From the Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases (C.L.S., J.J.H., D.M.L., S.S.), UT Health San Antonio, San Antonio, TX; Department of Population Health Sciences (C.L.S., J.J.H.), UT Health San Antonio, San Antonio, TX; Department of Neurology (C.L.S., J.J.H., A.S.B., D.M.L., H.J.A., S.S.), Boston University School of Medicine, Boston, MA; The Framingham Heart Study (C.L.S., J.J.H., A.S.B., V.R., D.M.L., D.H., H.J.A., S.S.), Framingham, MA; Department of Biostatistics (J.J.H., A.S.B.), Boston University School of Public Health, Boston, MA; Department of Medicine (V.R.), Boston University School of Medicine, Boston, MA; Department of Epidemiology (V.R.), Boston University School of Public Health, Boston, MA; Center for Computing and Data Sciences (V.R.), Boston University, Boston, MA; Imaging of Dementia and Aging Laboratory and Center for Neurosciences (P.M., C.S.D.), Davis, CA; Department of Neurology (C.S.D.), UC Davis School of Medicine, Sacramento, CA; Sanford School of Medicine (W.S.H.), University of South Dakota, Sioux Falls, SD; and Fatty Acid Research Institute (W.S.H.), Sioux Falls, SD.
Neurology. 2022 Dec 5;99(23):e2572-e2582. doi: 10.1212/WNL.0000000000201296.
Diet may be a key contributor to brain health in midlife. In particular, omega-3 fatty acids have been related to better neurologic outcomes in older adults. However, studies focusing on midlife are lacking. We investigated the cross-sectional association of red blood cell (RBC) omega-3 fatty acid concentrations with MRI and cognitive markers of brain aging in a community-based sample of predominantly middle-aged adults and further explore effect modification by genotype.
We included participants from the Third-Generation and Omni 2 cohorts of the Framingham Heart Study attending their second examination. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentrations were measured from RBC using gas chromatography, and the Omega-3 index was calculated as EPA + DHA. We used linear regression models to relate omega-3 fatty acid concentrations to brain MRI measures (i.e., total brain, total gray matter, hippocampal, and white matter hyperintensity volumes) and cognitive function (i.e., episodic memory, processing speed, executive function, and abstract reasoning) adjusting for potential confounders. We further tested for interactions between omega-3 fatty acid levels and genotype (e4 carrier vs noncarrier) on MRI and cognitive outcomes.
We included 2,183 dementia-free and stroke-free participants (mean age of 46 years, 53% women, 22% -e4 carriers). In multivariable models, higher Omega-3 index was associated with larger hippocampal volumes (standard deviation unit beta ±standard error; 0.003 ± 0.001, = 0.013) and better abstract reasoning (0.17 ± 0.07, = 0.013). Similar results were obtained for DHA or EPA concentrations individually. Stratification by -e4 status showed associations between higher DHA concentrations or Omega-3 index and larger hippocampal volumes in -e4 noncarriers, whereas higher EPA concentrations were related to better abstract reasoning in -e4 carriers. Finally, higher levels of all omega-3 predictors were related to lower white matter hyperintensity burden but only in -e4 carriers.
Our results, albeit exploratory, suggest that higher omega-3 fatty acid concentrations are related to better brain structure and cognitive function in a predominantly middle-aged cohort free of clinical dementia. These associations differed by genotype, suggesting potentially different metabolic patterns by APOE status. Additional studies in middle-aged populations are warranted to confirm these findings.
饮食可能是中年人大脑健康的关键因素。特别是，ω-3 脂肪酸与老年人更好的神经学结果有关。然而，目前缺乏针对中年人的研究。我们在一个以中年为主的社区样本中，调查了红细胞（RBC）ω-3 脂肪酸浓度与 MRI 以及认知标记物之间的横断面关联，并进一步探讨了基因型的影响修饰。
我们纳入了参加弗雷明汉心脏研究第三代和 Omni 2 队列的参与者，他们正在进行第二次检查。使用气相色谱法从 RBC 中测量二十二碳六烯酸（DHA）和二十碳五烯酸（EPA）的浓度，并计算 EPA+DHA 的ω-3 指数。我们使用线性回归模型将 ω-3 脂肪酸浓度与脑 MRI 测量值（即总脑、总灰质、海马体和白质高信号体积）和认知功能（即情景记忆、处理速度、执行功能和抽象推理）相关联，同时调整了潜在的混杂因素。我们还进一步测试了 ω-3 脂肪酸水平与 基因型（e4 携带者与非携带者）之间在 MRI 和认知结果上的相互作用。
我们纳入了 2183 名无痴呆和无中风的参与者（平均年龄 46 岁，53%为女性，22%为 -e4 携带者）。在多变量模型中，较高的ω-3 指数与较大的海马体体积相关（标准差单位β±标准误；0.003±0.001， = 0.013），并且与更好的抽象推理相关（0.17±0.07， = 0.013）。对于 DHA 或 EPA 浓度的个体而言，也得到了类似的结果。按 -e4 状态分层显示，在 -e4 非携带者中，较高的 DHA 浓度或 ω-3 指数与较大的海马体体积相关，而在 -e4 携带者中，较高的 EPA 浓度与更好的抽象推理相关。最后，所有 ω-3 预测因子的水平较高与白质高信号负担较低有关，但仅在 -e4 携带者中。
我们的结果虽然是探索性的，但表明在一个没有临床痴呆的以中年为主的队列中，较高的 ω-3 脂肪酸浓度与更好的大脑结构和认知功能相关。这些关联因 基因型而异，提示 APOE 状态可能存在不同的代谢模式。需要在中年人群中进行更多的研究来证实这些发现。
