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Age differences in arterial and venous extra-cerebral blood flow in healthy adults: contributions of vascular risk factors and genetic variants

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An Erratum to this article was published on 04 April 2017

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Abstract

Sufficient cerebral blood flow (CBF) and venous drainage are critical for normal brain function, and their alterations can affect brain aging. However, to date, most studies focused on arterial CBF (inflow) with little attention paid to the age differences in venous outflow. We measured extra-cerebral arterial and venous blood flow rates with phase-contrast MRI and assessed the influence of vascular risk factors and genetic polymorphisms (ACE insertion/deletion, COMT val158met, and APOEε4) in 73 adults (age 18–74 years). Advanced age, elevated vascular risk, ACE Deletion, and COMT met alleles were linked to lower in- and outflow, with no effects of APOE ε4 noted. Lower age-related CBF rate was unrelated to brain volume and was observed only in val homozygotes of COMTval158met. Thus, in a disease-free population, age differences in CBF may be notable only in persons with high vascular risk and carriers of genetic variants associated with vasoconstriction and lower dopamine availability. It remains to be established if treatments targeting alleviation of the mutable factors can improve the course of cerebrovascular aging in spite of the immutable genetic influence.

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  • 04 April 2017

    An erratum to this article has been published.

References

  • Aanerud J, Borghammer P, Chakravarty MM, Vang K, Rodell AB, Jónsdottir KY, Møller A, Ashkanian M, Vafaee MS, Iversen P, Johannsen P, Gjedde A (2012) Brain energy metabolism and blood flow differences in healthy aging. J Cereb Blood Flow Metab 32(7):1177–1187. doi:10.1038/jcbfm.2012.18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ances BM, Liang CL, Leontiev O, Perthen JE, Fleisher AS, Lansing AE, Buxton RB (2009) Effects of aging on cerebral blood flow, oxygen metabolism, and blood oxygenation level dependent responses to visual stimulation. Hum Brain Mapp 30(4):1120–1132. doi:10.1002/hbm.20574

    Article  PubMed  PubMed Central  Google Scholar 

  • Armulik A, Genové G, Betsholtz C (2011) Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell 21(2):193–215. doi:10.1016/j.devcel.2011.07.001

    Article  CAS  PubMed  Google Scholar 

  • Arndt S, Cohen G, Alliger RJ, Swayze VW II, Andreasen NC (1991) Problems with ratio and proportion measures of imaged cerebral structures. Psychiatry Res Neuroimaging 40:79–89

    Article  CAS  PubMed  Google Scholar 

  • Attwell D, Laughlin SB (2001) An energy budget for signaling in the grey matter of the brain. J Cereb Blood Flow Metab 21:1133–1145

    Article  CAS  PubMed  Google Scholar 

  • Ayanzen RH, Bird CR, Keller PJ, McCully FJ, Theobald MR, Heiserman JE (2000) Cerebral MR venography: normal anatomy and potential diagnostic pitfalls. AJNR 21:74–78

    CAS  PubMed  Google Scholar 

  • Bäckman L, Nyberg L, Lindenberger U, Li SC, Farde L (2006) The correlative triad among aging, dopamine, and cognition: current status and future prospects. Neurosci Biobehav Rev 30(6):791–807

    Article  PubMed  Google Scholar 

  • Bäckman L, Lindenberger U, Li SC, Nyberg L (2010) Linking cognitive aging to alterations in dopamine neurotransmitter functioning: recent data and future avenues. Neurosci Biobehav Rev 34(5):670–677. doi:10.1016/j.neubiorev.2009.12.008

    Article  PubMed  Google Scholar 

  • Bautista LE, Vargas CI, Oróstegui M, Gamarra G (2008) Population-based case-control study of renin-angiotensin system genes polymorphisms and hypertension among Hispanics. Hypertens Res 31(3):401–408. doi:10.1291/hypres.31.401

    Article  CAS  PubMed  Google Scholar 

  • Benetos A, Gautier S, Ricard S, Topouchian J, Asmar R, Poirier O, Larosa E, Guize L, Safar M, Soubrier F, Cambien F (1996) Influence of angiotensin-converting enzyme and angiotensin II type 1 receptor gene polymorphisms on aortic stiffness in normotensive and hypertensive patients. Circulation 94:698–703

    Article  CAS  PubMed  Google Scholar 

  • Billman GE (2011) Heart rate variability—a historical perspective. Front Physiol 2:86. doi:10.3389/fphys.2011.00086. (eCollection 2011)

    Article  PubMed  PubMed Central  Google Scholar 

  • Casey CS, Atagi Y, Yamazaki Y, Shinohara M, Tachibana M, Fu Y, Bu G, Kanekiyo T (2015) Apolipoprotein E inhibits cerebrovascular pericyte mobility through a RhoA protein-mediated pathway. J Bio Chem 290(22):14208–14217. doi:10.1074/jbc.M114.625251 (Epub 2015 Apr 22)

    Article  CAS  Google Scholar 

  • Chen JJ, Rosas HD, Salat DH (2011) Age-associated reductions in cerebral blood flow are independent from regional atrophy. Neuroimage 55:468–478. doi:10.1016/j.neuroimage.2010.12.032

    Article  PubMed  Google Scholar 

  • Chung CP, Lin YJ, Chao AC, Lin SJ, Chen YY, Wang YJ, Hu HH (2010 Jugular venous hemodynamic changes with aging. Ultrasound Med Biol 36(11):1776–1782. doi:10.1016/j.ultrasmedbio.2010.07.006

    Article  PubMed  Google Scholar 

  • Ciuti G, Righi D, Forzoni L, Fabbri A, Pignone AM (2013) Differences between internal jugular vein and vertebral vein flow examined in real time with the use of multigate ultrasound color Doppler. Am J Neuroradiol 34(10):2000–2004. doi:10.3174/ajnr.A3557 (Epub 2013 May 30)

    Article  CAS  PubMed  Google Scholar 

  • Dalkara T, Alarcon-Martinez L (2015) Cerebral microvascular pericytes and neurogliovascular signaling in health and disease. Brain Res 1623:3–17. doi:10.1016/j.brainres.2015.03.047 (Epub 2015 Apr 8)

    Article  CAS  PubMed  Google Scholar 

  • Damoiseaux JS, Viviano RP, Yuan P, Raz N (2016) Differential effect of age on posterior and anterior hippocampal functional connectivity. Neuroimage 133:468–476. doi:10.1016/j.neuroimage.2016.03.047 (Epub 2016 Mar 28)

    Article  PubMed  PubMed Central  Google Scholar 

  • Dixon RA, DeCarlo CA, MacDonald SWS, Vergote D, Jhamandas J and Westaway D (2014) APOE and COMT polymorphisms are complementary biomarkers of status, stability, and transitions in normal aging and early mild cognitive impairment. Front Aging Neurosci 6:236. doi:10.3389/fnagi.2014.00236

    Article  PubMed  PubMed Central  Google Scholar 

  • Doepp F, Schreiber SJ, von Münster T, Rademacher J, Klingebiel R, Valdueza JM (2004) How does the blood leave the brain? A systematic ultrasound analysis of cerebral venous drainage patterns. Neuroradiology 46(7):565–570

    Article  PubMed  Google Scholar 

  • Dolui S, Wang Z, Wang DJ, Mattay R, Finkel M, Elliott M, Desiderio L, Inglis B, Mueller B, Stafford RB, Launer LJ, Jacobs DR Jr, Bryan RN, Detre JA (2016) Comparison of non-invasive MRI measurements of cerebral blood flow in a large multisite cohort. J Cereb Blood Flow Metab 36:1244–1256. doi:10.1177/0271678X16646124 (Epub 2016 May 3)

    Article  PubMed  PubMed Central  Google Scholar 

  • ElSankari S, Balédent O, van Pesch V, Christian Sindic C, de Broqueville Q, Duprez T (2013) Concomitant analysis of arterial, venous, and CSF flows using phase-contrast MRI: a quantitative comparison between MS patients and healthy controls. J Cer Blood Flow Metab 33:1314–1321. doi:10.1038/jcbfm.2013.95

    Article  Google Scholar 

  • Feng W, Utriainen D, Trifan G, Sethi S, Hubbard D, Haacke EM (2012) Quantitative flow measurements in the internal jugular veins of multiple sclerosis patients using magnetic resonance imaging. Rev Recent Clin Trials 7(2):117–126

    Article  PubMed  Google Scholar 

  • Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12(3):189–198

    Article  CAS  PubMed  Google Scholar 

  • Greenfield JC Jr, Tindall GT (1968) Effect of norepinephrine, epinephrine, and angiotensin on blood flow in the internal carotid artery of man. J Clin Invest 47(7):1672–1684

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haacke EM, Patrick JL (1986) Reducing motion artifacts in two-dimensional Fourier transform imaging. Magn Reson Imaging 4(4):359–376

    Article  CAS  PubMed  Google Scholar 

  • Haacke EM, Feng W, Utriainen D, Trifan G, Wu Z, Latif Z, Katkuri Y, Hewett J, Hubbard D (2012) Patients with multiple sclerosis with structural venous abnormalities on MR imaging exhibit an abnormal flow distribution of the internal jugular veins. J Vasc Interv Radiol 23(1):60–68 .e1–e3. doi:10.1016/j.jvir.2011.09.027

    Google Scholar 

  • Haacke EM, Sethi, SK, Ultriainen DT (2015) The role of magnetic resonance imaging in assessing venous vascular abnormalities in the head and neck: a demonstration of cerebrospinal venous insufficiency in a subset of multiple sclerosis patients. Veins Lymphat 4:5012

    Article  Google Scholar 

  • Hagen K, Pettersen E, Stovner LJ, Skorpen F, Holmen J, Zwart J-A (2007) High systolic blood pressure is associated with val/val genotype in the catechol-O-Methyltransferase gene. Am J Hyp 20:21–26

    Article  CAS  Google Scholar 

  • Hajjar I, Sorond F, Lipsitz LA (2015) Apolipoprotein E, carbon dioxide vasoreactivity, and cognition in older adults: effect of hypertension. J Am Ger Soc 63(2):276–281

    Article  Google Scholar 

  • Hall CN, Reynell C, Gesslein B, Hamilton NB, Mishra A, Sutherland BA, O’Farrell FM, Buchan AM, Lauritzen M, Attwell D (2014) Capillary pericytes regulate cerebral blood flow in health and disease. Nature 508(7494):55–60

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hassan A, Lansbury A, Catto AJ, Guthrie A, Spencer J, Craven C, Grant PJ, Bamford JM (2002) Angiotensin converting enzyme insertion/deletion genotype is associated with leukoaraiosis in lacunar syndromes. J Neurol Neurosurg Psychiatry 72(3):343–346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Henriksen OM, Jensen LT, Krabbe K, Guldberg P, Teerlink T, Rosturp E (2014) Resting brain perfusion and selected vascular risk factors in healthy elderly subjects. PLoS One 9(5):e97363. doi:10.1371/journal.pone.0097363

    Article  PubMed  PubMed Central  Google Scholar 

  • Hutchison JL, Lu H, Rypma B (2013) Neural mechanisms of age-related slowing: the ∆CBF/∆CMRO2 ratio mediates age-differences in BOLD signal and human performance. Cereb Cortex 23:2337–2346. doi:10.1093/cercor/bhs233 (Epub 2012 Aug 8)

    Article  PubMed  Google Scholar 

  • Jagust W (2013) Vulnerable neural systems and the borderland of brain aging and neurodegeneration. Neuron 77(2):219–234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Janciauskiene SM, Erikson C, Warkentin S (2009) A link between sICAM-1, ACE and parietal blood flow in the aging brain. Neurobiol Aging 30(9):1504–1511. doi:10.1016/j.neurobiolaging.2007.08.025 (Epub 2008 Feb 19)

    Article  CAS  PubMed  Google Scholar 

  • Jiang J, Kokeny P, Ying W, Magnano C, Zivadinov R, Mark Haacke E (2015) Quantifying errors in flow measurement using phase contrast magnetic resonance imaging: comparison of several boundary detection methods. Magn Reson Imaging 33(2):185–193. doi:10.1016/j.mri.2014.10.009 (Epub 2014 Nov 12)

    Article  PubMed  Google Scholar 

  • Jose PA, Eisner GM, Felder RA (2003) Regulation of blood pressure by dopamine receptors. Nephron Physiol 95(2):19–27

    Article  Google Scholar 

  • Kim SM, Kim MJ, Rhee HY, Ryu CW, Kim EJ, Petersen ET, Jahng GH (2013) Regional cerebral perfusion in patients with Alzheimer’s disease and mild cognitive impairment: effect of APOE epsilon4 allele. Neuroradiology 55(1):25–34. doi:10.1007/s00234-012-1077-x. (Epub 2012 Jul 25)

    Article  PubMed  Google Scholar 

  • Lao JI, Montoriol C, Morer I, Beyer K (2005) Genetic contribution to aging: deleterious and helpful genes define life expectancy. Ann N Y Acad Sci 1057:50–63

    Article  CAS  PubMed  Google Scholar 

  • Lee A, Qiu A (2016) Modulative effects of COMT haplotype on age-related associations with brain morphology. Hum Brain Mapp. doi:10.1002/hbm.23161 (Epub ahead of print)

    PubMed Central  Google Scholar 

  • Lindenberger U, von Oertzen T, Ghisletta P, Hertzog C (2011) Cross-sectional age variance extraction: what’s change got to do with it? Psychol Aging 26(1):34–47

    Article  PubMed  Google Scholar 

  • Liu Y, Zhu X, Feinberg D, Guenther M, Gregori J, Weiner MW, Schuff N (2012) Arterial spin labeling MRI study of age and gender effects on brain perfusion hemodynamics. Magn Reson Med 68(3):912–922. doi:10.1002/mrm.23286 (Epub 2011 Dec 2)

    Article  PubMed  Google Scholar 

  • Lo YM, Lau TK, Chan LY, Leung TN, Chang AM (2000) Quantitative analysis of the bidirectional fetomaternal transfer of nucleated cells and plasma DNA. Clin Chem 46(9):1301–1309

    CAS  PubMed  Google Scholar 

  • Lotz J, Meier C, Leppert A, Galanski M (2002) Cardiovascular flow measurement with phase-contrast MR imaging: basic facts and implementation. Radiographics 22:651–671. doi:10.1148/radiographics.22.3.g02ma11651

    Article  PubMed  Google Scholar 

  • Lynch AI, Arnett DK, Pankow JS, Miller MB, North KE, Eckfeldt JH, Hunt SC, Rao DC, Djoussé L (2007) Sex-specific effects of ACE I/D and AGT-M235T on pulse pressure: the HyperGEN Study. Hum Gen 122(1):33–40

    Article  CAS  Google Scholar 

  • Magnano C, Belov P, Krawiecki J, Hagemeier J, Beggs C, Zivadinov R (2016) Internal jugular vein cross-sectional area enlargement is associated with aging in healthy individuals. PLoS One 11(2):e0149532. doi:10.1371/journal.pone.0149532 (eCollection 2016)

    Article  PubMed  PubMed Central  Google Scholar 

  • Mathalon DH, Sullivan EV, Rawles JM, Pfefferbaum A (1993) Correction for head size in brain-imaging measurement. Psychiatry Res Neuroimaging 50:121–139

    Article  CAS  PubMed  Google Scholar 

  • Mattace-Raso FU, van der Cammen TJ, Sayed-Tabatabaei FA, van Popele NM, Asmar R, Schalekamp MA, Hofman A, van Duijn CM, Witteman JC (2004) Angiotensin-converting enzyme gene polymorphism and common carotid stiffness. The Rotterdam Study. Atherosclerosis 174:121–126

    Article  CAS  PubMed  Google Scholar 

  • Meng L, Hou W, Chui J, Han R, Gelb AW (2015) Cardiac output and cerebral blood flow: the integrated regulation of brain perfusion in adult humans. Anesthesiology 123(5):1198–1208. doi:10.1097/ALN.0000000000000872

    Article  PubMed  Google Scholar 

  • Messina EJ, Weiner R, Kaley G (1975) Inhibition of bradykinin vasodilation and potentiation of norepinephrine and angiotensin vasoconstriction by inhibitors of prostaglandin synthesis in skeletal muscle of the rat. Circ Res 37(4):430–437

    Article  CAS  PubMed  Google Scholar 

  • Mohtasib RS, Lumley G, Goodwin JA, Emsley HC, Sluming V, Parkes LM (2012) Calibrated fMRI during a cognitive Stroop task reveals reduced metabolic response with increasing age. Neuroimage 59(2):1143–1151. doi:10.1016/j.neuroimage.2011.07.092

    Article  PubMed  Google Scholar 

  • Montesanto A, Crocco P, Tallaro F, Pisani F, Mazzei B, Mari V, Corsonello A, Lattanzio F, Passarino G, Rose G (2013) Common polymorphisms in nitric oxide synthase (NOS) genes influence quality of aging and longevity in humans. Biogerontology 14(2):177–186. doi:10.1007/s10522-013-9421-z (Epub 2013 Apr 10)

    Article  CAS  PubMed  Google Scholar 

  • Morgan DG, May PC, Finch CE (1987) Dopamine and serotonin systems in human and rodent brain: effects of age and neurodegenerative disease. J Am Ger Soc 35(4):334–345

    Article  CAS  Google Scholar 

  • Morra L, Zade D, McGlinchey RE, Milberg WP (2013) Normal aging and cognition: the unacknowledged contribution of cerebrovascular risk factors. Neuropsychol Dev Cog B Aging Neuropsychol Cog 20(3):271–297. doi:10.1080/13825585.2012.693905

    Article  CAS  Google Scholar 

  • Morris BJ, Zee RY, Schrader AP (1994) Different frequencies of angiotensin-converting enzyme genotypes in older hypertensive individuals. J Clin Invest 94:1085–1089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Després JP, Fullerton HJ, Howard VJ, Huffman MD, Judd SE, Kissela BM, Lackland DT, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Matchar DB, McGuire DK, Mohler ER 3rd, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Willey JZ, Woo D, Yeh RW, Turner MB; American Heart Association Statistics Committee and Stroke Statistics Subcommittee (2015) Heart disease and stroke statistics–2015 update: a report from the American Heart Association. Circulation 131(4): e29–322. doi:10.1161/CIR.0000000000000152. (Epub 2014 Dec 17)

    Article  PubMed  Google Scholar 

  • Nayak KS, Nielsen JF, Bernstein MA, Markl M, D Gatehouse P, M Botnar R, Saloner D, Lorenz C, Wen H, S Hu B, Epstein FH, N Oshinski J, Raman SV (2015) Cardiovascular magnetic resonance phase contrast imaging. J Cardiovasc Magn Reson 17:71. doi:10.1186/s12968-015-0172-7

    Article  PubMed  PubMed Central  Google Scholar 

  • Nishijima Y, Akamatsu Y, Weinstein PR, Liu J (2015) Collaterals: implications in cerebral ischemic diseases and therapeutic interventions. Brain Res 623:18–29. doi:10.1016/j.brainres.2015.03.006 (Epub 2015 Mar 11)

    Article  Google Scholar 

  • Nyberg L, Andersson M, Kauppi K, Lundquist A, Persson J, Pudas S, Nilsson LG (2014) Age-related and genetic modulation of frontal cortex efficiency. J Cogn Neurosci 26(4):746–754. doi:10.1162/jocn_a_00521 (Epub 2013 Nov 18)

    Article  PubMed  Google Scholar 

  • Papenberg G, Salami A, Persson J, Lindenberger U, Bäckman L (2015) Genetics and functional imaging: effects of APOE, BDNF, COMT, and KIBRA in aging. Neuropsychol Rev 25(1):47–62. doi:10.1007/s11065-015-9279-8 (Epub 2015 Feb 10)

    Article  PubMed  Google Scholar 

  • Parkes LM, Rashid W, Chard DT, Tofts PS (2004) Normal cerebral perfusion measurements using arterial spin labeling: reproducibility, stability, and age and gender effects. Magn Reson Med 51:736–743. doi:10.1002/mrm.20023

    Article  PubMed  Google Scholar 

  • Pucheu A, Evans J, Thomas D, Scheuble C, Pucheu M (1994) Doppler ultrasonography of normal neck veins. J Clin Ultrasound 22(6):367–373

    Article  CAS  PubMed  Google Scholar 

  • Raz N (2000) Aging of the brain and its impact on cognitive performance: integration of structural and functional findings. In: Craik FIM, Salthouse TA (eds) Handbook of aging and cognition—II. Erlbaum, Mahwah, pp 1–90

    Google Scholar 

  • Raz N, Lustig C (2014) Genetic variants and cognitive aging: destiny or a nudge? Psychol Aging 29(2):359–362. doi:10.1037/a0036893

    Article  PubMed  Google Scholar 

  • Raz N, Rodrigue KM (2006) Differential aging of the brain: Patterns, cognitive correlates and modifiers. Neurosci Biobehav Rev 30:730–748

    Article  PubMed  Google Scholar 

  • Raz N, Rodrigue KM, Kennedy KM, Land S (2009) Genetic and vascular modifiers of age-sensitive cognitive skills: effects of COMT, BDNF, ApoE and hypertension. Neuropsychology 23:105–116

    Article  PubMed  PubMed Central  Google Scholar 

  • Raz N, Dahle CL, Rodrigue KM, Kennedy KM, Land S (2011) Effects of age, genes, and pulse pressure on executive functions in healthy adults. Neurobiol Aging 32:1124–1137

    Article  PubMed  Google Scholar 

  • Saidi S, Zammiti W, Slamia LB, Ammou SB, Almawi WY, Mahjoub T (2009) Interaction of angiotensin-converting enzyme and apolipoprotein E gene polymorphisms in ischemic stroke involving large-vessel disease. J Thromb Thromb 27(1):68–74

    Article  CAS  Google Scholar 

  • Schrauben EM, Anderson AG, Johnson KM, Wieben O (2015) Respiratory-induced venous blood flow effects using flexible retrospective double-gating. J Magn Reson Imaging 42(1):211–216. doi:10.1002/jmri.24746 (Epub 2014 Sep 11)

    Article  PubMed  Google Scholar 

  • Sethi SK, Utriainen D, Daugherty AM, Feng W, Hewett JJ, Raz N, Haacke EM (2015) Jugular venous flow abnormalities in multiple sclerosis patients compared to normal controls. J Neuroimaging 25(4):600–607. doi:10.1111/jon.12183 (Epub 2014 Oct 15)

    Article  PubMed  Google Scholar 

  • Shan ZY, Vinkhuyzen AA, Thompson PM, McMahon KL, Blokland GA, de Zubicaray GI, Calhoun V, Martin NG, Visscher PM, Wright MJ, Reutens DC (2016). Genes influence the amplitude and timing of brain hemodynamic responses. NeuroImage 124(Pt A):663–671. doi:10.1016/j.neuroimage.2015.09.016. (Epub 2015 Sep 12)

    Google Scholar 

  • Shenkin HA, Scheuerman WG, Spitz EB, Groff RA (1949) The effects of change of position upon the cerebral circulation of man. J Appl Physiol 2(6):317–326

    CAS  PubMed  Google Scholar 

  • Shirahata N, Henriksen L, Vorstrup S, Holm S, Lauritzen M, Paulson OB, Lassen NA (1985) Regional cerebral blood flow assessed by 133Xe inhalation and emission tomography: normal values. J Comput Assist Tomogr 9(5):861–866

    Article  CAS  PubMed  Google Scholar 

  • Shrout PE, Fleiss JL (1979) Intraclass correlations: uses in assessing rater reliability. Psychol Bull 86(2):420–428

    Article  CAS  PubMed  Google Scholar 

  • Smith SM (2002) Fast robust automated brain extraction. Hum Brain Mapp 17(3):143–155

    Article  PubMed  Google Scholar 

  • Song Y, Stampfer MJ, Liu S (2004) Meta-analysis: apolipoprotein E genotypes and risk for coronary heart disease. Annals Int Med 141:137–147

    Article  Google Scholar 

  • Stoquart-Elsankari S, Lehmann P, Villette A, Czosnyka M, Meyer ME, Deramond H, Balédent O (2009) A phase-contrast MRI study of physiologic cerebral venous flow. J Cereb Blood Flow Metab 29:1208–1215. doi:10.1038/sj.jcbfm.jcbfm200929

    Article  PubMed  Google Scholar 

  • Taniwaki H, Kawagishi T, Emoto M, Shoji T, Hosoi M, Kogawa K, Nishizawa Y, Morii H (1999) Association of ACE gene polymorphism with arterial stiffness in patients with type 2 diabetes. Diabetes Care 22:1858–1864

    Article  CAS  PubMed  Google Scholar 

  • Tarnoki AD, Tarnoki DL, Giannoni MF, Baracchini C, Meneghetti G, Cardaioli G, Medda E, Stazi MA, Cotichini R, Fagnani C, Nisticò L, Lucatelli P, Fanelli F, Berczi V, Garami Z, Littvay L, Schillaci G (2014) Heritability of cerebral arterial velocity and resistance. J Cardiovasc Med (Hagerstown) (Epub ahead of print)

  • ten Dam VH, van den Heuvel DM, de Craen AJ, Bollen EL, Murray HM, Westendorp RG, Blauw GJ, van Buchem MA (2007) Decline in total cerebral blood flow is linked with increase in periventricular but not deep white matter hyperintensities. Radiology 243(1):198–203

    Article  PubMed  Google Scholar 

  • Thambisetty M, Beason-Held L, An Y, Kraut MA, Resnick SM (2010) APOE ε4 genotype and longitudinal changes in cerebral blood flow in normal aging. Arch Neurol 67(1):93–98

    Article  PubMed  PubMed Central  Google Scholar 

  • Thomason ME, Waugh CE, Glover GH, Gotlib IH (2009) COMT genotype and resting brain perfusion in children. NeuroImage 48(1):217–222

    Article  PubMed  PubMed Central  Google Scholar 

  • van Es AC, van der Grond J, ten Dam VH, de Craen AJ, Blauw GJ, Westendorp RG, Admiraal-Behloul F, van Buchem MA; PROSPER Study Group (2010). Associations between total cerebral blood flow and age related changes of the brain. PLoS One 5(3):e9825. doi:10.1371/journal.pone.0009825

    Article  PubMed  PubMed Central  Google Scholar 

  • Vauquelin G, Michotte Y, Smolders I, Sarre S, Ebinger G, Dupont A, Vanderheyden P (2002) Cellular targets for angiotensin II fragments: pharmacological and molecular evidence. J Renin Angiotensin Aldosterone Syst 3(4):195–204

    Article  CAS  PubMed  Google Scholar 

  • Vernooij MW, van der Lugt A, Ikram MA, Wielopolski PA, Vrooman HA, Hofman A, Krestin GP, Breteler MMB (2008) Total cerebral blood flow and total brain perfusion in the general population: the Rotterdam Scan Study. J Cereb Blood Flow Metab 28:412–419

    Article  PubMed  Google Scholar 

  • von Bohlen und Halbach O, Albrecht D (2006) The CNS renin-angiotensin system. Cell Tiss Res 326(2):599–616. doi:10.1007/s00441-006-0190-8

    Article  Google Scholar 

  • Yaffe K, Hoang TD, Byers AL, Barnes DE, Friedl KE (2014) Lifestyle and health-related risk factors and risk of cognitive aging among older veterans. Alzheimers Dement 10(3 Suppl):S111–121. doi:10.1016/j.jalz.2014.04.010

    Article  PubMed  Google Scholar 

  • Zamboni P, Sisini F, Menegatti E, Taibi A, Malagoni AM, Morovic S, Gambaccini M (2013) An ultrasound model to calculate the brain blood outflow through collateral vessels: a pilot study. BMC Neurol 13:81. doi:10.1186/1471-2377-13-81

    Article  PubMed  PubMed Central  Google Scholar 

  • Zarrinkoob L, Ambarki K, Wåhlin A, Birgander R, Eklund A, Malm J (2015) Blood flow distribution in cerebral arteries. J Cereb Blood Flow Metab 35(4):648–654. doi:10.1038/jcbfm.2014.241

    Article  PubMed  PubMed Central  Google Scholar 

  • Zeng C, Zhang M, Asico LD, Eisner GM, Jose PA (2007) The dopaminergic system in hypertension. Clin Sci (Lond) 112(12):583–597

    Article  CAS  Google Scholar 

  • Zhang Y, Brady M, Smith S (2001) Segmentation of brain MR images through a hidden Markov random field model and the expectation–maximization algorithm. IEEE Trans Med Imag 20(1):45–57

    Article  CAS  Google Scholar 

  • Zhao M, Amin-Hanjani S, Ruland S, Curcio AP, Ostergren L, Charbel FT (2007) Regional cerebral blood flow using quantitative MR angiography. AJNR 28(8):1470–1473

    Article  CAS  PubMed  Google Scholar 

  • Zhu S, Wang Z, Wu X, Shu Y, Lu D (2014) Apolipoprotein E polymorphism is associated with lower extremity deep venous thrombosis: color-flow Doppler ultrasound evaluation. Lipids Health Dis 13:21

    Article  PubMed  PubMed Central  Google Scholar 

  • Zivadinov R, Chung CP (2013) Potential involvement of the extracranial venous system in central nervous system disorders and aging. BMC Med 11:260. doi:10.1186/1741-7015-11-260

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported in part by a Grant from the National Institute on Aging R37 AG011230 to NR and National Heart, Lung and Blood Institute Grant R42 HL112580 to EMH. AMD was supported by a Beckman Institute Postdoctoral Fellowship at the University of Illinois at Urbana-Champaign, with funding provided by the Arnold and Mabel Beckman Foundation. The authors gratefully acknowledge Dr. Susan Land, Director of Wayne State University Applied Genomics Technology Center who conducted DNA analysis.

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  1. Institute of Gerontology, Wayne State University, 87 E Ferry St. 226 Knapp Bldg., Detroit, MI, 48202, USA

    Naftali Raz, Ana M. Daugherty & Muzamil Arshad

  2. Department of Psychology, Wayne State University, 5057 Woodward Ave., Detroit, MI, 48202, USA

    Naftali Raz

  3. Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, 405 N Matthews Ave., Urbana, IL, 61801, USA

    Ana M. Daugherty

  4. The MRI Institute of Biomedical Research, 440 E Ferry St., Detroit, MI, 48202, USA

    Sean K. Sethi & E. Mark Haacke

  5. Department of Psychiatry and Behavioral Sciences, Wayne State University, 3990 John R, Detroit, MI, 48201, USA

    Muzamil Arshad

  6. Department of Radiology, Wayne State University, 3990 John R, Detroit, MI, 48201, USA

    E. Mark Haacke

Authors
  1. Naftali Raz
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  2. Ana M. Daugherty
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  3. Sean K. Sethi
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  4. Muzamil Arshad
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  5. E. Mark Haacke
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Corresponding author

Correspondence to Naftali Raz.

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An erratum to this article is available at https://doi.org/10.1007/s00429-017-1398-y.

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Raz, N., Daugherty, A.M., Sethi, S.K. et al. Age differences in arterial and venous extra-cerebral blood flow in healthy adults: contributions of vascular risk factors and genetic variants. Brain Struct Funct 222, 2641–2653 (2017). https://doi.org/10.1007/s00429-016-1362-2

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  • DOI: https://doi.org/10.1007/s00429-016-1362-2

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