背景:轻度行为障碍(MBI)是阿尔茨海默病和相关痴呆(ADRD)的高危人群,利用与晚年紧急和持续性神经精神症状(NPS)相关的风险。MBI可以作为以后生活中出现的认知症状(轻度认知障碍,MCI)。这些结构不是相互排斥的,并且可以共同发生。我们描述了MBI之间的关系,海马和内嗅皮层的灰质体积,认知功能正常(NC)和MCI的老年人发生认知功能下降。
方法:来自国家阿尔茨海默病协调中心统一数据集的7242名参与者。规范形态测量图像统计工具用于生成双侧海马和内嗅皮质的灰质体积的估计值。按年龄标准化,性别,颅内总容积,和图像质量。使用被告方评估的神经精神清单问卷评估NPS,根据已发布的算法得出MBI分数。使用多变量线性回归在NC和MCI中分别对MBI状态和感兴趣区域之间的关联进行建模。调整教育和临床MRI访问间隔时间。使用Cox比例风险回归对MBI状态与事件认知下降之间的关联进行建模。
结果:参与者特征总结在表1中。根据图1和图2,患有MBI的NC参与者双侧海马的灰质体积较低(B=-0.40,95CI:[-0.66,-0.15],p=.004),发生MCI或痴呆的风险更大,比没有MBI的人(HR=3.34,95CI:[2.04,5.48),p<.001)。与NCMBI参与者相比,NCMBI参与者的双侧内嗅皮层的灰质体积也较低。虽然没有统计学意义(B=-0.13,95CI:[-0.35,-0.08],p=.22)。在MCI中,MBI的参与者在两个海马中的双侧灰质体积较低(B=-0.46,95CI:[-0.80,-0.12],p=0.01)和内嗅皮层(B=-0.42,95CI:[-0.76,-0.12],p=.009),并且有更高的痴呆进展率(HR=4.13,95CI:[2.45,6.94),p<.001),比那些没有MBI。
结论:我们的研究结果表明,评估无痴呆的老年人的MBI状态与认知状态相结合,可以确定一个群体比没有MBI的群体在ADRD连续体中更远,在关键ADRD区域有更大的基线萎缩和更高的进展率更晚的认知阶段。
BACKGROUND: Mild behavioral impairment (MBI) identifies a high-risk group for Alzheimer\'s disease and related dementias (ADRD), leveraging the risk associated with later-life emergent and persistent neuropsychiatric symptoms (NPS). MBI may act as a complementary behavioral analog to later-life emergent cognitive symptoms (mild cognitive impairment, MCI). These constructs are not mutually exclusive and can co-occur. We characterized the relationship between MBI, grey matter volume in the hippocampus and entorhinal cortex, and incident cognitive decline in older adults with normal cognition (NC) and MCI.
METHODS: Seven-hundred-forty-two participants were included from the National Alzheimer\'s Coordinating Center Uniform Dataset. The Normative Morphometry Image Statistics tool was used to generate estimates of grey matter volume for the bilateral hippocampi and entorhinal cortices, normalized by age, sex, total intracranial volume, and image quality. NPS were evaluated using the informant-rated Neuropsychiatric Inventory Questionnaire, from which MBI scores were derived based on a published algorithm. Associations between MBI status and the regions-of-interest were modelled separately in NC and MCI using multivariable linear regressions, adjusting for education and clinical-MRI visit interval time. Associations between MBI status and incident cognitive decline were modelled using Cox proportional hazards regressions.
RESULTS: Participant characteristics are summarized in Table 1. As per Figures 1 and 2, NC participants with MBI had lower grey matter volume in the bilateral hippocampi (B = -0.40, 95%CI:[-0.66, -0.15], p = .004), and a greater hazard of incident MCI or dementia, than those without MBI (HR = 3.34, 95%CI:[2.04, 5.48), p<.001). NC MBI+ participants also had lower grey matter volume in the bilateral entorhinal cortices compared to NC MBI- participants, although not statistically significant (B = -0.13, 95%CI:[-0.35, -0.08], p = .22). In MCI, participants with MBI had lower grey matter volume bilaterally in both the hippocampus (B = -0.46, 95%CI:[-0.80, -0.12], p = .01) and entorhinal cortex (B = -0.42, 95%CI:[-0.76, -0.12], p = .009), and had greater progression-rates to dementia (HR = 4.13, 95%CI:[2.45, 6.94), p<.001), than those without MBI.
CONCLUSIONS: Our findings suggest that evaluating dementia-free older adults for MBI status in conjunction with cognitive status identifies a group further along the ADRD continuum than those without MBI, who have greater baseline atrophy in key ADRD regions and greater progression rates to later cognitive stages.