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Abstract

BACKGROUND: Aging is characterized by cognitive decline, including episodic and working memory impairments, which can lead to loss of autonomy. Among older adults, one quarter, referred to here as "decliners", show greater-than-average cognitive decline for their age group without reporting memory complaints. To prevent or slow this accelerated decline and maintain a good quality of life in seniors, nutrition represents a promising approach. OBJECTIVE: This study evaluates the effect of a 3-month fish hydrolysate (FH) supplementation on memory performance in healthy older adults identified as decliners. The primary outcome of this study was the PALTEA (Paired Associates Learning Total Error Adjusted) score, assessing episodic memory. METHODS: In this double-blind, randomized, placebo-controlled trial, 53 healthy older adults (60-73 years; MMSE >27; PALTEA ≥41) received either FH (1g of low-molecular-weight peptides and 30mg of n-3 long-chain polyunsaturated fatty acids) or placebo daily for 3 months. Cognitive performance was assessed using CANTAB. Statistical analyses were performed using ANCOVA adjusting for baseline values, age and education level, with significance set at p<0.05. RESULTS: FH supplementation significantly improved PALTEA scores versus placebo (p=0.003; β= -11.75; CI:[-19.30;-4.19]), with more patterns completed (p<0.001; β= 1.34; CI:[0.58;2.09]) and fewer errors at higher levels (6 and 8 patterns; p=0.040; β= -3.66; CI:[-7.15;-0.17] and p=0.004; β= -5.74; CI:[-9.60;-1.89]). Working memory showed partial improvement, notably spatial working memory strategy score (p=0.018; β= -1.26; CI:[-2.31;-0.22]). Verbal recognition did not differ between groups. FH supplementation increased erythrocyte n-3 PUFAs levels (p=0.036; β= 0.80; CI:[0.05;1.54]), and reduced serum CRP levels (p=0.038; β= -0.33; CI:[-0.63;-0.02]) and inflammation status score (p=0.046; β= -0.35; CI:[-0.69;-0.01]). CONCLUSION: Three months of FH supplementation improved episodic memory and working memory in older adults with accelerated cognitive decline, alongside a better n-3 PUFA profile and reduced inflammation, supporting FH as a promising strategy to promote healthy cognitive aging. This trial was registered at clinicaltrials.gov as NCT04910399.

Referenced In

N-3 Fatty Acids and Cognitive Decline: New Evidence and Old Questions

A new study published last week in the American Journal of Clinical Nutrition purported to find benefits of a peptide and fatty-acid supplement on cognitive function in older adults, stirring up a long-running debate.

Does eating or supplementing with n-3 polyunsaturated fatty acids (PUFAs) help to slow cognitive decline? Could they help prevent or treat conditions like Alzheimer’s?

New Study Suggests Fish Hydrolysate Improves Episodic and Working Memory

The study randomized 53 healthy older adults to receive either fish hydrolysate or a placebo, and tracked their cognitive performance for three months.

Fish “hydrolysate” is a supplement containing low molecular weight peptides and n-3 PUFAs. Two of the study’s authors worked for a company manufacturing such products.

They found:

  • People taking the supplement performed better on a test of visuospatial learning and episodic memory.  

  • The supplementation group performed better on some measures of working memory, with no differences on others.

The authors mention that larger-scale trials often find no impact of PUFAs on global cognition or in specific areas, but that results are inconsistent. However, with its small sample size, this study doesn’t clear much up.

Do n-3 PUFAs Have Cognitive Benefits?

There are other suggestions that PUFAs may have benefits. In fact, two systematic reviews and meta-analyses found a benefit for mild cognitive impairment.

One 2024 review included 12 studies with 1,124 participants in total. They found evidence of a benefit relative to placebo on global cognition, but noted no differences in language fluency or executive functions. The authors also pointed out that more evidence is needed.

Another review from 2019 looked at 7 randomized controlled trials with 434 participants in total, and found improvements in cognition among elderly adults with mild cognitive impairment. In this (and the previous) review, the authors noted that results varied substantially between studies.

A More Complicated Picture

Evidence for specific conditions like Alzheimer’s is less convincing. For example, one longitudinal study looking at 819 people with Alzheimer’s disease found that omega-3 PUFA supplementation actually accelerated cognitive decline.

The authors of this study point to another review which noted improvements at lower dosages but issues at higher dosages.

Overall, while n-3 fatty acids may help mild cognitive impairments at lower doses, the evidence is shakier for more serious issues and higher dosages.

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