Omega-3 Fatty Acids May Help Explain Women’s Higher Alzheimer’s Disease Risk

Omega-3 fatty acids and Alzheimer’s disease

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 in women with Alzheimer’s.

The researchers did not detect equivalent lipid shifts between men with Alzheimer’s and men without the condition. This suggests that these fats may influence the disease differently according to sex.

Lipids have long been overlooked in Alzheimer’s research

The results support a hypothesis, neglected for decades, that links fat droplets to Alzheimer’s disease.

Tau tangles and amyloid plaques have historically received greater attention. But lipids are also hallmarks of the disease in the brain, suggesting that fatty-acid metabolism is somehow disrupted.

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

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

The team examined the lipid libraries of 841 participants from six European countries.

Relative to participants with good cognitive health or mild cognitive impairment, those with Alzheimer’s disease had significantly higher levels of ‘unhealthy’ saturated fatty acids and significantly lower levels of beneficial unsaturated fatty acids 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.”

Sex differences in blood lipids and cognitive impairment

The study assessed hundreds of individual lipids, carried in the bloodstream by lipoproteins such as LDL and HDL. Several lipids in women were linked with Alzheimer’s disease and cognitive impairment, whereas men did not show the same patterns.

Compared with healthy women, women with Alzheimer’s had fewer lipoproteins carrying attached omega fatty acids.

“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.”

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

Moreover, many Alzheimer’s drug trials still fail to analyse differences between sexes, even when those differences seem substantial at first glance.

Consequently, scientists do not know why women are more likely to develop Alzheimer’s, or how to address it. Although women typically live longer, men at older ages remain 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 finally arriving.

The study was published in Alzheimer’s & Dementia.