Chronic Ischemia and Neurocognition

https://doi.org/10.1016/j.nic.2007.03.002Get rights and content

Cognitive impairment from a major stroke as a consequence of carotid disease is an acknowledged clinical outcome; however, cognitive impairment without major stroke is open to discussion. The three recognized mechanisms for cognitive dysfunction from internal carotid artery are microembolization, white-matter disease, and hypoperfusion. The last has been most difficult to characterize physiologically. In this article, the authors review evidence supporting the existence of chronic ischemia in the brain and its direct impact on cognitive functions. By incorporating the pathophysiology of chronic ischemia into the algorithm of the management of carotid artery disease, we may be able to extend the goals of carotid artery revascularization beyond merely preventing stroke to include preventing or reversing cognitive decline.

Section snippets

Evidence of impaired cognition due to carotid artery disease

Cognitive impairment has been reported in a wide spectrum of clinical studies in patients who have carotid disease, most frequently in global terms rather than as a specific, neurocognitive profile. Fischer [1], [2] was the first to postulate an association between cerebral hypoperfusion and dementia, based on a necropsy study of a demented patient who had bilateral carotid occlusion. A few years later, Carey and colleagues [3] reported dementia in four patients who had bilateral carotid

Hypoperfusion

The refinement of new imaging techniques that measure cerebral hemodynamics directly has advanced our understanding of the relationship between hypoperfusion in carotid diseases and cognitive impairment. Tatemichi and colleagues [25] documented the case of a 55-year-old man with bilateral internal carotid and unilateral vertebral artery occlusions presenting with a subacute onset of severe behavioral and cognitive changes. Quantitative cerebral blood flow (CBF) and positron emission tomography

Chronic ischemia and neuronal impairment

If hypoperfusion is the primary model for the link between carotid disease and cognitive impairment, one must provide evidence that

  • Chronic ischemia exists and results in neuronal dysfunction.

  • Chronic ischemia and neuronal dysfunction are reversible.

  • Chronic ischemia and reversibility correlate with functional behavioral measures.

Animal studies can provide a pure model of chronic cerebral hypoperfusion. Ohta and colleagues [118] investigated the effect of chronic cerebral ischemia on learning

Summary

Substantial evidence indicates that chronic ischemia is a progressive, dynamic process that may manifest with cognitive dysfunction as the ischemic conditions persist, with functional deficits becoming evident and additional neuronal infarction prevailing if chronic ischemia is not reversed. By incorporating the pathophysiology of chronic ischemia into the algorithm of the management of carotid artery disease, we may be able to extend the goals of carotid artery revascularization beyond merely

References (136)

  • K. Kishikawa et al.

    Effects of carotid endarterectomy on cerebral blood flow and neuropsychological test performance in patients with high-grade carotid stenosis

    J Neurol Sci

    (2003)
  • N. Brand et al.

    Left or right carotid endarterectomy in patients with atherosclerotic disease: ipsilateral effects on cognition?

    Brain Cogn

    (2004)
  • E.R. Bossema et al.

    Does carotid endarterectomy improve cognitive functioning?

    J Vasc Surg

    (2005)
  • M. Aleksic et al.

    Cognitive function remains unchanged after endarterectomy of unilateral internal carotid artery stenosis under local anaesthesia

    Eur J Vasc Endovasc Surg

    (2006)
  • C. Jansen et al.

    Prediction of intracerebral haemorrhage after carotid endarterectomy by clinical criteria and intraoperative transcranial Doppler monitoring: results of 233 operations

    Eur J Vasc Surg

    (1994)
  • M. Yonekura et al.

    Long-term evaluation of cerebral blood flow, transient ischemic attacks, and stroke after STA-MCA anastomosis

    Surg Neurol

    (1982)
  • J.H. Rapp et al.

    Atheroemboli to the brain: size threshold for causing acute neuronal cell death

    J Vasc Surg

    (2000)
  • M.J. Grigg et al.

    The significance of cerebral infarction and atrophy in patients with amaurosis fugax and transient ischemic attacks in relation to internal carotid artery stenosis: a preliminary report

    J Vasc Surg

    (1988)
  • I. Gore et al.

    Observations on the fate of cholesterol emboli

    J Atheroscler Res

    (1964)
  • T.S. Padayachee et al.

    The detection of microemboli in the middle cerebral artery during cardiopulmonary bypass: a transcranial Doppler ultrasound investigation using membrane and bubble oxygenators

    Ann Thorac Surg

    (1987)
  • I. Skoog et al.

    15-year longitudinal study of blood pressure and dementia

    Lancet

    (1996)
  • F.M. Gunning-Dixon et al.

    Neuroanatomical correlates of selected executive functions in middle-aged and older adults: a prospective MRI study

    Neuropsychologia

    (2003)
  • M. Fisher

    Senile dementia—a new explanation of its causation

    Can Med Assoc J

    (1951)
  • M. Fisher

    Occlusion of the carotid arteries: further experiences

    AMA Arch Neurol Psychiatry

    (1954)
  • J.B. Carey et al.

    The metabolism of bile acids with special reference to liver injury

    Medicine (Baltimore)

    (1966)
  • F.C. Bakker et al.

    Cognitive disorders in patients with occlusive disease of the carotid artery: a systematic review of the literature

    J Neurol

    (2000)
  • R. Hemmingsen et al.

    Intellectual function in patients with transient ischaemic attacks (TIA) or minor stroke. Long-term improvement after carotid endarterectomy

    Acta Neurol Scand

    (1982)
  • A.D. Baird et al.

    Can neuropsychological tests detect the sites of cerebrovascular stenoses and occlusions?

    Neurosurgery

    (1984)
  • W. Hamster et al.

    Neuropsychological changes associated with stenoses or occlusions of the carotid arteries. A comparative psychometric study

    Eur Arch Psychiatry Neurol Sci

    (1984)
  • H. Nielsen et al.

    A neuropsychological study of 12 patients with transient ischemic attacks before and after EC/IC bypass surgery

    Acta Neurol Scand

    (1985)
  • D. Younkin et al.

    Superficial temporal-middle cerebral artery anastomosis: effects on vascular, neurologic, and neuropsychological functions

    Neurology

    (1985)
  • R. Hemmingsen et al.

    Carotid surgery, cognitive function, and cerebral blood flow in patients with transient ischemic attacks

    Ann Neurol

    (1986)
  • T. Benke et al.

    Neuropsychological deficits in asymptomatic carotid artery stenosis

    Acta Neurol Scand

    (1991)
  • F.C. Bakker et al.

    Cognitive impairment in patients with carotid artery occlusion and ipsilateral transient ischemic attacks

    J Neurol

    (2003)
  • M.P. Kelly et al.

    Carotid artery disease, carotid endarterectomy, and behavior

    Arch Neurol

    (1980)
  • W. van den Burg et al.

    Carotid endarterectomy: does it improve cognitive or motor functioning?

    Psychol Med

    (1985)
  • E.B. Mathiesen et al.

    Reduced neuropsychological test performance in asymptomatic carotid stenosis: the Tromso Study

    Neurology

    (2004)
  • M.M. Breteler et al.

    Cardiovascular disease and distribution of cognitive function in elderly people: the Rotterdam Study

    BMJ

    (1994)
  • A. Auperin et al.

    Ultrasonographic assessment of carotid wall characteristics and cognitive functions in a community sample of 59- to 71-year-olds. The EVA Study Group

    Stroke

    (1996)
  • J.R. Cerhan et al.

    Correlates of cognitive function in middle-aged adults. Atherosclerosis Risk in Communities (ARIC) Study Investigators

    Gerontology

    (1998)
  • L.H. Kuller et al.

    Relationship between ApoE, MRI findings, and cognitive function in the Cardiovascular Health Study

    Stroke

    (1998)
  • S.C. Johnston et al.

    Cognitive impairment and decline are associated with carotid artery disease in patients without clinically evident cerebrovascular disease

    Ann Intern Med

    (2004)
  • T.K. Tatemichi et al.

    Dementia associated with bilateral carotid occlusions: neuropsychological and haemodynamic course after extracranial to intracranial bypass surgery

    J Neurol Neurosurg Psychiatry

    (1995)
  • H. Yamauchi et al.

    Atrophy of the corpus callosum associated with cognitive impairment and widespread cortical hypometabolism in carotid artery occlusive disease

    Arch Neurol

    (1996)
  • Y. Tsuda et al.

    Cortical blood flow and cognition after extracranial-intracranial bypass in a patient with severe carotid occlusive lesions. A three-year follow-up study

    Acta Neurochir (Wien)

    (1994)
  • O.P. Almeida et al.

    The mind of a failing heart: a systematic review of the association between congestive heart failure and cognitive functioning

    Intern Med J

    (2001)
  • G. Zuccala et al.

    Hypotension and cognitive impairment: selective association in patients with heart failure

    Neurology

    (2001)
  • P.M. Pullicino et al.

    Cognitive impairment in congestive heart failure?: embolism vs hypoperfusion

    Neurology

    (2001)
  • H. Kamishirado et al.

    Effect of enalapril maleate on cerebral blood flow in patients with chronic heart failure

    Angiology

    (1997)
  • D. Georgiadis et al.

    Cerebrovascular reactivity is impaired in patients with cardiac failure

    Eur Heart J

    (2000)

    • Cited by (25)

    • The neuron-astrocyte-microglia triad in CA3 after chronic cerebral hypoperfusion in the rat: Protective effect of dipyridamole

      2017, Experimental Gerontology
      Citation Excerpt :

      In our study, dipyridamole was tested in the 2VO model to evaluate its protective role against the physiopathological mechanisms that the ischemic insult exerts in the CA3 region of the hippocampus. Brain chronic hypoperfusion, caused by partial carotid occlusion during aging, represents a chronic, dynamic process that causes multiple progressive alterations, and eventually leads to neurodegeneration (Ozacmak et al. 2007; Farkas et al. 2007) and vascular dementia (Chmayssani et al. 2007). The CA1 region of the hippocampus results particularly vulnerable to decreased blood flow and glucose supply caused by 2VO occlusion, that cause failure of neuronal signaling, and impairments in hippocampally-based forms of memory (De Jong et al. 1999; Liu et al. 2005; Farkas et al. 2006; Melani et al. 2010; Lana et al. 2013).

    • Asymptomatic carotid stenosis and cognitive improvement using transcervical stenting with protective flow reversal technique

      2014, European Journal of Vascular and Endovascular Surgery
      Citation Excerpt :

      This explains why neuropsychological evaluation could be a sensitive outcome measure in primary or secondary prevention. In keeping with the findings from previous studies,23,24 these results indicate that cognitive function in patients with asymptomatic carotid stenosis is below the established parameters of normality. Overall cognitive performance was affected (32.0%), and particularly information processing (62.5%), executive function (12.0%), and memory (56.0%).

    • ADC mapping of chronic cerebral hypoperfusion induced by carotid artery stenosis

      2011, Journal of Neuroradiology
      Citation Excerpt :

      Carotid stenosis may induce a chronic hypoperfusion. To assess changes in brain perfusion in carotid disease, a number of techniques have been used such as parenchymography [4] and CT perfusion [5]. Diffusion-weighted MR is a technique that images the molecular motion of tissue [6,7], which allows for the acquisition of a measure of fractional anisotropy [8].

    • Vascular Cognitive Impairment

      2010, Brocklehurst's Textbook of Geriatric Medicine and Gerontology

    • One-year Cognitive Outcomes Associated with Carotid Artery Stent Placement

      2010, Journal of Vascular and Interventional Radiology

    • Carotid Artery Ultrasound and Echocardiography Testing to Lower the Prevalence of Alzheimer's Disease

      2009, Journal of Stroke and Cerebrovascular Diseases
      Citation Excerpt :

      A strong correlation between AD and VaD that can develop later in life and increased IMT of the carotid arteries resulting from progressive atherosclerosis was first reported in the Rotterdam Study more than a decade ago.75 This finding was confirmed in a larger, population-based prospective cohort study with a mean follow-up of 9 years that included nearly 8000 elderly persons,76 and in other independent studies.77-81 The degree of carotid artery narrowing appears to correlate with the extent of cognitive loss.

    View all citing articles on Scopus

    This article was supported by NIH grant R01 NS048212-01A1 and the Richard and Jenny Levine Research Fund.

    View full text
    Copyright © 2007 Elsevier Inc. All rights reserved.