Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 581, Heidelberg, Germany.
Network Aging Research, Heidelberg University, Bergheimer Straße 20, Heidelberg, Germany.
Alzheimers Res Ther. 2021 Aug 30;13(1):145. doi: 10.1186/s13195-021-00889-2.
To understand the potential for early intervention and prevention measures in Alzheimer's disease, the association between risk factors and early pathological change needs to be assessed. Hence, the aim of this study was to determine whether risk factors of Alzheimer's clinical syndrome (clinical AD), such as body mass index (BMI), are associated with Aβ misfolding in blood, a strong risk marker for AD among older adults.
Information on risk factors and blood samples were collected at baseline in the ESTHER study, a population-based cohort study of older adults (age 50-75 years) in Germany. Aβ misfolding in blood plasma was analyzed using an immuno-infrared-sensor in a total of 872 participants in a nested case-control design among incident dementia cases and matched controls. Associations between risk factors and Aβ misfolding were assessed by multiple logistic regression. For comparison, the association between the risk factors and AD incidence during 17 years of follow-up was investigated in parallel among 5987 cohort participants.
An inverse association with Aβ misfolding was seen for BMI at age 50 based on reported weight history (aOR 0.64, 95% CI 0.43-0.96, p = 0.03). Similar but not statistically significant associations were seen for BMI at baseline (i.e., mean age 68) and at age 40. No statistically significant associations with Aβ misfolding were found for other risk factors, such as diabetes, smoking, and physical activity. On the other hand, low physical activity was associated with a significantly reduced risk of developing clinical AD compared to physical inactivity.
Our results support that AD pathology may be detectable and associated with reduced weight even in middle adulthood, many years before clinical diagnosis of AD. Physical activity might reduce the risk of onset of AD symptoms.
为了了解阿尔茨海默病早期干预和预防措施的潜力，需要评估风险因素与早期病理变化之间的关系。因此，本研究旨在确定阿尔茨海默病临床综合征（临床 AD）的风险因素，如体重指数（BMI），是否与老年人群中 AD 的强烈风险标志物——血液中的 Aβ 错误折叠有关。
在德国一项基于人群的老年（50-75 岁）队列研究 ESTHER 中，在基线时收集了风险因素和血液样本信息。在一项嵌套病例对照设计中，使用免疫红外传感器分析了共 872 名新发痴呆病例和匹配对照者的血液血浆 Aβ 错误折叠情况。使用多因素逻辑回归评估风险因素与 Aβ 错误折叠之间的关系。为了进行比较，还在 5987 名队列参与者中平行研究了这些风险因素与 17 年随访期间 AD 发生率之间的关系。
基于报告的体重史，发现 50 岁时 BMI 与 Aβ 错误折叠呈负相关（优势比 0.64，95%置信区间 0.43-0.96，p=0.03）。在基线（即平均年龄 68 岁）和 40 岁时也观察到类似但无统计学意义的关联。其他风险因素，如糖尿病、吸烟和身体活动，与 Aβ 错误折叠之间没有统计学上的显著关联。另一方面，与不活动相比，低身体活动与显著降低发生临床 AD 的风险相关。
我们的研究结果支持 AD 病理学可能在中年时期，甚至在临床诊断 AD 多年前就可以被检测到，并与体重减轻有关。身体活动可能会降低 AD 症状发作的风险。
