Influence of galantamine on vasomotor reactivity in Alzheimer's disease and vascular dementia due to cerebral microangiopathy

Background and Purpose - Recent reports suggest that vascular factors play a crucial role in the development and progression of Alzheimer's disease. We aimed to assess vasomotor reactivity in patients with Alzheimer's disease and vascular dementia due to microangiopathy using transcranial Doppler sonography and near-infrared spectroscopy during a CO2 exposition task. Methods - The normalized CO2 reactivity assessed at the middle cerebral artery and the oxygenated and deoxygenated hemoglobin of the frontal cortex were obtained. To investigate the impact of cholinergic deficiency known for Alzheimer's disease on vasomotor reactivity, both groups were reinvestigated during treatment with the acetylcholine esterase inhibitor galantamine. Results - Transcranial Doppler analysis revealed significantly reduced normalized CO2 reactivity for Alzheimer's disease and vascular dementia. Vasomotor reactivity assessed by near-infrared spectroscopy was decreased in patients with vascular dementia, but not in Alzheimer's disease. Galantamine treatment showed a beneficial effect, normalizing these parameters close to age-matched control levels. Conclusions - Our results suggest that Alzheimer's disease is associated with a lack of vasomotor reactivity, which might be associated with disturbed autoregulation indicating a potential risk for a decreased protection of brain tissue against blood pressure changes. Additionally, a diminished increase of cortical oxygenated hemoglobin during the CO2 test was apparent in patients with vascular dementia. Galantamine treatment influenced vascular reactivity in the CO2 test, thus providing evidence for the cholinergic deficiency, thereby adding to vascular dysregulation in Alzheimer's disease, but also indicating an important role of cholinergic system dysfunction for vascular dementia.