Flavonoids, cognition, and dementia: actions, mechanisms, and potential therapeutic utility for Alzheimer disease

Free Radic Biol Med. 2012 Jan 1;52(1):35-45. doi: 10.1016/j.freeradbiomed.2011.09.010. Epub 2011 Sep 17.

Abstract

There is increasing evidence that the consumption of flavonoid-rich foods can beneficially influence normal cognitive function. In addition, a growing number of flavonoids have been shown to inhibit the development of Alzheimer disease (AD)-like pathology and to reverse deficits in cognition in rodent models, suggestive of potential therapeutic utility in dementia. The actions of flavonoid-rich foods (e.g., green tea, blueberry, and cocoa) seem to be mediated by the direct interactions of absorbed flavonoids and their metabolites with a number of cellular and molecular targets. For example, their specific interactions within the ERK and PI3-kinase/Akt signaling pathways, at the level of receptors or kinases, have been shown to increase the expression of neuroprotective and neuromodulatory proteins and increase the number of, and strength of, connections between neurons. Concurrently, their effects on the vascular system may also lead to enhancements in cognitive performance through increased brain blood flow and an ability to initiate neurogenesis in the hippocampus. Additional mechanisms have been suggested for the ability of flavonoids to delay the initiation of and/or slow the progression of AD-like pathology and related neurodegenerative disorders, including a potential to inhibit neuronal apoptosis triggered by neurotoxic species (e.g., oxidative stress and neuroinflammation) or disrupt amyloid β aggregation and effects on amyloid precursor protein processing through the inhibition of β-secretase (BACE-1) and/or activation of α-secretase (ADAM10). Together, these processes act to maintain the number and quality of synaptic connections in key brain regions and thus flavonoids have the potential to prevent the progression of neurodegenerative pathologies and to promote cognitive performance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / enzymology*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology
  • Amyloid Precursor Protein Secretases / antagonists & inhibitors
  • Amyloid Precursor Protein Secretases / metabolism
  • Amyloid beta-Peptides / antagonists & inhibitors
  • Animals
  • Brain / drug effects
  • Brain / enzymology*
  • Brain / pathology
  • Brain / physiopathology
  • Cognition / drug effects*
  • Enzyme Activation / drug effects
  • Flavonoids / pharmacology*
  • Gene Expression
  • Humans
  • Mice
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Neurogenesis / drug effects*
  • Neurogenesis / physiology
  • Neurons / drug effects
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Signal Transduction*

Substances

  • Amyloid beta-Peptides
  • Flavonoids
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Amyloid Precursor Protein Secretases