Liu Xiaoran, Sacks Frank M, Beck Todd, Tangney Christy C, Willett Walter C, Yassine Hussein, Dhana Klodian, Aggarwal Neelum T, Rajan Kumar B, Barnes Lisa L
Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, IL, United States; Department of Internal Medicine, Rush University Medical Center, Chicago, IL, United States.
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
Am J Clin Nutr. 2025 Aug 27. doi: 10.1016/j.ajcnut.2025.08.012.
Alzheimer disease (AD) prevention is a public health priority, yet the impact of dietary carotenoids on cognitive decline, particularly in apolipoprotein E (APOE) ε4 carriers, remains unclear.
The objective of this study was to examine whether the APOE ε4 genotype modifies the relationship between blood carotenoid concentrations and global cognition.
This study was conducted within the Mediterranean-Dietary Approaches to Stop Hypertension intervention for neurodegenerative delay trial, a 3-y randomized controlled trial comparing the effects of the Mediterranean-Dietary Approaches to Stop Hypertension intervention for neurodegenerative delay diet with the usual diet on global cognition in older adults. Eligible participants were ≥65 y, had a body mass index (in kg/m) >25, a family history of AD, suboptimal diets, and a Montreal cognitive assessment score ≥22. The primary outcome was 3-y change in global cognitive function, assessed using a validated composite cognitive score converted to standardized units (SUs). Baseline plasma carotenoid concentrations were measured in a subgroup of participants (n = 442). Mixed-effects models were used to test the interaction between APOE ε4 status and baseline carotenoid concentrations on cognitive trajectories.
The mean age was 70.0 y for noncarriers (n = 308) and 69.4 y for APOE ε4 carriers (n = 134). Among APOE ε4 carriers, a 1-unit increment in plasma total carotenoids at baseline was associated with higher global cognitive scores [β = 0.17 SU; 95% confidence interval (CI): 0.06, 0.28 SU; P = 0.009]. Similar associations were observed for β-carotene (β = 0.13 SU; 95% CI: 0.05, 0.21 SU; P = 0.001), α-carotene (β = 0.09 SU; 95% CI: 0.02, 0.15 SU; P = 0.008), lutein plus zeaxanthin (β = 0.14 SU; 95% CI: 0.04, 0.25 SU; P = 0.008), lycopene (β = 0.17 SU; 95% CI: 0.07, 0.28 SU; P = 0.005), and β-cryptoxanthin (β = 0.13 SU; 95% CI: 0.05, 0.21 SU; P = 0.03). Associations in noncarriers were weaker or nonsignificant.
Higher plasma carotenoid concentrations were associated with slower cognitive decline in APOE ε4 carriers, potentially mitigating genetic risk. This trial was registered at clinicaltrials.gov as NCT02817074.
阿尔茨海默病（AD）的预防是公共卫生的重点，但膳食类胡萝卜素对认知衰退的影响，尤其是对载脂蛋白E（APOE）ε4携带者的影响仍不明确。
本研究旨在探讨APOE ε4基因型是否会改变血液类胡萝卜素浓度与整体认知之间的关系。
本研究是在地中海饮食预防高血压干预延缓神经退行性变试验中进行的，这是一项为期3年的随机对照试验，比较地中海饮食预防高血压干预延缓神经退行性变饮食与常规饮食对老年人整体认知的影响。符合条件的参与者年龄≥65岁，体重指数（kg/m²）>25，有AD家族史，饮食欠佳，且蒙特利尔认知评估得分≥22。主要结局是整体认知功能的3年变化，使用经过验证的综合认知评分转换为标准化单位（SU）进行评估。在一部分参与者（n = 442）中测量了基线血浆类胡萝卜素浓度。使用混合效应模型来测试APOE ε4状态与基线类胡萝卜素浓度在认知轨迹上的相互作用。
非携带者（n = 308）的平均年龄为70.0岁，APOE ε4携带者（n = 134）的平均年龄为69.4岁。在APOE ε4携带者中，基线时血浆总类胡萝卜素每增加1个单位，与更高的整体认知评分相关[β = 0.17 SU；95%置信区间（CI）：0.06，0.28 SU；P = 0.009]。对于β-胡萝卜素（β = 0.13 SU；95% CI：0.05，0.21 SU；P = 0.001）、α-胡萝卜素（β = 0.09 SU；95% CI：0.02，0.15 SU；P = 0.008）、叶黄素加玉米黄质（β = 0.14 SU；95% CI：0.04，0.25 SU；P = 0.008）、番茄红素（β = 0.17 SU；95% CI：0.07，0.28 SU；P = 0.005）和β-隐黄质（β = 0.13 SU；95% CI：0.05，0.21 SU；P = 0.03）也观察到了类似的关联。非携带者中的关联较弱或无统计学意义。
较高的血浆类胡萝卜素浓度与APOE ε4携带者认知衰退较慢相关，可能会减轻遗传风险。该试验在clinicaltrials.gov上注册为NCT02817074。
