Ballarini Tommaso, Melo van Lent Debora, Brunner Julia, Schröder Alina, Wolfsgruber Steffen, Altenstein Slawek, Brosseron Frederic, Buerger Katharina, Dechent Peter, Dobisch Laura, Duzel Emrah, Ertl-Wagner Birgit, Fliessbach Klaus, Freiesleben Silka Dawn, Frommann Ingo, Glanz Wenzel, Hauser Dietmar, Haynes John Dylan, Heneka Michael T, Janowitz Daniel, Kilimann Ingo, Laske Christoph, Maier Franziska, Metzger Coraline Danielle, Munk Matthias, Perneczky Robert, Peters Oliver, Priller Josef, Ramirez Alfredo, Rauchmann Boris, Roy Nina, Scheffler Klaus, Schneider Anja, Spottke Annika, Spruth Eike Jakob, Teipel Stefan J, Vukovich Ruth, Wiltfang Jens, Jessen Frank, Wagner Michael
German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
German Center for Neurodegenerative Diseases (DZNE), Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.
Neurology. 2021 Jun 15;96(24):e2920-e2932. doi: 10.1212/WNL.0000000000012067.
To determine whether following a Mediterranean-like diet (MeDi) relates to cognitive functions and in vivo biomarkers for Alzheimer disease (AD), we analyzed cross-sectional data from the German DZNE-Longitudinal Cognitive Impairment and Dementia Study. METHOD: The sample (n=512, mean age: 69.5±5.9 years) included 169 cognitively normal participants and subjects at higher AD risk (53 with relatives with AD, 209 with subjective cognitive decline, and 81 with mild cognitive impairment). We defined MeDi adherence based on the Food Frequency Questionnaire. Brain volume outcomes were generated via voxel-based morphometry on T1-MRI and cognitive performance with an extensive neuropsychological battery. AD-related biomarkers (Aβ42/40 ratio, pTau181) in cerebrospinal fluid were assessed in n=226 individuals. We analyzed the associations between MeDi and the outcomes with linear regression models controlling for several covariates. Additionally, we applied hypothesis-driven mediation and moderation analysis.
Higher MeDi adherence related to larger mediotemporal gray matter volume (p<0.05 FWE corrected), better memory (β±SE = 0.03 ± 0.02; p=0.038), and less amyloid (Aβ42/40 ratio, β±SE = 0.003 ± 0.001; p=0.008) and pTau181 pathology (β±SE = -1.96±0.68; p=0.004). Mediotemporal volume mediated the association between MeDi and memory (40% indirect mediation). Finally, MeDi favorably moderated the associations between Aβ42/40 ratio, pTau181 and mediotemporal atrophy. Results were consistent correcting for ApoE-ε4 status.
Our findings corroborate the view of MeDi as a protective factor against memory decline and mediotemporal atrophy. Importantly, they suggest that these associations might be explained by a decrease of amyloidosis and tau-pathology. Longitudinal and dietary intervention studies should further examine this conjecture and its treatment implications.
为了确定遵循地中海式饮食（MeDi）是否与认知功能及阿尔茨海默病（AD）的体内生物标志物有关，我们分析了来自德国神经退行性疾病中心纵向认知障碍与痴呆研究的横断面数据。方法：样本（n = 512，平均年龄：69.5±5.9岁）包括169名认知正常的参与者以及AD风险较高的受试者（53名有AD亲属，209名有主观认知衰退，81名有轻度认知障碍）。我们根据食物频率问卷定义MeDi依从性。通过基于体素的形态测量法在T1加权磁共振成像（MRI）上生成脑容量结果，并使用广泛的神经心理测试组合评估认知表现。在n = 226名个体中评估脑脊液中与AD相关的生物标志物（Aβ42/40比率，pTau181）。我们使用控制了多个协变量的线性回归模型分析MeDi与结果之间的关联。此外，我们进行了假设驱动的中介和调节分析。结果：更高的MeDi依从性与更大的中颞叶灰质体积相关（p<0.05，经家族性错误率校正）、更好的记忆力（β±标准误 = 0.03 ± 0.02；p = 0.038）以及更少的淀粉样蛋白（Aβ42/40比率，β±标准误 = 0.003 ± 0.001；p = 0.008）和pTau181病理（β±标准误 = -1.96±0.68；p = 0.004）。中颞叶体积介导了MeDi与记忆力之间的关联（40%间接中介）。最后，MeDi有利地调节了Aβ42/40比率、pTau181与中颞叶萎缩之间的关联。校正载脂蛋白E-ε4状态后结果一致。结论：我们的研究结果证实了MeDi作为预防记忆力衰退和中颞叶萎缩的保护因素的观点。重要的是，它们表明这些关联可能由淀粉样变性和tau病理的减少来解释。纵向和饮食干预研究应进一步检验这一推测及其治疗意义。
