Sundermann Erin E, Biegon Anat, Rubin Leah H, Lipton Richard B, Landau Susan, Maki Pauline M
Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
Department of Neurology, State University of New York, New York, NY, USA.
J Alzheimers Dis. 2017;56(3):947-957. doi: 10.3233/JAD-160716.
There is a growing recognition of sex differences in Alzheimer's disease (AD). Females show an advantage over males on tests of verbal memory, which are used to diagnose AD and its precursor, amnestic mild cognitive impairment (aMCI). Women retain this advantage in aMCI despite reduced hippocampal volume and temporal lobe glucose metabolism. Here we examined whether this female advantage endures despite evidence of AD-specific pathology, cortical amyloid-β (Aβ) deposition measured with [18F]AV45 (florbetapir) positron emission tomography. Participants with normal cognition (N = 304), aMCI (N = 515), and AD dementia (N = 175) were drawn from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Across and within diagnostic groups, we conducted linear regressions to examine the interaction of sex with cortical Aβ burden on immediate and delayed recall on the Rey Auditory Verbal Learning Test (RAVLT) adjusting for age, education, and APOE4. In the overall group, sex by cortical Aβ interaction was significant for delayed recall only. Overall, delayed recall performance was significantly better in women versus men among those with low to moderate Aβ burden, but women and men performed similarly among those with high Aβ burden. In diagnosis-stratified analyses, a significant sex by cortical Aβ interaction was observed for delayed recall in the aMCI group, but not in the normal or AD dementia groups. Thus, women maintain a verbal memory advantage over men in aMCI despite similar levels of AD pathology. Although this advantage may benefit women by delaying verbal memory impairment until more advanced pathology, it may also delay diagnosis of aMCI and treatment intervention.
人们越来越认识到阿尔茨海默病(AD)存在性别差异。在用于诊断AD及其前驱疾病——遗忘型轻度认知障碍(aMCI)的言语记忆测试中,女性表现优于男性。尽管海马体积减小和颞叶葡萄糖代谢降低,但女性在aMCI中仍保持这一优势。在这里,我们研究了尽管有AD特异性病理证据,即通过[18F]AV45(氟代贝他吡)正电子发射断层扫描测量的皮质淀粉样β(Aβ)沉积,这种女性优势是否依然存在。认知正常(N = 304)、aMCI(N = 515)和AD痴呆(N = 175)的参与者来自阿尔茨海默病神经影像学倡议(ADNI)。在诊断组之间和组内,我们进行了线性回归,以检验性别与皮质Aβ负荷在雷伊听觉言语学习测试(RAVLT)即时和延迟回忆上的相互作用,并对年龄、教育程度和APOE4进行了调整。在总体组中,仅延迟回忆的性别与皮质Aβ相互作用具有显著性。总体而言,在Aβ负荷低至中度的人群中,女性的延迟回忆表现明显优于男性,但在Aβ负荷高的人群中,女性和男性的表现相似。在诊断分层分析中,aMCI组在延迟回忆方面观察到显著的性别与皮质Aβ相互作用,但在正常或AD痴呆组中未观察到。因此,尽管AD病理水平相似,但女性在aMCI中仍保持言语记忆优势。尽管这种优势可能通过将言语记忆损害推迟到更晚期的病理阶段而使女性受益,但它也可能延迟aMCI的诊断和治疗干预。