Common Carotid Artery Calcification Impacts on Cognitive Function in Older Patients

  • Nicola Di Daniele
  • Roberto Celotto
  • Danilo Alunni Fegatelli
  • Marco Gabriele
  • Valentina Rovella
  • Angelo ScuteriEmail author
Original Article



Cognitive impairment and dementia represent an emerging health problem. Cardiovascular (CV) risk factors contribute to cognitive impairment.


To investigate the effect of vascular calcification on cognitive impairment and dementia, independently of plaque and traditional CV risk factors.


Four hundred and sixty-nine patients (age of 78.6 ± 6.1 years, 74.4% women) were studied. Traditional CV risk factors levels, cognitive function (MMSE), brain CT scan, and other vascular parameters were measured. Common Carotid Artery (CCA) plaque and calcification were evaluated by ultrasound.


CCA calcification was associated with a lower MMSE score than in subjects with no CCA calcification (23.7 ± 0.3 versus 25.5 ± 0.8; p = 0.015), after controlling for age, sex, education, blood pressure levels, diabetes, creatinine, lipid lowering therapy, neuroimaging alteration, and CCA plaque. Similarly, CCA calcification was associated with higher odds of dementia regardless of the presence of CCA plaque (OR 1.70, 95% CI 1.01–2.94, p < 0.05). This trend was not observed when stratifying patients according to the presence of CCA plaque.


CCA calcification is associated with cognitive impairment and dementia, independently of established CV risk factors and CCA plaque. The impact of arterial calcification on cognition seems largely independent of arterial stiffness.


Vascular calcification Cognitive impairment Dementia Arterial stiffness Vascular aging 


Compliance with Ethical Standards

Conflict of interest

No Author has any conflict of interest to disclose.

Research involving human participants

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.



Financial disclosure

The Authors declare that they have no financial interests to disclose.


  1. 1.
    World Alzheimer Report 2015. The global impact of dementia.
  2. 2.
    Scuteri A, Lakatta EG. Bringing prevention in geriatrics: evidence from cardiovascular medicine supporting the new challenge. Exp Gerontol. 2013;48:64–8.CrossRefGoogle Scholar
  3. 3.
    Scuteri A. Brain injury as end-organ damage in hypertension. Lancet Neurol. 2012;11:1015–7.CrossRefGoogle Scholar
  4. 4.
    Scuteri A, Di Daniele N. Are hemodynamic factors involved in cognitive impairment? Hypertension. 2016;67:34–5.CrossRefGoogle Scholar
  5. 5.
    Scuteri A, Morrell CH, Orrù M, Strait JB, Tarasov KV, Ferreli LA, Loi F, Pilia MG, Delitala A, Spurgeon H, Najjar SS, AlGhatrif M, Lakatta EG. Longitudinal perspective on the conundrum of central arterial stiffness, blood pressure, and aging. Hypertension. 2014;64:1219–27.CrossRefGoogle Scholar
  6. 6.
    Farasat SM, Morrell CH, Scuteri A, Ting CT, Yin FC, Spurgeon HA, Chen CH, Lakatta EG, Najjar SS. Pulse pressure is inversely related to aortic root diameter implications for the pathogenesis of systolic hypertension. Hypertension. 2008;51:196–202.CrossRefGoogle Scholar
  7. 7.
    Scuteri A, Chen CH, Yin FCP, Chih TT, Spurgeon HA, Lakatta EG. Functional correlates of central arterial geometric phenotypes. Hypertension. 2001;38:1471–5.CrossRefGoogle Scholar
  8. 8.
    O’Rourke MF, Safar ME. Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy. Hypertension. 2005;46:200–4.CrossRefGoogle Scholar
  9. 9.
    Scuteri A, Cacciafesta M, Di Bernardo MG, De Propris AM, Recchi D, Celli V, Cicconetti P. Marigliano V pulsatile versus steady-state component of blood pressure in elderly females: an independent risk factor for cardiovascular disease? J Hypertens. 1995;13(185):191.Google Scholar
  10. 10.
    Speer MY, Yang HY, Brabb T, Leaf E, Look A, Lin WL, Frutkin A, Dichek D, Giachelli CM. Smooth muscle cells give rise to osteochondrogenic precursors and chondrocytes in calcifying arteries. Circ Res. 2009;104:733–41.CrossRefGoogle Scholar
  11. 11.
    Burke AP, Weber DK, Kolodgie FD, Farb A, Taylor AJ, Virmani R. Pathophysiology of calcium deposition in coronary arteries. Herz. 2001;26:239–44.CrossRefGoogle Scholar
  12. 12.
    Hunt KJ, Pankow JS, Offenbacher S, Kritchevsky SB, Duncan BB, Shahar E, Sharrett AR, Heiss G. B-mode ultrasound-detected carotid artery lesions with and without acoustic shadowing and their association with markers of inflammation and endothelial activation: the atherosclerosis risk in communities study. Atherosclerosis. 2002;162:145–55.CrossRefGoogle Scholar
  13. 13.
    Niederhoffer N, Lartaud-Idjouadiene I, Giummelly P, Duvivier C, Peslin R, Atkinson J. Calcification of medial elastic fibers and aortic elasticity. Hypertension. 1997;29:999–1006.CrossRefGoogle Scholar
  14. 14.
    Scuteri A, Wang H. Pulse wave velocity as a marker of cognitive impairment in the elderly. J Alzheimers Dis. 2014;42(Suppl 4):S401–10.CrossRefGoogle Scholar
  15. 15.
    Bos D, Vernooij MW, de Bruijn RF, Koudstaal PJ, Hofman A, Franco OH, van der Lugt A, Ikram MA. Atherosclerotic calcification is related to a higher risk of dementia and cognitive decline. Alzheimers Dement. 2015;11:639–47.CrossRefGoogle Scholar
  16. 16.
    Kao HW, Liou M, Chung HW, Liu HS, Tsai PH, Chiang SW, Chou MC, Peng GS, Huang GS, Hsu HH, Chen CY. High Agatston calcium score of intracranial carotid artery: a significant risk factor for cognitive impairment. Medicine (Baltimore). 2015;94:e1546.CrossRefGoogle Scholar
  17. 17.
    Weimar C, Winkler A, Dlugaj M, Lehmann N, Hennig F, Bauer M, Kröger K, Kälsch H, Mahabadi AA, Dragano N, Moebus S, Hoffmann B, Jöckel KH, Erbel R, Heinz Nixdorf Recall Study Investigative Group. Ankle-Brachial Index but neither intima media thickness nor coronary artery calcification is associated with mild cognitive impairment. J Alzheimers Dis. 2015;47:433–42.CrossRefGoogle Scholar
  18. 18.
    Scuteri A, Palmieri L, Lo Noce C, Giampaoli S. Age-related changes in cognitive domains: a population-based study. Aging Clin Exp Res. 2005;17:367–73.CrossRefGoogle Scholar
  19. 19.
    Scuteri A, Coluccia R, Castello L, Nevola E, Brancati AM, Volpe M. Left ventricular mass increase is associated with cognitive decline and dementia in the elderly independently of blood pressure. Eur Heart J. 2009;30:1525–9.CrossRefGoogle Scholar
  20. 20.
    Scuteri A, Morrell CH, Orru’ M, AlGhatrif M, Saba PS, Terracciano A, Ferreli LA, Loi F, Marongiu M, Pilia MG, Delitala A, Tarasov KV, Schlessinger D, Ganau A, Cucca F, Lakatta EG. Gender specific profiles of white coat and masked hypertension impacts on arterial structure and function in the SardiNIA study. Int J Cardiol. 2016;217:92–8.CrossRefGoogle Scholar
  21. 21.
    Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I. Reichek N Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol. 1986;57:450–8.CrossRefGoogle Scholar
  22. 22.
    Scuteri A, Rovella V, Alunni Fegatelli D, Gabriele M, Di Daniele N. An operational definition of SHATS (Systemic Hemodynamic Atherosclerotic Syndrome): Role of arterial stiffness and blood pressure variability in elderly hypertensive subjects. Int J Cardiol. 2018;263:132–7.CrossRefGoogle Scholar
  23. 23.
    ESH/ESC Task Force for the Management of Arterial Hypertension. 2013 Practice guidelines for the management of arterial hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC): ESH/ESC Task Force for the Management of Arterial Hypertension. J Hypertens. 2013;31:1925–38.CrossRefGoogle Scholar
  24. 24.
    Scuteri A, Modestino A, Frattari A, Di Daniele N, Tesauro M. Occurrence of hypotension in older participants. Which 24-hour ABPM parameter better correlate with? J Gerontol A Biol Sci Med Sci. 2012;67:804–10.CrossRefGoogle Scholar
  25. 25.
    Guo J, Fujiyoshi A, Willcox B, Choo J, Vishnu A, Hisamatsu T, Ahuja V, Takashima N, Barinas-Mitchell E, Kadota A, Evans RW, Miura K, Edmundowicz D, Masaki K, Shin C, Kuller LH, Ueshima H, Sekikawa A, ERA JUMP Study Group. Increased aortic calcification is associated with arterial stiffness progression in multiethnic middle-aged men. Hypertension. 2017;69:102–8.CrossRefGoogle Scholar
  26. 26.
    Laucyte-Cibulskiene A, Petraviciute M, Gudynaite M, Gumbys L, Valanciene D, Galiauskiene K, Ryliskyte L, Rimsevicius L, Miglinas M, Strupas K. Mismatch between stiffness in elastic and muscular arteries as a predictor of vascular calcification in dialysis patients. Aging Clin Exp Res. 2018;30:375–82.CrossRefGoogle Scholar
  27. 27.
    Scuteri A, Orru M, Morrell C, Piras MG, Taub D, Schlessinger D, Uda M, Lakatta EG. Independent and additive effects of cytokine patterns and the metabolic syndrome on arterial aging in the SardiNIA Study. Atherosclerosis. 2011;215:459–64.CrossRefGoogle Scholar
  28. 28.
    Shroff R, Long DA, Shanahan C. Mechanistic insights into vascular calcification in CKD. J Am Soc Nephrol JASN. 2013;24:179–89.CrossRefGoogle Scholar
  29. 29.
    Tsao CW, Pencina KM, Massaro JM, Benjamin EJ, Levy D, Vasan RS, Hoffmann U, O’Donnell CJ, Mitchell GF. Cross-sectional relations of arterial stiffness, pressure pulsatility, wave reflection, and arterial calcification. Arterioscler Thromb Vasc Biol. 2014;34:2495–500.CrossRefGoogle Scholar
  30. 30.
    Nicholson CJ, Singh K, Saphirstein RJ, Gao YZ, Li Q, Chiu JG, Leavis P, Verwoert GC, Mitchell GF, AortaGen Consortium, Porter T, Morgan KG. Reversal of aging-induced increases in aortic stiffness by targeting cytoskeletal protein-protein interfaces. J Am Heart Assoc. 2018;7:e008926. Scholar
  31. 31.
    Sadekova N, Vallerand D, Guevara E, Lesage F, Girouard H. Carotid calcification in mice: a new model to study the effects of arterial stiffness on the brain. J Am Heart Assoc. 2013;2(3):e00022.CrossRefGoogle Scholar
  32. 32.
    Scuteri A, Tesauro M, Guglini L, Lauro D, Fini M, Di Daniele N. Aortic stiffness and hypotension episodes are associated with impaired cognitive function in older subjects with subjective complaints of memory loss. Int J Cardiol. 2013;169:371–7.CrossRefGoogle Scholar
  33. 33.
    Sadekova N, Iulita MF, Vallerand D, Muhire G, Bourmoum M, Claing A, Girouard H. Arterial stiffness induced by carotid calcification leads to cerebral gliosis mediated by oxidative stress. J Hypertens. 2018;36:286–98.CrossRefGoogle Scholar
  34. 34.
    Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53:695–9.CrossRefGoogle Scholar
  35. 35.
    Pendlebury ST, Cuthbertson FC, Welch SJ, Mehta Z, Rothwell PM. Underestimation of cognitive impairment by Mini-Mental State Examination versus the Montreal Cognitive Assessment in patients with transient ischemic attack and stroke: a population-based study. Stroke. 2010;41:1290–3.CrossRefGoogle Scholar
  36. 36.
    Scuteri A, Tesauro M, Di Daniele N. Preventive geriatrics the cross-talk between arterial and brain aging: a lifelong condition. Exp Gerontol. 2017;87(Pt B):148–50.CrossRefGoogle Scholar
  37. 37.
    Zamboni G, Griffanti L, Jenkinson M, Mazzucco S, Li L, Küker W, Pendlebury ST, Rothwell PM, Oxford Vascular Study. White matter imaging correlates of early cognitive impairment detected by the Montreal Cognitive Assessment after transient ischemic attack and minor stroke. Stroke. 2017;48:1539–47.CrossRefGoogle Scholar
  38. 38.
    Pikilidou MI, Yavropoulou MP, Scuteri A. Can antihypertensive medication interfere with the vicious cycle between hypertension and vascular calcification? Cardiovasc Drugs Ther. 2014;28:61–71.CrossRefGoogle Scholar

Copyright information

© Italian Society of Hypertension 2019

Authors and Affiliations

  • Nicola Di Daniele
    • 1
  • Roberto Celotto
    • 1
  • Danilo Alunni Fegatelli
    • 2
  • Marco Gabriele
    • 1
  • Valentina Rovella
    • 1
  • Angelo Scuteri
    • 3
    Email author
  1. 1.Hypertension and Nephrology Unit, Department of Medicine, Policinico Tor VergataUniversita’di Roma Tor VergataRomeItaly
  2. 2.Department of Public Health and Infectious DiseaseUniversity “La Sapienza”RomeItaly
  3. 3.Department of Medical, Surgical, and Experimental SciencesUniversity of SassariSassariItaly

Personalised recommendations