Christian Doppler may never have imagined it, but his most famous discovery has been utilized to link cerebral emboli, or tiny blood clots, with both Alzheimer disease and vascular dementia. Writing in the April 28 British Medical Journal online, Charles McCollum and colleagues at the University of Manchester, England, report that Doppler ultrasound of the middle cerebral arteries detects an increased frequency of emboli in both groups of patients. The finding not only raises more questions about the links between the cardiovascular system and dementia, but strengthens the case that AD and vascular dementia share a common etiology.

First author Nitin Purandare and colleagues used the transcranial Doppler technique to compare the frequency of spontaneous cerebral emboli (SCE) in 170 patients and 150 age- and sex-matched controls—half the patients had been diagnosed with AD and half with vascular dementia. A single hour of Doppler sonography detected emboli in 40 and 31 percent of AD and vascular dementia patients, respectively. In contrast, only 15 and 14 percent of respective controls had detectable emboli. When present, the median numbers of emboli detected were two for both AD and vascular dementia, and only one for controls. The authors calculated an odds ratio for SCE of 3.2 and 4.8 for AD and vascular dementia, respectively.

Purandare and colleagues suggest that SCE may represent a “potentially preventable or treatable cause of dementia.” They may also help in diagnosis (see comment from Jack De la Torre, Case Western Reserve University, below). The authors also write that “the similar frequency of emboli in both types of dementia suggests a common cause.” But how these emboli form is unclear. While the authors did find a correlation between SCEs and all major cardiovascular risk factors (including high blood pressure, serum cholesterol and triglyceride levels, smoking, angina, stroke, diabetes) among controls, that correlation did not exist in the dementia groups. The authors suggest that if monitored for longer, all dementia patients might turn out to have detectable emboli, and that if SCEs were universal among the dementia group, then no cardiovascular risk factor association would exist. However, it may also be reasonable to expect that longer measurements would also detect more emboli among controls, or that among the patients some would turn out to have many more emboli than others. Purandare and colleagues also suggest that other mechanisms, such as inflammation, might underlie the association between SCEs and dementia.

One other possible link between dementia and emboli could be venous-to-arterial circulation shunts. These allow venous emboli to enter the arterial circulation through circulatory system defects, such as in the heart’s atrial-ventricular septa, or abnormal pulmonary passageways (fistulas) that connect the venous and arterial systems. The authors tested for such shunts directly, again using transcranial Doppler, but this time after injecting an emulsion of microbubbles of air in saline into the antecubital vein in the arm. (Microbubble sonography is a common method to detect patent foramen ovale, or the failure of the interatrial septum to form during early postnatal development. That septum is essential to divide the left and right atria and isolate the pulmonary circulation).

Though Purandare and colleagues did find that slightly more patients than controls had venous-arterial shunts, the results were not statistically significant. The authors do note, however, that their study, based on a small pilot trial of 35 patients, turned out to have insufficient power to detect any real differences between cases and controls.—Tom Fagan.

Reference:
Purandare N, Burns A, Daly KJ, Hardicre J, Morris J, Macfarlane G, McCollum C. Cerebral emboli as a potential cause of Alzheimer’s disease and vascular dementia: case-control study. April 28, 2006. British Medical Journal online. Abstract

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  1. There is considerable evidence indicating that many forms of heart disease and embolic stroke in elderly people are major risk factors for Alzheimer disease (AD). This is a monumental medical problem when one considers that heart disease and stroke are the leading causes of death and long-term disability in the United States and in the industrialized world. Thus, elderly patients that survive heart disease or stroke may have a good chance of ending their life with AD. Now, Dr. Purandare and his colleagues show that spontaneous cerebral emboli, which can occur in patients with carotid artery or cardiac pathology, are significantly more frequent in both Alzheimer disease and vascular dementia (VaD) when compared to a nondemented control group. This group found that the similar frequency of emboli in both AD and VaD suggests that both dementias share coincident risk factors and a common pathophysiological cause.

    These findings by the Manchester-based investigators seem to add fuel to the often-made postmortem observation that it is unusual for a patient with AD to die without evidence of some vascular-related condition that causes a reduction in cerebral blood flow. A final point to be made from the Manchester study is that assessment of spontaneous cerebral emboli was made using a transcranial Doppler technique (TCD) of cerebral blood flow signals. I have predicted TCD one day will become a cost-effective, standard office tool to detect potential AD patients with high accuracy (de la Torre, 2005). Such an approach would ideally target preventive treatment of candidate AD patients prior to widespread neurodegeneration.

    References:

    . Is Alzheimer's disease preceded by neurodegeneration or cerebral hypoperfusion?. Ann Neurol. 2005 Jun;57(6):783-4. PubMed.

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Paper Citations

  1. . Cerebral emboli as a potential cause of Alzheimer's disease and vascular dementia: case-control study. BMJ. 2006 May 13;332(7550):1119-24. PubMed.

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  1. . Cerebral emboli as a potential cause of Alzheimer's disease and vascular dementia: case-control study. BMJ. 2006 May 13;332(7550):1119-24. PubMed.

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  1. No Pressure, But Could Hypertension Medication Prevent AD?

Primary Papers

  1. . Cerebral emboli as a potential cause of Alzheimer's disease and vascular dementia: case-control study. BMJ. 2006 May 13;332(7550):1119-24. PubMed.