Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Stockholm University, Stockholm, Sweden.
J Alzheimers Dis. 2012;32(3):721-31. doi: 10.3233/JAD-2012-120922.
Alzheimer's disease (AD) is a major cause of functional dependence, poor quality of life, institutionalization, and mortality among elderly people. As a multifactorial disorder, AD has been frequently linked to vascular risk factors (e.g., smoking, hypertension, obesity, diabetes, hyperlipidemia, and inflammation) in numerous prospective cohort studies of the general population. Systematic reviews and meta-analyses of prospective studies have from the life-course perspective revealed an age-dependent association with the risk of AD for several vascular risk factors such as high blood pressure, obesity, and high total cholesterol, such that possessing these factors in mid-life, but not necessarily in late-life, is associated with an increased risk of AD. The biological plausibility for vascular risk factors to be involved in the pathogenesis and clinical manifestation of Alzheimer syndrome is partly supported by population-based neuroimaging and neuropathological studies. However, randomized controlled trials that target those major cardiovascular risk factors (e.g., antihypertensive, cholesterol-lowering, and anti-inflammatory therapies) have generally failed to prove as efficacious preventative approaches for AD. To bridge the gap, the multifactorial nature of AD and the proper time-window for intervention should be taken into account in the future when designing preventative interventions against this devastating disorder.
阿尔茨海默病（AD）是导致老年人功能依赖、生活质量下降、住院和死亡的主要原因。作为一种多因素疾病，AD 经常与血管危险因素（如吸烟、高血压、肥胖、糖尿病、高脂血症和炎症）有关，这在许多普通人群的前瞻性队列研究中得到了证实。从生命历程的角度来看，对前瞻性研究的系统评价和荟萃分析显示，几种血管危险因素（如高血压、肥胖和总胆固醇高）与 AD 的风险呈年龄依赖性关联，即这些因素存在于中年而非晚年与 AD 风险增加有关。血管危险因素参与阿尔茨海默病综合征发病机制和临床表现的生物学合理性部分得到了基于人群的神经影像学和神经病理学研究的支持。然而，针对这些主要心血管危险因素（如降压、降脂和抗炎治疗）的随机对照试验通常未能证明这些方法对 AD 具有预防作用。为了缩小这一差距，在设计针对这种破坏性疾病的预防干预措施时，应考虑 AD 的多因素性质和适当的干预时间窗。
