Cited by 456Alzheimer's disease research and treatmentsMedicinal Plants and NeuroprotectionDementia and Cognitive Impairment Research

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

Williams, Robert J., Spencer, Jeremy P.E.·2012·Free Radical Biology and Medicine

DOI 10.1016/j.freeradbiomed.2011.09.010

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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.

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Authors: Williams, R. J., & Spencer, J. P. E.
Affiliations: University of Bath (GB)
University of Reading (GB)
Corresponding author: Spencer, Jeremy P.E.
Venue: Free Radical Biology and Medicine
Publisher: Elsevier BV
Published: 2012-01
Volume: 52
Issue: 1
Pages: 35-45
ISSN: 0891-5849 (ISSN-L)
DOI: 10.1016/j.freeradbiomed.2011.09.010
OpenAlex: W2000424893
Cited by: 448
References: 222
Citations by year: 2026: 11 · 2025: 17 · 2024: 28 · 2023: 16 · 2022: 36 · 2021: 34 · 2020: 36 · 2019: 38 · 2018: 34 · 2017: 42 · 2016: 34 · 2015: 37 · 2014: 36 · 2013: 33 · 2012: 15
FWCI: 2.91
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Free Radical Biology and Medicine (publishedVersion)
PubMed (publishedVersion)
Funders: Alzheimer's Society
Biotechnology and Biological Sciences Research Council (BB/G005702/1, BB/E023185/1, BB/F008953/1)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: flavonoids, Alzheimer's disease, dementia, flavonoid-rich foods, green tea, blueberry, Theobroma cacao, flavonoid metabolites, ERK signaling, PI3K/Akt signaling, neuroprotection, neurogenesis, hippocampus, cerebral blood flow, neuronal apoptosis, oxidative stress, neuroinflammation, amyloid-beta aggregation, APP processing, BACE1, ADAM10, synaptic connectivity, cognitive function, neurodegeneration
MeSH terms: Alzheimer Disease, Animals, Brain, Cognition, Enzyme Activation, Flavonoids, Humans, Neurons, Signal Transduction, Gene Expression, Amyloid beta-Peptides, Phosphatidylinositol 3-Kinases, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Proto-Oncogene Proteins c-akt, Mice, Rats, Amyloid Precursor Protein Secretases, Neurogenesis

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

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