New research shows that intake of higher levels of omega-3 polyunsaturated fatty acids (PUFAs) is associated with larger hippocampus size and better abstract reasoning in healthy middle-aged adults.
Lead study author Dr. Claudia L. Satizabal, assistant professor in the Department of Population Health Sciences at the University of Texas at San Antonio, told us that the results suggest that the brain-boosting effects of omega-3 PUFAs begin in middle age. Medscape Medical News.
“Although the diet is better, patients should be encouraged to increase their omega 3 intake through diet or supplements,” Satizabal said.
The findings were published online on October 5 at Neurology.
Major dietary sources of omega-3 include oily fish such as salmon and sardines.
Previous research has linked higher levels of omega 3 to better cognitive function and a reduced risk of Alzheimer’s disease. “But studies on younger populations are not as frequent,” Satizabal said. “We wanted to see if these benefits could start earlier.”
The current analysis included 2183 participants from the Framingham Heart Study without dementia or stroke. Of these, 2109 were from the third-generation cohort and 74 were from the nonwhite Omni cohort.
Initiated in 1948, Framingham is a community-based, multigenerational study to investigate the determinants of cardiovascular disease. Omni groups were later added to reflect changing demographics. Participants ranged in age from 24 to 83 (mean age 46), and 53 percent were women.
The researchers measured levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the two most abundant omega-3 polyunsaturated fatty acids, from red blood cells. They also calculated the omega-3 index as the sum of EPA and DHA.
All participants underwent brain MRI. Among other brain measurements, the researchers were interested in hippocampal volume and white matter hyperintensity (WMH).
Satizabal noted that the hippocampus, a key region involved in memory, shrinks with the onset of dementia. WMH indicates the presence of small-vessel disease in the brain, she said.
Participants completed a detailed neuropsychological battery. The tests assessed delayed episodic memory, processing speed, and executive function. Similarity tests are used to assess abstract reasoning.
In addition to other possible confounders, the researchers adjusted for vascular risk factors such as systolic blood pressure, antihypertensive medications, smoking, diabetes, total cholesterol to high-density lipoprotein ratio, body mass index, use of lipid-lowering medications and prevalent cardiovascular disease.
They also examined standard deviation units (SDUs) to assess whether omega-3 levels were “as much as possible,” Satizabal said.
Additionally, to assess whether slightly higher levels of omega-3s were beneficial, the researchers divided fatty acid levels into quartiles and used the bottom quartile as a reference group.
more could be better
The results show that for each SDU increase in the log-transformed omega-3 index, there is a correlation of 0.003 cm3 Larger hippocampal volume relative to intracranial volume (phosphorus = .04). Similar results were obtained for DHA or EPA concentrations, respectively.
There was a threshold effect on DHA levels and Omega-3 index, with participants in the top three quartiles having greater hippocampal volume compared with participants in the bottom quartile.
Satizabal noted that there was an effect even in the second-to-last group, suggesting that “just slightly” higher omega 3 levels “are enough to show an effect.”
After adjusting for vascular risk factors, the association between higher omega-3 levels and larger hippocampal volume remained significant.
Regarding cognition, the researchers found that higher levels of all omega-3 predictors were associated with better abstract reasoning abilities. For the omega-3 index, the SDU is 0.17 (phosphorus = .013).
Being in the top three quartiles of the EPA level was associated with better performance on the similarity test compared to the bottom EPA quartile. The association remained after adjustment for vascular risk factors.
Satizabal noted that these results were surprising because study participants were thought to have normal cognitive abilities. “We didn’t expect to see many differences,” she said.
“Interesting” APOE results
The researchers also investigated the role of APOE, whose primary function is to transport fatty acids in the body. About 22 percent of the participants had at least one APOE-e4 allele linked to Alzheimer’s disease.
Elevated DHA levels and Omega-3 index were associated with larger hippocampal volume only in APOE-e4 non-carriers.
Higher levels of all omega-3 PUFA markers were associated with lower WMH burden, and higher EPA levels were associated with better abstract reasoning — but only in APOE-e4 carriers.Again, these associations persisted after adjusting for vascular risk factors.
“Interestingly, we actually saw the greatest benefit in e4 carriers. As omega 3 increased, they reduced the burden of small vessel disease,” Satizabal said.
Previous animal studies have elucidated the possible mechanism of omega 3. DHA and EPA deficiency in mice have been shown to lead to downregulation of presynaptic vesicle proteins and glutamate receptor subunits at hippocampal synapses. Hippocampal volume and other brain health signals were greater in older mice fed a diet rich in omega-3s.
Satizabal noted that the new results may help explain why some studies in which participants increased their omega-3 intake did not show positive brain effects. “It may have been because the intervention started too late,” she said.
Comment Medscape Medical NewsElaine Jones, MD, a teleneurologist in Sarasota, Fla., and a fellow at the American Academy of Neurology, said the study “certainly supports trends we’ve noticed” in people who follow healthy lifestyles that include eating less meat And less processed meat, more fish, fresh fruits and vegetables.
“More and more things are showing that omega-3s may have some benefits,” said Jones, who was not involved in the study.
The study, which highlights the benefits of eating omega-3s early in life, is “exciting,” she added.
“A lot of dementia research has focused on people who have been diagnosed or have overt features of dementia; so it’s good to look at this more middle-aged person,” Jones said.
“I’m a firm believer that once you have a preclinical or clinical diagnosis, the horse will come out of the barn,” she added.
Jones noted that one study was limited in that its population was predominantly white and middle-class, but “there are huge racial disparities in dementia.” She said she wanted to see if the results apply to other populations.
The research was funded by the National Heart, Lung, and Blood Institute, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke. Satizabal has received a new researcher study grant from the Alzheimer’s Association to promote diversity. Jones reported no relevant financial relationships.
Neurology. Published online October 5, 2022.Summary
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