Abstract
More than a dozen epidemiological studies have reported that reduced levels or intake
of omega-3 fatty acids or fish consumption is associated with increased risk for age-related
cognitive decline or dementia such as Alzheimer's disease (AD). Increased dietary
consumption or blood levels of docosahexaenoic acid (DHA) appear protective for AD
and other dementia in multiple epidemiological studies; however, three studies suggest
that the ApoE4 genotype limits protection. DHA is broadly neuroprotective via multiple
mechanisms that include neuroprotective DHA metabolites, reduced arachidonic acid
metabolites, and increased trophic factors or downstream trophic signal transduction.
DHA is also protective against several risk factors for dementia including head trauma,
diabetes, and cardiovascular disease. DHA is specifically protective against AD via
additional mechanisms: It limits the production and accumulation of the amyloid β
peptide toxin that is widely believed to drive the disease; and it also suppresses
several signal transduction pathways induced by Aβ, including two major kinases that
phosphorylate the microtubule-associated protein tau and promote neurofibrillary tangle
pathology. Based on the epidemiological and basic research data, expert panels have
recommended the need for clinical trials with omega-3 fatty acids, notably DHA, for
the prevention or treatment of age-related cognitive decline—with a focus on the most
prevalent cause, AD. Clinical trials are underway to prevent and treat AD. Results
to-date suggest that DHA may be more effective if it is begun early or used in conjunction
with antioxidants.
Keywords
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Article info
Publication history
Published online: August 25, 2009
Footnotes
☆Sources of support: This work was supported by NCCAM R01AT3008 and NIA R01AG13471.
Identification
Copyright
Published by Elsevier Inc.
