'Precision' Nutrition? DHA Benefit Modified by AD Genetic Risk

Debra L. Beck

May 07, 2021

In cognitively unimpaired middle-aged adults at high genetic risk for Alzheimer's disease (AD), higher intake of dietary docosahexaenoic acid (DHA) was associated with greater resistance to disease-related brain atrophy on neuroimaging.   

DHA intake, measured using a food frequency questionnaire, was found to be significantly related to greater cortical thickness, the AD signature in individuals homozygous for APOE-ε4, that is with two copies of the risk allele, but not in nonhomozygotes.

This association strengthened in a propensity score analysis that matched participants for risk factors.

"What we saw was that in patients with two APOE-ε4 alleles compared to those with one or none, increasing self-reported DHA intake related to more preserved cortical thickness in these areas associated with AD risk and progression that we refer to as the AD signature," reported lead author Aleix Sala-Vila, PharmD, PhD, from BarcelonaBeta Brain Research Center, in Barcelona, Spain.

"So, in other words, the people with the highest genetic risk for Alzheimer's because of the APOE allele, those were the patients who had benefit from greater fish intake," he added.

"This is important because it gives us a clue on how to test whether this simple lifestyle intervention — namely eating more fatty fish — can be tested. Maybe we need to test the intervention in this enriched target group," Sala-Vila suggested in an interview.

Sala-Vila and colleagues published their findings in the American Journal of Clinical Nutrition.

No significant associations were seen between DHA intake and either episodic memory or executive function. Nor was there an association between DHA intake and evidence of white matter hyperintensities, an indication of cerebral small vessel disease burden.  

Overall, in both homozygotes and nonhomozygotes, a nonsignificant trend was seen toward a lower prevalence of cerebral microbleeds (CMBs) in the lobar regions of the brain (odds ratio, 0.446; P = .055), which are mostly related to the accumulation of amyloid proteins in the walls of blood vessels.

Fatty fish is the main dietary source of DHA, a fatty acid critical for brain function. Whether dietary DHA prevents or slows cognitive decline or AD is still a matter of debate.

"We've seen that if you look at the brains of Alzheimer's patients and compare to nonsufferers of Alzheimer's, you see that in those with AD the amount of DHA is lower, but this is mostly observational data so we have to be cautious in making any conclusions."

In a study published last year and reported by Medscape Medical News, Sala-Vila and colleagues shared observational data showing that regular consumers of foods rich in omega-3 fatty acids had an improved prognosis after ST-segment myocardial infarction.

In that study, the researchers avoided the perils of food frequency questionnaires, but instead assessed tissue levels of EPA and alpha-linolenic acid (ALA) by measuring serum phosphatidylcholine (PC) levels, which reflect dietary intake during the previous 3 or 4 weeks.

He is currently working on collecting circulating omega-3 measures in this current study cohort too.  

Precision Nutrition?

"The findings suggest a role of APOE-ε4 as a conditional modulator in AD-preventive regimes, strengthening the potential relevance of precision nutrition during preclinical stages in neurodegenerative disease prevention," write Omar Yaxmehen Bello-Chavolla, MD, PhD, National Autonomous University of Mexico, Mexico City, and colleagues in an accompanying editorial.

This "positive step forward for precision nutrition" is consistent with recent evidence supporting the role of nutritional habits in both AD and cardiovascular disease risk management, said the editorial writers.

The researchers studied 340 participants from the ALFA Study, a project being carried out at the new BarcelonaBeta Brain Research Center (BBRC).

BBRC was the brainchild of Pasqual Maragall, mayor of Barcelona from 1982-1997. Maragall announced in 2007 his diagnosis of AD and his plans for the Pasqual Maragall Foundation, a private, nonprofit foundation dedicated to the study of the disease. BBRC was created in 2012 for that purpose.

The ALFA Study is a research platform to identify early pathophysiological characteristics of Alzheimer's disease, with the goal of developing prevention strategies.

ALFA was launched in 2013 and has enrolled 2742 cognitively unimpaired middle-aged adults (45-75 years), almost half of whom (47.5%) have one or more parents diagnosed with AD before the age of 75 years.

"I think the most interesting feature of this cohort is the enrichment of carriers of APOE," said Sala-Vila.

From the 340 enrolled, 122 were noncarriers of APOE-ε4, 157 were carriers of one allele, and 61 were carriers of two alleles.

"Because almost half of the ALFA cohort have family members with Alzheimer's disease, they are a really committed group," said Sala-Vila. "When Maragall started the foundation he said, 'No, where is it written that Alzheimer's cannot be defeated?' And that's the foundation of our research at BarcelonaBeta — providing high-quality scientific evidence to better understand the disease and find ways of preventing it or slowing progression."

The study was supported by "la Caixa" Foundation and the Catalan government. Sala-Vila is the recipient of grant support from several organizations and foundations.  

Am J Clin Nutr. Published online March 18, 2021. Full text, Editorial

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