What Is the Link between Docosahexaenoic Acid, Cognitive Impairment, and Alzheimer’s Disease in the Elderly?

Cognitive impairment in the elderly, particularly in the form of Alzheimer’s disease (AD), has emerged in the past 20 years as a major challenge to the quality of life for the elderly and their caregivers, and to healthcare resources. AD is the most common form of dementia and the primary neurodegenerative disorder in the elderly. Once it is clinically diagnosed, there is little prospect of improving the prognosis of AD. Cognitive deficits can progress gradually over many decades before reaching the clinical threshold for the diagnosis of AD (Petersen et al., 2001; Jorm et al., 2007). As the population ages, the prevalence of cognitive impairment leading to dementia and AD is expected to increase. Most of the subjects with mild cognitive impairment will progress to AD at a rate of 10%–15% per year compared with healthy control subjects who convert at a rate of 1%–2% per year (Petersen et al., 2001; Solfrizzi et al., 2006). The cause of the progression of cognitive impairment to dementia and AD is not established. Genetic factors have been implicated and the apolipoprotein E ɛ4 allele is the genetic risk factor most associated with AD (Mahley et al., 2006). It is plausible that genetic factors, especially genes involved in lipid metabolism and transport, interact with environmental factors for lowering or increasing the risk of AD. Since aging is unavoidable and there is not yet a cure for AD, strategies to identify environmental factors lowering risk of AD are essential. Therefore, research on potentially modifiable risk factors for cognitive impairment, such as diet, is of great relevance. Several studies showed that cognitive impairment in the elderly is associated with deficiencies of micronutrients and macronutrients (Rosenberg and Miller, 1992; Grant, 1999; Dye et al., 2000; Gonzalez-Gross et al., 2001; Gillette Guyonnet et al., 2007). Among macronutrients, there is increasing interest in the possible impact of dietary fatty acids on cognitive impairment and dementia. One class of dietary fatty acids closely associated with the function of the brain is the ω3 polyunsaturated fatty acids (PUFA), particularly docosahexaenoic acid (DHA), which is a major component of the membrane phospholipids in the brain. Fish and seafood (shellfish and crustacean) consumption is the main dietary source of preformed DHA. Most epidemiological studies, but not all, suggest that fish and seafood consumption might protect the elderly from developing cognitive impairment or dementia including AD (reviewed in Gillette Guyonnet et al., 2007). Whether ω3 PUFA from fish and seafood, especially DHA, might be the principal contributors in preventing cognitive impairment and dementia in the elderly is presently debated. Previous reviews describing the relationship between ω3 PUFA and cognitive decline reported an inconclusive association (Maclean et al., 2005; Gillette Guyonnet et al., 2007; Plourde et al., 2007). Therefore, this chapter examines the possible link between fish and seafood or DHA intakes and cognitive impairment and dementia including AD with emphasis on three types of human studies—evaluation of epidemiological studies on fish and seafood or DHA intake, analysis of DHA levels in blood or brain tissues, and clinical trials of supplementation with DHA-enriched oils in cognitively impaired nondemented (CIND) elderly and AD patients. In view of the literature as it stands presently, we sought to answer the following questions: (1) Does the intake of fish and seafood protect against cognitive impairment and its progression to dementia such as AD in the elderly?, (2) What is the biological evidence from tissue fatty acid analyses that DHA plays a significant role in the protective effect of fish and seafood consumption?, and (3) is DHA alone effective in the treatment of cognitive impairment and AD?