MANCHESTER, England, April 28  Spontaneous cerebral blood clots appear to be a common pathology of Alzheimer's disease and vascular dementia, and they may be targets for prevention or treatment of both disorders, according to researchers here.
In a study comparing patients with each form of dementia with age- and sex-matched controls, surgeon Charles McCollum, M.D., of the University of Manchester and colleagues found that spontaneous cerebral emboli were significantly more frequent in patients with Alzheimer's or vascular dementia.
Action Points
- Explain to interested patients that this study points to blood clots in the brain as a possible cause of or contributor to Alzheimer's disease and vascular dementia.
- Caution patients that Alzheimer's disease is a complex disorder whose origins and causes are poorly defined and are surrounded by considerable controversy.
"The frequency of spontaneous cerebral emboli was similar in Alzheimer's disease and vascular dementia, which may explain the similarity in risk factors between these two dementias with differing final pathology," the investigators wrote in the early online edition of BMJ, formerly theBritish Medical Journal.
The findings lend credence to the theory that some dementias may be caused by silent cerebral infarctions or "mini-strokes."
Both Alzheimer's and vascular dementia are associated with vascular risk factors such as smoking, hypertension, high cholesterol, and diabetes, as well as carotid atherosclerosis, the authors noted.
They speculated that spontaneous cerebral emboli of vascular or cardiac origin--such as atrial fibrillation, valvular heart disease, or a shunt from the venous to the arterial circulation caused by defects such as patent foramen ovale--could be a common feature of both Alzheimer's disease and vascular dementia, which together account for about 80% of all dementia cases.
To test this theory, they used a minimally invasive transcranial Doppler technique to determine the frequency of spontaneous cerebral emboli, carotid artery disease, and venous-to-arterial shunts in 85 patients with Alzheimer's, 85 with vascular dementia, and 150 controls. Some of the patients had been part of a smaller pilot study of the monitoring technique.
The patients with dementia had cardiovascular risk factors similar to those of controls, although patients with vascular dementia were significantly more likely to have had a history of stroke or transient ischemic attacks.
Patients with vascular dementia were also more likely than those with Alzheimer's patients to have a history of stroke, TIA, use of antiplatelet drugs (P for all < 0.001), hypertension (P = 0.01), and lower HDL cholesterol levels (P = 0.03).
"These factors are all likely to lead a clinician to diagnose vascular dementia or, in the case of antiplatelet drugs, a consequence of that diagnosis," Dr. McCollum and colleagues wrote.
During a single hour of transcranial Doppler monitoring, they found that spontaneous cerebral emboli occurred in 40% of the patients with Alzheimer's disease and in 37% of those with vascular dementia, but in only 15% and 14% of the respective controls. The remarkable frequency of spontaneous cerebral emboli during a single hour in patients with dementia raises the possibility that the true prevalence is even higher and that emboli would be detected in many more patients if they were monitored over several hours.
Two or more emboli were seen during the course of monitoring in 21% of patients in each dementia group, compared with 9%-11% of controls.
The odds ratio for spontaneous cerebral emboli was 3.22 (95% confidence interval, 1.52 to 6.81) for Alzheimer's disease and 4.80 (95% CI, 1.83 to 12.58) for vascular dementia.
Even after adjusting for cardiovascular risk factors, the odds ratios for emboli and dementia remained significant, at 2.70 (95% CI, 1.18 to 6.21) for Alzheimer's disease and 5.36 (95% CI, 1.24 to 23.18) for vascular dementia.
When they looked at carotid artery disease, they found that there were no statistically significant differences in moderate or severe stenosis of either internal carotid artery between the dementia groups and controls.
When they looked for shunts from the venous circulation to the arterial circulation, they found that they found clinically significant shunts in 32% of the Alzheimer's patients, 29% of those with vascular dementia, 22% of the controls for Alzheimer's disease and 20% of the controls for the vascular dementia patients.
The odds ratio for shunts was 1.57 (95% CI, 0.80 to 3.07) for Alzheimer's disease and 1.67 (95% CI, 0.81 to 3.41) for vascular dementia. When they excluded from the analysis patients who had taken part in the pilot study, however, they found that the differences between the dementia patients and controls were not statistically significant.
There were also no significant difference in major shunts between the dementia groups and controls.
"As expected, spontaneous cerebral emboli were associated with all the major cardiovascular risk factors in controls," the investigators wrote. "We found no such association in dementia patients, implying that spontaneous cerebral emboli may be universal in dementia."
Primary Source
BMJ-British Medical Journal
Source Reference: Purandare N et al. BMJ doi 10.1136/bmj.38814.696493.AE