Challenges to determining whether DHA can protect against age-related cognitive decline

Abstract

DHA, an omega-3 fatty acid, is an important constituent of brain membranes and has a key role in brain development and function. This review aims to highlight recent research on DHA's role during age-related cognitive decline and Alzheimer's disease. Animal and in vitro studies have provided some interesting mechanistic leads, especially on brain glucose metabolism, that may be involved in neuroprotection by DHA. However, results from human studies are more mitigated, perhaps due to changing DHA metabolism during aging. Recent innovative tools such as 13 C-DHA for metabolic studies and 11 C-DHA for PET provide interesting opportunities to study factors that affect DHA homeostasis during aging and to better understand whether and how to use DHA to delay or treat Alzheimer's disease.

Long-chain n-3 PUFAs from fish oil enhance resting state brain glucose utilization and reduce anxiety in an adult nonhuman primate, the grey mouse lemur

“…In a recent study, we confi rmed that rats on an n-3 PUFA-defi cient diet exhibited lower brain uptake of glucose ( 6 ). Such a decrease can, at least partly, explain the behavioral changes observed during n-3 PUFA defi ciency.…”

Docosahexaenoic Acid and Cognition throughout the Lifespan

“…Accordingly, diabetes patients are more likely to develop dementia [ 317 ]. Interestingly, animal and in vitro studies identify positive effects of DHA on endothelial and glial GLUT1 levels and brain glucose uptake [ 318 , 319 , 320 , 321 ].…”

2-Hydroxy-Docosahexaenoic Acid Is Converted Into Heneicosapentaenoic Acid via α-Oxidation: Implications for Alzheimer’s Disease Therapy

“…There is evidence from cell and animal models that therapies based on nutritional supplement with DHA have neuroprotective effects (Morris et al, 2003;Su, 2010;Dyall, 2015;Hennebelle et al, 2015;Belkouch et al, 2016). However, administration of DHA and/or EPA to AD patients in clinical trials has only been effective in small groups of patients with a mild-to-moderate pathology (Freund-Levi et al, 2006;Quinn et al, 2010).…”