08/21/2016
Cerebrovascular effects of flavonoids
Dementia is a serious degenerative disease effecting predominantly elderly people with the two most common forms of this illness being Alzheimer’s and vascular dementia. The factors affecting dementia are age, hypertension, arteriosclerosis, diabetes mellitus, smoking, atrial fibrillation and those with the ApoE4 genotype [11]. There is evidence to suggest that flavonoids may be capable of preventing many forms of cerebrovascular disease, including those associated with stroke and dementia [21, 23]. There is powerful evidence for the beneficial effects of flavonoids on endothelial function and peripheral blood flow [90] and these vascular effects are potentially significant as increased cerebrovascular function is known to facilitate adult neurogenesis in the hippocampus [32] (Fig. 3). Indeed, new hippocampal cells are clustered near blood vessels, proliferate in response to vascular growth factors and may influence memory [74]. As well as new neuronal growth, increases in neuronal spine density and morphology are considered vital for learning and memory [35]. Changes in spine density, morphology and motility have been shown to occur with paradigms that induce synaptic, as well as altered sensory experience, and lead to alterations in synaptic connectivity and strength between neuronal partners, affecting the efficacy of synaptic communication. These events are mediated at the cellular and molecular level and are strongly correlated with memory and learning.
Efficient cerebral blood flow is also vital for optimal brain function, with several studies indicating that there is a decrease in cerebral blood flow (CBF) in patients with dementia [71, 87]. Brain imaging techniques, such as ‘functional magnetic resonance imaging’ (fMRI) and ‘trans-cranial Doppler ultrasound’ (TCD) has shown that there is a correlation between CBF and cognitive function in humans [87]. For example, cerebral blood flow velocity is significantly lower in patients with Alzheimer disease and low CBF is also associated with incipient markers of dementia. In contrast, non demented subjects with higher CBF were less likely to develop dementia. Flavonoids have been shown to exert a positive effect on cerebral blood flow (CBF) in humans [29, 31]. After consumption of a flavanol-rich cocoa drink, the ‘flow oxygenation level dependent’ (BOLD)-fMRI showed an increase in blood flow in certain regions of the brain, along with a modification of the BOLD response to task switching. Furthermore, ‘arterial spin-labelling sequence magnetic resonance imaging’ (ASL-MRI) [127] also indicated that cocoa flavanols increase CBF up to a maximum of two hours after ingestion of the flavanol-rich drink. In support of these findings, an increase in cerebral blood flow through the middle cerebral artery has been reported after the consumption of flavanol-rich cocoa using TCD [29].