Moderating effects of sex on the impact of diagnosis and amyloid positivity on verbal memory and hippocampal volume.
Moderating effects of sex on the impact of diagnosis and amyloid positivity on verbal memory and hippocampal volume.
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DOI：
10.1186/s13195-017-0300-8
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发表时间：
2017-09-12
期刊：
影响因子：
--
通讯作者：
Alzheimer’s Disease Neuroimaging Initiative
中科院分区：
文献类型：
--
作者：
Caldwell JZK;Berg JL;Cummings JL;Banks SJ;Alzheimer’s Disease Neuroimaging Initiative
阿尔茨海默病（AD）对男性和女性的影响不同，但性别对痴呆前期阶段的影响尚不清楚。本研究的目的是检查性别是否调节florbetapir正电子发射断层扫描（PET）淀粉样蛋白阳性（A+）对正常认知（NC）和早期轻度认知障碍（eMCI）的言语学习和记忆能力以及海马体积（HV）的影响。纳入了来自阿尔茨海默病神经影像学倡议（第二队列[ADNI 2]和Grand Opportunity队列[ADNI-GO]）的742名NC参与者和eMCI参与者。所有患者均测量了基线florbetapir PET，526例患者测量了筛选访视HV。回归调节模型用于检查A+对Rey听觉言语学习测试学习和延迟回忆以及左右HV（根据颅内总体积调整）的影响是否受诊断和性别调节。年龄、筛查时的认知、教育和载脂蛋白E ε4携带状态均得到控制。具有A+的女性，而不是具有florbetapir PET淀粉样蛋白阴性（A-）的女性，eMCI表现出较差的学习能力。对于NC女性，A+与学习没有关系。相比之下，A+男性倾向于学习较差，无论诊断如何。言语延迟回忆也有类似的趋势：A+而不是A-的女性，eMCI倾向于减少延迟回忆; NC女性或男性没有观察到影响。海马神经元分析表明，具有A+的女性，而不是具有A-的女性，eMCI，倾向于较小的右HV;没有观察到NC女性的显著A+效应。男性在A+ eMCI中表现出相似的但不显著的右HV较小模式，但在A− eMCI或NC男性中则不然。左侧HV未观察到性别的交互作用。NC女性的语言学习和记忆得分强于A+，而A+ eMCI女性失去了这一优势。相比之下，A+对男性得分的影响不太显著或根本没有影响，并且对NC和eMCI患者的影响较小。性别略微调节A+和诊断与右HV的关系，例如NC女性未显示A+效应，而A+ eMCI女性在神经完整性方面失去了优势;男性的模式不太清楚。这些发现表明，患有A+ eMCI的女性（即，前驱AD）具有不同的神经和认知下降，这对于在AD的早期检测和治疗剂的开发中考虑性别具有意义。
Alzheimer’s disease (AD) impacts men and women differently, but the effect of sex on predementia stages is unclear. The objective of this study was to examine whether sex moderates the impact of florbetapir positron emission tomography (PET) amyloid positivity (A+) on verbal learning and memory performance and hippocampal volume (HV) in normal cognition (NC) and early mild cognitive impairment (eMCI). Seven hundred forty-two participants with NC and participants with eMCI from the Alzheimer’s Disease Neuroimaging Initiative (second cohort [ADNI2] and Grand Opportunity Cohort [ADNI-GO]) were included. All had baseline florbetapir PET measured, and 526 had screening visit HV measured. Regression moderation models were used to examine whether A+ effects on Rey Auditory Verbal Learning Test learning and delayed recall and right and left HV (adjusted for total intracranial volume) were moderated by diagnosis and sex. Age, cognition at screening, education, and apolipoprotein E ε4 carrier status were controlled. Women with A+, but not those with florbetapir PET amyloid negative (A-),eMCI showed poorer learning. For women with NC, there was no relationship of A+ with learning. In contrast, A+ men trended toward poorer learning regardless of diagnosis. A similar trend was found for verbal delayed recall: Women with A+, but not A-, eMCI trended toward reduced delayed recall; no effects were observed for women with NC or for men. Hippocampal analyses indicated that women with A+, but not those with A−, eMCI, trended toward smaller right HV; no significant A+ effects were observed for women with NC. Men showed similar, though nonsignificant, patterns of smaller right HV in A+ eMCI, but not in men with A− eMCI or NC. No interactive effects of sex were noted for left HV. Women with NC showed verbal learning and memory scores robust to A+, and women with A+ eMCI lost this advantage. In contrast, A+ impacted men’s scores less significantly or not at all, and comparably across those with NC and eMCI. Sex marginally moderated the relationship of A+ and diagnosis with right HV, such that women with NC showed no A+ effect and women with A+ eMCI lost that advantage in neural integrity; the pattern in men was less clear. These findings show that women with A+ eMCI (i.e., prodromal AD) have differential neural and cognitive decline, which has implications for considering sex in early detection of AD and development of therapeutics.
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影响因子：
11.2
作者：
Landau, Susan M.;Mintun, Mark A.;Joshi, Abhinay D.;Koeppe, Robert A.;Petersen, Ronald C.;Aisen, Paul S.;Weiner, Michael W.;Jagust, William J.
通讯作者：
Jagust, William J.
影响因子：
12.7
作者：
Jack CR Jr;Barrio JR;Kepe V
通讯作者：
Kepe V
影响因子：
4
作者：
Ardekani, Babak A.;Convit, Antonio;Bachman, Alvin H.
通讯作者：
Bachman, Alvin H.
影响因子：
3.7
作者：
Ewers, Michael;Insel, Philip;Weiner, Michael W.
通讯作者：
Weiner, Michael W.
DOI：
10.1080/13803395.2015.1132298
发表时间：
2016
影响因子：
2.2
作者：
Gale SD;Baxter L;Thompson J
通讯作者：
Thompson J