Our studies suggest that APOE4 carriers have abnormalities in brain DHA metabolism that precede the onset of Alzheimer?s disease (AD) dementia. Early and long term high dose DHA supplementation in APOE4 animal models preserves cognitive functions. Subgroup analyses of several randomized clinical trials suggest that APOE4 carriers may benefit for omega-3 supplementation prior to the onset of AD. In the DHA Brain Delivery Trial (R01AG054434) we are studying the effect of APOE4 on the response to DHA supplementation in 160 non-demented adults randomized to 2 grams of DHA daily vs placebo for 6 months. The goal of DHA brain delivery study is to determine the effect of APOE genotype on brain DHA levels (using cerebrospinal fluid) and on brain functional connectivity after DHA supplementation, providing novel information on mechanisms for APOE4 mediated AD risk. We seek to extend Brain DHA Delivery Trial from 6 months to two years to allow detecting meaningful changes in cognitive and imaging outcomes. Supplemental funds are requested to enhance participant recruitment and allow the addition of neuropsychology testing.
Carrying the APOE ?4 allele is the strongest genetic risk factor for developing Alzheimer?s disease. The goal of this project is to identify whether carrying the APOE ?4 allele is associated with reduced DHA delivery to the brain. This information will help us identify the target population that could benefit from DHA supplementation to prevent cognitive decline. Given the large risk associated with this genotype, the potential public health impact of a safe and inexpensive supplementation could have wide-spread applicability, especially in terms of reduced AD incidence.
| Yassine, Hussein N; Croteau, Etienne; Rawat, Varun et al. (2017) DHA brain uptake and APOE4 status: a PET study with [1-11C]-DHA. Alzheimers Res Ther 9:23 |
| Yassine, Hussein N; Braskie, Meredith N; Mack, Wendy J et al. (2017) Association of Docosahexaenoic Acid Supplementation With Alzheimer Disease Stage in Apolipoprotein E ?4 Carriers: A Review. JAMA Neurol 74:339-347 |
| Yassine, Hussein N (2017) Targeting prodromal Alzheimer's disease: too late for prevention? Lancet Neurol 16:946-947 |
| Yassine, Hussein N; Schneider, Lon S (2017) Lessons from the Multidomain Alzheimer Preventive Trial. Lancet Neurol 16:585-586 |
