Skip to main content

The heart-brain connection: mechanistic insights and models

Netherlands Heart Journal volume 21, pages 55–57 (2013)Cite this article

Abstract

While both cardiac dysfunction and progressive loss of cognitive function are prominent features of an ageing population, surprisingly few studies have addressed the link between the function of the heart and brain. Recent literature indicates that autoregulation of cerebral flow is not able to protect the brain from hypoperfusion when cardiac output is reduced or atherosclerosis is prominent. This suggests a close link between cardiac function and large vessel atherosclerosis on the one hand and brain perfusion and cognitive functioning on the other. Mechanistically, the presence of vascular pathology leads to chronic cerebral hypoperfusion, blood brain barrier breakdown and inflammation that most likely precede neuronal death and neurodegeneration. Animal models to study the effects of chronic cerebral hypoperfusion are available, but they have not yet been combined with cardiovascular models.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. Iadecola C, Nedergaard M. Glial regulation of the cerebral microvasculature. Nat Neurosci. 2007;10:1369–76.

    PubMed  Article  CAS  Google Scholar 

  2. Paulson OB, Hasselbalch SG, Rostrup E, et al. Cerebral blood flow response to functional activation. J Cereb Blood Flow Metab. 2010;30:2–14.

    PubMed  Article  Google Scholar 

  3. van Beek AH, Claassen JA, Rikkert MG, et al. Cerebral autoregulation: an overview of current concepts and methodology with special focus on the elderly. J Cereb Blood Flow Metab. 2008;28:1071–85.

    PubMed  Article  Google Scholar 

  4. Moskowitz MA, Lo EH, Iadecola C. The science of stroke: mechanisms in search of treatments. Neuron. 2010;67:181–98.

    PubMed  Article  CAS  Google Scholar 

  5. Gorelick PB, Scuteri A, Black SE, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the american heart association/american stroke association. Stroke. 2011;42:2672–713.

    PubMed  Article  Google Scholar 

  6. Paulson OB, Jarden JO, Godtfredsen J, et al. Cerebral blood-flow in patients with congestive heart-failure treated with captopril. Am J Med. 1984;76:91–5.

    PubMed  Article  CAS  Google Scholar 

  7. Choi BR, Kim JS, Yang YJ, et al. Factors associated with decreased cerebral blood flow in congestive heart failure secondary to idiopathic dilated cardiomyopathy. Am J Cardiol. 2006;97:1365–9.

    PubMed  Article  Google Scholar 

  8. Jefferson AL, Himali JJ, Au R, et al. Relation of left ventricular ejection fraction to cognitive aging (from the Framingham heart study). Am J Cardiol. 2011;108:1346–51.

    PubMed  Article  Google Scholar 

  9. Roman DD, Kubo SH, Ormaza S, et al. Memory improvement following cardiac transplantation. J Clin Exp Neuropsychol. 1997;19:692–7.

    PubMed  Article  CAS  Google Scholar 

  10. Dixit NK, Vazquez LD, Cross NJ, et al. Cardiac resynchronization therapy: a pilot study examining cognitive change in patients before and after treatment. Clin Cardiol. 2010;33:84–8.

    PubMed  Article  Google Scholar 

  11. Petrucci RJ, Rogers JG, Blue L, et al. Neurocognitive function in destination therapy patients receiving continuous-flow vs pulsatile-flow left ventricular assist device support. J Heart Lung Transplant. 2012;31:27–36.

    PubMed  Article  Google Scholar 

  12. Tranmer BI, Keller TS, Kindt GW, et al. Loss of cerebral regulation during cardiac output variations in focal cerebral ischemia. J Neurosurg. 1992;77:253–9.

    PubMed  Article  CAS  Google Scholar 

  13. Bakker FC, Klijn CJ, Jennekens-Schinkel A, et al. Cognitive impairment in patients with carotid artery occlusion and ipsilateral transient ischemic attacks. J Neurol. 2003;250:1340–7.

    PubMed  Article  Google Scholar 

  14. Bakker FC, Klijn CJ, van der Grond J, et al. Cognition and quality of life in patients with carotid artery occlusion: a follow-up study. Neurology. 2004;62:2230–5.

    PubMed  Article  CAS  Google Scholar 

  15. Bakker FC, Klijn CJ, Jennekens-Schinkel A, et al. Cognitive impairment is related to cerebral lactate in patients with carotid artery occlusion and ipsilateral transient ischemic attacks. Stroke. 2003;34:1419–24.

    PubMed  Article  CAS  Google Scholar 

  16. Goto T, Baba T, Honma K, et al. Magnetic resonance imaging findings and postoperative neurologic dysfunction in elderly patients undergoing coronary artery bypass grafting. Ann Thorac Surg. 2001;72:137–42.

    PubMed  Article  CAS  Google Scholar 

  17. Selnes OA, Gottesman RF, Grega MA, et al. Cognitive and neurologic outcomes after coronary-artery bypass surgery. New Engl J Med. 2012;366:250–7.

    PubMed  Article  CAS  Google Scholar 

  18. Bos D, van der Rijk MJM, Geeraedts TEA, et al. Intracranial carotid artery atherosclerosis prevalence and risk factors in the general population. Stroke. 2012;43:1878–84.

    PubMed  Article  Google Scholar 

  19. Bos D, Ikram MA, Elias-Smale SE, et al. Calcification in major vessel beds relates to vascular brain disease. Arterioscler Thromb Vasc Biol. 2011;31:2331–7.

    PubMed  Article  CAS  Google Scholar 

  20. Bos D, Vernooij MW, Elias-Smale SE, et al. Atherosclerotic calcification relates to cognitive function and to brain changes on magnetic resonance imaging. Alzheimers Dement. 2012.

  21. Shibata M, Ohtani R, Ihara M, et al. White matter lesions and glial activation in a novel mouse model of chronic cerebral hypoperfusion. Stroke. 2004;35:2598–603.

    PubMed  Article  Google Scholar 

  22. Shibata M, Yamasaki N, Miyakawa T, et al. Selective impairment of working memory in a mouse model of chronic cerebral hypoperfusion. Stroke. 2007;38:2826–32.

    PubMed  Article  Google Scholar 

  23. Fujita Y, Ihara M, Ushiki T, et al. Early protective effect of bone marrow mononuclear cells against ischemic white matter damage through augmentation of cerebral blood flow. Stroke. 2010;41:2938–43.

    PubMed  Article  Google Scholar 

  24. Nishio K, Ihara M, Yamasaki N, et al. A mouse model characterizing features of vascular dementia with hippocampal atrophy. Stroke. 2010;41:1278–84.

    PubMed  Article  Google Scholar 

  25. Coltman R, Spain A, Tsenkina Y, et al. Selective white matter pathology induces a specific impairment in spatial working memory. Neurobiol Aging. 2011;32.

  26. Nakamura A, Rokosh DG, Paccanaro M, et al. LV systolic performance improves with development of hypertrophy after transverse aortic constriction in mice. Am J Physiol Heart Circ Physiol. 2001;281:H1104–12.

    PubMed  CAS  Google Scholar 

  27. Chintalgattu V, Ai D, Langley RR, et al. Cardiomyocyte PDGFR-beta signaling is an essential component of the mouse cardiac response to load-induced stress. J Clin Invest. 2010;120:472–84.

    PubMed  Article  CAS  Google Scholar 

  28. Poulet R, Gentile MT, Vecchione C, et al. Acute hypertension induces oxidative stress in brain tissues. J Cerebral Blood Flow Metab. 2006;26:253–62.

    Article  CAS  Google Scholar 

  29. Carnevale D, Mascio G, Ajmone-Cat MA, et al. Role of neuroinflammation in hypertension-induced brain amyloid pathology. Neurobiol Aging. 2012;33.

  30. Gentile MT, Poulet R, Di Pardo A, et al. Beta-amyloid deposition in brain is enhanced in mouse models of arterial hypertension. Neurobiol Aging. 2009;30:222–8.

    PubMed  Article  CAS  Google Scholar 

  31. Carnevale D, Mascio G, D’Andrea I, et al. Hypertension induces brain beta-amyloid accumulation, cognitive impairment, and memory deterioration through activation of receptor for advanced glycation end products in brain vasculature. Hypertension. 2012;60:188–97.

    PubMed  Article  CAS  Google Scholar 

  32. Okamoto Y, Yamamoto T, Kalaria RN, et al. Cerebral hypoperfusion accelerates cerebral amyloid angiopathy and promotes cortical microinfarcts. Acta Neuropathol. 2012;123:381–94.

    PubMed  Article  CAS  Google Scholar 

  33. Zlokovic BV. The blood–brain barrier in health and chronic neurodegenerative disorders. Neuron. 2008;57:178–201.

    PubMed  Article  CAS  Google Scholar 

  34. Marchesi C, Paradis P, Schiffrin EL. Role of the renin-angiotensin system in vascular inflammation. Trends Pharmacol Sci. 2008;29:367–74.

    PubMed  Article  CAS  Google Scholar 

  35. Gill R, Tsung A, Billiar T. Linking oxidative stress to inflammation: toll-like receptors. Free Radic Biol Med. 2010;48:1121–32.

    PubMed  Article  CAS  Google Scholar 

  36. Sim FJ, Zhao C, Penderis J, et al. The age-related decrease in CNS remyelination efficiency is attributable to an impairment of both oligodendrocyte progenitor recruitment and differentiation. J Neurosci. 2002;22:2451–9.

    PubMed  CAS  Google Scholar 

  37. Simpson JE, Fernando MS, Clark L, et al. White matter lesions in an unselected cohort of the elderly: astrocytic, microglial and oligodendrocyte precursor cell responses. Neuropathol Appl Neurobiol. 2007;33:410–9.

    PubMed  Article  CAS  Google Scholar 

  38. Arai K, Lo EH. Astrocytes protect oligodendrocyte precursor cells via MEK/ERK and PI3K/Akt signaling. J Neurosci Res. 2010;88:758–63.

    PubMed  CAS  Google Scholar 

  39. Savva GM, Wharton SB, Ince PG, et al. Age, neuropathology, and dementia. New Engl J Med. 2009;360:2302–9.

    PubMed  Article  CAS  Google Scholar 

  40. Armulik A, Genove G, Mae M, et al. Pericytes regulate the blood–brain barrier. Nature. 2010;468:557–U231.

    PubMed  Article  CAS  Google Scholar 

  41. Bell RD, Winkler EA, Singh I, et al. Apolipoprotein E controls cerebrovascular integrity via cyclophilin A. Nature. 2012;485:512–6.

    PubMed  Article  CAS  Google Scholar 

Download references

Author information

Affiliations

  1. Department of Pathology, L2-110, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands

    K. Ritz

  2. Department of Radiology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, the Netherlands

    M. A. van Buchem

  3. Department of Pathology, M2-206, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands

    M. J. Daemen

Authors
  1. K. Ritz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. A. van Buchem
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. J. Daemen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. J. Daemen.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ritz, K., van Buchem, M.A. & Daemen, M.J. The heart-brain connection: mechanistic insights and models. Neth Heart J 21, 55–57 (2013). https://doi.org/10.1007/s12471-012-0348-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12471-012-0348-9

Keywords

  • Cerebral hypoperfusion
  • Cardiovascular dysfunction
  • Cognitive decline
  • Neurodegeneration
  • Heart and brain