采用 [¹¹C]UCB-J PET 测量早期阿尔茨海默病突触密度的主成分分析。

Principal component analysis of synaptic density measured with [C]UCB-J PET in early Alzheimer's disease.

机构信息

Alzheimer's Disease Research Unit, Yale University School of Medicine, One Church Street, 8(th) Floor, New Haven, CT 06510, USA; Department of Psychiatry, Yale University School of Medicine, 300 George Street, New Haven, CT 06510, USA; Pain Research, Informatics, Multi-morbidities, and Education Center, VA Connecticut Healthcare System, West Haven, CT, USA.

出版信息

Neuroimage Clin. 2023;39:103457. doi: 10.1016/j.nicl.2023.103457. Epub 2023 Jun 22.

DOI:10.1016/j.nicl.2023.103457

PMID:37422964

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10338149/

Abstract

BACKGROUND

Synaptic loss is considered an early pathological event and major structural correlate of cognitive impairment in Alzheimer's disease (AD). We used principal component analysis (PCA) to identify regional patterns of covariance in synaptic density using [C]UCB-J PET and assessed the association between principal components (PC) subject scores with cognitive performance.

METHODS

[C]UCB-J binding was measured in 45 amyloid + participants with AD and 19 amyloid- cognitively normal participants aged 55-85. A validated neuropsychological battery assessed performance across five cognitive domains. PCA was applied to the pooled sample using distribution volume ratios (DVR) standardized (z-scored) by region from 42 bilateral regions of interest (ROI).

RESULTS

Parallel analysis determined three significant PCs explaining 70.2% of the total variance. PC1 was characterized by positive loadings with similar contributions across the majority of ROIs. PC2 was characterized by positive and negative loadings with strongest contributions from subcortical and parietooccipital cortical regions, respectively, while PC3 was characterized by positive and negative loadings with strongest contributions from rostral and caudal cortical regions, respectively. Within the AD group, PC1 subject scores were positively correlated with performance across all cognitive domains (Pearson r = 0.24-0.40, P = 0.06-0.006), PC2 subject scores were inversely correlated with age (Pearson r = -0.45, P = 0.002) and PC3 subject scores were significantly correlated with CDR-sb (Pearson r = 0.46, P = 0.04). No significant correlations were observed between cognitive performance and PC subject scores in CN participants.

CONCLUSIONS

This data-driven approach defined specific spatial patterns of synaptic density correlated with unique participant characteristics within the AD group. Our findings reinforce synaptic density as a robust biomarker of disease presence and severity in the early stages of AD.

摘要

背景

突触丢失被认为是阿尔茨海默病（AD）中的早期病理事件和认知障碍的主要结构相关因素。我们使用主成分分析（PCA）来识别使用 [C]UCB-J PET 测量的突触密度的区域协变模式，并评估主要成分（PC）与认知表现的受试者得分之间的关联。

方法

在年龄在 55-85 岁的 45 名 AD 患者和 19 名淀粉样蛋白认知正常的参与者中测量了 [C]UCB-J 结合。使用经过验证的神经心理学测试评估了五个认知领域的表现。PCA 应用于通过 42 个双侧感兴趣区（ROI）的区域标准化（z 评分）的分布体积比（DVR）的合并样本。

结果

平行分析确定了三个解释总方差 70.2%的显著 PC。PC1 的特征是在大多数 ROI 中具有相似贡献的正负荷。PC2 的特征是正负荷和负负荷，最强的贡献来自皮质下和顶枕叶皮质区域，而 PC3 的特征是正负荷和负负荷，最强的贡献来自额侧和尾侧皮质区域。在 AD 组中，PC1 受试者得分与所有认知领域的表现呈正相关（Pearson r=0.24-0.40，P=0.06-0.006），PC2 受试者得分与年龄呈负相关（Pearson r=-0.45，P=0.002），PC3 受试者得分与 CDR-sb 显著相关（Pearson r=0.46，P=0.04）。在 CN 参与者中，认知表现与 PC 受试者得分之间没有观察到显著相关性。