Omega-3 Fats May Help Explain Women’s Higher Alzheimer’s Risk

Something about the female brain appears to leave it more vulnerable to Alzheimer's disease.

New research indicates that ‘healthy’ unsaturated fats, including omega-3, could account for part of this difference.

Women generally have higher concentrations of omega-3 fatty acids than men. Yet the present analysis found an unexpected shortage of these lipid molecules among women with Alzheimer's.

Omega-3 fats and Alzheimer's disease in women

The researchers did not identify equivalent lipid differences when comparing men with Alzheimer's with men without the condition. This suggests that these fats may influence the disease in different ways according to sex.

The results add weight to a long-neglected hypothesis that links fat droplets to Alzheimer's disease. Although tau tangles and amyloid plaques have historically received more attention, lipids are also a hallmark of the disease in the brain, suggesting that fatty-acid metabolism is somehow disrupted.

A recent Lancet Commission for Dementia estimated that high levels of low-density lipoprotein in midlife account for 7 percent of Alzheimer's risk. LDL transports cholesterol and fatty acids throughout the body.

According to the current study, led by researchers at King's College London, this risk factor may help explain why women develop Alzheimer's at twice the rate of men.

The team examined the lipid profiles of 841 participants from six European countries. Compared with participants with good cognitive health or mild cognitive impairment, those with Alzheimer's disease had substantially higher levels of ‘unhealthy’ saturated fatty acids and substantially lower levels of healthy unsaturated fats, such as omega-3.

"Our study suggests that women should make sure they are getting omega fatty acids in their diet – through fatty fish or via supplements," says pharmaceutical scientist Cristina Legido-Quigley from King's College.

"However, we need clinical trials to determine if shifting the lipid composition can influence the biological trajectory of Alzheimer's Disease."

Lipoproteins, sex differences and cognitive impairment

The study assessed hundreds of individual lipids, transported in the blood by lipoproteins such as LDL and HDL. Several lipids were linked with Alzheimer's disease and cognitive impairment in women, but these same patterns did not appear in men.

Women with Alzheimer's had fewer lipoproteins carrying attached omega fatty acids than healthy women.

"While this study shows that women with Alzheimer's had lower levels of some unsaturated fats compared with men, further work is needed," says Julia Dudley, Head of Research at Alzheimer's Research UK, who was not involved in the study.

"This includes understanding the mechanisms behind this difference and finding out if lifestyle changes, including diet, could have a role."

Addressing the sex bias in brain-ageing research

Brain-ageing research has historically had an extreme sex bias. In 2019, only 5 percent of published neuroscience or psychiatry studies examined the effect of sex.

Furthermore, many Alzheimer's drug trials still fail to assess sex differences, even where such differences seem clearly significant.

As a result, scientists do not know why women are more likely to develop Alzheimer's, or how this risk should be addressed. Women typically live longer, but even men at older ages are less likely than women of the same age to develop this form of dementia.

"Understanding how the disease works differently in women could help doctors tailor future treatments and health advice," says Dudley.

That research is now beginning to emerge.

The study was published in Alzheimer's & Dementia.