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Original Research

Open Access Special Issue

Cerebral blood flow velocity is associated with endothelial function in men

  • Nobuhiko Akazawa1,2
  • Hiroshi Kumagai3
  • Toru Yoshikawa4
  • Kanae Myoenzono5,6
  • Koichiro Tanahashi7
  • Seiji Maeda1,8

1Faculty of Health and Sport Sciences, University of Tsukuba, 305-8574 Tsukuba, Ibaraki, Japan

2Department of Sports Research, Japan Institute of Sports Sciences, 105-0056 Kita-ku, Tokyo, Japan

3The Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA

4Faculty of Health and Sport Sciences, Ryutsu Keizai University, 301-8555 Ryugasaki, Ibaraki, Japan

5Graduates School of Comprehensive Human Sciences, University of Tsukuba, 305-8574 Tsukuba, Ibaraki, Japan

6Humanome Lab Inc., 104-0045 Chuo-ku, Tokyo, Japan

7Department of Health and Sports Sciences, Kyoto Pharmaceutical University, 607-8414 Kyoto, Kyoto, Japan

8Faculty of Sport Sciences, Waseda University, 359-1192 Tokorozawa, Saitama, Japan

DOI: 10.31083/jomh.2021.049 Vol.17,Issue 3,July 2021 pp.41-46

Submitted: 23 April 2021 Accepted: 01 June 2021

Published: 08 July 2021

*Corresponding Author(s): Seiji Maeda E-mail:

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Background and objective: Reduction in cerebral blood flow with aging leads to cognitive decline and brain atrophy. Cerebrovascular hemodynamics are associated with vascular function. However, little is known about endothelial function in relation to cerebral blood flow at rest. The present study aimed to examine the association between microvascular endothelial function and middle cerebral blood flow.

Material and methods: This study involved 60 healthy middle-aged and elderly men. The microvascular endothelial function was measured via digital reactive hyperemia index using pulse amplitude tonometry, and the mean middle cerebral blood flow velocity and cerebrovascular conductance were measured using transcranial Doppler ultrasonography.

Results and conclusions: Reactive hyperemia index was significantly correlated with the mean middle cerebral blood flow velocity and cerebrovascular conductance. Multiple regression analysis further indicated that the correlation was significant after adjustment of covariates, such as age, body mass index, smoking status, medication history, blood pressure, and arterial stiffness. Further, Reactive hyperemia index was found to be a significant independent determinant of the mean middle cerebral blood flow velocity and cerebrovascular conductance. The present study demonstrated that vascular endothelial function is associated with cerebral blood flow and is an independent potential confounding factor in healthy middle-aged and older men.


Vascular function; Brain; Blood flow

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Nobuhiko Akazawa,Hiroshi Kumagai,Toru Yoshikawa,Kanae Myoenzono,Koichiro Tanahashi,Seiji Maeda. Cerebral blood flow velocity is associated with endothelial function in men. Journal of Men's Health. 2021. 17(3);41-46.


[1] Bakker SL, de Leeuw FE, den Heijer T, Koudstaal PJ, Hofman A, Breteler MM. Cerebral Haemodynamics in the Elderly: the Rotterdam Study. Neuroepidemiology. 2004; 23: 178–184.

[2] Demirkaya S, Uluc K, Bek S, Vural O. Normal Blood Flow Velocities of Basal Cerebral Arteries Decrease with Advancing Age: a Transcranial Doppler Sonography Study. The Tohoku Journal of Experimental Medicine. 2008; 214: 145–149.

[3] de la Torre JC. Critically attained threshold of cerebral hypoperfusion: the CATCH hypothesis of Alzheimer’s pathogenesis. Neurobiology of Aging. 2000; 21: 331–342.

[4] Bertsch K, Hagemann D, Hermes M, Walter C, Khan R, Naumann E. Resting cerebral blood flow, attention, and aging. Brain Research. 2009; 1267: 77–88.

[5] Ruitenberg A, den Heijer T, Bakker SL, van Swieten JC, Koudstaal PJ, Hofman A, et al. Cerebral hypoperfusion and clinical onset of dementia: the Rotterdam Study. Annals of Neurology. 2005; 57: 789–794.

[6] Tsao CW, Seshadri S, Beiser AS, Westwood AJ, Decarli C, Au R, et al. Relations of arterial stiffness and endothelial function to brain aging in the community. Neurology. 2013; 81: 984–991.

[7] Seals DR, Nagy EE, Moreau KL. Aerobic exercise training and vascular function with ageing in healthy men and women. Journal of Physiology. 2019; 597: 4901–4914.

[8] Adji A, O’Rourke MF, Namasivayam M. Arterial stiffness, its assess-ment, prognostic value, and implications for treatment. American Journal of Hypertension. 2011; 24: 5–17.

[9] O’Rourke M, Stone J, Adji A, Kim MO, Ki Y, Wang JG, et al. The human systemic and cerebral circulations; contrasts in structure and function. Artery Research. 2020; 26: 197–211.

[10] Tarumi T, Ayaz Khan M, Liu J, Tseng BY, Tseng BM, Parker R, et al. Cerebral hemodynamics in normal aging: central artery stiffness, wave reflection, and pressure pulsatility. Journal of Cerebral Blood Flow and Metabolism. 2014; 34: 971–978.

[11] Tarumi T, Zhang R. Cerebral blood flow in normal aging adults: cardiovascular determinants, clinical implications, and aerobic fitness. Journal of Neurochemistry. 2018; 144: 595–608.

[12] Barnes JN, Corkery AT. Exercise Improves Vascular Function, but does this Translate to the Brain? Brain Plasticity. 2018; 4: 65–79.

[13] Hoth KF, Tate DF, Poppas A, Forman DE, Gunstad J, Moser DJ, et al. Endothelial function and white matter hyperintensities in older adults with cardiovascular disease. Stroke. 2007; 38: 308–312.

[14] Gonzales MM, Tarumi T, Tanaka H, Sugawara J, Swann-Sternberg T, Goudarzi K, et al. Functional imaging of working memory and peripheral endothelial function in middle-aged adults. Brain and Cognition. 2010; 73: 146–151.

[15] Aaslid R, Markwalder TM, Nornes H. Noninvasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral arteries. Journal of Neurosurgery. 1982; 57: 769–774.

[16] Bonetti PO, Pumper GM, Higano ST, Holmes DR, Kuvin JT, Lerman A. Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia. Journal of the American College of Cardiology. 2004; 44: 2137–2141.

[17] Akazawa N, Tanahashi K, Kosaki K, Kumagai H, Oikawa S, Hamasaki A, et al. The impact of aerobic fitness on arterial stiffness and adrenal cortex hormones in middle-aged and older adults. Endocrine Journal. 2020; 67: 1199–1205.

[18] Knottnerus IL, Ten Cate H, Lodder J, Kessels F, van Oostenbrugge RJ. Endothelial Dysfunction in Lacunar Stroke: a Systematic Review. Cerebrovascular Diseases. 2009; 27: 519–526.

[19] Lind L, Nylander R, Johansson L, Kullberg J, Ahlström H, Larsson EM. Endothelium-dependent vasodilation is related to the occurrence of cortical brain infarcts at MR imaging: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Clinical Physiology and Functional Imaging. 2017; 37: 194–197.

[20] Bakker SL, de Leeuw FE, de Groot JC, Hofman A, Koudstaal PJ, Breteler MM. Cerebral vasomotor reactivity and cerebral white matter lesions in the elderly. Neurology. 1999; 52: 578–583.

[21] Lavi S, Gaitini D, Milloul V, Jacob G. Impaired cerebral CO_2 vasoreactivity: association with endothelial dysfunction. American Journal of Physiology-Heart and Circulatory Physiology. 2006; 291: H1856–H1861.

[22] Hashimoto M, Eto M, Akishita M, Kozaki K, Ako J, Iijima K, et al. Correlation between flow-mediated vasodilatation of the brachial artery and intima-media thickness in the carotid artery in men. Arteriosclerosis, Thrombosis, and Vascular Biology. 1999; 19: 2795–2800.

[23] Naiberg MR, Newton DF, Goldstein BI. Flow-Mediated Dilation and Neurocognition: Systematic Review and Future Directions. Psychosomatic Medicine. 2016; 78: 192–207.

[24] Dede DS, Yavuz B, Yavuz BB, Cankurtaran M, Halil M, Ulger Z, et al. Assessment of endothelial function in Alzheimer’s disease: is Alzheimer’s disease a vascular disease? Journal of the American Geriatrics Society. 2007; 55: 1613–1617.

[25] Vendemiale G, Romano AD, Dagostino M, de Matthaeis A, Serviddio G. Endothelial dysfunction associated with mild cognitive impairment in elderly population. Aging Clinical and Experimental Research. 2013; 25: 247–255.

[26] Marshall RS, Lazar RM, Pile-Spellman J, Young WL, Duong DH, Joshi S, et al. Recovery of brain function during induced cerebral hypoperfusion. Brain. 2001; 124: 1208–1217.

[27] Lucas SJE, Ainslie PN, Murrell CJ, Thomas KN, Franz EA, Cotter JD. Effect of age on exercise-induced alterations in cognitive executive function: Relationship to cerebral perfusion. Experimental Gerontol-ogy. 2012; 47: 541–551.

[28] Deanfield JE, Halcox JP, Rabelink TJ. Endothelial Function and Dysfunction: testing and clinical relevance. Circulation. 2007; 115: 1285–1295.

[29] Meredith IT, Currie KE, Anderson TJ, Roddy MA, Ganz P, Creager MA. Postischemic vasodilation in human forearm is dependent on endothelium-derived nitric oxide. The American Journal of Physiol-ogy. 1996; 270: H1435–H1440.

[30] Rosenberry R, Nelson MD. Reactive hyperemia: a review of methods, mechanisms, and considerations. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2020; 318: R605–R618.

[31] White RP, Deane C, Vallance P, Markus HS. Nitric oxide synthase inhibition in humans reduces cerebral blood flow but not the hyperemic response to hypercapnia. Stroke. 1998; 29: 467–472.

[32] Kielstein JT, Donnerstag F, Gasper S, Menne J, Kielstein A, Martens-Lobenhoffer J, et al. ADMA increases arterial stiffness and decreases cerebral blood flow in humans. Stroke. 2006; 37: 2024–2029.

[33] Presa JL, Saravia F, Bagi Z, Filosa JA. Vasculo-neuronal coupling and neurovascular coupling at the neurovascular unit: impact of hypertension. Frontiers in Physiology. 2020; 11: 584135.

[34] Longden TA, Dabertrand F, Koide M, Gonzales AL, Tykocki NR, Brayden JE, et al. Capillary K+—sensing initiates retrograde hyperpo-larization to increase local cerebral blood flow. Nature Neuroscience. 2017; 20: 717–726.

[35] Celermajer DS. Reliable endothelial function testing: at our fingertips?Circulation. 2008; 117: 2428–2430.

[36] Hamburg NM, Benjamin EJ. Assessment of Endothelial Function Using Digital Pulse Amplitude Tonometry. Trends in Cardiovascular Medicine. 2009; 19: 6–11.

[37] Matsue Y, Yoshida K, Nagahori W, Ohno M, Suzuki M, Matsumura A, et al. Peripheral microvascular dysfunction predicts residual risk in coronary artery disease patients on statin therapy. Atherosclerosis. 2014; 232: 186–190.

[38] Cerqueira A, Quelhas-Santos J, Sampaio S, Ferreira I, Relvas M, Mar-ques N, et al. Endothelial dysfunction is associated with cerebrovascular events in pre-dialysis CKD patients: a prospective study. Life. 2021; 11: 128.

[39] Alexandrov AV, Sloan MA, Wong LK, Douville C, Razumovsky AY, Koroshetz WJ, et al. Practice standards for transcranial Doppler ultrasound: part I–test performance. Journal of Neuroimaging. 2007; 17: 11–18.

[40] Keage HA, Churches OF, Kohler M, Pomeroy D, Luppino R, Bartolo ML, et al. Cerebrovascular function in aging and dementia: a systematic review of transcranial Doppler studies. Dementia and Geriatric Cognitive Disorders Extra. 2012; 2: 258–270.

[41] Serrador JM, Picot PA, Rutt BK, Shoemaker JK, Bondar RL. MRI measures of middle cerebral artery diameter in conscious humans during simulated orthostasis. Stroke. 2000; 31: 1672–1678.

[42] Green DJ, Hopkins ND, Jones H, Thijssen DH, Eijsvogels TM, Yeap BB. Sex differences in vascular endothelial function and health in humans: impacts of exercise. Experimental Physiology. 2016; 101: 230–242.

[43] Farajdokht F, Farhoudi M, Majdi A, Zamanlu M, Sadigh-Eteghad S, Vahedi S, et al. Testosterone may hold therapeutic promise for the treatment of ischemic stroke in aging: a closer look at laboratory findings. Advanced Pharmaceutical Bulletin. 2019; 9: 48–55.

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