Dietary fish hydrolysate improves episodic memory in healthy elderly with lower level of memory performance: a double-blind, randomized, placebo-controlled clinical study

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. OBJECTIVES: This study evaluates the effect of a 3-mo fish hydrolysate (FH) supplementation on memory performance in healthy older adults identified as decliners. The primary outcome of this study was the Paired Associates Learning Total Error Adjusted (PALTEA) score, assessing episodic memory. METHODS: In this double-blind, randomized, placebo-controlled trial, 53 healthy older adults (60-73 y; Mini-Mental State Examination >27; PALTEA ≥41) received either FH [1 g of low-molecular-weight peptides and 30 mg n-3 (ω-3) long-chain polyunsaturated fatty acids (PUFAs)] or placebo daily for 3 mo. Cognitive performance was assessed using the Cambridge Neuropsychological Test Automated Battery. Statistical analyses were performed using analysis of covariance, adjusting for baseline values, age, and education level, with significance set at P < 0.05. RESULTS: FH supplementation significantly improved PALTEA scores compared with placebo [P = 0.003; β = -11.75; confidence interval (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 the 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 PUFA levels (P = 0.036; β = 0.80; CI: 0.05, 1.54), and reduced serum C-reactive protein 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). CONCLUSIONS: 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.