Sex differences in Alzheimer risk Brain imaging of endocrine vs chronologic aging
Sex differences in Alzheimer risk Brain imaging of endocrine vs chronologic aging
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DOI：
10.1212/wnl.0000000000004425
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发表时间：
2017-09-26
期刊：
影响因子：
9.9
通讯作者：
Brinton, Roberta Diaz
中科院分区：
文献类型：
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作者：
Mosconi, Lisa;Berti, Valentina;Brinton, Roberta Diaz
目的：这项观察性多模态脑成像研究调查了临床和认知正常的女性和年龄匹配的男性在内分泌过渡状态时迟发性阿尔茨海默病（AD）风险的内表型的出现。方法：对42名40- 60岁认知正常的女性（15名无症状围绝经期[CNT]， 13名围绝经期[PERI]， 14名绝经后[MENO]）和18名年龄和教育程度相匹配的男性进行检查。所有患者都进行了体积MRI， f -18-氟-2-脱氧葡萄糖(FDG)-PET（葡萄糖代谢）和匹兹堡复合B-PET扫描（β -淀粉样蛋白沉积，AD病理的标志）。结果：正如预期的那样，MENO组比PERI和CNT组更老。除此之外，各组在临床和神经心理学测量以及APOE4分布方面具有可比性。与CNT女性和男性相比，在控制年龄的情况下，PERI和MENO组AD内表型指标增加，包括代谢低下、A β沉积增加、AD易感区域灰质和白质体积减少（p< 0.001）。AD生物标志物异常在MENO中最高，在PERI中居中，在CNT中最低（p< 0.001）。apoe4阳性MENO女性的β沉积比其他组加重（p< 0.001）。结论：多模态脑成像显示AD内表型的发展存在性别差异，提示临床前AD阶段在女性衰老过程中较早，且与围绝经期内分泌转变相吻合。这些数据表明，对妇女进行治疗干预的最佳时机是在内分泌老化过程的早期。
Objective: This observational multimodality brain imaging study investigates emergence of endophenotypes of late-onset Alzheimer disease (AD) risk during endocrine transition states in a cohort of clinically and cognitively normal women and age-matched men.Methods: Forty-two 40- to 60-year-old cognitively normalwomen (15 asymptomatic perimenopausal by age [CNT], 13 perimenopausal [PERI], and 14 postmenopausal [MENO]) and 18 age-and education-matched men were examined. All patients had volumetric MRI, F-18-fluoro-2-deoxyglucose (FDG)-PET (glucose metabolism), and Pittsburgh compound B-PET scans (beta-amyloid [A beta] deposition, a hallmark of AD pathology).Results: As expected, the MENO group was older than the PERI and CNT groups. Otherwise, groups were comparable on clinical and neuropsychological measures and APOE4 distribution. Compared to CNT women and to men, and controlling for age, PERI and MENO groups exhibited increased indicators of AD endophenotype, including hypometabolism, increased A beta deposition, and reduced gray and white matter volumes in AD-vulnerable regions (p< 0.001). AD biomarker abnormalities were greatest in MENO, intermediate in PERI, and lowest in CNT women (p< 0.001). A beta deposition was exacerbated in APOE4-positive MENO women relative to the other groups (p< 0.001).Conclusions: Multimodality brain imaging indicates sex differences in development of the AD endophenotype, suggesting that the preclinical AD phase is early in the female aging process and coincides with the endocrine transition of perimenopause. These data indicate that the optimal window of opportunity for therapeutic intervention in women is early in the endocrine aging process.