Relationship between sex, APOE genotype, endocannabinoids and cognitive change in older adults with metabolic syndrome during a 3-year Mediterranean diet intervention.

IF 4.4 2区 医学 Q1 NUTRITION & DIETETICS Nutrition Journal Pub Date : 2024-06-12 DOI:10.1186/s12937-024-00966-w
Natalia Soldevila-Domenech, Beatriz Fagundo, Aida Cuenca-Royo, Laura Forcano, Maria Gomis-González, Anna Boronat, Antoni Pastor, Olga Castañer, Maria Dolores Zomeño, Albert Goday, Mara Dierssen, Khashayar Baghizadeh Hosseini, Emilio Ros, Dolores Corella, Miguel Ángel Martínez-González, Jordi Salas-Salvadó, Fernando Fernández-Aranda, Montserrat Fitó, Rafael de la Torre
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Abstract

Background: The Mediterranean diet (MedDiet) has demonstrated efficacy in preventing age-related cognitive decline and modulating plasma concentrations of endocannabinoids (eCBs) and N-acylethanolamines (NAEs, or eCB-like compounds), which are lipid mediators involved in multiple neurological disorders and metabolic processes. Hypothesizing that eCBs and NAEs will be biomarkers of a MedDiet intervention and will be related to the cognitive response, we investigated this relationship according to sex and apolipoprotein E (APOE) genotype, which may affect eCBs and cognitive performance.

Methods: This was a prospective cohort study of 102 participants (53.9% women, 18.8% APOE-ɛ4 carriers, aged 65.6 ± 4.5 years) from the PREDIMED-Plus-Cognition substudy, who were recruited at the Hospital del Mar Research Institute (Barcelona). All of them presented metabolic syndrome plus overweight/obesity (inclusion criteria of the PREDIMED-Plus) and normal cognitive performance at baseline (inclusion criteria of this substudy). A comprehensive battery of neuropsychological tests was administered at baseline and after 1 and 3 years. Plasma concentrations of eCBs and NAEs, including 2-arachidonoylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and N-docosahexaenoylethanolamine (DHEA), were also monitored. Baseline cognition, cognitive changes, and the association between eCBs/NAEs and cognition were evaluated according to gender (crude models), sex (adjusted models), and APOE genotype.

Results: At baseline, men had better executive function and global cognition than women (the effect size of gender differences was - 0.49, p = 0.015; and - 0.42, p = 0.036); however, these differences became nonsignificant in models of sex differences. After 3 years of MedDiet intervention, participants exhibited modest improvements in memory and global cognition. However, greater memory changes were observed in men than in women (Cohen's d of 0.40 vs. 0.25; p = 0.017). In men and APOE-ε4 carriers, 2-AG concentrations were inversely associated with baseline cognition and cognitive changes, while in women, cognitive changes were positively linked to changes in DHEA and the DHEA/AEA ratio. In men, changes in the OEA/AEA and OEA/PEA ratios were positively associated with cognitive changes.

Conclusions: The MedDiet improved participants' cognitive performance but the effect size was small and negatively influenced by female sex. Changes in 2-AG, DHEA, the OEA/AEA, the OEA/PEA and the DHEA/AEA ratios were associated with cognitive changes in a sex- and APOE-dependent fashion. These results support the modulation of the endocannabinoid system as a potential therapeutic approach to prevent cognitive decline in at-risk populations.

Trial registration: ISRCTN89898870.

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在为期 3 年的地中海饮食干预期间,患有代谢综合征的老年人的性别、APOE 基因型、内源性大麻素与认知变化之间的关系。
背景:地中海饮食(MedDiet)在预防与年龄有关的认知能力下降和调节血浆中的内源性大麻素(eCBs)和 N-酰乙醇胺(NAEs,或 eCB 类化合物)浓度方面已被证明具有疗效。我们推测 eCBs 和 NAEs 将成为 MedDiet 干预的生物标志物,并与认知反应有关,因此我们根据可能影响 eCBs 和认知表现的性别和载脂蛋白 E(APOE)基因型对这种关系进行了调查:这是一项前瞻性队列研究,从 PREDIMED-Plus-Cognition 子研究中招募了 102 名参与者(53.9% 为女性,18.8% 为 APOE-ɛ4 携带者,年龄为 65.6 ± 4.5 岁),他们都来自巴塞罗那德尔马医院研究所(Hospital del Mar Research Institute)。他们均患有代谢综合征和超重/肥胖症(PREDIMED-Plus 的纳入标准),基线认知能力正常(本子研究的纳入标准)。在基线及 1 年和 3 年后进行了全面的神经心理学测试。此外,还监测了 eCB 和 NAE 的血浆浓度,包括 2-丙烯酰甘油 (2-AG)、anandamide (AEA)、油酰乙醇酰胺 (OEA)、棕榈酰乙醇酰胺 (PEA) 和 N-二十二碳六烯乙醇胺 (DHEA)。根据性别(粗略模型)、性别(调整模型)和 APOE 基因型评估了基线认知、认知变化以及 eCBs/NAEs 与认知之间的关联:基线时,男性的执行功能和整体认知能力优于女性(性别差异的效应大小为-0.49,p = 0.015;和-0.42,p = 0.036);然而,在性别差异模型中,这些差异变得不显著。经过 3 年的 MedDiet 干预后,参与者的记忆力和整体认知能力略有改善。然而,与女性相比,男性的记忆力变化更大(Cohen's d 为 0.40 vs. 0.25;p = 0.017)。在男性和 APOE-ε4 携带者中,2-AG 浓度与基线认知和认知变化成反比,而在女性中,认知变化与 DHEA 和 DHEA/AEA 比率的变化成正比。在男性中,OEA/AEA 和 OEA/PEA 比率的变化与认知变化呈正相关:结论:"健康饮食 "改善了参与者的认知能力,但其效果很小,且受女性性别的负面影响。2-AG、DHEA、OEA/AEA、OEA/PEA 和 DHEA/AEA 比率的变化与认知能力的变化相关,且与性别和 APOE 有关。这些结果支持将调节内源性大麻素系统作为预防高危人群认知能力下降的潜在治疗方法:试验注册:ISRCTN89898870。
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来源期刊
Nutrition Journal
Nutrition Journal NUTRITION & DIETETICS-
CiteScore
9.80
自引率
0.00%
发文量
68
审稿时长
4-8 weeks
期刊介绍: Nutrition Journal publishes surveillance, epidemiologic, and intervention research that sheds light on i) influences (e.g., familial, environmental) on eating patterns; ii) associations between eating patterns and health, and iii) strategies to improve eating patterns among populations. The journal also welcomes manuscripts reporting on the psychometric properties (e.g., validity, reliability) and feasibility of methods (e.g., for assessing dietary intake) for human nutrition research. In addition, study protocols for controlled trials and cohort studies, with an emphasis on methods for assessing dietary exposures and outcomes as well as intervention components, will be considered. Manuscripts that consider eating patterns holistically, as opposed to solely reductionist approaches that focus on specific dietary components in isolation, are encouraged. Also encouraged are papers that take a holistic or systems perspective in attempting to understand possible compensatory and differential effects of nutrition interventions. The journal does not consider animal studies. In addition to the influence of eating patterns for human health, we also invite research providing insights into the environmental sustainability of dietary practices. Again, a holistic perspective is encouraged, for example, through the consideration of how eating patterns might maximize both human and planetary health.
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