Brain delivery of supplemental docosahexaenoic acid (DHA): A randomized placebo-controlled clinical trial.

Background: Past clinical trials of docosahexaenoic Acid (DHA) supplements for the prevention of Alzheimer's disease (AD) dementia have used lower doses and have been largely negative. We hypothesized that larger doses of DHA are needed for adequate brain bioavailability and that APOE4 is associated with reduced delivery of DHA and eicosapentaenoic acid (EPA) to the brain before the onset of cognitive impairment.

Methods: 33 individuals were provided with a vitamin B complex (1 mg vitamin B12, 100 mg of vitamin B6 and 800 mcg of folic acid per day) and randomized to 2,152 mg of DHA per day or placebo over 6 months.

APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline.

Vascular contributions to dementia and Alzheimer's disease are increasingly recognized. Recent studies have suggested that breakdown of the blood-brain barrier (BBB) is an early biomarker of human cognitive dysfunction, including the early clinical stages of Alzheimer's disease. The E4 variant of apolipoprotein E (APOE4), the main susceptibility gene for Alzheimer's disease, leads to accelerated breakdown of the BBB and degeneration of brain capillary pericytes, which maintain BBB integrity.

Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction.

Vascular contributions to cognitive impairment are increasingly recognized as shown by neuropathological, neuroimaging, and cerebrospinal fluid biomarker studies. Moreover, small vessel disease of the brain has been estimated to contribute to approximately 50% of all dementias worldwide, including those caused by Alzheimer's disease (AD). Vascular changes in AD have been typically attributed to the vasoactive and/or vasculotoxic effects of amyloid-β (Aβ), and more recently tau.