Challenge study: The efficacy of fish oil supplementation on cognitive performance in MCI patients and the influence of the APOE-epsilon4 allele.

During the last years there has been growing interest in the hypothesis that
high intake of fish and marine n-3 polyunsaturated fatty acids (PUFAs) might
play a protective role against age-related loss of cognitive function. Several
mechanisms that may underlie this relationship have been postulated. N-3 PUFAs
may reduce oxidative stress, have an anti-inflammatory action and have been
linked with aspects of neuron function, including neurotransmission, membrane
fluidity, ion channel and enzyme regulation and gene expression. Furthermore,
there are indications that individuals carrying the APOE-*4 allele respond
differently to n-3 PUFA supplementation. Our hypothesis is that subjects
receiving fish oil supplements will perform better on cognitive performance
tests. Furthermore, we hypothesize that this might be caused by an improved
cerebral perfusion. Next to that we also investigate the influence of APOE4
status on these outcomes measures.

To study the short term effects of a pharmacological dose of fish oil on
cognitive performance and on cerebral blood flow. Furthermore, we want to
investigate whether carriers of the APOE*4 allele respond differently to fish
oil treatment compared to non-carriers.

Randomized, placebo-controlled, double-blind trial where subjects will be
supplemented with fish oil during 4 weeks.

One group (n=20) receives capsules containing an amount of 3g EPA-DHA daily and
the other group (n=20) receives placebo capsules.

To be able to enter the study, participants need to fill out a short
questionnaire with some questions regarding diet and lifestyle and a blood
sample to determine APOE4 status will be collected. When an individual is
eligible for participation baseline measurements will be performed. These
consist of a battery of neuropsychological tests, which takes 30 minutes to be
performed. Next to that cerebral blood flow will be measured using
Trans-cranial Doppler. This measurement is safe and non-invasive, but a
possible burden for the subjects is that this measurement takes 1.5 hours. Also
a blood sample will be collected to determine n-3 fatty acid status and for
isolation of peripheral blood mononuclear cells (PBMC). The baseline
measurements will be repeated at the end of the study which is after 4 weeks.
During the 4-week intervention participants will consume 9 capsules a day,
preceded by a 1-week run-in period with the purpose to get used to consuming
the capsules. Participants will keep a diary where they keep track of missed
capsules, adverse events and other disease or medicine related events.
To summarize the burden for the participants: blood sample: 3x; site visits:
3x; questionnaire: 1x; neuropsychological tests: 2x; Trans-cranial Doppler: 2x;
consuming capsules: 5 weeks (including run-in).