Filling a research gap: Omega-3 biomarkers and early-onset dementia

Recently published in Clinical Nutrition, the longitudinal study, “Blood omega-3 is inversely related to risk of early-onset dementia,” demonstrates a link between higher omega-3 levels and lower risk of early-onset dementia (a diagnosis before age 65).¹ Using data from the UK Biobank, the researchers analyzed omega-3 levels (total omega-3, DHA, and non-DHA omega-3) and early-onset dementia in 217,122 participants ages 40–64, with an average follow up period of 8.3 years.

Here, Aleix Sala-Vila, PhD, Associate scientist at Fatty Acid Research Institute (FARI) and lead study author explains how objectively measured blood levels of omega-3 fatty acids are associated with a substantially lower risk of developing early-onset dementia, and how both DHA and other omega-3 fatty acids may contribute to brain health. Sala-Vila, also a research fellow at Hospital del Mar Research Institute - cardiovascular risk and nutrition group, Barcelona, Spain, explains emerging biological mechanisms and outlines future large-scale efforts to clarify the role of omega-3s in dementia prevention across the lifespan.

Nutritional Outlook: If you could summarize the results of this longitudinal study into one message, what would it be?

We found that higher plasma levels of omega-3 were inversely related to the risk of incident early onset dementia (diagnosed before age 65), similarly to what has been repeatedly observed in late onset dementia (diagnosed at age of 65 or over, which is the most common one).

Nutritional Outlook: Most research regarding omega-3s and cognitive decline focuses on older adults. What prompted your team to specifically investigate early-onset dementia, and what were your initial expectations?

To fill a gap. This particular form of the disease is under-explored, probably because it is much less prevalent than the late onset one. And this is unfair, since this disease is quite devastating: they might have extra requirements because of the disease's "non-normative" timing, along with practical factors like jobs and/or dependent relatives. Dr. Hendriks and colleagues published a very nice paper in 2023 stating that many modifiable risk factors were related to incident early onset dementia in the UK Biobank Study, but omega-3 were overlooked there. Many of the risk factors appearing in that paper were actually the same than those for late onset dementia. This gave us confidence to examine associations for omega-3.

Nutritional Outlook: Your study looked at circulating omega-3 levels rather than self-reported dietary intake. Can you explain why measuring blood biomarkers is a more reliable metric for this type of longitudinal study?

Methods based on self-reporting have been instrumental in this type of research for decades. However, these methods have limitations such as misreporting, misremembering, and out of date nutritional databases. The use of objective biomarkers addresses this limitation: they bypass human bias and memory errors, reducing systematic under- or over-reporting; they provide more accurate and precise exposure measurement; they capture biological availability, not just intake; and finally, they improve cross-population comparisons (making them suitable for international studies).

Nutritional Outlook: Omega-3s consist primarily of EPA, DHA, and ALA. In your findings, did one specific fatty acid show a more robust correlation with lower dementia risk than the others, and what might that that tell us about the biological mechanism at work?

Most of the research on the field focused on DHA, because it is the main dietary omega-3 and it is greatly incorporated in the brain since the very earliest life. However, there is an increasing interest in whether other non-DHA fatty acids might be associated with brain health, as well. Because of methodological limitations of the UK Biobank, we could not investigate independent associations for each individual omega-3: given that only "total omega-3" and "DHA" are available, we decided to estimate "non-DHA omega-3" as a whole, by doing simple maths. Both DHA and non-DHA omega-3 showed inverse significant associations, but those for non-DHA omega-3 were somewhat stronger. This points to that omega-3 other than DHA might also contribute to brain health. Pre-clinical research (in animals, in cells) is unveiling mechanisms explaining these actions: similarly to DHA, these fatty acids also can affect the biophysical membrane properties, promote/inhibit gene expression, and might be converted to anti-inflammatory lipid mediators.

Nutritional Outlook: What has your previous research indicated about the effects of supplementation with omega-3 and what would future studies aim to discover?

A quite consistent finding is that one can get benefits of including all types of omega-3 in the regular diet. We are now leading a project pooling data from nearly 20 cohorts from worldwide on omega-3 biomarkers and incident dementia, which will be the largest study ever. We are confident to get results quite soon.

Reference

1. McEvoy, E. Longitudinal study finds higher omega-3 levels associated with reduced risk of early-onset dementia. January 16, 2026. https://www.nutritionaloutlook.com/view/longitudinal-study-finds-higher-omega-3-levels-linked-to-lower-risk-of-early-onset-dementia (Accessed 2026-01-29).