Impaired Peripheral Endothelial Microvascular Responsiveness in Alzheimer's Disease

Abstract

Background: The concept that the neurotoxicity of amyloid β protein could partly result from vascular effects that may be detected in peripheral microcirculation is new. Methods: We compared peripheral endothelial vascular responses of patients with early clinically confirmed Alzheimer's disease (AD) to that of people with normal cognition and those with other forms of dementia. Acetylcholine (ACh) was iontophoresed into the skin and the resultant vasodilator response was measured using laser Doppler flowmetery. Results:The ratio of ACh response to saline (ratio E/S) was determined. Mean ± SEM of ratios E/S were 8.8 ± 0.9 for controls (n = 168), 1.4 ± 0.1 for AD patients (n = 80) and 3.1 ± 0.5 for other dementia (n = 84). Using the optimal cut-off point of E/S ratio of 1.9, an 80% diagnostic sensitivity and specificity for AD have been observed. When the control sample was filtered for those with cardiovascular diseases and with MMSE < 28, this improved the specificity to 90% (n = 119). Furthermore, 15 subjects were randomly drawn from a longitudinal healthy ageing study. Five of those subjects met the criteria for mild cognitive impairment (MCI) after eight years of follow up using a battery of cognitive tests. When tested for their E/S ratio in a blind fashion, the skin test successfully identified those subjects. Conclusions: The results support our hypothesis that endothelial alterations can be detected early in the course of the disease. We suggest that this simple skin test could potentially be applied as diagnostic adjunct in patients with mild cognitive symptoms or those with early clinical evidence of AD.

Reduced plasma levels of P-selectin and L-selectin in a pilot study from Alzheimer disease: relationship with neuro-degeneration

“…Impaired of cerebral hemodynamics has been recently described in AD patients (Stefani et al 2009). Moreover, impaired peripheral endothelial responsiveness a assessed by laser Doppler flowmetery after acetylcholine activation in AD was found (Khalil et al 2007). Finally, microvascular damage and platelet abnormalities in early AD has been described (Borroni et al 2002).…”

Markers of endothelial dysfunction in older subjects with late onset Alzheimer's disease or vascular dementia

“…More interesting, Deane et al [34] have shown that, at the level of blood brain barrier, sVCAM-1 expression is increased by an up-regulation of RAGE (receptor for advanced end glycation products) caused by an increased flow of circulating free β amyloid [34]. Finally, an impairment in peripheral endothelial micro vascular responsiveness has been recently reported in Alzheimer's patients [35].…”

Cardiovascular Risk Factors, Cerebrovascular Disease Burden, and Healthy Brain Aging

“…31 Another study showed that in patients with AD or MCI, discernible changes were detected in endothelial function, compared with controls of similar age. 32 Both these studies imply that vascular and endothelial dysfunction may be the primary event, before the onset of the clinical syndrome of AD.…”