthood. Neuropsychology 26(2): 133-43. (2012).
[74]
Ho AJ, Raji CA, Becker JT, Lopez OL, Kuller LH, Hua X, et al. The effects of physical activity, education, and body mass index on the aging brain. Hum Brain Mapp 32(9): 1371-82. (2011).
[75]
Bugg JM, Head D. Exercise moderates age-related atrophy of the medial temporal lobe. Neurobiol Aging 32(3): 506-14. (2011).
[76]
Smith JC, Nielson KA, Woodard JL, Seidenberg M, Durgerian S, Antuono P, et al. Interactive effects of physical activity and APOE-ε4 on BOLD semantic memory activation in healthy elders. Neuroimage 54(1): 635-44. (2011).
[77]
Flöel A, Ruscheweyh R, Krüger K, Willemer C, Winter B, Völker K, et al. Physical activity and memory functions: Are neurotrophins and cerebral gray matter volume the missing link? Neuroimage 49(3): 2756-63. (2010).
[78]
Peters J, Dauvermann M, Mette C, Platen P, Franke J, Hinrichs T, et al. Voxel-based morphometry reveals an association between aerobic capacity and grey matter density in the right anterior insula Neuroscience163(4): 1102-08 (2009).
[79]
Gordon BA, Rykhlevskaia EI, Brumback CR, Lee Y, Elavsky S, Konopack JF, et al. Neuroanatomical correlates of aging, cardiopulmonary fitness level, and education. Psychophysiology 45(5): 825-38. (2008).
[80]
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 58(2): 176-80. (2003).
[81]
Sakurai R, Fujiwara Y, Yasunaga M, Takeuchi R, Murayama Y, Ohba H, et al. Regional cerebral glucose metabolism and gait speed in healthy community-dwelling older women. JGerontolA BiolSciMedSci 69(1758-535X (Electronic)): 1519-27 (2014).
[82]
Deeny SP, Winchester J, Nichol K, Roth SM, Wu JC, Dick M, et al. Cardiovascular fitness is associated with altered cortical glucose metabolism during working memory in ε4 carriers. Alzheimers Dement 8(4): 352-6. (2012).
[83]
Jack CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA research framework: Toward a biological definition of Alzheimer’s disease. Alzheimers Dement 14(4): 535-62. (2018).
[84]
Winter B, Breitenstein C, Mooren FC, Voelker K, Fobker M, Lechtermann A, et al. High impact running improves learning. Neurobiol Learn Mem 87(4): 597-609. (2007).
[85]
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).
[86]
Hörder H, Johansson L, Guo X, Grimby G, Kern S, Östling S, et al. Midlife cardiovascular fitness and dementia. Neurology 0: 10.1212/WNL.0000000000005290 (2018).
[87]
Andel R, Crowe M, Pedersen NL, Fratiglioni L, Johansson B, Gatz M. Physical exercise at midlife and risk of dementia three decades later: a population-based study of Swedish twins. J Gerontol- Ser A Biol Sci Med Sci 63(1): 62-6. (2008).
[88]
Mattsson N, Insel PS, Donohue M, Landau S, Jagust WJ, Shaw LM, et al. Independent information from cerebrospinal fluid amyloid- b and florbetapir imaging in Alzheimer ’ s disease. Brain 2014: 772-83. (2015).
[89]
Ossenkoppele R, Jansen WJ, Rabinovici GD, Knol DL, van der Flier WM, van Berckel BNM, et al. Prevalence of amyloid PET positivity in dementia syndromes. JAMA 313(19): 1939. (2015).
[90]
Jansen WJ, Ossenkoppele R, Knol DL, Tijms BM, Scheltens P, Verhey FRJ, et al. Prevalence of cerebral amyloid pathology in persons without dementia JAMA313(19): 1924 (2015).
[91]
Nigam SM, Xu S, Kritikou JS, Marosi K, Brodin L, Mattson MP. Exercise and BDNF reduce Aβ production by enhancing α-secretase processing of APP. J Neurochem 142(2): 286-96. (2017).
[92]
Alkadhi KA, Dao AT. Exercise decreases BACE and APP levels in the hippocampus of a rat model of Alzheimer’s disease Mol Cell Neurosci 86 (February 2017): 25-29 (2018).
[93]
Moore KM, Girens RE, Larson SK, Jones MR, Restivo JL, Holtzman DM, et al. A spectrum of exercise training reduces soluble Aβ in a dose-dependent manner in a mouse model of Alzheimer’s disease. Neurobiol Dis 85: 218-24. (2016).
[94]
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 56(1): 297-303. (2017).
[95]
Solomon A, Turunen H, Ngandu T, Peltonen M, Levälahti E, Helisalmi S, et al. Effect of the apolipoprotein e genotype on cognitive change during a multidomain lifestyle intervention a subgroup analysis of a randomized clinical trial. JAMA Neurol 75(4): 462-70. (2018).
[96]
Soto I, Graham LC, Richter HJ, Simeone SN, Radell JE, Grabowska W, et al. APOE Stabilization by exercise prevents aging neurovascular dysfunction and complement induction. PLoS Biol 13(10): 1-33. (2015).
[97]
Huijgen J, Samson S. The hippocampus:a central node in a large-scale brain network for memory. Rev Neurol (Paris) 171(3): 204-16. (2015).
[98]
Smith JC, Nielson KA, Antuono P, Lyons J-A, Hanson RJ, Butts AM, et al. Semantic memory functional MRI and cognitive function after exercise intervention in mild cognitive impairment. J Alzheimers Dis 37(1): 197-215. (2013).
[99]
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 2(AUG): 1-17. (2010).
[100]
Chirles TJ, Reiter K, Weiss LR, Alfini AJ, Nielson KA, Smith JC. Exercise training and functional connectivity changes in mild cognitive impairment and healthy elders. J Alzheimers Dis 57(3): 845-56. (2017).
[101]
Groot C, Hooghiemstra AM. Raijmakers P, van Berckel B, Scheltens P, Scherder E, van der Flier W, et al. The effect of physical activity on cognitive function in patients with dementia: A meta-analysis of randomized control trials. Ageing Res Rev 25(2016): 13-23 (2016).
[102]
Heyn P, Abreu BC, Ottenbacher KJ. The effects of exercise training on elderly persons with cognitive impairment and dementia: a meta-analysis. Arch Phys Med Rehabil 85(10): 1694-704. (2004).
[103]
Frederiksen KS, Larsen CT, Hasselbalch SG, Christensen AN, Høgh P, Wermuth L, et al. A 16-week aerobic exercise intervention does not affect hippocampal volume and cortical thickness in mild to moderate alzheimer’s disease. Front Aging Neurosci 10: 1-10. (2018).
[104]
Hoffmann K. Sobol N a., Frederiksen KS, Beyer N, Vogel A, Vestergaard K, et al. Moderate-to-high intensity physical exercise in patients with Alzheimer’s disease: a randomized controlled trial. J Alzheimers Dis 50(2): 443-53. (2015).
[105]
Frederiksen KS, Verdelho A, Madureira S, Bäzner H, O’Brien JT, Fazekas F, et al. Physical activity in the elderly is associated with improved executive function and processing speed: the LADIS Study. Int J Geriatr Psychiatry (2014).
[106]
Deeny SP, Poeppel D, Zimmerman JB, Roth SM, Brandauer J, Witkowski S, et al. Exercise, APOE, and working memory: MEG and behavioral evidence for benefit of exercise in epsilon4 carriers. Biol Psychol 78(2): 179-87. (2008).
[107]
Roseman M, Milette K, Bero LA, Coyne JC, Lexchin J, Turner EH, et al. Reporting of conflicts of interest in meta-analyses of trials of pharmacological treatments. JAMA 305(10): 1008-17. (2011).


Rights & PermissionsPrintExport Cite as


Article Details

VOLUME: 16
ISSUE: 4
Year: 2019
Page: [362 - 378]
Pages: 17
DOI: 10.2174/1567205016666190315095151
Price: $58

Article Metrics

PDF: 29
HTML: 3
EPUB: 1
PRC: 1