McCollum presented the results of a study exploring the hypothesis that multiple microemboli over many years may be a cause of dementia at the CX Symposium yesterday, and concluded that emboli "may be universal to dementia sufferers".
Approximately 24 million people worldwide live with dementia, and Alzheimer’s disease and vascular dementia account for nearly 90% of these cases. Yet the pathophysiology of the brain damage in these common dementias remains unknown.
Asymptomatic cerebral emboli are frequent in carotid artery disease and, said McCollum, are known to increase the risk of stroke, which is itself an important cause of dementia. McCollum and his team hypothesised that emboli may also cause diffuse cerebral damage leading to dementia.
The team arrived at this hypothesis based upon the observations that multiple cerebral emboli during cardiopulmonary bypass in open heart surgery were associated with memory loss, and that emboli released during hip surgery only enter the cerebral circulation if there is patent foramen ovale when paradoxical embolisation was almost inevitable. The researchers were also influenced by the YAMIS study (Young adult myocardial infarction and ischaemic stroke), which showed that patent foramen ovale, allowing paradoxical emboli, was frequent in young adults suffering ischaemic stroke.
To test the hypothesis, the team used Doppler ultrasound to quantify the embolic load in 170 Alzheimer’s disease and vascular dementia patients and 170 age- and sex-matched controls.
Right to left shunt, suggestive of a patent foramen ovale, was found in 32% and 29% of Alzheimer’s disease and vascular dementia patients respectively, but in only 22% and 20% of their matched controls.
During a single hour of transcranial Doppler ultrasound monitoring, spontaneous cerebral emboli were detected in 40% and 37% of Alzheimer’s disease and vascular dementia patients respectively, compared with only 15% and 14% of control subjects.
"This was not statistically significant but a surprisingly strong association between spontaneous cerebral emboli and dementia was found," said McCollum. "This suggests that most, if not all, dementia subjects would have spontaneous cerebral emboli if monitored over several hours."
One hundred and forty four patients with dementia were followed at six-monthly intervals for two years to explore the impact of spontaneous cerebral emboli on the progression of dementia, as measured with the Alzheimer’s Disease Assessment Scale Cognitive subscale (ADAS-cog).
In patients who had spontaneous cerebral emboli initially, ADAS-cog deteriorated from a mean of 22.9 to 30.0 at six months, compared with 23.2 and 26.5 in spontaneous cerebral emboli negative patients. But this trend was no longer statistically significant at two years, said McCollum.
