Thurston Rebecca C, Maki Pauline, Chang Yuefang, Wu Minjie, Aizenstein Howard J, Derby Carol A, Karikari Thomas K
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA; Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA; Department of Psychology, University of Pittsburgh, Pittsburgh, PA.
Department of Psychiatry, University of Illinois at Chicago, Chicago, IL; Department of Psychology, University of Illinois at Chicago, Chicago, IL; Department of Obstetrics and Gynecology, University of Illinois at Chicago, Chicago, IL.
Am J Obstet Gynecol. 2024 Mar;230(3):342.e1-342.e8. doi: 10.1016/j.ajog.2023.11.002. Epub 2023 Nov 7.
Identifying risk factors for Alzheimer disease in women is important as women compose two-thirds of individuals with Alzheimer disease. Previous work links vasomotor symptoms, the cardinal menopausal symptom, with poor memory performance and alterations in brain structure, function, and connectivity. These associations are evident when vasomotor symptoms are monitored objectively with ambulatory skin conductance monitors.
This study aimed to determine whether vasomotor symptoms are associated with Alzheimer disease biomarkers.
Between 2017 and 2020, the MsBrain study enrolled 274 community-dwelling women aged 45 to 67 years who had a uterus and at least 1 ovary and were late perimenopausal or postmenopausal status. The key exclusion criteria included neurologic disorder, surgical menopause, and recent use of hormonal or nonhormonal vasomotor symptom treatment. Women underwent 24 hours of ambulatory skin conductance monitoring to assess vasomotor symptoms. Plasma concentrations of Alzheimer disease biomarkers, including amyloid β 42-to-amyloid β 40 ratio, phosphorylated tau (181 and 231), glial fibrillary acidic protein, and neurofilament light, were measured using a single-molecule array (Simoa) technology. Associations between vasomotor symptoms and Alzheimer disease biomarkers were assessed via linear regression models adjusted for age, race and ethnicity, education, body mass index, and apolipoprotein E4 status. Additional models adjusted for estradiol and sleep.
A total of 248 (mean age, 59.06 years; 81% White; 99% postmenopausal status) of enrolled MsBrain participants contributed data. Objectively assessed vasomotor symptoms occurring during sleep were associated with significantly lower amyloid β 42/amyloid β 40, (beta, -.0010 [standard error, .0004]; P=.018; multivariable), suggestive of greater brain amyloid β pathology. The findings remained significant after additional adjustments for estradiol and sleep.
Nighttime vasomotor symptoms may be a marker of women at risk of Alzheimer disease. It is yet unknown if these associations are causal.
鉴于女性占阿尔茨海默病患者的三分之二，识别女性阿尔茨海默病的风险因素很重要。先前的研究将血管舒缩症状（主要的更年期症状）与记忆力减退以及脑结构、功能和连通性的改变联系起来。当使用动态皮肤电导监测仪客观监测血管舒缩症状时，这些关联很明显。
本研究旨在确定血管舒缩症状是否与阿尔茨海默病生物标志物相关。
在2017年至2020年期间，MsBrain研究招募了274名年龄在45至67岁之间、有子宫且至少有1个卵巢、处于围绝经期晚期或绝经后状态的社区居住女性。主要排除标准包括神经系统疾病、手术绝经以及近期使用激素或非激素血管舒缩症状治疗。女性接受了24小时的动态皮肤电导监测以评估血管舒缩症状。使用单分子阵列（Simoa）技术测量阿尔茨海默病生物标志物的血浆浓度，包括淀粉样β蛋白42与淀粉样β蛋白40的比值、磷酸化tau蛋白（181和231）、胶质纤维酸性蛋白和神经丝轻链。通过对年龄、种族和族裔、教育程度、体重指数和载脂蛋白E4状态进行调整的线性回归模型评估血管舒缩症状与阿尔茨海默病生物标志物之间的关联。其他模型对雌二醇和睡眠进行了调整。
共有248名（平均年龄59.06岁；81%为白人；99%处于绝经后状态）参与MsBrain研究的受试者提供了数据。睡眠期间客观评估的血管舒缩症状与显著更低的淀粉样β蛋白42/淀粉样β蛋白40相关（β值为 -0.0010 [标准误为0.0004]；P = 0.018；多变量），提示脑淀粉样β蛋白病变更严重。在对雌二醇和睡眠进行额外调整后，这些发现仍然显著。
夜间血管舒缩症状可能是有阿尔茨海默病风险女性的一个标志物。这些关联是否具有因果关系尚不清楚。
