背景:据报道,阿尔茨海默病(AD)患者的脉络丛(ChP)体积增大,并且与认知能力呈负相关。然而,其临床诊断和预测价值,ChP影响AD连续体的机制尚不清楚。
方法:这项前瞻性队列研究纳入了中国影像学的607名参与者[健康对照(HC):110,轻度认知障碍(MCI):269,AD痴呆:228],生物标志物,2021年1月1日至2022年12月31日之间的生活方式研究。在AD连续体中的497名患者中,138例进行腰椎穿刺脑脊液(CSF)标志测试。ChP体积与CSF病理标志之间的关系(Aβ42,Aβ40,Aβ42/40,tTau,和pTau181),神经心理学测验[小型精神状态检查(MMSE),蒙特利尔认知评估(MoCA)神经精神量表(NPI),和日常生活活动(ADL)得分],和多模态神经影像学测量[灰质体积,皮质厚度,和校正脑血流量(cCBF)]使用部分Spearman相关性进行分析。四种神经影像学测量[ChP体积,海马体积,侧脑室容积(LVV),和内嗅皮层厚度(ECT)]对CSF标志和神经心理学测试之间的关系进行了检查。4种神经影像学方法在识别AD痴呆患者中的脑Aβ42变化或区分的能力,使用接收器工作特性分析确定MCI和HC,通过线性回归评估其与基线时神经心理学测验评分的关联.使用广义线性混合效应模型在AD连续体上评估了四种神经影像学指标的变化率与神经心理学测试评分之间的纵向关联。
结果:参与者的平均年龄为65.99±8.79岁。AD痴呆患者的基线ChP体积最大(P<0.05)。ChP体积增大与Aβ42和Aβ40水平降低相关;MMSE和MoCA较低,NPI和ADL评分较高;体积较低,皮质厚度,其他认知相关区域的cCBF和cCBF(均P<0.05)。ChP体积介导Aβ42和Aβ40水平与MMSE评分的关联(19.08%和36.57%),Aβ42水平介导了ChP体积与MMSE或MoCA评分的相关性(39.49%和34.36%)。仅ChP体积比单独LVV更好地识别脑Aβ42变化(AUC=0.81vs.0.67,P=0.04)和单独EC厚度(AUC=0.81vs.0.63,P=0.01),并且与单独海马体积相比,MCI患者的分化更好(AUC=0.85vs.0.81,P=0.01),和单独的LVV(AUC=0.85vs.0.82,P=0.03)。联合ChP和海马体积显着增加了区分AD痴呆患者脑Aβ42变化和患者的能力,MCI和HCs组与单纯海马体积比较(均P<0.05)。校正年龄后,性别,多年的教育,APOEε4状态,eTIV,和海马体积,ChP体积与MMSE相关,MoCA,NPI,和基线时的ADL评分,ChP体积的快速增大与NPI评分的快速恶化有关,平均随访10.03±4.45个月(均P<0.05)。
结论:ChP体积可能是与神经退行性改变和临床AD表现相关的一种新的神经影像学指标。它可以更好地检测AD的早期阶段并预测预后。并显着提高了海马对AD连续体的鉴别诊断能力。
BACKGROUND: Enlarged choroid plexus (ChP) volume has been reported in patients with Alzheimer\'s disease (AD) and inversely correlated with cognitive performance. However, its clinical diagnostic and predictive value, and mechanisms by which ChP impacts the AD continuum remain unclear.
METHODS: This prospective cohort study enrolled 607 participants [healthy control (HC): 110, mild cognitive impairment (MCI): 269, AD dementia: 228] from the Chinese Imaging, Biomarkers, and Lifestyle study between January 1, 2021, and December 31, 2022. Of the 497 patients on the AD continuum, 138 underwent lumbar puncture for cerebrospinal fluid (CSF) hallmark testing. The relationships between ChP volume and CSF pathological hallmarks (Aβ42, Aβ40, Aβ42/40, tTau, and pTau181), neuropsychological tests [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), and Activities of Daily Living (ADL) scores], and multimodal neuroimaging measures [gray matter volume, cortical thickness, and corrected cerebral blood flow (cCBF)] were analyzed using partial Spearman\'s correlation. The mediating effects of four neuroimaging measures [ChP volume, hippocampal volume, lateral ventricular volume (LVV), and entorhinal cortical thickness (ECT)] on the relationship between CSF hallmarks and neuropsychological tests were examined. The ability of the four neuroimaging measures to identify cerebral Aβ42 changes or differentiate among patients with AD dementia, MCI and HCs was determined using receiver operating characteristic analysis, and their associations with neuropsychological test scores at baseline were evaluated by linear regression. Longitudinal associations between the rate of change in the four neuroimaging measures and neuropsychological tests scores were evaluated on the AD continuum using generalized linear mixed-effects models.
RESULTS: The participants\' mean age was 65.99 ± 8.79 years. Patients with AD dementia exhibited the largest baseline ChP volume than the other groups (P < 0.05). ChP volume enlargement correlated with decreased Aβ42 and Aβ40 levels; lower MMSE and MoCA and higher NPI and ADL scores; and lower volume, cortical thickness, and cCBF in other cognition-related regions (all P < 0.05). ChP volume mediated the association of Aβ42 and Aβ40 levels with MMSE scores (19.08% and 36.57%), and Aβ42 levels mediated the association of ChP volume and MMSE or MoCA scores (39.49% and 34.36%). ChP volume alone better identified cerebral Aβ42 changes than LVV alone (AUC = 0.81 vs. 0.67, P = 0.04) and EC thickness alone (AUC = 0.81 vs.0.63, P = 0.01) and better differentiated patients with MCI from HCs than hippocampal volume alone (AUC = 0.85 vs. 0.81, P = 0.01), and LVV alone (AUC = 0.85 vs.0.82, P = 0.03). Combined ChP and hippocampal volumes significantly increased the ability to differentiate cerebral Aβ42 changes and patients among AD dementia, MCI, and HCs groups compared with hippocampal volume alone (all P < 0.05). After correcting for age, sex, years of education, APOE ε4 status, eTIV, and hippocampal volume, ChP volume was associated with MMSE, MoCA, NPI, and ADL score at baseline, and rapid ChP volume enlargement was associated with faster deterioration in NPI scores with an average follow-up of 10.03 ± 4.45 months (all P < 0.05).
CONCLUSIONS: ChP volume may be a novel neuroimaging marker associated with neurodegenerative changes and clinical AD manifestations. It could better detect the early stages of the AD and predict prognosis, and significantly enhance the differential diagnostic ability of hippocampus on the AD continuum.