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Vascular health and cognitive function in older adults with cardiovascular disease

Artery Research volume 2, pages 35–43 (2008)Cite this article

Summary

Background

We hypothesized that changes in vascular flow dynamics resulting from age and cardiovascular disease (CVD) would correlate to neurocognitive capacities, even in adults screened to exclude dementia and neurological disease. We studied endothelial-dependent as well as endothelial-independent brachial responses in older adults with CVD to study the associations of vascular responses with cognition. Comprehensive neurocognitive testing was used to discern which specific cognitive domain(s) correlated with the vascular responses.

Methods

Eighty-eight independent, community-dwelling older adults (70.02 ±7.67 years) with mild to severe CVD were recruited. Enrollees were thoroughly screened to exclude neurological disease and dementia. Flow-mediated (endothelial-dependent) and nitroglycerin-mediated (endothelial-independent) brachial artery responses were assessed using 2-D ultrasound. Cognitive functioning was assessed using comprehensive neuropsychological testing. Linear regression analyses were used to evaluate the relationships between the endothelial-dependent and endothelial-independent vascular flow dynamics and specific domains of neurocognitive function.

Results

Endothelial-dependent and endothelial-independent brachial artery responses both correlated with neurocognitive testing indices. The strongest independent relationship was between endothelial function and measures of attention-executive functioning.

Conclusions

Endothelial-dependent and endothelial-independent vascular responsiveness correlate with neurocognitive performance among older CVD patients, particularly in the attention-executive domain. While further study is needed to substantiate causal relationships, our data demonstrate that brachial responses serve as important markers of risk for common neurocognitive changes. Learning and behavior-modifying therapeutic strategies that compensate for such common, insidious neurocognitive limitations will likely improve caregiving efficacy.

References

  1. Ludmer PL, Selwyn AP, Shook TL, Wayne RR, Mudge GH, Alexander RW, et al. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med 1986;315:1046–51.

    Google Scholar 

  2. Egashira K, Inou T, Hirooka Y, Yamada A, Urabe Y, Takeshita A. Evidence of impaired endothelium-dependent coronary vasodilatation in patients with angina pectoris and normal coronary angiograms. N Engl J Med 1993;328(23):1659–64.

    Google Scholar 

  3. Mitchell GF, Guo CY, Benjamin EJ, Larson MG, Keyes MJ, Vita JA, et al. Cross-sectional correlates of increased aortic stiffness in the community: the Framingham heart study. Circulation 2007;115(20):2628–36.

    Google Scholar 

  4. Gerhard M, Roddy MA, Creager SJ, Creager MA. Aging progressively impairs endothelium-dependent vasodilation in forearm resistance vessels of humans. Hypertension 1996;27(4): 849–53.

    Google Scholar 

  5. Taddei S, Virdis A, Mattei P, Ghiadoni L, Gennari A, Fasolo CB, et al. Aging and endothelial function in normotensive subjects and patients with essential hypertension. Circulation 1995; 91(7):1981–7.

    Google Scholar 

  6. Kass DA. Ventricular arterial stiffening: integrating the patho-physiology. Hypertension 2005;46(1):185–93.

    Google Scholar 

  7. Neunteufl T, Katzenschlager R, Hassan A, Klaar U, Schwarzacher S, Glogar D, et al. Systemic endothelial dysfunction is related to the extent and severity of coronary artery disease. Atherosclerosis 1997;129(1):111–8.

    Google Scholar 

  8. Al-Shaer MH, Choueiri NE, Correia ML, Sinkey CA, Barenz TA, Haynes WG. Effects of aging and atherosclerosis on endothelial and vascular smooth muscle function in humans. Int J Cardiol 2006;109(2):201–6.

    Google Scholar 

  9. Yeboah J, Crouse JR, Hsu FC, Burke GL, Herrington DM. Brachial flow-mediated dilation predicts incident cardiovascular events in older adults: the cardiovascular health study. Circulation 2007;115(18):2390–7.

    Google Scholar 

  10. Fathi R, Haluska B, Isbel N, Short L, Marwick TH. The relative importance of vascular structure and function in predicting cardiovascular events. J Am Coll Cardiol 2004; 43(4):616–23.

    Google Scholar 

  11. Uehata A, Lieberman EH, Gerhard MD, Anderson TJ, Ganz P, Polak JF, et al. Noninvasive assessment of endothelium-depen-dent flow-mediated dilation of the brachial artery. Vasc Med 1997;2(2):87–92.

    Google Scholar 

  12. Anderson TM, Uehata A, Gerhard MD, Meredith IT, Knab S, Delagrange D, et al. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol 1995;26(5):1235–41.

    Google Scholar 

  13. Verma S, Buchanan MR, Anderson TJ. Endothelial function testing as a biomarker of vascular disease. Circulation 2003;108: 2054–9.

    Google Scholar 

  14. Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 2002;39(2):257–65.

    Google Scholar 

  15. Lakatta EG. Age-associated cardiovascular changes in health: impact on cardiovascular disease in older persons. Heart Fail Rev 2002;7(1):29–49 (Review).

    Google Scholar 

  16. Solfrizzi V, Panza F, Colacicco AM, D’Introno A, Capurso C, Torres F, et al. Italian longitudinal study on aging working group. Vascular risk factors, incidence of MCI, and rates of progression to dementia. Neurology 2004;63(10):1882–91.

    Google Scholar 

  17. Panza F, Solfrizzi V, Colacicco AM, D’Intrano A, Caputso C, Delparigi A, et al. Cerebrovascular disease in the elderly: lipoprotein metabolism and cognitive decline. Aging Clin Exp Res 2006;18(2):144–8.

    Google Scholar 

  18. Bowler JV, Hachinski V. Vascular cognitive impairment: a new approach to vascular dementia. Baillieres Clin Neurol 1995; 4:357–76.

    Google Scholar 

  19. Hanon O, Haulon S, Lenoir H, Seux ML, Rigaud AS, Safar M, et al. Relationship between arterial stiffness and cognitive function in elderly subjects with complaints of memory loss. Stroke 2005;36:2193–7.

    Google Scholar 

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

    Google Scholar 

  21. DeCarli C, Miller BL, Swan GE, Reed T, Wolf PA, Carmelli D. Cerebrovascular and brain morphologic correlates of mild cognitive impairment in the National Heart, Lung, and Blood Institute Twin Study. Arch Neurol 2001;58:643–7.

    Google Scholar 

  22. Andresen J, Shari NI, Bryan Jr RM. Endothelial influences on cerebrovascular tone. Appl Physiol 2006;100:318–27.

    Google Scholar 

  23. Scuteri A, Tesauro M, Appolloni S, Preziosi F, Brancati AM, Volpe M, et al. Arterial stiffness as an independent predictor of longitudinal changes in cognitive function in the older individual. J Hypertens 2007;25(5):1035–40.

    Google Scholar 

  24. Scuteri A, Brancati AM, Gianni W, Assisi A, Volpe M. Arterial stiffness is an independent risk factor for cognitive impairment in the elderly: a pilot study. J Hypertens 2005 Jun;23(6):1211–6.

    Google Scholar 

  25. Moser DJ, Hoth KF, Robinson RG, Paulsen JS, Sinkey CA, Benjamin ML, et al. Blood vessel function and cognition in elderly patients with atherosclerosis. Stroke 2004;35:e369–72.

    Google Scholar 

  26. Moser DJ, Robinson RG, Hynes SM, Reese RL, Arndt S, Paulsen JS, et al. Neuropsychological performance is associated with vascular function in patients with atherosclerotic vascular disease. Arterioscler Thromb Vasc Biol 2007;27: 141–6.

    Google Scholar 

  27. Folstein MF, Folstein SE, McHugh PR. ‘‘Mini-mental state’’. A practical method for grading the cognitive state of patients for the clinician. J Psychiatry Res 1975;12:189–98.

    Google Scholar 

  28. Kathiresan S, Gona P, Larson MG, Vita JA, Mitchell GF, Tofler GH, et al. Cross-sectional relations of multiple bio-markers from distinct biological pathways to brachial artery endothelial function. Circulation 2006;113(7):938–45.

    Google Scholar 

  29. Jurica P, Leitten CL, Mattis S. Dementia Rating Scale-2 (DRS-2). Odessa, FL: Psychological Assessment Resources; 1998.

    Google Scholar 

  30. Smith GE, Ivnik RJ, Malec JF, Kokmen E, Tangalos E, Petersen RC. Psychometric properties of the Mattis Dementia Rating Scale. Assessment 1994;1:123–32.

    Google Scholar 

  31. Kaplan E, Goodglass H, Weintraub S. Boston Naming Test. Philadelphia: Lea and Febiger; 1983.

    Google Scholar 

  32. Lezak M. Neuropsychological assessment. New York, NY: Oxford University Press; 1995.

    Google Scholar 

  33. The Hooper visual organization test. Los Angeles, CA: Western Psychological Services; 1983.

  34. Wechsler D. Manual for the Wechsler Adult Intelligence Scale. 3rd ed. San Antonio, TX: The Psychological Corporation; 1979.

    Google Scholar 

  35. Delis D, Kramer J, Kaplan E, Ober BA. Manual: California Verbal Learning Test, adult version. San Antonio, TX: Psychological Corporation; 1987.

    Google Scholar 

  36. Benedict R. Brief Visuospatial Memory Test – revised: professional manual. Odessa, FL: Psychological Assessment Resources; 1994.

    Google Scholar 

  37. Reitan R. Validity of the Trail Making Test as an indicator of organic brain damage. Percept Mot Skills 1958;8:271–6.

    Google Scholar 

  38. Golden C. Stroop color and word task: a manual for clinical and experimental uses. Wood Dale, IL: Stoeling; 1978.

    Google Scholar 

  39. Eslinger P, Damasio A, Benton A. The Iowa screening battery for mental status assessment. Iowa City, IA: University of Iowa; 1984.

    Google Scholar 

  40. Klove H. Clinical neuropsychology. In: Forster FM, editor. The medical clinics of North America. New York: Saunders; 1963.

    Google Scholar 

  41. Moser DJ, Cohen RA, Clark MM, Aloia MS, Tate BA, Stefanik S, et al. Neuropsychological functioning among cardiac rehabilitation patients. J Cardiopulm Rehabil 1999;19:91–7.

    Google Scholar 

  42. Pugh KG, Kiely DK, Milberg WP, Lipsitz L. Selective impairment of frontal-executive cognitive function in African Americans with cardiovascular risk factors. J Am Geriatr Soc 2003;51: 1439–44.

    Google Scholar 

  43. Meguro K, Constans JM, Shimada M, Yamaguchi S, Ishizaki J, Ishii H, et al. Corpus callosum atrophy, white matter lesions, and frontal executive dysfunction in normal aging and Alzheimer’s disease. A community-based study: the Tajiri Project. Int Psychogeriatr 2003;15(1):9–25.

    Google Scholar 

  44. Najjar SS, Scuteri A, Lakatta EG. Arterial aging: is it an immutable cardiovascular risk factor? Hypertension 2005;46: 454–62.

    Google Scholar 

  45. Jefferson AL, Poppas A, Paul RH, Cohen RA. Systemic hypoper-fusion is associated with executive dysfunction in geriatric cardiac patients. Neurobiol Aging 2007;28(3):477–83.

    Google Scholar 

  46. Girouard H, Iadecola C. Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease. J Appl Physiol 2006;100:328–35.

    Google Scholar 

  47. Landmesser U, Harrison DG, Drexler H. Oxidant stress – a major cause of reduced endothelial nitric oxide availability in cardiovascular disease. Eur J Clin Pharmacol 2006;62(Suppl 13):13–9.

    Google Scholar 

  48. Preik M, Kelm M, Feelisch M, Strauer BE. Impaired effectiveness of nitric oxide-donors in resistance arteries of patients with arterial hypertension. J Hypertens 1996;14: 903–8.

    Google Scholar 

  49. Adams MR, Robinson J, McCredie R, Seale JP, Sorensen KE, Deanfield JE, et al. Smooth muscle dysfunction occurs independently of impaired endothelium-dependent dilation in adults at risk of atherosclerosis. J Am Coll Cardiol 1998; 32:123–7.

    Google Scholar 

  50. Cohen RA, Waters WF. Psychophysiological correlates of levels and stages of cognitive processing. Neuropsychologia 1985;23: 243–56.

    Google Scholar 

  51. Porges SW, Doussard-Roosevelt JA, Portales AL, Greenspan SI. Infant regulation of the vagal ‘‘brake’’ predicts child behavior problems: a psychobiological model of social behavior. Dev Psychobiol 1996;29:697–712.

    Google Scholar 

  52. Taylor AL, Ziesche S, Yancy C, Carson P, D’Agostino Jr R, Ferdinand K, et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med 2004;351: 2049–57.

    Google Scholar 

  53. Kalinowski I, Dobrucki T, Malinski T. Race-specific differences in endothelial function predisposition of African Americans to vascular diseases. Circulation 2004;109:2511–7.

    Google Scholar 

  54. Asahi M, Huang Z, Thomas S, Yoshimura S, Sumii T, Mori T, et al. Protective effects of statins involving both eNOS and tPA in focal cerebral ischemia. J Cereb Blood Flow Metab 2005;25(6): 722–9.

    Google Scholar 

  55. Yamada M, Huang Z, Dalkara T, Endres M, Laufs U, Waeber C, et al. Endothelial nitric oxide synthase-dependent cerebral blood flow augmentation by L-arginine after chronic statin treatment. J Cereb Blood Flow Metab 2000;20(4):709–17.

    Google Scholar 

  56. Miida T, Hirayama S, Nakamura Y. Cholesterol-independent effects of statins and new therapeutic targets: ischemic stroke and dementia. J Atheroscler Thromb 2004;11(5):253–64.

    Google Scholar 

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Authors and Affiliations

  1. Division of Cardiology, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA, USA

    Daniel E. Forman, Nicole Wake & Marie Gerhard-Herman

  2. Geriatric Research, Education, and Clinical Care, VA Boston Healthcare System, Harvard Medical School, Boston, MA, USA

    Daniel E. Forman

  3. Department of Psychiatry and Human Behavior, Brown Medical School, Providence, RI, USA

    Ronald A. Cohen & Makoto Ono

  4. Department of Medicine, National Jewish and Medical Research Centre, Denver, CO, USA

    Karin F. Hoth

  5. Department of Psychology, University of Texas at Austin, Austin, TX, USA

    Andreana P. Haley

  6. Department of Cardiology, Rhode Island Hospital, Brown Medical School, Providence, RI, USA

    Athena Poppas

  7. Department of Psychiatry, University of Iowa, IA, USA

    David J. Moser

  8. Department of Psychology, Kent State University, Kent, OH, USA

    John Gunstad

  9. Department of Psychology, University of Missouri, St Louis, MO, USA

    Robert H. Paul

  10. Department of Neurology, Alzheimer’s Disease Center, Boston University School of Medicine, Boston, MA, USA

    Angela L. Jefferson

  11. Department of Radiology, Brigham and Women’s Hospital, Boston, MA, USA

    David F. Tate

  12. Department of Psychiatry, University of Colorado at Denver and Health Sciences Centre, Denver, CO, USA

    Karin F. Hoth

Authors
  1. Daniel E. Forman
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  2. Ronald A. Cohen
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  3. Karin F. Hoth
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  4. Andreana P. Haley
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  5. Athena Poppas
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  6. David J. Moser
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  7. John Gunstad
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  8. Robert H. Paul
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  9. Angela L. Jefferson
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  10. David F. Tate
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  11. Makoto Ono
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  12. Nicole Wake
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  13. Marie Gerhard-Herman
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Corresponding author

Correspondence to Daniel E. Forman.

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This is an open access article distributed under the CC BY-NC license. https://doi.org/creativecommons.org/licenses/by/4.0/

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Forman, D.E., Cohen, R.A., Hoth, K.F. et al. Vascular health and cognitive function in older adults with cardiovascular disease. Artery Res 2, 35–43 (2008). https://doi.org/10.1016/j.artres.2008.01.001

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  • DOI: https://doi.org/10.1016/j.artres.2008.01.001

Keywords

Artery Research

ISSN: 1876-4401

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