Cleveland Clinic Lou Ruvo Center for Brain Health, 888 West Bonneville Avenue, Las Vegas, NV, 89106, USA.
Alzheimers Res Ther. 2017 Sep 12;9(1):72. doi: 10.1186/s13195-017-0300-8.
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.
阿尔茨海默病（AD）对男性和女性的影响不同，但性别对痴呆前阶段的影响尚不清楚。本研究的目的是探讨性别是否调节氟比他滨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）中言语学习和记忆表现以及海马体积（HV）的影响。
共纳入来自阿尔茨海默病神经影像学倡议（第二队列[ADNI2]和大机遇队列[ADNI-GO]）的 742 名 NC 患者和 eMCI 患者。所有患者均进行基线氟比他滨 PET 测量，526 名患者进行筛查时 HV 测量。回归调节模型用于检验 A 对 Rey 听觉言语学习测试学习和延迟回忆以及右和左 HV（根据总颅内体积进行调整）的影响是否受到诊断和性别的调节。控制了年龄、筛查时的认知、教育和载脂蛋白 E ε4 携带者状态。
A 阳性（A+）但无氟比他滨 PET 淀粉样蛋白阴性（A-）的女性 eMCI 患者的学习成绩较差。对于 NC 女性，A 与学习无关系。相比之下，无论诊断如何，A 阳性的男性学习成绩都呈下降趋势。言语延迟回忆也呈现出类似的趋势：A+但不是 A-的女性 eMCI 患者的延迟回忆呈下降趋势；NC 女性或男性则没有这种影响。海马分析表明，A+但不是 A-的女性 eMCI 患者的右侧 HV 呈缩小趋势；NC 女性没有明显的 A 影响。男性在 A eMCI 中也表现出类似但无统计学意义的右侧 HV 缩小，但在 A eMCI 或 NC 男性中则没有。左 HV 无性别交互作用。
NC 女性的言语学习和记忆评分对 A 有很强的抵抗力，而 A+的 eMCI 女性则失去了这种优势。相比之下，A 对男性的影响较小或根本没有，并且在 NC 和 eMCI 患者中也相当。性别适度调节 A 和诊断与右侧 HV 的关系，即 NC 女性没有 A 效应，A+的 eMCI 女性失去了神经完整性优势；男性的模式则不太清楚。这些发现表明，A+的 eMCI 女性（即前驱 AD）有不同的神经和认知衰退，这对考虑 AD 的早期检测和治疗药物的开发中考虑性别具有重要意义。
