Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada.
Department of Radiology and Nuclear Medicine, Faculty of Medicine, Laval University, Québec, Canada.
J Clin Endocrinol Metab. 2021 Sep 27;106(10):e4260-e4274. doi: 10.1210/clinem/dgab135.
Chronic obesity is associated with several complications, including cognitive impairment and dementia. However, we have only piecemeal knowledge of the mechanisms linking obesity to central nervous system damage. Among candidate mechanisms are other elements of obesity-associated metabolic syndrome, such as hypertension, dyslipidemia, and diabetes, but also systemic inflammation. While there have been several neuroimaging studies linking adiposity to changes in brain morphometry, a comprehensive investigation of the relationship has so far not been done.
To identify links between adiposity and cognitive dysfunction.
This observational cohort study (UK Biobank), with an 8-year follow-up, included more than 20 000 participants from the general community, with a mean age of 63 years. Only participants with data available on both baseline and follow-up timepoints were included. The main outcome measures were cognitive performance and mediator variables: hypertension, diabetes, systemic inflammation, dyslipidemia, gray matter measures, and cerebrovascular disease (volume of white matter hyperintensities on magnetic resonance imaging).
Using structural equation modeling, we found that body mass index, waist-to-hip ratio, and body fat percentage were positively related to higher plasma C-reactive protein, dyslipidemia, hypertension, and diabetes. In turn, hypertension and diabetes were related to cerebrovascular disease. Finally, cerebrovascular disease was associated with lower cortical thickness and volume and higher subcortical volumes, but also cognitive deficits (largest significant pcorrected = 0.02).
We show that adiposity is related to poor cognition, with metabolic consequences of obesity and cerebrovascular disease as potential mediators. The outcomes have clinical implications, supporting a role for the management of adiposity in the prevention of late-life dementia and cognitive decline.
慢性肥胖与多种并发症相关，包括认知障碍和痴呆。然而，我们对将肥胖与中枢神经系统损伤联系起来的机制只有零碎的了解。候选机制包括肥胖相关代谢综合征的其他因素，如高血压、血脂异常和糖尿病，以及全身炎症。虽然已经有几项神经影像学研究将肥胖与大脑形态计量学的变化联系起来，但迄今为止还没有对这种关系进行全面的调查。
确定肥胖与认知功能障碍之间的联系。
这是一项观察性队列研究（英国生物库），随访时间为 8 年，包括来自普通社区的 20000 多名参与者，平均年龄为 63 岁。只有在基线和随访时间点都有数据的参与者才被纳入研究。主要观察指标是认知表现和中介变量：高血压、糖尿病、全身炎症、血脂异常、灰质测量值和脑血管疾病（磁共振成像上的脑白质高信号体积）。
使用结构方程模型，我们发现体重指数、腰围与臀围比值和体脂肪百分比与较高的血浆 C 反应蛋白、血脂异常、高血压和糖尿病呈正相关。反过来，高血压和糖尿病与脑血管疾病有关。最后，脑血管疾病与皮质厚度和体积降低以及皮质下体积增加有关，但也与认知缺陷有关（最大显著校正 p 值为 0.02）。
我们表明，肥胖与认知能力下降有关，肥胖的代谢后果和脑血管疾病是潜在的中介因素。这些结果具有临床意义，支持通过管理肥胖来预防老年痴呆症和认知能力下降。
