OBJECTIVE Diabetes is a well-known risk factor for dementia. We investigated the association between (pre)diabetes and older brain age and whether this can be attenuated by modifiable lifestyle behaviors. RESEARCH DESIGN AND METHODS The study included 31,229 dementia-free adults from the UK Biobank between the ages of 40 and 70. Glycemic status (normoglycemia, prediabetes, or diabetes) was ascertained based on medical history, medication use, and HbA1c measured at baseline. Information on cardiometabolic risk factors (obesity, hypertension, low HDL, and high triglycerides) and lifestyle behaviors (smoking, drinking, and physical activity) was also collected at baseline. Participants underwent up to two brain MRI scans over 11 years of follow-up. Brain age was estimated using a machine learning model based on 1,079 brain MRI phenotypes and used to calculate brain age gap (BAG; i.e., brain age minus chronological age). RESULTS At baseline, 13,518 participants (43.3%) had prediabetes and 1,149 (3.7%) had diabetes. Prediabetes (β = 0.22 [95% CI 0.10, 0.34]) and diabetes (2.01 [1.70, 2.32]) were both associated with significantly higher BAG, and diabetes was further associated with significant increase in BAG over time (0.27 [0.01, 0.53]). The association between (pre)diabetes and higher BAG was more pronounced in men and in people with two or more cardiometabolic risk factors. In joint exposure analysis, having a healthy lifestyle (i.e., no smoking, no heavy drinking, and high physical activity) significantly attenuated the diabetes-BAG association. CONCLUSIONS Diabetes and even prediabetes are associated with accelerated brain aging, especially among men and people with poor cardiometabolic health. However, a healthy lifestyle may counteract this.

中文翻译：

---

糖尿病、糖尿病前期和大脑衰老：健康生活方式的作用


目的 糖尿病是众所周知的痴呆风险因素。我们研究了糖尿病前期与大脑年龄增长之间的关联，以及是否可以通过改变生活方式来减弱这种关联。研究设计和方法 该研究纳入了来自英国生物银行的 31,229 名年龄在 40 至 70 岁之间的无痴呆成年人。根据病史、药物使用情况和基线测量的 HbA1c 确定血糖状态（血糖正常、糖尿病前期或糖尿病）。基线时还收集了有关心脏代谢危险因素（肥胖、高血压、低 HDL 和高甘油三酯）和生活方式行为（吸烟、饮酒和体力活动）的信息。在 11 年的随访期间，参与者接受了多达两次脑部 MRI 扫描。使用基于 1,079 个大脑 MRI 表型的机器学习模型估算大脑年龄，并用于计算大脑年龄差距（BAG；即大脑年龄减去实际年龄）。结果 在基线时，13,518 名参与者 (43.3%) 患有糖尿病前期，1,149 名参与者 (3.7%) 患有糖尿病。糖尿病前期 (β = 0.22 [95% CI 0.10, 0.34]) 和糖尿病 (2.01 [1.70, 2.32]) 均与 BAG 显着升高相关，糖尿病进一步与 BAG 随着时间的推移显着升高相关 (0.27 [0.01, 0.53] ]）。糖尿病前期与较高 BAG 之间的关联在男性和具有两种或多种心脏代谢危险因素的人群中更为明显。在联合暴露分析中，健康的生活方式（即不吸烟、不酗酒和高体力活动）可显着减弱糖尿病与 BAG 的关联。结论 糖尿病甚至糖尿病前期与大脑加速老化有关，尤其是男性和心脏代谢健康状况不佳的人。然而，健康的生活方式可能会抵消这一点。