Cardiovascular contributions to dementia: beyond individual risk factors.
Cardiovascular contributions to dementia: beyond individual risk factors.
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心血管对痴呆症的影响：超越个体危险因素。
DOI：
10.1017/s1041610219001285
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发表时间：
2019
影响因子：
7
通讯作者：
Perales-Puchalt,Jaime
中科院分区：
文献类型：
--
作者：
Kaufman,CarolynS;Perales-Puchalt,Jaime
痴呆症在全球范围内构成严重的公共卫生威胁。1990年至2016年，痴呆症患者人数增加了一倍多，从2020万人增加到4380万人，主要是由于人口老龄化（Nichols等人，2019年）。痴呆是全球第五大死亡原因，并导致严重残疾（Nichols et al.，2019年）。由于没有治愈的办法，预计这些趋势在可预见的未来将继续下去。因此，我们迫切需要更好地了解痴呆症的风险机制，以推进这种毁灭性疾病的预防策略。几种风险因素与痴呆风险增加相关，包括但不限于糖尿病、缺乏身体活动、吸烟、中年高血压和肥胖、抑郁症和低教育程度（Norton et al.，2014）。不良的脑血管健康已被确定为血管性痴呆的主要原因，血管性痴呆是痴呆的第二大类型。然而，阿尔茨海默病（AD）（痴呆的主要原因）的发病机制仍然存在争议（Wetland等人，2017年）。从历史上看，许多AD研究都集中在淀粉样蛋白假说上，该假说认为β-淀粉样蛋白斑块沉积在大脑中是AD的主要原因（哈代和希金斯，1992）。然而，最近针对β-淀粉样蛋白的临床试验未能带来显著的益处，该领域已开始转向多模式方法来理解痴呆症的病理生理学，该方法考虑代谢，炎症和血管影响，特别是在疾病的早期阶段（Makin，2018）。例如，最近一项使用来自阿尔茨海默病神经成像倡议研究的数据的研究发现，脑血管失调是AD发展期间最早的病理事件，随后是β-淀粉样蛋白沉积、代谢功能障碍、功能障碍和结构萎缩的变化;这些发现表明血管健康不良对痴呆发展的早期阶段的重要贡献（Iturria-Medina et al.，2016）。事实上，血管健康在痴呆风险中发挥主要作用的想法在过去二十年中已经获得了牵引力，并且美国中风协会和美国心脏协会发布了一项联合科学声明，强调了心血管对痴呆的重要性（Gorelick等人，2011).虽然早期关于心血管对痴呆的作用的研究集中在个体风险因素上（Kalaria，2003），但越来越多的文献开始回答关于这些风险因素作用的更复杂的问题。例如，研究表明，中年肥胖可能增加痴呆的风险，但晚年肥胖可能具有保护作用（Wetland等人，2017年）。心血管危险因素经常共同发生，最近的研究表明，心血管因素可能对痴呆的发展具有累积影响（Perales et al.，2018年，Perales‐Puchalt等人，2019年）。然而，关于特定心血管危险因素对痴呆症发展的累积影响是否是相加或协同作用，文献中仍然存在空白。在最新一期的《国际老年精神病学》中，Shaaban及其同事（2019）通过进一步探索心血管健康与痴呆症之间的联系来解决这一差距，他们的研究题为“血管和心脏代谢风险因素对全因痴呆症风险的独立和联合影响：一项前瞻性人群研究”。这项纵向队列研究包括对来自美国经济不景气的小城镇人口的1，701名参与者进行多达10次年度研究访问。作者选择了对血管和…
Dementia poses a serious public health threat worldwide. The number of people living with dementia more than doubled between 1990 and 2016, from 20.2 million to 43.8 million individuals, primarily due to an increasingly older population (Nichols et al., 2019). Dementia is the fifth leading cause of death globally and causes substantial disability (Nichols et al., 2019). With no cure, these trends are projected to continue for the foreseeable future. Thus, we desperately need a better understanding of dementia risk mechanisms to advance prevention strategies for this devastating disease. Several risk factors are associated with an increased risk of dementia, including but not limited to diabetes, physical inactivity, smoking, midlife hypertension and obesity, depression and low educational attainment (Norton et al., 2014). Poor cerebrovascular health has been established as the primary cause of vascular dementia, the second leading type of dementia. However, the pathogenesis of Alzheimer’s disease (AD), the leading cause of dementia, remains controversial (Pase et al., 2017). Historically, much of AD research has focused on the amyloid hypothesis, which posits that beta-amyloid plaque deposition in the brain is the primary cause of AD (Hardy and Higgins, 1992). However, recent clinical trials targeting beta-amyloid have failed to deliver significant benefits, and the field has begun to shift toward a multi-modal approach to understanding dementia pathophysiology that considers metabolic, inflammatory and vascular influences, particularly in early stages of disease (Makin, 2018). For example, one recent study using data from the Alzheimer’s Disease Neuroimaging Initiative study found cerebrovascular dysregulation is the earliest pathological event during AD development, followed by changes in beta-amyloid deposition, metabolic dysfunction, functional impairment and structural atrophy; these findings suggest a central contribution of poor vascular health to early stages of dementia development (Iturria-Medina et al., 2016). Indeed, the idea of vascular health playing a primary role in dementia risk has gained traction over the last two decades, and the American Stroke Association and American Heart Association released a joint scientific statement highlighting the importance of cardiovascular contributions to dementia (Gorelick et al., 2011).While early studies of cardiovascular contributions to dementia focused on individual risk factors (Kalaria, 2003), the growing literature is starting to answer more complex questions about the role of these risk factors. For example, studies show that mid-life obesity may increase the risk of dementia but late-life obesity may be protective (Pase et al., 2017). Cardiovascular risk factors often co-occur, and recent studies show that cardiovascular factors may have a cumulative impact on the development of dementia (Perales et al., 2018, Perales‐Puchalt et al., 2019). However, there remains a gap in the literature regarding whether the cumulative impact of specific cardiovascular risk factors on the development of dementia acts additively or synergistically. In the current issue of International Psychogeriatrics, Shaaban and colleagues (2019) address this gap by further exploring the connection between cardiovascular health and dementia with their study entitled “Independent and joint effects of vascular and cardiometabolic risk factor pairs for risk of all-cause dementia: a prospective population-based study.” This longitudinal cohort study included up to 10 annual study visits for the 1,701 participants from an economically depressed small-town population in the United States. The authors selected pairs of vascular and …