Division of Geriatric Psychiatry, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
School for Mental Health and Neuroscience, Alzheimer Centre, Limburg, Maastricht University, Maastricht, the Netherlands.
JAMA Netw Open. 2020 Feb 5;3(2):e200121. doi: 10.1001/jamanetworkopen.2020.0121.
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.
To determine whether widowhood status and level of brain β-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 β-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.
Cognitive performance was measured using the Preclinical Alzheimer Cognitive Composite.
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 β-amyloid levels (β = -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 β-amyloid levels exhibited steeper cognitive decline (β = -0.22; 95% CI, -0.42 to -0.03; P = .02), indicating both independent and interactive associations of β-amyloid levels and widowhood with cognition. In a secondary model using dichotomous β-amyloid-marital status groupings, the rate of cognitive decline among widowed participants with high β-amyloid was nearly 3 times faster than among married participants with high β-amyloid (widowed, high β-amyloid: β, -0.33; 95% CI, -0.46 to -0.19; P < .001; married, high β-amyloid: β, -0.12; 95% CI, -0.18 to -0.01; P < .001).
In a sample of cognitively unimpaired older adults, being widowed was associated with accelerated β-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.
为了降低由于阿尔茨海默病导致的临床损伤的发病率，确定处于最高风险的老年人至关重要。丧偶可能是认知正常的老年人在阿尔茨海默病发病途径中加速临床进展的一个未被识别的因素。
确定丧偶状况和大脑β-淀粉样蛋白（即阿尔茨海默病病理蛋白）水平是否与认知正常的老年人认知能力下降呈累加或交互相关。
设计、地点和参与者：在这项队列研究中，来自哈佛衰老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）的参与者接受了使用匹兹堡化合物 B 正电子发射断层扫描进行的新皮质β-淀粉样蛋白水平的基线评估，以及 4 次年度认知评估。数据于 2010 年 9 月至 2017 年 2 月收集，并于 2018 年 7 月至 2019 年 7 月进行分析。
使用 Preclinical Alzheimer Cognitive Composite 评估认知表现。
在 257 名参与者中，有 153 名（59.5%）为女性，平均（SD）年龄为 73.5（6.1）岁；145 名参与者（56.4%）已婚（66 [45.5%] 名女性），77 名（30.0%）未婚（56 [72.7%] 名女性），35 名（13.6%）丧偶（31 [88.6%] 名女性）。与已婚参与者相比，丧偶参与者在调整年龄、性别、社会经济地位、抑郁和β-淀粉样蛋白水平后认知表现恶化（β=-0.11；95%CI，-0.19 至-0.04；P=.002），而已婚和未婚参与者之间无差异。此外，基线β-淀粉样蛋白水平较高的丧偶参与者认知下降更为明显（β=-0.22；95%CI，-0.42 至-0.03；P=.02），这表明β-淀粉样蛋白水平和丧偶与认知之间存在独立和交互关联。在使用二分类β-淀粉样蛋白-婚姻状况分组的二次模型中，丧偶且β-淀粉样蛋白水平较高的参与者的认知下降速度几乎是丧偶且β-淀粉样蛋白水平较高的已婚参与者的 3 倍（丧偶且β-淀粉样蛋白水平较高：β，-0.33；95%CI，-0.46 至-0.19；P<.001；已婚且β-淀粉样蛋白水平较高：β，-0.12；95%CI，-0.18 至-0.01；P<.001）。
在认知正常的老年人样本中，丧偶与 3 年内与β-淀粉样蛋白相关的认知衰退加速有关。认知正常的丧偶老年人特别容易发生阿尔茨海默病的临床进展，这强调了需要增加对这一高风险群体的研究关注和基于证据的干预措施。
