Novakova Martinkova Julie, Ferretti Maria Teresa, Ferrari Alberto, Lerch Ondrej, Matuskova Veronika, Secnik Juraj, Hort Jakub
Cognitive Center, Department of Neurology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
Women's Brain Project, Gunterhausen, Switzerland.
Front Psychiatry. 2023 Mar 8;14:1039239. doi: 10.3389/fpsyt.2023.1039239. eCollection 2023.
Choroid plexus (CP)-related mechanisms have been implicated in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease. In this pilot study, we aimed to elucidate the association between longitudinal changes in CP volume, sex and cognitive impairment.
We assessed longitudinal changes in CP volume in a cohort of = 613 subjects across = 2,334 datapoints from ADNI 2 and ADNI-GO, belonging to cognitively unimpaired (CN), stable mild cognitive impairment (MCI), clinically diagnosed Alzheimer's disease dementia (AD) or convertor (to either AD or MCI) subgroups. CP volume was automatically segmented and used as a response variable in linear mixed effect models with random intercept clustered by patient identity. Temporal effects of select variables were assessed by interactions and subgroup analyses.
We found an overall significant increase of CP volume in time (14.92 mm per year, 95% confidence interval, CI (11.05, 18.77), < 0.001). Sex-disaggregated results showed an annual rate of increase 9.48 mm in males [95% CI (4.08, 14.87), < 0.001], and 20.43 mm in females [95% CI (14.91, 25.93), < 0.001], indicating more than double the rate of increase in females, which appeared independent of other temporal variables. The only diagnostic group with a significant CP increase as compared to CN was the convertors group, with an increase of 24.88 mm/year [95% CI (14, 35.82), < 0.001]. ApoE exhibited a significant temporal effect, with the E4 homozygote group's CP increasing at more than triple the rate of non-carrier or heterozygote groups [40.72, 95% CI (25.97, 55.46), < 0.001 vs. 12.52, 95% CI (8.02, 17.02), < 0.001 for ApoE E4 homozygotes and E4 non-carriers, respectively], and may have modified the diagnostic group relationship.
Our results contribute to potential mechanisms for sex differences in cognitive impairment with a novel finding of twice the annual choroid plexus enlargement in females and provide putative support for CP-related mechanisms of cognitive deterioration and its relationship to ApoE E4.
脉络丛（CP）相关机制已被认为与包括阿尔茨海默病在内的神经退行性疾病的发病机制有关。在这项初步研究中，我们旨在阐明CP体积的纵向变化、性别与认知障碍之间的关联。
我们评估了来自阿尔茨海默病神经成像计划（ADNI）2和ADNI-GO的613名受试者队列中CP体积的纵向变化，这些受试者共有2334个数据点，分属于认知未受损（CN）、稳定轻度认知障碍（MCI）、临床诊断的阿尔茨海默病痴呆（AD）或转化者（转化为AD或MCI）亚组。CP体积通过自动分割获得，并作为线性混合效应模型中的响应变量，随机截距按患者身份聚类。通过交互作用和亚组分析评估选定变量的时间效应。
我们发现CP体积随时间总体显著增加（每年增加14.92立方毫米，95%置信区间，CI（11.05，18.77），P<0.001）。按性别分类的结果显示，男性年增长率为9.48立方毫米[95%CI（4.08，14.87），P<0.001]，女性为20.43立方毫米[95%CI（14.91，25.93），P<0.001]，表明女性的增长率是男性的两倍多，且这一增长似乎与其他时间变量无关。与CN相比，CP体积显著增加的唯一诊断组是转化者组，年增加量为24.88立方毫米/年[95%CI（14，35.82），P<0.001]。载脂蛋白E（ApoE）表现出显著的时间效应，E4纯合子组的CP增长速度是非携带者或杂合子组的三倍多[40.72，95%CI（25.97，55.46），P<0.001，而ApoE E4纯合子和E4非携带者分别为12.52，95%CI（8.02，17.02），P<0.001]，并且可能改变了诊断组之间的关系。
我们的研究结果有助于揭示认知障碍中性别差异的潜在机制，有一项新发现是女性脉络丛每年增大的速度是男性的两倍，并为与CP相关的认知衰退机制及其与ApoE E4 的关系提供了推测性支持。
