The risk for dementia, a major contributor to incapacitation and institutionalization, rises rapidly as we age, doubling every 5 y after age 65. Tens of millions of new Alzheimer's disease (AD) and other dementia cases are projected as elderly populations increase around the world, creating a projected dementia epidemic for which most nations are not prepared. Thus, there is an urgent need for prevention approaches that are safe, effective, and affordable. This review addresses the potential of one promising candidate, the (n-3) fatty acid docosahexaenoic acid (DHA), which appears to slow pathogenesis of AD and possibly vascular dementia. DHA is pleiotropic, acting at multiple steps to reduce the production of the β-amyloid peptide, widely believed to initiate AD. DHA moderates some of the kinases that hyperphosphorylate the -protein, a component of the neurofibrillary tangle. DHA may help suppress insulin/neurotrophic factor signaling deficits, neuroinflammation, and oxidative damage that contribute to synaptic loss and neuronal dysfunction in dementia. Finally, DHA increases brain levels of neuroprotective brain-derived neurotrophic factor and reduces the (n-6) fatty acid arachidonate and its prostaglandin metabolites that have been implicated in promoting AD. Clinical trials suggest that DHA or fish oil alone can slow early stages of progression, but these effects may be apolipoprotein E genotype specific, and larger trials with very early stages are required to prove efficacy. We advocate early intervention in a prodromal period with nutrigenomically defined subjects with an appropriately designed nutritional supplement, including DHA and antioxidants.
Greg M. Cole and Sally A. Frautschy DHA May Prevent Age-Related Dementia Journal of Nutrition 2010 April Departments of Medicine and Neurology, University of California, Los Angeles, CA 90095; Geriatric Research, Education, and Clinical Center, Greater Los Angeles Veterans Affairs Healthcare System, VA Medical Center, North Hills, CA 91343.