背景:主观认知衰退(SCD)是与阿尔茨海默病病理有关的痴呆的早期阶段。使用扩散张量成像在SCD中发现白质变化,但是在基于体素张量的方法中存在已知的局限性。基于Fixel的分析(FBA)可以帮助了解白质纤维的变化,以及它们如何与SCD患者的神经退行性蛋白和多结构域行为数据相关。
方法:2018-2022年在台湾东北社区医学研究队列中招募认知正常的健康成年人,分为SCD和正常对照(NC)。参与者接受评估以评估认知能力,精神状态,身体活动水平,和容易疲劳。使用免疫磁性还原技术测量神经变性蛋白。使用全脑FBA收集并分析多壳扩散MRI数据,比较组间结果并将其与多领域评估相关联。
结果:最终登记包括33名SCD和46名NC参与者,在年龄上没有显著差异,性别,或者团体之间的教育。SCD在双侧额上纵向束II(SLFII)处的纤维束横截面大于NC(pFWE<0.05)。这些白质变化与血浆Aβ42水平呈负相关(r=-0.38,p=0.01),与主观认知主诉的AD8评分(r=0.42,p=0.004)和汉密尔顿焦虑量表的焦虑程度评分呈正相关(Ham-A,r=0.35,p=0.019)。FBA指标和血液生物标志物的维度分析发现,血浆神经丝轻链与call体剪接处的纤维密度(pFWE<0.05)和右丘脑的纤维束横截面(pFWE<0.05)呈正相关。进一步检查SCD分组如何在FBA指标和多域评估的相关性之间相互作用,显示call体纤维密度与字母数字排序认知评分(pFWE<0.01)和休闲活动疲劳(pFWE<0.05)之间存在相互作用。
结论:基于FBA,我们的调查提示SCD白质结构改变.SLFII纤维横截面的增大与血浆Aβ42和神经精神症状有关,这表明SCD中潜在的早期轴索营养不良与阿尔茨海默病病理相关。call体的脾也是SCD轴突变性和认知改变的关键区域。
BACKGROUND: Subjective cognitive decline (SCD) is an early stage of dementia linked to Alzheimer\'s disease pathology. White matter changes were found in SCD using diffusion tensor imaging, but there are known limitations in voxel-wise tensor-based methods. Fixel-based analysis (FBA) can help understand changes in white matter fibers and how they relate to neurodegenerative proteins and multidomain behavior data in individuals with SCD.
METHODS: Healthy adults with normal cognition were recruited in the Northeastern Taiwan Community Medicine Research Cohort in 2018-2022 and divided into SCD and normal control (NC). Participants underwent evaluations to assess cognitive abilities, mental states, physical activity levels, and susceptibility to fatigue. Neurodegenerative proteins were measured using an immunomagnetic reduction technique. Multi-shell diffusion MRI data were collected and analyzed using whole-brain FBA, comparing results between groups and correlating them with multidomain assessments.
RESULTS: The final enrollment included 33 SCD and 46 NC participants, with no significant differences in age, sex, or education between the groups. SCD had a greater fiber-bundle cross-section than NC (pFWE < 0.05) at bilateral frontal superior longitudinal fasciculus II (SLFII). These white matter changes correlate negatively with plasma Aβ42 level (r = -0.38, p = 0.01) and positively with the AD8 score for subjective cognitive complaints (r = 0.42, p = 0.004) and the Hamilton Anxiety Rating Scale score for the degree of anxiety (Ham-A, r = 0.35, p = 0.019). The dimensional analysis of FBA metrics and blood biomarkers found positive correlations of plasma neurofilament light chain with fiber density at the splenium of corpus callosum (pFWE < 0.05) and with fiber-bundle cross-section at the right thalamus (pFWE < 0.05). Further examination of how SCD grouping interacts between the correlations of FBA metrics and multidomain assessments showed interactions between the fiber density at the corpus callosum with letter-number sequencing cognitive score (pFWE < 0.01) and with fatigue to leisure activities (pFWE < 0.05).
CONCLUSIONS: Based on FBA, our investigation suggests white matter structural alterations in SCD. The enlargement of SLFII\'s fiber cross-section is linked to plasma Aβ42 and neuropsychiatric symptoms, which suggests potential early axonal dystrophy associated with Alzheimer\'s pathology in SCD. The splenium of the corpus callosum is also a critical region of axonal degeneration and cognitive alteration for SCD.