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Brain Arterial Diameters and Cognitive Performance: The Northern Manhattan Study

  • Jose Gutierrez (a1), Erin Kulick (a1) (a2), Yeseon Park Moon (a1), Chuanhui Dong (a3) (a4), Ken Cheung (a5), Bagci Ahmet (a6), Yaakov Stern (a1), Noam Alperin (a6), Tatjana Rundek (a3) (a4) (a7), Ralph L. Sacco (a3), Clinton B. Wright (a8) and Mitchell S.V. Elkind (a1) (a2)...


Objectives: To test the hypothesis that brain arterial diameters are associated with cognitive performance, particularly in arteries supplying domain-specific territories. Methods: Stroke-free participants in the Northern Manhattan Study were invited to have a brain MRI from 2003–2008. The luminal diameters of 13 intracranial arterial segments were obtained using time-of-flight magnetic resonance angiogram (MRA), and then averaged and normalized into a global score and region-specific arterial diameters. Z-Scores for executive function, semantic memory, episodic memory and processing speed were obtained at MRI and during follow-up. Adjusted generalized additive models were used to assess for associations. Results: Among the 1034 participants with neurocognitive testing and brain MRI, there were non-linear relationships between left anterior (ACA) and middle cerebral artery (MCA) diameter and semantic memory Z-scores (χ2=10.00; DF=3; p=.019), and left posterior cerebral artery (PCA) and posterior communicating artery (Pcomm) mean diameter and episodic memory Z-scores (χ2=9.88; DF=3; p=.020). Among the 745 participants who returned for 2nd neuropsychological testing, on average 5.0±0.4 years after their MRI, semantic memory change was associated non-linearly with the left PCA/Pcomm mean diameter (χ2=13.09; DF=3; p=.004) and with the right MCA/ACA mean diameter (χ2=8.43; DF=3; p=.03). In both cross-sectional and longitudinal analyses, participants with the larger brain arterial diameters had more consistently lower Z-scores and greater decline than the rest of the participants. Conclusions: Brain arterial diameters may have downstream effects in brain function presenting as poorer cognition. Identifying the mechanisms and the directionality of such interactions may increase the understanding of the vascular contribution to cognitive impairment and dementia. (JINS, 2018, 24, 335–346)


Corresponding author

Correspondence and reprint requests to: Jose Gutierrez, 710 W 168th Street, 6th Floor, Suite 639, New York, NY, 10032. E-mail:


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Baldo, J.V., Arévalo, A., Patterson, J.P., & Dronkers, N.F. (2013). Grey and white matter correlates of picture naming: Evidence from a voxel-based lesion analysis of the Boston Naming Test. Cortex, 49(3), 658667. doi: 10.1016/j.cortex.2012.03.001
Bouissou, H., Emery, M., & Sorbara, R. (1975). Age related changes of the middle cerebral artery and a comparison with the radial and coronary artery. Angiology, 26(3), 257268.
Brown, W.R., & Thore, C.R. (2011). Review: Cerebral microvascular pathology in ageing and neurodegeneration. Neuropathology and Applied Neurobiology, 37(1), 5674. doi: 10.1111/j.1365-2990.2010.01139.x
Bryden, P., & Roy, E. (2005). A new method of administering the Grooved Pegboard Test: Performance as a function of handedness and sex. Brain and Cognition, 58(3), 258268.
Chmayssani, M., Lazar, R.M., Hirsch, J., & Marshall, R.S. (2009). Reperfusion normalizes motor activation patterns in large-vessel disease. Annals of Neurology, 65(2), 203208. doi: 10.1002/ana.21554
D’Elia, L., & Satz, P. (1996). Color trails test. Luyz, FL: Psychological Assessment Resources.
de Leeuw, F.E., Richard, F., de Groot, J.C., van Duijn, C.M., Hofman, A., Van Gijn, J., & Breteler, M.M. (2004). Interaction between hypertension, apoE, and cerebral white matter lesions. Stroke, 35(5), 10571060. doi: 10.1161/01.str.0000125859.71051.83
DeCarli, C., Maisog, J., Murphy, D.G., Teichberg, D., Rapoport, S.I., & Horwitz, B. (1992). Method for quantification of brain, ventricular, and subarachnoid CSF volumes from MR images. Journal of Computer Assisted Tomography, 16(2), 274284.
Duff, K., & Ramezani, A. (2015). Regression-based normative formulae for the repeatable battery for the assessment of neuropsychological status for older adults. Archives of Clinical Neuropsychology, 30(7), 600604. doi: 10.1093/arclin/acv052
Duff, K., Schoenberg, M.R., Mold, J.W., Scott, J.G., & Adams, R.L. (2011). Gender differences on the Repeatable Battery for the Assessment of Neuropsychological Status subtests in older adults: Baseline and retest data. Journal of Clinical and Experimental Neuropsychology, 33(4), 448455. doi: 10.1080/13803395.2010.533156
Echt, D.S., Liebson, P.R., Mitchell, L.B., Peters, R.W., Obias-Manno, D., Barker, A.H., et al. (1991). Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. New England Journal of Medicine, 324(12), 781788. doi: 10.1056/nejm199103213241201
Forteza, A., Echeverria, Y., Haussen, D.C., Gutierrez, J., Wiley, E., & De Gusmao, C. (2010). Cerebral vasomotor reactivity monitoring in posterior reversible encephalopathy syndrome. BMJ Case Reports, 2010. doi: 10.1136/bcr.10.2009.2345
Frearson, W., & Eysenck, H.J. (1986). Intelligence, reaction time (RT) and a new ‘odd-man-out’ RT paradigm. Personality and Individual Differences, 7(6), 807817. doi: 10.1016/0191-8869(86)90079-6
Gorelick, P.B., Scuteri, A., Black, S.E., Decarli, C., Greenberg, S.M., Iadecola, C., & Seshadri, S. (2011). Vascular contributions to cognitive impairment and dementia: A statement for healthcare professionals from the american heart association/american stroke association. Stroke, 42(9), 26722713. doi:STR.0b013e3182299496 [pii] 10.1161/STR.0b013e3182299496.
Gosling, R.G., & Budge, M.M. (2003). Terminology for describing the elastic behavior of arteries. Hypertension, 41(6), 11801182. doi: 10.1161/01.hyp.0000072271.36866.2a
Gutierrez, J. (2014). Dolichoectasia and the risk of stroke and vascular disease: A critical appraisal. Current Cardiology Reports, 16(9), 525. doi: 10.1007/s11886-014-0525-0
Gutierrez, J., Bagci, A., Gardener, H., Rundek, T., Ekind, M.S., Alperin, N., & Wright, C.B. (2014). Dolichoectasia diagnostic methods in a multi-ethnic, stroke-free cohort: Results from the northern Manhattan study. Journal of Neuroimaging, 24(3), 226231. doi: 10.1111/j.1552-6569.2012.00781.x
Gutierrez, J., Cheung, H.W., Bagci, A., Rundek, T., Alperin, N., Sacco, R., & Wright, C. (2016). Brain arterial diameters as biomarkers of cognitive performance: Results from the Northern Manhattan Study. Neurology, 86(16), P2.246.
Gutierrez, J., Cheung, K., Bagci, A., Rundek, T., Alperin, N., Sacco, R.L., & Elkind, M.S. (2015). Brain arterial diameters as a risk factor for vascular events. Journal of the American Heart Association, 4(8), e002289. doi: 10.1161/JAHA.115.002289
Gutierrez, J., Elkind, M.S., Cheung, K., Rundek, T., Sacco, R.L., & Wright, C.B. (2015). Pulsatile and steady components of blood pressure and subclinical cerebrovascular disease: The Northern Manhattan Study. Journal of Hypertension, 33(10), 21152122. doi: 10.1097/HJH.0000000000000686
Gutierrez, J., Honig, L., Elkind, M.S., Mohr, J.P., Goldman, J., Dwork, A.J., & Marshall, R.S. (2016). Brain arterial aging and its relationship to Alzheimer dementia. Neurology, 86(16), 15071515. doi: 10.1212/WNL.0000000000002590
Gutierrez, J., Sultan, S., Bagci, A., Rundek, T., Alperin, N., Elkind, M.S., & Wright, C.B. (2013). Circle of Willis configuration as a determinant of intracranial dolichoectasia. Cerebrovascular Diseases, 36(5-6), 446453. doi: 10.1159/000356347
Hebert, L.E., Weuve, J., Scherr, P.A., & Evans, D.A. (2013). Alzheimer disease in the United States (2010-2050) estimated using the 2010 census. Neurology, 80(19), 17781783. doi: 10.1212/WNL.0b013e31828726f5
Hendrikse, J., van Raamt, A.F., van der Graaf, Y., Mali, W.P., & van der Grond, J. (2005). Distribution of cerebral blood flow in the circle of Willis. Radiology, 235(1), 184189. doi:10.1148/radiol.2351031799
Hillis, A.E., Barker, P.B., Wityk, R.J., Aldrich, E.M., Restrepo, L., Breese, E.L., & Work, M. (2004). Variability in subcortical aphasia is due to variable sites of cortical hypoperfusion. Brain and Language, 89(3), 524530. doi: 10.1016/j.bandl.2004.01.007
Honig, L.S., Kukull, W., & Mayeux, R. (2005). Atherosclerosis and AD: Analysis of data from the US National Alzheimer’s Coordinating Center. Neurology, 64(3), 494500. doi:64/3/494 [pii] 10.1212/01.WNL.0000150886.50187.30.
Hughes, T.M., Kuller, L.H., Barinas-Mitchell, E.J., Mackey, R.H., McDade, E.M., Klunk, W.E., & Lopez, O.L. (2013). Pulse wave velocity is associated with beta-amyloid deposition in the brains of very elderly adults. Neurology, 81(19), 17111718. doi: 10.1212/01.wnl.0000435301.64776.37
Kaplan, E., Goodglass, H., & Weintraub, S. (2001). Boston naming test. Austin, TX: Pro-ed.
Knecht, S., Dräger, B., Deppe, M., Bobe, L., Lohmann, H., Flöel, A., & Henningsen, H. (2000). Handedness and hemispheric language dominance in healthy humans. Brain, 123(12), 25122518. doi: 10.1093/brain/123.12.2512
Kubis, N., Checoury, A., Tedgui, A., & Levy, B.I. (2001). Adaptive common carotid arteries remodeling after unilateral internal carotid artery occlusion in adult patients. Cardiovascular Research, 50(3), 597602.
Ogasawara, K., Yukawa, H., Kobayashi, M., Mikami, C., Konno, H., Terasaki, T., & Ogawa, A. (2003). Prediction and monitoring of cerebral hyperperfusion after carotid endarterectomy by using single-photon emission computerized tomography scanning. Journal of Neurosurgery, 99(3), 504510. doi: 10.3171/jns.2003.99.3.0504
Li, Z., Yuan, A., Han, G., Gao, G., & Li, Q. (2014). Rank-based tests for identifying multiple genetic variants associated with quantitative traits. Annals of Human Genetics, 78(4), 306310. doi: 10.1111/ahg.12067
Marmarou, A., Takagi, H., & Shulman, K. (1980). Biomechanics of brain edema and effects on local cerebral blood flow. Advances in Neurology, 28, 345358.
McSweeny, A.J., Naugle, R.I., Chelune, G.J., & Lüders, H. (1993). “T Scores for Change”: An illustration of a regression approach to depicting change in clinical neuropsychology. The Clinical Neuropsychologist, 7(3), 300312.
Meinzer, M., Wilser, L., Flaisch, T., Eulitz, C., Rockstroh, B., Conway, T., & Crosson, B. (2009). Neural signatures of semantic and phonemic fluency in young and old adults. Journal of Cognitive Neuroscience, 21(10), 20072018. doi: 10.1162/jocn.2009.21219
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, 134(Pt 11), 33983407. doi: 10.1093/brain/awr253
Ochi, N., Kohara, K., Tabara, Y., Nagai, T., Kido, T., Uetani, E., & Miki, T. (2010). Association of central systolic blood pressure with intracerebral small vessel disease in Japanese. American Journal of Hypertension, 23(8), 889894. doi: 10.1038/ajh.2010.60
Ott, C., Raff, U., Harazny, J.M., Michelson, G., & Schmieder, R.E. (2013). Central pulse pressure is an independent determinant of vascular remodeling in the retinal circulation. Hypertension, 61(6), 13401345. doi: 10.1161/hypertensionaha.111.00617
Peters, R., Beckett, N., Fagard, R., Thijs, L., Wang, J.G., Forette, F., & Bulpitt, C. (2013). Increased pulse pressure linked to dementia: Further results from the Hypertension in the Very Elderly Trial - HYVET. Journal of Hypertension, 31(9), 18681875. doi: 10.1097/HJH.0b013e3283622cc6
Roher, A.E., Esh, C., Kokjohn, T.A., Kalback, W., Luehrs, D.C., Seward, J.D., & Beach, T.G. (2003). Circle of willis atherosclerosis is a risk factor for sporadic Alzheimer’s disease. Arteriosclerosis, Thrombosis, and Vascular Biology, 23(11), 20552062. doi: 10.1161/01.ATV.0000095973.42032.44
Sacco, R.L., Boden-Albala, B., Gan, R., Chen, X., Kargman, D.E., Shea, S., & Hauser, W.A. (1998). Stroke Incidence among White, Black, and Hispanic Residents of an urban community: The Northern Manhattan Stroke Study. American Journal of Epidemiology, 147(3), 259268.
Sacco, R.L., Kargman, D.E., Gu, Q., & Zamanillo, M.C. (1995). Race-ethnicity and determinants of intracranial atherosclerotic cerebral infarction. The Northern Manhattan Stroke Study. Stroke, 26(1), 1420.
Schaefer, E.J., Lamon-Fava, S., Jenner, J.L., McNamara, J.R., Ordovas, J.M., Davis, C.E., & Levy, R.I. (1994). Lipoprotein(a) levels and risk of coronary heart disease in men. The lipid Research Clinics Coronary Primary Prevention Trial. JAMA, 271(13), 9991003.
Sorbara, R. (1972). Étude comparative du vieillissement des artères du polygone de Willis. [Toulouse]: Université Paul-Sabatier.
Stuss, D.T., Alexander, M.P., Palumbo, C.L., Buckle, L., Sayer, L., & Pogue, J. (1994). Organizational strategies with unilateral or bilateral frontal lobe injury in word learning tasks. Neuropsychology, 8(3), 355.
Szabo, K., Forster, A., Jager, T., Kern, R., Griebe, M., Hennerici, M.G., & Gass, A. (2009). Hippocampal lesion patterns in acute posterior cerebral artery stroke: Clinical and MRI findings. Stroke, 40(6), 20422045. doi: 10.1161/strokeaha.108.536144
Tomaszewki Farias, S., Harrington, G., Broomand, C., & Seyal, M. (2005). Differences in functional MR imaging activation patterns associated with confrontation naming and responsive naming. AJNR American Journal of Neuroradiology, 26(10), 24922499.
Tombaugh, T.N., Kozak, J., & Rees, L. (1999). Normative data stratified by age and education for two measures of verbal fluency: FAS and animal naming. Archives of Clinical Neuropsychology, 14(2), 167177.
Tsao, C.W., Seshadri, S., Beiser, A.S., Westwood, A.J., Decarli, C., Au, R., & Mitchell, G.F. (2013). Relations of arterial stiffness and endothelial function to brain aging in the community. Neurology, 81(11), 984991. doi: 10.1212/WNL.0b013e3182a43e1c
van der Zwan, A., Hillen, B., Tulleken, C.A., & Dujovny, M. (1993). A quantitative investigation of the variability of the major cerebral arterial territories. Stroke, 24(12), 19511959.
Vermeer, S.E., Prins, N.D., den Heijer, T., Hofman, A., Koudstaal, P.J., & Breteler, M.M. (2003). Silent brain infarcts and the risk of dementia and cognitive decline. New England Journal of Medicine, 348(13), 12151222. doi: 10.1056/NEJMoa022066348/13/1215 [pii].
Zeeman, G.G., Hatab, M., & Twickler, D.M. (2003). Maternal cerebral blood flow changes in pregnancy. American Journal of Obstetrics and Gynecology, 189(4), 968972. doi: 10.1067/S0002-9378(03)00820-2



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