Hostname: page-component-586b7cd67f-2plfb Total loading time: 0 Render date: 2024-11-22T06:16:37.101Z Has data issue: false hasContentIssue false
  • English
  • Français

Exercise, Arterial Stiffness, and Cerebral Vascular Function: Potential Impact on Brain Health

Published online by Cambridge University Press:  06 May 2021

Jill N. Barnes Open the ORCID record for Jill N. Barnes [Opens in a new window] ,
Andrew G. Pearson ,
Adam T. Corkery ,
Nicole A. Eisenmann  and
Kathleen B. Miller
Jill N. Barnes*
Affiliation:
Bruno Balke Biodynamics Laboratory, Department of Kinesiology, University of Wisconsin-Madison, Madison, WI53706, USA Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI53705, USA
Andrew G. Pearson
Affiliation:
Bruno Balke Biodynamics Laboratory, Department of Kinesiology, University of Wisconsin-Madison, Madison, WI53706, USA
Adam T. Corkery
Affiliation:
Bruno Balke Biodynamics Laboratory, Department of Kinesiology, University of Wisconsin-Madison, Madison, WI53706, USA
Nicole A. Eisenmann
Affiliation:
Bruno Balke Biodynamics Laboratory, Department of Kinesiology, University of Wisconsin-Madison, Madison, WI53706, USA
Kathleen B. Miller
Affiliation:
Bruno Balke Biodynamics Laboratory, Department of Kinesiology, University of Wisconsin-Madison, Madison, WI53706, USA
*
*Correspondence and reprint requests to: Jill N. Barnes, Ph.D., Department of Kinesiology, University of Wisconsin-Madison, 1300 University Avenue, Madison, WI 53706, USA. Email: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Exercise is associated with higher cognitive function and is a promising intervention to reduce the risk of dementia. With advancing age, there are changes in the vasculature that have important clinical implications for brain health and cognition. Primary aging and vascular risk factors are associated with increases in arterial stiffness and pulse pressure, and reductions in peripheral vascular function.

Objective:

The purpose is to discuss the epidemiological, observational, and mechanistic evidence regarding the link between age-related changes in vascular health and brain health.

Methods:

We performed a literature review and integrated with our published data.

Results:

Epidemiological evidence suggests a link between age-related increases in arterial stiffness and lower cognitive function, which may be mediated by cerebral vascular function, including cerebral vasoreactivity and cerebral pulsatility. Age-associated impairments in central arterial stiffness and peripheral vascular function have been attenuated or reversed through lifestyle behaviors such as exercise. Greater volumes of habitual exercise and higher cardiorespiratory fitness are associated with beneficial effects on both peripheral vascular health and cognition. Yet, the extent to which exercise directly influences cerebral vascular function and brain health, as well as the associated mechanisms remains unclear.

Conclusion:

Although there is evidence that exercise positively impacts cerebral vascular function, more research is necessary in humans to optimize experimental protocols and address methodological limitations and physiological considerations. Understanding the impact of exercise on cerebral vascular function is important for understanding the association between exercise and brain health and may inform future intervention studies that seek to improve cognition.

Keywords

AgingCardiorespiratory fitnessCerebral blood flowCognitive functionEndothelial functionImagingPulsatility
Type
Critical Review
Information
Journal of the International Neuropsychological Society , Volume 27 , Issue 8 , September 2021 , pp. 761 - 775
Copyright
Copyright © INS. Published by Cambridge University Press, 2021

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Ahlskog, J.E., Geda, Y.E., Graff-Radford, N.R., & Petersen, R.C. (2011). Physical exercise as a preventive or disease-modifying treatment of dementia and brain aging. Mayo Clinic Proceedings, 86(9), 876–884. doi: 10.4065/mcp.2011.0252.CrossRefGoogle Scholar
Albrecht, D., Isenberg, A.L., Stradford, J., Monreal, T., Sagare, A., Pachicano, M., … Pa, J. (2020). Associations between Vascular Function and Tau PET Are Associated with Global Cognition and Amyloid. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 40(44), 8573–8586. doi: 10.1523/JNEUROSCI.1230-20.2020.CrossRefGoogle ScholarPubMed
Alfini, AJ., Weiss, L.R., Nielson, K.A., Verber, M.D., & Smith, J.C. (2019). Resting cerebral blood flow after exercise training in mild cognitive impairment. Journal of Alzheimer’s Disease: JAD, 67(2), 671–684. doi: 10.3233/JAD-180728.CrossRefGoogle ScholarPubMed
Allen, A. & Messier, C. (2013). Plastic changes in the astrocyte GLUT1 glucose transporter and beta-tubulin microtubule protein following voluntary exercise in mice. Behavioural Brain Research, 240, 95–102. doi: 10.1016/j.bbr.2012.11.025.CrossRefGoogle ScholarPubMed
Arrick, D.M., Yang, S., Li, C., Cananzi, S., & Mayhan, W.G. (2014). Vigorous exercise training improves reactivity of cerebral arterioles and reduces brain injury following transient focal ischemia. Microcirculation, 21(6), 516–523. doi: 10.1111/micc.12127.CrossRefGoogle ScholarPubMed
Arvanitakis, Z., Capuano, A.W., Leurgans, S.E., Bennett, D.A., & Schneider, J.A. (2016). Relation of cerebral vessel disease to Alzheimer’s disease dementia and cognitive function in elderly people: a cross-sectional study. Lancet Neurology, 15(9), 934–943. doi: 10.1016/S1474-4422(16)30029-1.CrossRefGoogle ScholarPubMed
Ashor, A.W., Lara, J., Siervo, M., Celis-Morales, C., & Mathers, J.C. (2014). Effects of exercise modalities on arterial stiffness and wave reflection: a systematic review and meta-analysis of randomized controlled trials. PLoS One, 9(10), e110034. doi: 10.1371/journal.pone.0110034.CrossRefGoogle ScholarPubMed
Bailey, D.M., Marley, C.J., Brugniaux, J.V., Hodson, D., New, K.J., Ogoh, S., & Ainslie, P.N. (2013). Elevated aerobic fitness sustained throughout the adult lifespan is associated with improved cerebral hemodynamics. Stroke; A Journal of Cerebral Circulation, 44(11), 3235–3238. doi: 10.1161/STROKEAHA.113.002589.CrossRefGoogle ScholarPubMed
Bakker, S.L., de Leeuw, F.E., den Heijer, T., Koudstaal, P.J., Hofman, A., & Breteler, M.M. (2004). Cerebral haemodynamics in the elderly: the Rotterdam study. Neuroepidemiology, 23(4), 178–184. doi: 10.1159/000078503.CrossRefGoogle ScholarPubMed
Barnes, J.N., Harvey, R.E., Zuk, S.M., Lundt, E.S., Lesnick, T.G., Gunter, J.L., … Kantarci, K. (2017). Aortic hemodynamics and white matter hyperintensities in normotensive postmenopausal women. Journal of Neurology, 264(5), 938–945. doi: 10.1007/s00415-017-8476-1.CrossRefGoogle ScholarPubMed
Barnes, J.N., Schmidt, J.E., Nicholson, W.T., & Joyner, M.J. (2012). Cyclooxygenase inhibition abolishes age-related differences in cerebral vasodilator responses to hypercapnia. Journal of Applied Physiology, 112(11), 1884–1890. doi: 10.1152/japplphysiol.01270.2011.CrossRefGoogle ScholarPubMed
Barnes, J.N., Taylor, J.L., Kluck, B.N., Johnson, C.P., & Joyner, M.J. (2013). Cerebrovascular reactivity is associated with maximal aerobic capacity in healthy older adults. Journal of Applied Physiology, 114(10), 1383–1387. doi: 10.1152/japplphysiol.01258.2012.CrossRefGoogle ScholarPubMed
Baumbach, G.L. (1996). Effects of increased pulse pressure on cerebral arterioles. Hypertension, 27(2), 159–167. doi: 10.1161/01.hyp.27.2.159.CrossRefGoogle ScholarPubMed
Bos, D., Wolters, F.J., Darweesh, S.K.L., Vernooij, M.W., de Wolf, F., Ikram, M.A., & Hofman, A. (2018). Cerebral small vessel disease and the risk of dementia: a systematic review and meta-analysis of population-based evidence. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, 14(11), 1482–1492. doi: 10.1016/j.jalz.2018.04.007.CrossRefGoogle ScholarPubMed
Braz, I.D., Fluck, D., Lip, G.Y.H., Lundby, C., & Fisher, J.P. (2017). Impact of aerobic fitness on cerebral blood flow and cerebral vascular responsiveness to CO2 in young and older men. Scandinavian Journal of Medicine and Science in Sports, 27(6), 634–642. doi: 10.1111/sms.12674.CrossRefGoogle Scholar
Brown, B.M., Sohrabi, H.R., Taddei, K., Gardener, S.L., Rainey-Smith, S.R., Peiffer, J.J., … Dominantly Inherited Alzheimer, Network. (2017). Habitual exercise levels are associated with cerebral amyloid load in presymptomatic autosomal dominant Alzheimer’s disease. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, 13(11), 1197–1206. doi: 10.1016/j.jalz.2017.03.008.CrossRefGoogle ScholarPubMed
Brown, L.S., Foster, C.G., Courtney, J.M., King, N.E., Howells, D.W., & Sutherland, B.A. (2019). Pericytes and neurovascular function in the healthy and diseased brain. Frontiers in Cellular Neuroscience, 13, 282. doi: 10.3389/fncel.2019.00282.CrossRefGoogle ScholarPubMed
Chapman, S.B., Aslan, S., Spence, J.S., Defina, L.F., Keebler, M.W., Didehbani, N., & Lu, H. (2013). Shorter term aerobic exercise improves brain, cognition, and cardiovascular fitness in aging. Frontiers in Aging Neuroscience, 5, 75. doi: 10.3389/fnagi.2013.00075.CrossRefGoogle Scholar
Church, D.D., Hoffman, J.R., Mangine, G.T., Jajtner, A.R., Townsend, J.R., Beyer, K.S., … Stout, J.R. (2016). Comparison of high-intensity vs. high-volume resistance training on the BDNF response to exercise. Journal of Applied Physiology, 121(1), 123–128. doi: 10.1152/japplphysiol.00233.2016.CrossRefGoogle ScholarPubMed
Cohen, B.E., Edmondson, D., & Kronish, I.M. (2015). State of the art review: depression, stress, anxiety, and cardiovascular disease. American Journal of Hypertension, 28(11), 1295–1302. doi: 10.1093/ajh/hpv047.CrossRefGoogle Scholar
Contrepois, K., Wu, S., Moneghetti, K.J., Hornburg, D., Ahadi, S., Tsai, M.S., … Snyder, M.P. (2020). Molecular choreography of acute exercise. Cell, 181(5), 1112–1130 e1116. doi: 10.1016/j.cell.2020.04.043.CrossRefGoogle ScholarPubMed
Cook, J.N., DeVan, A.E., Schleifer, J.L., Anton, M.M., Cortez-Cooper, M.Y., & Tanaka, H. (2006). Arterial compliance of rowers: implications for combined aerobic and strength training on arterial elasticity. American Journal of Physiology - Heart and Circulatory Physiology, 290(4), H1596–1600. doi: 10.1152/ajpheart.01054.2005.CrossRefGoogle ScholarPubMed
Cortez-Cooper, M.Y., DeVan, A.E., Anton, M.M., Farrar, R.P., Beckwith, K.A., Todd, J.S., & Tanaka, H. (2005). Effects of high intensity resistance training on arterial stiffness and wave reflection in women. American Journal of Hypertension, 18(7), 930–934. doi: 10.1016/j.amjhyper.2005.01.008. CrossRefGoogle ScholarPubMed
Cotman, C.W., Berchtold, N.C., & Christie, L.A. (2007). Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends in Neurosciences, 30(9), 464–472. doi: 10.1016/j.tins.2007.06.011.Google Scholar
Coverdale, N.S., Gati, J.S., Opalevych, O., Perrotta, A., & Shoemaker, J.K. (2014). Cerebral blood flow velocity underestimates cerebral blood flow during modest hypercapnia and hypocapnia. Journal of Applied Physiology, 117(10), 1090–1096. doi: 10.1152/japplphysiol.00285.2014.CrossRefGoogle ScholarPubMed
de la Torre, J.C. (2004). Is Alzheimer’s disease a neurodegenerative or a vascular disorder? Data, dogma, and dialectics. Lancet Neurology, 3(3), 184–190. doi: 10.1016/S1474-4422(04)00683-0.CrossRefGoogle ScholarPubMed
de Leon, M.J., Li, Y., Okamura, N., Tsui, W.H., Saint-Louis, L.A., Glodzik, L., … Rusinek, H. (2017). Cerebrospinal fluid clearance in Alzheimer disease measured with dynamic PET. Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine, 58(9), 1471–1476. doi: 10.2967/jnumed.116.187211.CrossRefGoogle ScholarPubMed
de Roos, A., van der Grond, J., Mitchell, G., & Westenberg, J. (2017). Magnetic resonance imaging of cardiovascular function and the brain: is dementia a cardiovascular-driven disease? Circulation, 135(22), 2178–2195. doi: 10.1161/CIRCULATIONAHA.116.021978.CrossRefGoogle ScholarPubMed
DeSouza, C.A., Shapiro, L.F., Clevenger, C.M., Dinenno, F.A., Monahan, K.D., Tanaka, H., & Seals, D.R. (2000). Regular aerobic exercise prevents and restores age-related declines in endothelium-dependent vasodilation in healthy men. Circulation, 102(12), 1351–1357. doi: 10.1161/01.cir.102.12.1351.CrossRefGoogle ScholarPubMed
Ding, J., Mitchell, G.F., Bots, M.L., Sigurdsson, S., Harris, T.B., Garcia, M., … Launer, L.J. (2015). Carotid arterial stiffness and risk of incident cerebral microbleeds in older people: the Age, Gene/Environment Susceptibility (AGES)-Reykjavik study. Arteriosclerosis, Thrombosis, and Vascular Biology, 35(8), 1889–1895. doi: 10.1161/ATVBAHA.115.305451.CrossRefGoogle ScholarPubMed
Egan, B. & Zierath, J.R. (2013). Exercise metabolism and the molecular regulation of skeletal muscle adaptation. Cell Metabolism, 17(2), 162–184. doi: 10.1016/j.cmet.2012.12.012.CrossRefGoogle ScholarPubMed
Egashira, K., Inou, T., Hirooka, Y., Kai, H., Sugimachi, M., Suzuki, S., … Takeshita, A. (1993). Effects of age on endothelium-dependent vasodilation of resistance coronary artery by acetylcholine in humans. Circulation, 88(1), 77–81. doi: 10.1161/01.cir.88.1.77.CrossRefGoogle ScholarPubMed
Elias, M.F., Robbins, M.A., Budge, M.M., Abhayaratna, W.P., Dore, G.A., & Elias, P.K. (2009). Arterial pulse wave velocity and cognition with advancing age. Hypertension, 53(4), 668–673. doi: 10.1161/HYPERTENSIONAHA.108.126342.CrossRefGoogle ScholarPubMed
Endres, M., Gertz, K., Lindauer, U., Katchanov, J., Schultze, J., Schrock, H., … Laufs, U. (2003). Mechanisms of stroke protection by physical activity. Annals of Neurology, 54(5), 582–590. doi: 10.1002/ana.10722.CrossRefGoogle ScholarPubMed
Erickson, K.I., Hillman, C., Stillman, C.M., Ballard, R.M., Bloodgood, B., Conroy, D.E., … For Physical Activity Guidelines Advisory, C. (2019). Physical activity, cognition, and brain outcomes: a review of the 2018 physical activity guidelines. Medicine & Science in Sports & Exercise, 51(6), 1242–1251. doi: 10.1249/MSS.0000000000001936.CrossRefGoogle ScholarPubMed
Erickson, K.I., Prakash, R.S., Voss, M.W., Chaddock, L., Hu, L., Morris, K.S., … Kramer, A.F. (2009). Aerobic fitness is associated with hippocampal volume in elderly humans. Hippocampus, 19(10), 1030–1039. doi: 10.1002/hipo.20547.CrossRefGoogle ScholarPubMed
Erickson, K.I., Raji, C.A., Lopez, O.L., Becker, J.T., Rosano, C., Newman, A.B., … Kuller, L.H. (2010). Physical activity predicts gray matter volume in late adulthood: the Cardiovascular Health Study. Neurology, 75(16), 1415–1422. doi: 10.1212/WNL.0b013e3181f88359.CrossRefGoogle ScholarPubMed
Fierstra, J., Sobczyk, O., Battisti-Charbonney, A., Mandell, D.M., Poublanc, J., Crawley, A.P., … Fisher, J.A. (2013). Measuring cerebrovascular reactivity: what stimulus to use? The Journal of Physiology, 591(23), 5809–5821. doi: 10.1113/jphysiol.2013.259150.CrossRefGoogle ScholarPubMed
Flodin, P., Jonasson, L.S., Riklund, K., Nyberg, L., & Boraxbekk, C.J. (2017). Does aerobic exercise influence intrinsic brain activity? An aerobic exercise intervention among healthy old adults. Frontiers in Aging Neuroscience, 9, 267. doi: 10.3389/fnagi.2017.00267.CrossRefGoogle ScholarPubMed
Furby, H.V., Warnert, E.A., Marley, C.J., Bailey, D.M., & Wise, R.G. (2019). Cardiorespiratory fitness is associated with increased middle cerebral arterial compliance and decreased cerebral blood flow in young healthy adults: a pulsed ASL MRI study. Journal of Cerebral Blood Flow & Metabolism, 271678X19865449. doi: 10.1177/0271678X19865449.CrossRefGoogle Scholar
Galvin, S.D., Celi, L.A., Thomas, K.N., Clendon, T.R., Galvin, I.E., Bunton, R.W., & Ainslie, P.N. (2010). Effects of age and coronary artery disease on cerebrovascular reactivity to carbon dioxide in humans. Anaesthesia and Intensive Care, 38(4), 710–717. doi: 10.1177/0310057X1003800415.CrossRefGoogle ScholarPubMed
Geda, Y.E., Roberts, R.O., Knopman, D.S., Christianson, T.J., Pankratz, V.S., Ivnik, R.J., … Rocca, W.A. (2010). Physical exercise, aging, and mild cognitive impairment: a population-based study. Archives of Neurology, 67(1), 80–86. doi: 10.1001/archneurol.2009.297.CrossRefGoogle ScholarPubMed
Gerhard, M., Roddy, M.A., Creager, S.J., & Creager, M.A. (1996). Aging progressively impairs endothelium-dependent vasodilation in forearm resistance vessels of humans. Hypertension, 27(4), 849–853. doi: 10.1161/01.hyp.27.4.849.CrossRefGoogle ScholarPubMed
Green, D.J., Hopman, M.T., Padilla, J., Laughlin, M.H., & Thijssen, D.H. (2017). Vascular adaptation to exercise in humans: role of Hemodynamic Stimuli. Physiological Reviews, 97(2), 495–528. doi: 10.1152/physrev.00014.2016.CrossRefGoogle ScholarPubMed
Green, D.J., Maiorana, A., O’Driscoll, G., & Taylor, R. (2004). Effect of exercise training on endothelium-derived nitric oxide function in humans. The Journal of Physiology, 561(Pt 1), 1–25. doi: 1 0.1113/jphysiol.2004.068197.CrossRefGoogle ScholarPubMed
Guadagni, V., Drogos, L.L., Tyndall, A.V., Davenport, M.H., Anderson, T.J., Eskes, G.A., … Poulin, M.J. (2020). Aerobic exercise improves cognition and cerebrovascular regulation in older adults. Neurology, 94(21), e2245–e2257. doi: 10.1212/WNL.0000000000009478.CrossRefGoogle ScholarPubMed
He, X.F., Liu, D.X., Zhang, Q., Liang, F.Y., Dai, G.Y., Zeng, J.S., … Lan, Y. (2017). Voluntary exercise promotes glymphatic clearance of amyloid beta and reduces the activation of astrocytes and microglia in aged mice. Frontiers in Molecular Neuroscience, 10, 144. doi: 10.3389/fnmol.2017.00144.CrossRefGoogle ScholarPubMed
Hoiland, R.L., Fisher, J.A., & Ainslie, P.N. (2019). Regulation of the cerebral circulation by arterial carbon dioxide. Comprehensive Physiology, 9(3), 1101–1154. doi: 10.1002/cphy.c180021.CrossRefGoogle ScholarPubMed
Iadecola, C. (2004). Neurovascular regulation in the normal brain and in Alzheimer’s disease. Nature Reviews Neuroscience, 5(5), 347–360. doi: 10.1038/nrn1387.CrossRefGoogle ScholarPubMed
Iadecola, C. (2017). The neurovascular unit coming of age: a journey through neurovascular coupling in health and disease. Neuron, 96(1), 17–42. doi: 10.1016/j.neuron.2017.07.030.CrossRefGoogle ScholarPubMed
Iliff, J.J. & Nedergaard, M. (2013). Is there a cerebral lymphatic system? Stroke, 44(6 Suppl 1), S93–S95. doi: 10.1161/STROKEAHA.112.678698.CrossRefGoogle Scholar
Intzandt, B., Sabra, D., Foster, C., Desjardins-Crepeau, L., Hoge, R.D., Steele, C.J., … Gauthier, C.J. (2020). Higher cardiovascular fitness level is associated with lower cerebrovascular reactivity and perfusion in healthy older adults. Journal of Cerebral Blood Flow & Metabolism, 40(7), 1468–1481. doi: 10.1177/0271678X19862873.CrossRefGoogle ScholarPubMed
Iturria-Medina, Y., Sotero, R.C., Toussaint, P.J., Mateos-Perez, J.M., Evans, A.C., & Alzheimer’s Disease Neuroimaging, I. (2016). Early role of vascular dysregulation on late-onset Alzheimer’s disease based on multifactorial data-driven analysis. Nature Communications, 7, 11934. doi: 10.1038/ncomms11934.CrossRefGoogle ScholarPubMed
Jaruchart, T., Suwanwela, N.C., Tanaka, H., & Suksom, D. (2016). Arterial stiffness is associated with age-related differences in cerebrovascular conductance. Experimental Gerontology, 73, 59–64. doi: 10.1016/j.exger.2015.11.006.CrossRefGoogle ScholarPubMed
Jiang, H., Jia, D., Zhang, B., Yang, W., Dong, Z., Sun, X., … Ge, J. (2020). Exercise improves cardiac function and glucose metabolism in mice with experimental myocardial infarction through inhibiting HDAC4 and upregulating GLUT1 expression. Basic Research in Cardiology, 115(3), 28. doi: 10.1007/s00395-020-0787-1.Google ScholarPubMed
Kalaria, R.N., & Harik, S.I. (1989). Reduced glucose transporter at the blood-brain barrier and in cerebral cortex in Alzheimer disease. Journal of Neurochemistry, 53(4), 1083–1088. doi: 10.1111/j.1471-4159.1989.tb07399.x.CrossRefGoogle Scholar
Kastrup, A., Dichgans, J., Niemeier, M., & Schabet, M. (1998). Changes of cerebrovascular CO2 reactivity during normal aging. Stroke, 29(7), 1311–1314. doi: 10.1161/01.str.29.7.1311.CrossRefGoogle ScholarPubMed
Kearney-Schwartz, A., Rossignol, P., Bracard, S., Felblinger, J., Fay, R., Boivin, J.M., … Zannad, F. (2009). Vascular structure and function is correlated to cognitive performance and white matter hyperintensities in older hypertensive patients with subjective memory complaints. Stroke; A Journal of Cerebral Circulation, 40(4), 1229–1236. doi: 10.1161/STROKEAHA.108.532853.CrossRefGoogle ScholarPubMed
Kisler, K., Nelson, A.R., Montagne, A., & Zlokovic, B.V. (2017). Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease. Nature Reviews Neuroscience, 18(7), 419–434. doi: 10.1038/nrn.2017.48.CrossRefGoogle ScholarPubMed
Kleinloog, J.P.D., Mensink, R.P., Ivanov, D., Adam, J.J., Uludag, K., & Joris, P.J. (2019). Aerobic Exercise Training Improves Cerebral Blood Flow and Executive Function: A Randomized, Controlled Cross-Over Trial in Sedentary Older Men. Frontiers in Aging Neuroscience, 11, 333. doi: 10.3389/fnagi.2019.00333.CrossRefGoogle ScholarPubMed
Kohn, J.C., Lampi, M.C., & Reinhart-King, C.A. (2015). Age-related vascular stiffening: causes and consequences. Frontiers in Genetics, 6, 112. doi: 10.3389/fgene.2015.00112.CrossRefGoogle ScholarPubMed
Kress, B.T., Iliff, J.J., Xia, M., Wang, M., Wei, H.S., Zeppenfeld, D., … Nedergaard, M. (2014). Impairment of paravascular clearance pathways in the aging brain. Annals of Neurology, 76(6), 845–861. doi: 10.1002/ana.24271.CrossRefGoogle ScholarPubMed
Kuring, J.K., Mathias, J.L., & Ward, L. (2018). Prevalence of depression, anxiety and PTSD in people with dementia: a systematic review and meta-analysis. Neuropsychology Review, 28(4), 393–416. doi: 10.1007/s11065-018-9396-2.CrossRefGoogle ScholarPubMed
Laing, K.K., Simoes, S., Baena-Caldas, G.P., Lao, P.J., Kothiya, M., Igwe, K.C., … Alzheimer’s Disease Neuroimaging, I. (2020). Cerebrovascular disease promotes tau pathology in Alzheimer’s disease. Brain Communications, 2(2), fcaa132. doi: 10.1093/braincomms/fcaa132.CrossRefGoogle ScholarPubMed
Latimer, C.S., Searcy, J.L., Bridges, M.T., Brewer, L.D., Popovic, J., Blalock, E.M., … Porter, N.M. (2011). Reversal of glial and neurovascular markers of unhealthy brain aging by exercise in middle-aged female mice. PLoS One, 6(10), e26812. doi: 10.1371/journal.pone.0026812.CrossRefGoogle ScholarPubMed
Lee, H.Y., & Oh, B.H. (2010). Aging and arterial stiffness. Circulation Journal: Official Journal of the Japanese Circulation Society, 74(11), 2257–2262. doi: 10.1253/circj.cj-10-0910.CrossRefGoogle ScholarPubMed
Liang, K.Y., Mintun, M.A., Fagan, A.M., Goate, A.M., Bugg, J.M., Holtzman, D.M., … Head, D. (2010). Exercise and Alzheimer’s disease biomarkers in cognitively normal older adults. Annals of Neurology, 68(3), 311–318. doi: 10.1002/ana.22096.CrossRefGoogle ScholarPubMed
Liu, P.Z. & Nusslock, R. (2018). Exercise-mediated neurogenesis in the hippocampus via BDNF. Frontiers in Neuroscience, 12, 52. doi: 10.3389/fnins.2018.00052.CrossRefGoogle ScholarPubMed
Lu, H., Xu, F., Rodrigue, K.M., Kennedy, K.M., Cheng, Y., Flicker, B., … Park, D.C. (2011). Alterations in cerebral metabolic rate and blood supply across the adult lifespan. Cerebral Cortex, 21(6), 1426–1434. doi: 10.1093/cercor/bhq224.CrossRefGoogle ScholarPubMed
Madureira, J., Castro, P., & Azevedo, E. (2017). Demographic and systemic hemodynamic influences in mechanisms of cerebrovascular regulation in healthy adults. Journal of Stroke and Cerebrovascular Diseases: The Official Journal of National Stroke Association, 26(3), 500–508. doi: 10.1016/j.jstrokecerebrovasdis.2016.12.003.CrossRefGoogle ScholarPubMed
McEniery, C.M., Wallace, S., Mackenzie, I.S., McDonnell, B., Yasmin, , Newby, D.E., … Wilkinson, I.B. (2006). Endothelial function is associated with pulse pressure, pulse wave velocity, and augmentation index in healthy humans. Hypertension, 48(4), 602–608. doi: 10.1161/01.HYP.0000239206.64270.5f.CrossRefGoogle ScholarPubMed
Mestre, H., Tithof, J., Du, T., Song, W., Peng, W., Sweeney, A.M., … Kelley, D.H. (2018). Flow of cerebrospinal fluid is driven by arterial pulsations and is reduced in hypertension. Nature Communications, 9(1), 4878. doi: 10.1038/s41467-018-07318-3.CrossRefGoogle ScholarPubMed
Mikhail Kellawan, J., Harrell, J.W., Schrauben, E.M., Hoffman, C.A., Roldan-Alzate, A., Schrage, W.G., & Wieben, O. (2016). Quantitative cerebrovascular 4D flow MRI at rest and during hypercapnia challenge. Magnetic Resonance Imaging, 34(4), 422–428. doi: 10.1016/j.mri.2015.12.016.CrossRefGoogle ScholarPubMed
Miller, K.B., Howery, A.J., Harvey, R.E., Eldridge, M.W., & Barnes, J.N. (2018). Cerebrovascular reactivity and central arterial stiffness in habitually exercising healthy adults. Frontiers in Physiology, 9, 1096. doi: 10.3389/fphys.2018.01096.CrossRefGoogle ScholarPubMed
Miller, K.B., Howery, A.J., Rivera-Rivera, L.A., Johnson, S.C., Rowley, H.A., Wieben, O., & Barnes, J.N. (2019). Age-related reductions in cerebrovascular reactivity using 4d flow MRI. Frontiers in Aging Neuroscience, 11, 281. doi: 10.3389/fnagi.2019.00281.CrossRefGoogle ScholarPubMed
Mitchell, G.F. (2008). Effects of central arterial aging on the structure and function of the peripheral vasculature: implications for end-organ damage. Journal of Applied Physiology, 105(5), 1652–1660. doi: 10.1152/japplphysiol.90549.2008.CrossRefGoogle ScholarPubMed
Mitchell, G.F., van Buchem, M.A., Sigurdsson, S., Gotal, J.D., Jonsdottir, M.K., Kjartansson, O., … Launer, L.J. (2011). Arterial stiffness, pressure and flow pulsatility and brain structure and function: the Age, Gene/Environment Susceptibility–Reykjavik study. Brain: A Journal of Neurology, 134(Pt 11), 3398–3407. doi: 10.1093/brain/awr253.CrossRefGoogle ScholarPubMed
Miyachi, M. (2013). Effects of resistance training on arterial stiffness: a meta-analysis. British Journal of Sports Medicine, 47(6), 393–396. doi: 10.1136/bjsports-2012-090488.CrossRefGoogle ScholarPubMed
Miyachi, M., Donato, A.J., Yamamoto, K., Takahashi, K., Gates, P.E., Moreau, K.L., & Tanaka, H. (2003). Greater age-related reductions in central arterial compliance in resistance-trained men. Hypertension, 41(1), 130–135. doi: 10.1161/01.hyp.0000047649.62181.88.CrossRefGoogle ScholarPubMed
Miyachi, M., Kawano, H., Sugawara, J., Takahashi, K., Hayashi, K., Yamazaki, K., … Tanaka, H. (2004). Unfavorable effects of resistance training on central arterial compliance: a randomized intervention study. Circulation, 110(18), 2858–2863. doi: 10.1161/01.CIR.0000146380.08401.99.CrossRefGoogle ScholarPubMed
Montagne, A., Nation, D.A., Pa, J., Sweeney, M.D., Toga, A.W., & Zlokovic, B.V. (2016). Brain imaging of neurovascular dysfunction in Alzheimer’s disease. Acta Neuropathologica, 131(5), 687–707. doi: 10.1007/s00401-016-1570-0.CrossRefGoogle ScholarPubMed
Muhire, G., Iulita, M.F., Vallerand, D., Youwakim, J., Gratuze, M., Petry, F.R., … Girouard, H. (2019). Arterial Stiffness Due to Carotid Calcification Disrupts Cerebral Blood Flow Regulation and Leads to Cognitive Deficits. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 8(9), e011630. doi: 10.1161/JAHA.118.011630.CrossRefGoogle ScholarPubMed
Murrell, C.J., Cotter, J.D., Thomas, K.N., Lucas, S.J., Williams, M.J., & Ainslie, P.N. (2012). Cerebral blood flow and cerebrovascular reactivity at rest and during sub-maximal exercise: Effect of age and 12-week exercise training. Age doi: 10.1007/s11357-012-9414-x.CrossRefGoogle Scholar
Nicholson, W.T., Vaa, B., Hesse, C., Eisenach, J.H., & Joyner, M.J. (2009). Aging is associated with reduced prostacyclin-mediated dilation in the human forearm. Hypertension, 53(6), 973–978. doi: 10.1161/HYPERTENSIONAHA.108.121483.CrossRefGoogle ScholarPubMed
Nigam, A., Mitchell, G.F., Lambert, J., & Tardif, J.C. (2003). Relation between conduit vessel stiffness (assessed by tonometry) and endothelial function (assessed by flow-mediated dilatation) in patients with and without coronary heart disease. American Journal of Cardiology, 92(4), 395–399. doi: 10.1016/s0002-9149(03)00656-8.CrossRefGoogle ScholarPubMed
Nualnim, N., Barnes, J.N., Tarumi, T., Renzi, C.P., & Tanaka, H. (2011). Comparison of central artery elasticity in swimmers, runners, and the sedentary. American Journal of Cardiology, 107(5), 783–787. doi: 10.1016/j.amjcard.2010.10.062.CrossRefGoogle ScholarPubMed
O’Keefe, E.L., O’Keefe, J.H., & Lavie, C.J. (2019). Exercise counteracts the cardiotoxicity of psychosocial stress. Mayo Clinic Proceedings, 94(9), 1852–1864. doi: 10.1016/j.mayocp.2019.02.022.CrossRefGoogle Scholar
O’Rourke, M.F., & Hashimoto, J. (2007). Mechanical factors in arterial aging: a clinical perspective. Journal of the American College of Cardiology, 50(1), 1–13. doi: 10.1016/j.jacc.2006.12.050.CrossRefGoogle ScholarPubMed
Palta, P., Sharrett, A.R., Wei, J., Meyer, M.L., Kucharska-Newton, A., Power, M.C., … Heiss, G. (2019). Central arterial stiffness is associated with structural brain damage and poorer cognitive performance: the ARIC study. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 8(2), e011045. doi: 10.1161/JAHA.118.011045.CrossRefGoogle ScholarPubMed
Pang, R., Wang, X., Pei, F., Zhang, W., Shen, J., Gao, X., & Chang, C. (2019). Regular exercise enhances cognitive function and intracephalic GLUT expression in Alzheimer’s disease model mice. Journal of Alzheimer’s Disease: JAD, 72(1), 83–96. doi: 10.3233/JAD-190328.CrossRefGoogle ScholarPubMed
Pase, M.P., Grima, N.A., Stough, C., Scholey, A., & Pipingas, A. (2014). Association of pulsatile and mean cerebral blood flow velocity with age and neuropsychological performance. Physiology & Behavior, 130, 23–27. doi: 10.1016/j.physbeh.2014.03.015.CrossRefGoogle ScholarPubMed
Pedersen, B.K. & Hoffman-Goetz, L. (2000). Exercise and the immune system: regulation, integration, and adaptation. Physiological Reviews, 80(3), 1055–1081. doi: 10.1152/physrev.2000.80.3.1055.CrossRefGoogle ScholarPubMed
Pialoux, V., Brown, A.D., Leigh, R., Friedenreich, C.M., & Poulin, M.J. (2009). Effect of cardiorespiratory fitness on vascular regulation and oxidative stress in postmenopausal women. Hypertension, 54(5), 1014–1020. doi: 10.1161/HYPERTENSIONAHA.109.138917.CrossRefGoogle ScholarPubMed
Rasmussen, M.K., Mestre, H., & Nedergaard, M. (2018). The glymphatic pathway in neurological disorders. Lancet Neurology, 17(11), 1016–1024. doi: 10.1016/S1474-4422(18)30318-1.CrossRefGoogle ScholarPubMed
Rasmussen, P., Brassard, P., Adser, H., Pedersen, M.V., Leick, L., Hart, E., … Pilegaard, H. (2009). Evidence for a release of brain-derived neurotrophic factor from the brain during exercise. Experimental Physiology, 94(10), 1062–1069. doi: 10.1113/expphysiol.2009.048512.CrossRefGoogle ScholarPubMed
Ringstad, G., Valnes, L.M., Dale, A.M., Pripp, A.H., Vatnehol, S.S., Emblem, K.E., … Eide, P.K. (2018). Brain-wide glymphatic enhancement and clearance in humans assessed with MRI. JCI Insight, 3(13). doi: 10.1172/jci.insight.121537.CrossRefGoogle Scholar
Rivera-Rivera, L.A., Turski, P., Johnson, K.M., Hoffman, C., Berman, S.E., Kilgas, P., … Wieben, O. (2016). 4D flow MRI for intracranial hemodynamics assessment in Alzheimer’s disease. Journal of Cerebral Blood Flow & Metabolism, 36(10), 1718–1730. doi: 10.1177/0271678X15617171.CrossRefGoogle ScholarPubMed
Robertson, A.D., Atwi, S., Kostoglou, K., Verhoeff, N., Oh, P.I., Mitsis, G.D., … MacIntosh, B.J. (2019). Cerebrovascular pulsatility during rest and exercise reflects hemodynamic impairment in stroke and cerebral small vessel disease. Ultrasound in Medicine & Biology, 45(12), 3116–3127. doi: 10.1016/j.ultrasmedbio.2019.08.019.CrossRefGoogle ScholarPubMed
Robertson, A.D., Tessmer, C.F., & Hughson, R.L. (2010). Association between arterial stiffness and cerebrovascular resistance in the elderly. Journal of Human Hypertension, 24(3), 190–196. doi: 10.1038/jhh.2009.56.CrossRefGoogle ScholarPubMed
Sadekova, N., Vallerand, D., Guevara, E., Lesage, F., & Girouard, H. (2013). Carotid calcification in mice: a new model to study the effects of arterial stiffness on the brain. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 2(3), e000224. doi: 10.1161/JAHA.113.000224.CrossRefGoogle Scholar
Sargurupremraj, M., Suzuki, H., Jian, X., Sarnowski, C., Evans, T.E., Bis, J.C., … Debette, S. (2020). Cerebral small vessel disease genomics and its implications across the lifespan. Nature Communications, 11(1), 6285. doi: 10.1038/s41467-020-19111-2.CrossRefGoogle ScholarPubMed
Schrauben, E.M., Johnson, K.M., Huston, J., Del Rio, A.M., Reeder, S.B., Field, A., & Wieben, O. (2014). Reproducibility of cerebrospinal venous blood flow and vessel anatomy with the use of phase contrast-vastly undersampled isotropic projection reconstruction and contrast-enhanced MRA. AJNR: American Journal of Neuroradiology, 35(5), 999–1006. doi: 10.3174/ajnr.A3779.CrossRefGoogle ScholarPubMed
Seals, D.R., Jablonski, K.L., & Donato, A.J. (2011). Aging and vascular endothelial function in humans. Clinical Science (London), 120(9), 357–375. doi: 10.1042/CS20100476.CrossRefGoogle ScholarPubMed
Severinsen, M.C.K. & Pedersen, B.K. (2020). Muscle-organ crosstalk: the emerging roles of Myokines. Endocrine Reviews, 41(4). doi: 10.1210/endrev/bnaa016.CrossRefGoogle Scholar
Shi, Y., Thrippleton, M.J., Makin, S.D., Marshall, I., Geerlings, M.I., de Craen, A.J.M., … Wardlaw, J.M. (2016). Cerebral blood flow in small vessel disease: a systematic review and meta-analysis. Journal of Cerebral Blood Flow & Metabolism, 36(10), 1653–1667. doi: 10.1177/0271678X16662891.CrossRefGoogle ScholarPubMed
Shibata, S., Fujimoto, N., Hastings, J.L., Carrick-Ranson, G., Bhella, P.S., Hearon, C.M. Jr., & Levine, B.D. (2018). The effect of lifelong exercise frequency on arterial stiffness. The Journal of Physiology, 596(14), 2783–2795. doi: 10.1113/JP275301.CrossRefGoogle ScholarPubMed
Silvestrini, M., Pasqualetti, P., Baruffaldi, R., Bartolini, M., Handouk, Y., Matteis, M., … Vernieri, F. (2006). Cerebrovascular reactivity and cognitive decline in patients with Alzheimer disease. Stroke; A Journal of Cerebral Circulation, 37(4), 1010–1015. doi: 10.1161/01.STR.0000206439.62025.97.CrossRefGoogle ScholarPubMed
Sofi, F., Valecchi, D., Bacci, D., Abbate, R., Gensini, G.F., Casini, A., & Macchi, C. (2011). Physical activity and risk of cognitive decline: a meta-analysis of prospective studies. Journal of Internal Medicine, 269(1), 107–117. doi: 10.1111/j.1365-2796.2010.02281.x.Google ScholarPubMed
Steen Jensen, C., Portelius, E., Siersma, V., Hogh, P., Wermuth, L., Blennow, K., … Hviid Simonsen, A. (2016). Cerebrospinal fluid amyloid beta and tau concentrations are not modulated by 16 weeks of moderate- to high-intensity physical exercise in patients with Alzheimer disease. Dementia and Geriatric Cognitive Disorders, 42(3–4), 146–158. doi: 10.1159/000449408.CrossRefGoogle Scholar
Stillman, C.M., Esteban-Cornejo, I., Brown, B., Bender, C.M., & Erickson, K.I. (2020). Effects of exercise on brain and cognition across age groups and health states. Trends in Neurosciences, 43(7), 533–543. doi: 10.1016/j.tins.2020.04.010.CrossRefGoogle ScholarPubMed
Sun, Z. (2015). Aging, arterial stiffness, and hypertension. Hypertension, 65(2), 252–256. doi: 10.1161/HYPERTENSIONAHA.114.03617.CrossRefGoogle ScholarPubMed
Sweeney, M.D., Kisler, K., Montagne, A., Toga, A.W., & Zlokovic, B.V. (2018). The role of brain vasculature in neurodegenerative disorders. Nature Neuroscience, 21(10), 1318–1331. doi: 10.1038/s41593-018-0234-x.CrossRefGoogle ScholarPubMed
Szablewski, L. (2017). Glucose Transporters in Brain: In Health and in Alzheimer’s Disease. Journal of Alzheimer’s Disease: JAD, 55(4), 1307–1320. doi: 10.3233/JAD-160841.CrossRefGoogle ScholarPubMed
Taddei, S., Virdis, A., Ghiadoni, L., Salvetti, G., Bernini, G., Magagna, A., & Salvetti, A. (2001). Age-related reduction of NO availability and oxidative stress in humans. Hypertension, 38(2), 274–279. doi: 10.1161/01.hyp.38.2.274.CrossRefGoogle ScholarPubMed
Takimoto, M., & Hamada, T. (2014). Acute exercise increases brain region-specific expression of MCT1, MCT2, MCT4, GLUT1, and COX IV proteins. Journal of Applied Physiology, 116(9), 1238–1250. doi: 10.1152/japplphysiol.01288.2013.Google ScholarPubMed
Tan, C.H., Low, K.A., Kong, T., Fletcher, M.A., Zimmerman, B., Maclin, E.L., … Fabiani, M. (2017). Mapping cerebral pulse pressure and arterial compliance over the adult lifespan with optical imaging. PLoS One, 12(2), e0171305. doi: 10.1371/journal.pone.0171305.CrossRefGoogle ScholarPubMed
Tanaka, H. (2019). Antiaging effects of Aerobic exercise on systemic arteries. Hypertension, HYPERTENSIONAHA11913179. doi: 10.1161/HYPERTENSIONAHA.119.13179.CrossRefGoogle Scholar
Tanaka, H., DeSouza, C.A., & Seals, D.R. (1998). Absence of age-related increase in central arterial stiffness in physically active women. Arteriosclerosis, Thrombosis, and Vascular Biology, 18(1), 127–132. doi: 10.1161/01.atv.18.1.127.CrossRefGoogle ScholarPubMed
Tanaka, H., Dinenno, F.A., Monahan, K.D., Clevenger, C.M., DeSouza, C.A., & Seals, D.R. (2000). Aging, habitual exercise, and dynamic arterial compliance. Circulation, 102(11), 1270–1275. doi: 10.1161/01.cir.102.11.1270.CrossRefGoogle ScholarPubMed
Tanaka, H., Dinenno, F.A., Monahan, K.D., DeSouza, C.A., & Seals, D.R. (2001). Carotid artery wall hypertrophy with age is related to local systolic blood pressure in healthy men. Arteriosclerosis, Thrombosis, and Vascular Biology, 21(1), 82–87. doi: 10.1161/01.atv.21.1.82.CrossRefGoogle ScholarPubMed
Tarasoff-Conway, J.M., Carare, R.O., Osorio, R.S., Glodzik, L., Butler, T., Fieremans, E., … de Leon, M.J. (2015). Clearance systems in the brain-implications for Alzheimer disease. Nature Reviews. Neurology, 11(8), 457–470. doi: 10.1038/nrneurol.2015.119.CrossRefGoogle ScholarPubMed
Thijssen, D.H., Carter, S.E., & Green, D.J. (2016). Arterial structure and function in vascular ageing: are you as old as your arteries? The Journal of Physiology, 594(8), 2275–2284. doi: 10.1113/JP270597.CrossRefGoogle Scholar
Thijssen, D.H., Rongen, G.A., van Dijk, A., Smits, P., & Hopman, M.T. (2007). Enhanced endothelin-1-mediated leg vascular tone in healthy older subjects. Journal of Applied Physiology, 103(3), 852–857. doi: 10.1152/japplphysiol.00357.2007.CrossRefGoogle ScholarPubMed
Thomas, B.P., Yezhuvath, U.S., Tseng, B.Y., Liu, P., Levine, B.D., Zhang, R., & Lu, H. (2013). Life-long aerobic exercise preserved baseline cerebral blood flow but reduced vascular reactivity to CO2. Journal of Magnetic Resonance Imaging: JMRI, 38(5), 1177–1183. doi: 10.1002/jmri.24090.Google Scholar
Thorin-Trescases, N., de Montgolfier, O., Pincon, A., Raignault, A., Caland, L., Labbe, P., & Thorin, E. (2018). The impact of pulse pressure on cerebrovascular events leading to age-related cognitive decline. American Journal of Physiology – Heart and Circulatory Physiology. doi: 10.1152/ajpheart.00637.2017.CrossRefGoogle Scholar
Toledo, J.B., Arnold, S.E., Raible, K., Brettschneider, J., Xie, S.X., Grossman, M., … Trojanowski, J.Q. (2013). Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer’s Coordinating Centre. Brain: A Journal of Neurology, 136(Pt 9), 2697–2706. doi: 10.1093/brain/awt188.CrossRefGoogle ScholarPubMed
Tomoto, T., Riley, J., Turner, M., Zhang, R., & Tarumi, T. (2020). Cerebral vasomotor reactivity during hypo- and hypercapnia across the adult lifespan. Journal of Cerebral Blood Flow & Metabolism, 40(3), 600–610. doi: 10.1177/0271678X19828327.CrossRefGoogle ScholarPubMed
Tymko, M.M., Ainslie, P.N., & Smith, K.J. (2018). Evaluating the methods used for measuring cerebral blood flow at rest and during exercise in humans. European Journal of Applied Physiology, 118(8), 1527–1538. doi: 10.1007/s00421-018-3887-y.CrossRefGoogle ScholarPubMed
Tzeng, Y.C., Ainslie, P.N., Cooke, W.H., Peebles, K.C., Willie, C.K., MacRae, B.A., … Rickards, C.A. (2012). Assessment of cerebral autoregulation: the quandary of quantification. American Journal of Physiology – Heart and Circulatory Physiology, 303(6), H658–671. doi: 10.1152/ajpheart.00328.2012.CrossRefGoogle ScholarPubMed
Vaitkevicius, P.V., Fleg, J.L., Engel, J.H., O’Connor, F.C., Wright, J.G., Lakatta, L.E., … Lakatta, E.G. (1993). Effects of age and aerobic capacity on arterial stiffness in healthy adults. Circulation, 88(4 Pt 1), 1456–1462. doi: 10.1161/01.cir.88.4.1456CrossRefGoogle ScholarPubMed
van der Kleij, L.A., Petersen, E.T., Siebner, H.R., Hendrikse, J., Frederiksen, K.S., Sobol, N.A., … Garde, E. (2018). The effect of physical exercise on cerebral blood flow in Alzheimer’s disease. NeuroImage: Clinical, 20, 650–654. doi: 10.1016/j.nicl.2018.09.003.CrossRefGoogle ScholarPubMed
van Praag, H., Christie, B.R., Sejnowski, T.J., & Gage, F.H. (1999). Running enhances neurogenesis, learning, and long-term potentiation in mice. Proceedings of the National Academy of Sciences of the United States of America, 96(23), 13427–13431. doi: 10.1073/pnas.96.23.13427.Google ScholarPubMed
van Praag, H., Fleshner, M., Schwartz, M.W., & Mattson, M.P. (2014). Exercise, energy intake, glucose homeostasis, and the brain. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 34(46), 15139–15149. doi: 10.1523/JNEUROSCI.2814-14.2014.CrossRefGoogle ScholarPubMed
van Praag, H., Kempermann, G., & Gage, F.H. (1999). Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nature Neuroscience, 2(3), 266–270. doi: 10.1038/6368.CrossRefGoogle ScholarPubMed
van Sloten, T.T., Protogerou, A.D., Henry, R.M., Schram, M.T., Launer, L.J., & Stehouwer, C.D. (2015). Association between arterial stiffness, cerebral small vessel disease and cognitive impairment: A systematic review and meta-analysis. Neuroscience and Biobehavioral Reviews, 53, 121–130. doi: 10.1016/j.neubiorev.2015.03.011.CrossRefGoogle ScholarPubMed
Verbree, J., Bronzwaer, A.S., Ghariq, E., Versluis, M.J., Daemen, M.J., van Buchem, M.A., … van Osch, M.J. (2014). Assessment of middle cerebral artery diameter during hypocapnia and hypercapnia in humans using ultra-high-field MRI. Journal of Applied Physiology, 117(10), 1084–1089. doi: 10.1152/japplphysiol.00651.2014.CrossRefGoogle ScholarPubMed
Veys, K., Fan, Z., Ghobrial, M., Bouche, A., Garcia-Caballero, M., Vriens, K., … De Bock, K. (2020). Role of the GLUT1 Glucose Transporter in Postnatal CNS Angiogenesis and Blood-Brain Barrier Integrity. Circulation Research, 127(4), 466–482. doi: 10.1161/CIRCRESAHA.119.316463.CrossRefGoogle ScholarPubMed
Vivar, C. & van Praag, H. (2017). Running changes the brain: the long and the short of it. Physiology, 32(6), 410–424. doi: 10.1152/physiol.00017.2017.CrossRefGoogle Scholar
von Holstein-Rathlou, S., Petersen, N.C., & Nedergaard, M. (2018). Voluntary running enhances glymphatic influx in awake behaving, young mice. Neuroscience Letters, 662, 253–258. doi: 10.1016/j.neulet.2017.10.035.CrossRefGoogle ScholarPubMed
Walker, A.E., Henson, G.D., Reihl, K.D., Morgan, R.G., Dobson, P.S., Nielson, E.I., … Donato, A.J. (2015). Greater impairments in cerebral artery compared with skeletal muscle feed artery endothelial function in a mouse model of increased large artery stiffness. The Journal of Physiology, 593(8), 1931–1943. doi: 10.1113/jphysiol.2014.285338.CrossRefGoogle Scholar
Watson, N.L., Sutton-Tyrrell, K., Rosano, C., Boudreau, R.M., Hardy, S.E., Simonsick, E.M., … Newman, A.B. (2011). Arterial stiffness and cognitive decline in well-functioning older adults. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 66(12), 1336–1342. doi: 10.1093/gerona/glr119.CrossRefGoogle ScholarPubMed
Webb, A.J., Simoni, M., Mazzucco, S., Kuker, W., Schulz, U., & Rothwell, P.M. (2012). Increased cerebral arterial pulsatility in patients with leukoaraiosis: arterial stiffness enhances transmission of aortic pulsatility. Stroke, 43(10), 2631–2636. doi: 10.1161/STROKEAHA.112.655837.CrossRefGoogle ScholarPubMed
Whyte, J.J. & Laughlin, M.H. (2010). The effects of acute and chronic exercise on the vasculature. Acta Physiologica (Oxford), 199(4), 441–450. doi: 10.1111/j.1748-1716.2010.02127.x.CrossRefGoogle ScholarPubMed
Winkler, E.A., Nishida, Y., Sagare, A.P., Rege, S.V., Bell, R.D., Perlmutter, D., … Zlokovic, B.V. (2015). GLUT1 reductions exacerbate Alzheimer’s disease vasculo-neuronal dysfunction and degeneration. Nature Neuroscience, 18(4), 521–530. doi: 10.1038/nn.3966.CrossRefGoogle ScholarPubMed
Wolters, F.J., Zonneveld, H.I., Hofman, A., van der Lugt, A., Koudstaal, P.J., Vernooij, M.W., … Heart-Brain Connection Collaborative Research, G. (2017). Cerebral perfusion and the risk of dementia: a population-based study. Circulation, 136(8), 719–728. doi: 10.1161/CIRCULATIONAHA.117.027448.CrossRefGoogle ScholarPubMed
Xu, T.Y., Staessen, J.A., Wei, F.F., Xu, J., Li, F.H., Fan, W.X., … Li, Y. (2012). Blood flow pattern in the middle cerebral artery in relation to indices of arterial stiffness in the systemic circulation. American Journal of Hypertension, 25(3), 319–324. doi: 10.1038/ajh.2011.223.CrossRefGoogle ScholarPubMed
Xu, X., Wang, B., Ren, C., Hu, J., Greenberg, D.A., Chen, T., … Jin, K. (2017). Age-related impairment of vascular structure and functions. Aging and Disease, 8(5), 590–610. doi: 10.14336/AD.2017.0430.CrossRefGoogle ScholarPubMed
Yang, T., Sun, Y., Lu, Z., Leak, R.K., & Zhang, F. (2017). The impact of cerebrovascular aging on vascular cognitive impairment and dementia. Ageing Research Reviews, 34, 15–29. doi: 10.1016/j.arr.2016.09.007.CrossRefGoogle ScholarPubMed
Yoshizawa, M., Maeda, S., Miyaki, A., Misono, M., Saito, Y., Tanabe, K., … Ajisaka, R. (2009). Effect of 12 weeks of moderate-intensity resistance training on arterial stiffness: a randomised controlled trial in women aged 32–59 years. British Journal of Sports Medicine, 43(8), 615–618. doi: 10.1136/bjsm.2008.052126.CrossRefGoogle ScholarPubMed
Zeller, K., Rahner-Welsch, S., & Kuschinsky, W. (1997). Distribution of Glut1 glucose transporters in different brain structures compared to glucose utilization and capillary density of adult rat brains. Journal of Cerebral Blood Flow & Metabolism, 17(2), 204–209. doi: 10.1097/00004647-199702000-00010.CrossRefGoogle ScholarPubMed
Zhai, F.F., Ye, Y.C., Chen, S.Y., Ding, F.M., Han, F., Yang, X.L., … Zhu, Y.C. (2018). Arterial Stiffness and Cerebral Small Vessel Disease. Frontiers in Neurology, 9, 723. doi: 10.3389/fneur.2018.00723.CrossRefGoogle ScholarPubMed
Zhao, Z., Nelson, A.R., Betsholtz, C., & Zlokovic, B.V. (2015). Establishment and Dysfunction of the Blood-Brain Barrier. Cell, 163(5), 1064–1078. doi: 10.1016/j.cell.2015.10.067.CrossRefGoogle ScholarPubMed
Zhu, Y.S., Tarumi, T., Tseng, B.Y., Palmer, D.M., Levine, B.D., & Zhang, R. (2013). Cerebral vasomotor reactivity during hypo- and hypercapnia in sedentary elderly and Masters athletes. Journal of Cerebral Blood Flow & Metabolism, 33(8), 1190–1196. doi: 10.1038/jcbfm.2013.66.CrossRefGoogle ScholarPubMed
Zlokovic, B.V. (2011). Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nature Reviews Neuroscience, 12(12), 723–738. doi: 10.1038/nrn3114.CrossRefGoogle ScholarPubMed