Zhai Weijie, Zhang Guimei, Wei Chunxiao, Zhao Meng, Sun Li
Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Jilin University, Changchun, China.
Cognitive Center, Department of Neurology, The First Hospital of Jilin University, Jilin University, Changchun, China.
Diabetes Obes Metab. 2025 Jul;27(7):3967-3983. doi: 10.1111/dom.16433. Epub 2025 May 2.
To explore the relationship between body mass index (BMI) and its changes in relation to cognitive decline across different cognitive status, while also examining the role of the APOE genotype in these associations.
A total of 23 255 individuals from the National Alzheimer's Coordinating Center (NACC) were analysed using multivariable logistic and Cox regression to assess BMI and its variability in relation to cognitive decline. Subgroup analyses were conducted to explore how APOE genotype interacts with BMI and cognitive decline.
Compared to individuals with normal cognition and normal BMI, being underweight was associated with a higher risk of developing MCI (HR 3.065, 95% CI: [1.156-8.126]) and dementia (HR 4.057, 95% CI: [1.433-11.483]). Over the 4.07-year follow-up, 9171 individuals experienced cognitive decline. Longitudinal analysis revealed that being overweight or obese was linked to a lower risk of cognitive decline across different cognitive status, including impaired not MCI, MCI and dementia, but had no effect on those with normal cognition. Additionally, compared to stable BMI, the hazard ratios (95% CI) for developing dementia were 2.336 (2.128-2.565) and 2.338 (2.119-2.581) for annual BMI gain or loss greater than 5%. However, different APOE genotypes may influence the effect of BMI and BMI variability on cognitive decline.
This research supports the 'obesity paradox' and highlights the critical role of APOE in modulating BMI's influence on cognitive health.
探讨体重指数（BMI）及其变化与不同认知状态下认知功能衰退之间的关系，同时研究载脂蛋白E（APOE）基因型在这些关联中的作用。
对来自国家阿尔茨海默病协调中心（NACC）的23255名个体进行分析，采用多变量逻辑回归和Cox回归评估BMI及其变异性与认知功能衰退的关系。进行亚组分析以探讨APOE基因型如何与BMI和认知功能衰退相互作用。
与认知正常且BMI正常的个体相比，体重过轻与发生轻度认知障碍（MCI）（风险比3.065，95%置信区间：[1.156 - 8.126]）和痴呆（风险比4.057，95%置信区间：[1.433 - 11.483]）的风险更高相关。在4.07年的随访期间，9171名个体出现了认知功能衰退。纵向分析显示，超重或肥胖与不同认知状态（包括非MCI受损、MCI和痴呆）下认知功能衰退的风险较低相关，但对认知正常者无影响。此外，与稳定的BMI相比，每年BMI增加或减少大于5%时发生痴呆的风险比（95%置信区间）分别为2.336（2.128 - 2.565）和2.338（2.119 - 2.581）。然而，不同的APOE基因型可能会影响BMI及其变异性对认知功能衰退的影响。
本研究支持“肥胖悖论”，并强调了APOE在调节BMI对认知健康影响方面的关键作用。
