Two recent reports add to the growing evidence that trouble in the circulatory system can lead to cognitive impairment and Alzheimer disease (AD). Ben Wolozin and colleagues report in the latest issue of the Journal of Alzheimer’s Disease that coronary artery bypass grafts (CABG), commonly known as “cabbages,” increase the risk for developing AD postsurgery, while Rudi Westendorp and colleagues report in the September issue of the journal Radiology that poor cerebral blood flow correlates with dementia in the elderly.

Wolozin, at Boston University, together with colleagues at Pfizer in Groton, Connecticut, and Northwestern University, the University of Chicago, and that VA Hospital in Hines, all in Illinois, followed over 5,000 patients who had undergone the CABG procedure between October 1996 and September 1997. First author Todd Lee and colleagues found that 119 of the patients developed AD during the five years following their operation. As a control, they also followed patients (just over 3,900 individuals) who had undergone angioplasty (percutaneous transluminal coronary angioplasty or PTCA). The relative risk for AD in the CABG group was almost twice that in the PTCA group—1.7-fold. The findings confirm previously documented postoperative cognitive decline in much smaller groups of patients following CABG surgery (see Selnes et al., 2001 and Newman et al., 2001). The analysis “demonstrates that there is a significant association between CABG surgery and subsequent cognitive decline, as demonstrated by the incidence of AD, when compared to a cohort undergoing PTCA,” write the authors.

Why the CABG procedure should increase the risk for AD is not entirely clear, but Lee and colleagues suggest that it could be due to an exacerbated decrease in cognitive, or neuronal, reserve. Neuronal reserve has been used to explain why a loss of brain matter can be more devastating to some than to others (see Buckner, 2004), and could be compromised by hypoperfusion during surgery (see ARF Live Discussion on the vascular hypothesis of AD).

The role of hypoperfusion in late-onset dementia is supported by the second paper. Using magnetic resonance imaging, Westendorp and colleagues at Leiden University, The Netherlands, measured total cerebral blood flow in a group of 48 volunteers, made up of 15 young, 16 elderly with optimal cognition, and 17 elderly patients with dementia (the study was first published online July 12). First author Aart Spilt and colleagues found that although those elderly volunteers who still retained optimal cognition had reduced blood flow compared to the younger group (551 mL/min versus 742 mL/min), those elderly with dementia fared even worse, having an average total cerebral blood flow of only 443 mL/min. The data are even more dramatic given that subjects with any vascular dementia, which would presumably skew the data toward even lower blood flow measurements in the dementia group, were excluded from the study.—Tom Fagan.

Reference:
Lee TA, Wolozin B, Weiss KB, Bednar MM. Assessment of the emergence of Alzheimer’s disease following coronary artery bypass graft surgery or percutaneous transluminal coronary angioplasty. J. Alzheimer’s Disease. August 2005;7:319-324. Abstract

Spilt A, Weverling-Rijnsburger AWE, Middelkoop HAM, van Der Flier WM, Gussekloo J, de Craen AJM, Bollen ELEM, Blauw GJ, van Buchem MA, Westendorp RGJ. Late-onset dementia: structural brain damage and total cerebral blood flow. Radiology. 2005;236:990-995. Abstract

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  1. Is it possible that coronary artery bypass grafting was more likely complicated by atrial fibrillation requiring digoxin therapy in those who later developed AD?

    I refer to my previous post in which I ask whether digoxin therapy may be a risk factor for the development of AD (see ARF related news story).

    The reduced cerebral blood flow as a result of AF is also something to consider.

    I also wonder whether the release of growth factors such as PDGF is more likely increased following CABG surgery.

  2. Rubinow et al. (1) find that amyloid fibrils bind digoxin and that this may explain the sensitivity to digitalis for some with amyloid cardiomyopathy. Does digoxin bind cerebral amyloid fibrils, and, if so, might this suggest that digoxin therapy is contraindicated for those with AD?

    It would be interesting to see whether there is an increased risk of AD for those in the Berendes et al. study (2), which reports increased digoxin levels for some critically ill patients who were not receiving treatment with cardiac glycosides.

    References:

    . Digoxin sensitivity in amyloid cardiomyopathy. Circulation. 1981 Jun;63(6):1285-8. PubMed.

    . Endogenous glycosides in critically ill patients. Crit Care Med. 2003 May;31(5):1331-7. PubMed.

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References

Paper Citations

  1. . Cognitive changes 5 years after coronary artery bypass grafting: is there evidence of late decline?. Arch Neurol. 2001 Apr;58(4):598-604. PubMed.
  2. . Report of the substudy assessing the impact of neurocognitive function on quality of life 5 years after cardiac surgery. Stroke. 2001 Dec 1;32(12):2874-81. PubMed.
  3. . Memory and executive function in aging and AD: multiple factors that cause decline and reserve factors that compensate. Neuron. 2004 Sep 30;44(1):195-208. PubMed.
  4. . Assessment of the emergence of Alzheimer's disease following coronary artery bypass graft surgery or percutaneous transluminal coronary angioplasty. J Alzheimers Dis. 2005 Aug;7(4):319-24. PubMed.
  5. . Late-onset dementia: structural brain damage and total cerebral blood flow. Radiology. 2005 Sep;236(3):990-5. PubMed.

Other Citations

  1. ARF Live Discussion

Further Reading

Papers

  1. . Late-onset dementia: structural brain damage and total cerebral blood flow. Radiology. 2005 Sep;236(3):990-5. PubMed.
  2. . Assessment of the emergence of Alzheimer's disease following coronary artery bypass graft surgery or percutaneous transluminal coronary angioplasty. J Alzheimers Dis. 2005 Aug;7(4):319-24. PubMed.

News

  1. Challenging Views of Alzheimer's Disease: Meeting Notes

Primary Papers

  1. . Late-onset dementia: structural brain damage and total cerebral blood flow. Radiology. 2005 Sep;236(3):990-5. PubMed.
  2. . Assessment of the emergence of Alzheimer's disease following coronary artery bypass graft surgery or percutaneous transluminal coronary angioplasty. J Alzheimers Dis. 2005 Aug;7(4):319-24. PubMed.