Cerebral emboli as a potential cause of Alzheimer's disease and vascular dementia: casecontrol study

Abstract

Objective To compare the occurrence of spontaneous cerebral emboli and venous to arterial circulation shunts in patients with Alzheimer's disease or vascular dementia and controls without dementia. Design Cross sectional case-control study. Setting Secondary care old age psychiatry services, Manchester. Participants 170 patients with dementia (85 with Alzheimer's disease, 85 with vascular dementia) and 150 age and sex matched controls. Patients on anticoagulant treatment, patients with severe dementia, and controls with marked cognitive impairment were excluded. Main outcome measures Frequencies of detection of spontaneous cerebral emboli during one hour monitoring of the middle cerebral arteries with transcranial Doppler and venous to arterial circulation shunts by a transcranial Doppler technique using intravenous microbubbles as an ultrasound contrast. Results Spontaneous cerebral emboli were detected in 32 (40%) of patients with Alzheimer's disease and 31 (37%) of those with vascular dementia compared with just 12 each (15% and 14%) of their controls, giving significant odds ratios adjusted for vascular risk factors of 2.70 (95% confidence interval 1.18 to 6.21) for Alzheimer's disease and 5.36 (1.24 to 23.18) for vascular dementia. These spontaneous cerebral emboli were not caused by carotid disease, which was equally frequent in dementia patients and their controls. A venous to arterial circulation shunt indicative of patent foramen ovale was found in 27 (32%) Alzheimer's disease patients and 25 (29%) vascular dementia patients compared with 19 (22%) and 17 (20%) controls, giving non-significant odds ratios of 1.57 (0.80 to 3.07) and 1.67 (0.81 to 3.41). Conclusion Spontaneous cerebral emboli were significantly associated with both Alzheimer's disease and vascular dementia. They may represent a potentially preventable or treatable cause of dementia.

On the early diagnosis of Alzheimer's Disease from multimodal signals: A survey

“…The pulsatility index (PI) has been found to increase in AD [176]. A few studies have also focused on cerebral micro-embolization, and have concluded that people suffering from dementia, both AD or VD, are more affected by this effect [190,191].…”

Carbon Monoxide and Iron Modulate Plasmatic Coagulation in Alzheimer’s disease

“…However, inhibition of Hmox in a murine model of AD involving a double transgenic mouse (APP swe /PS1 E9 ) significantly diminished the behavioral deficits and neuropathological changes over time compared to mice not administered a Hmox inhibitor [24]. When all these data are considered as a whole, Hmox enhanced coagulation could play a role in spontaneous thrombus formation not just in the peripheral circulation as documented by previous ultrasonic investigations [11,12], but perhaps more regionally (and intensely) in the microcirculation of the brain itself.…”

“…When our data are considered as a whole, CO and iron enhanced coagulation could play a role in spontaneous cerebral embolus formation in the setting of AD as documented by previous ultrasonic investigations [11,12]. Further, when coupled with normal or accelerated fibrinolysis, it is possible that microembolic or in situ thrombus formation within the brain occurs causing ischemic damage, but with timely lysis preventing large, clinically detectable neurologic defects.…”

“…In addition to the recently reviewed, original 'amyloid cascade hypothesis' [1], the development and progression of AD have been associated with viral infection [2], vascular damage from pulse pressure [3], regional deposition of metals, such as iron, resulting in oxidant injury [4][5][6][7][8], metabolic syndrome and morbid obesity [8][9][10], and long term exposure to spontaneous cerebral microemboli [11,12]. Of these various paradigms, the notion that spontaneous emboli, most likely due to systemic hypercoagulability, is of particular interest.…”

“…Alzheimer's disease (AD) is a major source of morbidity and mortality for millions of people worldwide, and intense investigation has led to multiple etiological constructs contributing to AD [1][2][3][4][5][6][7][8][9][10][11][12]. In addition to the recently reviewed, original 'amyloid cascade hypothesis' [1], the development and progression of AD have been associated with viral infection [2], vascular damage from pulse pressure [3], regional deposition of metals, such as iron, resulting in oxidant injury [4][5][6][7][8], metabolic syndrome and morbid obesity [8][9][10], and long term exposure to spontaneous cerebral microemboli [11,12].…”