Docosahexaenoic acid is the main long-chain omega-3
polyunsaturated fatty acids in the brain and accounts for 30-40% of
fatty acids in the grey matter of the human cortex. Although the influence of
docosahexaenoic acid on memory function is widely researched, its association with brain volumes is under investigated and its association with spatial navigation is virtually unknown. This is despite the fact that spatial navigation deficits are a new cognitive fingerprint for symptomatic and asymptomatic
Alzheimer's disease. We investigated the cross-sectional relationship between
docosahexaenoic acid levels and the major structural and cognitive markers of preclinical
Alzheimer's disease, namely hippocampal volume, entorhinal volume and spatial navigation ability. Fifty-three cognitively normal adults underwent volumetric magnetic resonance imaging, measurements of serum
docosahexaenoic acid (DHA, including
lysophosphatidylcholine DHA) and
APOE ε4 genotyping. Relative regional brain volumes were calculated and linear regression models were fitted to examine DHA associations with brain volume.
APOE genotype modulated serum DHA associations with entorhinal cortex volume and hippocampal volume. Linear models showed that greater serum DHA was associated with increased entorhinal cortex volume, but not hippocampal volume, in non APOΕ ε4 carriers.
APOE also interacted with serum
lysophosphatidylcholine DHA to predict hippocampal volume. After testing interactions between DHA and
APOE on brain volume, we investigated whether DHA and
APOE interact to predict spatial navigation performance on a novel virtual reality diagnostic test for
Alzheimer's disease in an independent population of
APOE genotyped adults (n = 46).
APOE genotype modulated DHA associations with spatial navigation performance, showing that DHA was inversely associated with path integration in
APOE ε4 carriers only. This exploratory analysis suggests that interventions aiming to increase DHA blood levels to protect against
cognitive decline should consider
APOE ε4 carrier status. Future work should focus on replicating our initial findings and establishing whether a specific dose of supplementary DHA, at a particular time in the preclinical disease course can have a positive impact on
Alzheimer's disease progression in
APOE ε4 carriers.