Associations of Widowhood and β-Amyloid With Cognitive Decline in Cognitively Unimpaired Older Adults
Associations of Widowhood and β-Amyloid With Cognitive Decline in Cognitively Unimpaired Older Adults
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DOI：
10.1001/jamanetworkopen.2020.0121
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发表时间：
2020-02-26
影响因子：
13.8
通讯作者：
Donovan, Nancy J.
中科院分区：
文献类型：
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作者：
Biddle, Kelsey D.;Jacobs, Heidi I. L.;Donovan, Nancy J.
为了减少阿尔茨海默病引起的临床损害发生率的上升，确定老年人的风险最高是至关重要的。在认知正常的老年人中，寡妇可能是一个未被认识到的因素，导致阿尔茨海默病的临床进展加快。目的探讨寡妇状态和脑内β-淀粉样蛋白(即阿尔茨海默病病理蛋白)水平与认知功能正常老年人认知功能减退的相关性。这项队列研究的设计、设置和参与者，来自哈佛老龄化大脑研究纵向队列的257名已婚、丧偶和未婚(即从未结婚、离婚或分居)的参与者，使用匹兹堡化合物B正电子发射断层扫描和4次年度认知评估，对新皮质β淀粉样蛋白水平进行了基线评估。数据收集时间为2010年9月至2017年2月，分析时间为2018年7月至2019年7月。主要结果和测量采用临床前阿尔茨海默病认知综合评定量表测量认知能力。结果257名受试者中女性153名(59.5%)，平均年龄73.5岁(6.1岁)，已婚145名(56.4%)，未婚77名(30.0%)，丧偶35名(13.6%)。与已婚参与者相比，丧偶参与者在调整了年龄、性别、社会经济地位、抑郁和β-淀粉样蛋白水平(Beta=-0.11；95%CI，-0.19至-0.04；P=0.002)后，认知表现更差，而已婚和未婚参与者之间没有观察到差异。此外，基线β-淀粉样蛋白水平较高的丧偶参与者表现出更陡峭的认知衰退(β=-0.22；95%CI，-0.42至-0.03；P=0.02)，这表明β-淀粉样蛋白水平和寡妇与认知能力既独立又相互关联。在使用二分β-淀粉样蛋白-婚姻状态分组的第二个模型中，具有高β-淀粉样蛋白的丧偶参与者的认知衰退速度几乎是已婚高β-淀粉样蛋白参与者的3倍(丧偶高β-淀粉样蛋白：-0.33；95%CI，-0.46-0.19；P<；.001；已婚，高β-淀粉样蛋白：-0.12；95%CI，-0.18-0.01；P<；.001)。结论和相关性：在认知能力未受损的老年人样本中，丧偶与3年内β淀粉样蛋白相关认知功能减退的加速相关。认知未受损的丧偶老年人特别容易发生阿尔茨海默病的临床进展，强调需要增加对这一高危群体的研究关注和循证干预。这项队列研究评估了寡居状态和淀粉样β蛋白水平与认知正常的老年人的认知下降是相加的还是交互作用的。问题是，在认知未受损的老年人中，丧偶是否是一个特定的风险因素，与认知正常、脑淀粉样蛋白水平较高的老年人认知能力下降的更快有关？在这项对257名社区居住的认知未受损的老年人进行的队列研究中，寡妇和β-淀粉样蛋白与认知能力下降存在相加和相互作用的关系。这些结果与人口统计因素、心血管疾病风险、抑郁、健康相关行为和社会支持因素无关。这意味着这些发现表明，寡妇可能是与阿尔茨海默病相关的认知能力下降的一个未被充分研究的风险因素，并突显了对这一高危群体加强研究和临床关注的必要性。
Importance To reduce the rising incidence of clinical impairment due to Alzheimer disease, it is essential to define older adults at highest risk. Widowhood may be an unrecognized factor contributing to accelerated clinical progression along the Alzheimer disease pathway among cognitively unimpaired older adults. Objective To determine whether widowhood status and level of brain beta-amyloid (ie, the Alzheimer disease pathologic protein) are additively or interactively associated with cognitive decline among cognitively unimpaired older adults. Design, Setting, and Participants In this cohort study, 257 married, widowed, and unmarried (ie, never married, divorced, or separated) participants from the Harvard Aging Brain Study longitudinal cohort underwent baseline evaluation of neocortical beta-amyloid levels using Pittsburgh compound B positron emission tomography and 4 annual cognitive assessments. Data were collected from September 2010 to February 2017 and analyzed from July 2018 to July 2019. Main Outcomes and Measures Cognitive performance was measured using the Preclinical Alzheimer Cognitive Composite. Results Of the 257 participants, 153 (59.5%) were women, and the mean (SD) age was 73.5 (6.1) years; 145 participants (56.4%) were married (66 [45.5%] women), 77 (30.0%) were unmarried (56 [72.7%] women), and 35 (13.6%) were widowed (31 [88.6%] women). Compared with married participants, widowed participants demonstrated worsening cognitive performance after adjusting for age, sex, socioeconomic status, depression, and beta-amyloid levels (beta = -0.11; 95% CI, -0.19 to -0.04; P = .002) with no difference observed between married and unmarried participants. Furthermore, widowed participants with higher baseline beta-amyloid levels exhibited steeper cognitive decline (beta = -0.22; 95% CI, -0.42 to -0.03; P = .02), indicating both independent and interactive associations of beta-amyloid levels and widowhood with cognition. In a secondary model using dichotomous beta-amyloid-marital status groupings, the rate of cognitive decline among widowed participants with high beta-amyloid was nearly 3 times faster than among married participants with high beta-amyloid (widowed, high beta-amyloid: beta, -0.33; 95% CI, -0.46 to -0.19; P < .001; married, high beta-amyloid: beta, -0.12; 95% CI, -0.18 to -0.01; P < .001). Conclusions and Relevance In a sample of cognitively unimpaired older adults, being widowed was associated with accelerated beta-amyloid-related cognitive decline during 3 years. Cognitively unimpaired, widowed older adults were particularly susceptible to Alzheimer disease clinical progression, emphasizing the need for increased research attention and evidenced-based interventions for this high-risk group.This cohort study evaluates whether widowhood status and amyloid-beta level are additively or interactively associated with cognitive decline among cognitively unimpaired older adults.Question Is widowhood a specific risk factor associated with more rapid cognitive decline among cognitively unimpaired older adults with higher levels of brain beta-amyloid, the Alzheimer disease biomarker? Findings In this cohort study of 257 community-dwelling cognitively unimpaired older adults, widowhood and beta-amyloid were additively and interactively associated with cognitive decline. These results were independent of demographic factors, cardiovascular disease risk, depression, health-related behaviors, and social support factors. Meaning These findings suggest that widowhood may be an understudied risk factor for cognitive decline associated with Alzheimer disease and highlight the need for increased research and clinical attention to this high-risk group.