Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
J Alzheimers Dis. 2019;67(3):795-819. doi: 10.3233/JAD181028.
Population-based clinic-pathological studies have established that the most common pathological substrate of dementia in community-dwelling elderly people is mixed, especially Alzheimer's disease (AD) and cerebrovascular ischemic disease (CVID), rather than pure AD. While these could be just two frequent unrelated comorbidities in the elderly, epidemiological research has reinforced the idea that mid-life (age <65 years) vascular risk factors increase the risk of late-onset (age ≥ 65 years) dementia, and specifically AD. By contrast, healthy lifestyle choices such as leisure activities, physical exercise, and Mediterranean diet are considered protective against AD. Remarkably, several large population-based longitudinal epidemiological studies have recently indicated that the incidence and prevalence of dementia might be decreasing in Western countries. Although it remains unclear whether these positive trends are attributable to neuropathologically definite AD versus CVID, based on these epidemiological data it has been estimated that a sizable proportion of AD cases could be preventable. In this review, we discuss the current evidence about modifiable risk factors for AD derived from epidemiological, preclinical, and interventional studies, and analyze the opportunities for therapeutic and preventative interventions.
基于人群的临床病理研究已经证实，在社区居住的老年人中，痴呆最常见的病理基础是混合性的，特别是阿尔茨海默病（AD）和脑血管缺血性疾病（CVID），而不是单纯的 AD。虽然这两种疾病在老年人中可能只是两种常见的不相关的合并症，但流行病学研究强化了这样一种观点，即中年（年龄<65 岁）血管危险因素会增加晚年（年龄≥65 岁）痴呆症的风险，特别是 AD。相比之下，休闲活动、体育锻炼和地中海饮食等健康的生活方式选择被认为可以预防 AD。值得注意的是，最近几项大型基于人群的纵向流行病学研究表明，西方国家的痴呆症发病率和患病率可能正在下降。尽管尚不清楚这些积极趋势是否归因于神经病理学上明确的 AD 与 CVID，但根据这些流行病学数据估计，相当一部分 AD 病例可能是可以预防的。在这篇综述中，我们讨论了来自流行病学、临床前和干预研究的关于 AD 可改变风险因素的最新证据，并分析了治疗和预防干预的机会。
