后皮质萎缩和早发型典型阿尔茨海默病的表型特异性代谢模式。
Phenotype-specific metabolic patterns in Posterior cortical atrophy and early-onset typical Alzheimer's disease.
作者信息
Lu Jiaying, Chen Keliang, Lin Huamei, Ju Zizhao, Ge Jingjie, Lu Jie, Guan Yihui, Guo Qihao, Chu Shuguang, Zhao Qianhua, Zuo Chuantao, Wu Ping
机构信息
Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, No.518, East Wuzhong Road, Shanghai, 200235, China.
National Center for Neurological Disorders & National Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
出版信息
Ann Nucl Med. 2025 May;39(5):506-517. doi: 10.1007/s12149-025-02025-8. Epub 2025 Feb 28.
OBJECTIVE
Posterior cortical atrophy (PCA) is generally considered an atypical variant of Alzheimer's disease (AD) and is an important component of early-onset AD. Symptomatologic heterogeneity has led to a high rate of misdiagnosis or delayed diagnosis of early-onset AD. We sought to establish the phenotypic-specific metabolic patterns of PCA and early-onset typical AD (tAD) and to assess whether phenotype-specific neuroimaging biomarkers are more valuable for disease recognition.
METHODS
Patients accepting F-FDG PET with an onset age younger than 65 years (PCA, n = 40; early-onset tAD, n = 37; behavioral variant frontotemporal dementia (bv-FTD), n = 35) and healthy controls (HCs, n = 30) were enrolled and divided into two cohorts for pattern establishment and validation, respectively. Similarities and differences between patterns were assessed by pattern topography, expression, classification performance and correlation with clinical severity.
RESULTS
PCA-related pattern (PCARP) was characterized by extensively relative hypometabolism in the parietal lobe, occipital lobe, temporal lobe, cingulate gyrus, and relative hypermetabolism mainly in vermis, thalamus. Early-onset tAD-related pattern (EOtADRP) was characterized by relative hypometabolism mainly in the middle frontal gyrus, angular gyrus, precuneus, middle temporal gyrus, cingulate gyrus, caudate, and relative hypermetabolism mainly in vermis, thalamus, postcentral gyrus. PCARP and EOtADRP were closely related in topography (r = 0.909, P < 0.001) and expression (r = 0.862, P < 0.001). High accuracies in distinguishing corresponding patient group from HC were found in both, while only PCARP was capable of phenotype discrimination (PCA versus early-onset tAD; area under the receiver operating characteristic curve [AUC] = 0.84-0.88 for PCARP, AUC = 0.57-0.62 for EOtADRP) and distinguishment between PCA/early-onset tAD and bv-FTD (AUC = 1.00/0.91 for PCARP, AUC = 0.73/0.62 for EOtADRP). PCARP showed great potential in detecting clinical severity in both phenotypes whereas EOtADRP only worked in early-onset tAD.
CONCLUSION
PCARP outperformed EOtADRP in phenotype discrimination with better potential in severity assessment.
目的
后皮质萎缩（PCA）通常被认为是阿尔茨海默病（AD）的一种非典型变体，是早发性AD的重要组成部分。症状学异质性导致早发性AD的误诊率或延迟诊断率较高。我们试图建立PCA和早发性典型AD（tAD）的表型特异性代谢模式，并评估表型特异性神经影像学生物标志物对疾病识别是否更有价值。
方法
纳入发病年龄小于65岁的接受F-FDG PET检查的患者（PCA组，n = 40；早发性tAD组，n = 37；行为变异型额颞叶痴呆（bv-FTD）组，n = 35）和健康对照者（HC组，n = 30），并分别分为两个队列用于模式建立和验证。通过模式拓扑结构、表达、分类性能以及与临床严重程度的相关性评估模式之间的异同。
结果
PCA相关模式（PCARP）的特征是顶叶、枕叶、颞叶、扣带回广泛相对代谢减低，主要在蚓部、丘脑相对代谢增高。早发性tAD相关模式（EOtADRP）的特征是主要在额中回、角回、楔前叶、颞中回、扣带回、尾状核相对代谢减低，主要在蚓部、丘脑、中央后回相对代谢增高。PCARP和EOtADRP在拓扑结构（r = 0.909，P < 0.001）和表达（r = 0.862，P < 0.001）方面密切相关。两者在将相应患者组与HC区分开方面都具有较高的准确性，而只有PCARP能够进行表型鉴别（PCA与早发性tAD；PCARP的受试者工作特征曲线下面积[AUC] = 0.84 - 0.88，EOtADRP的AUC = 0.57 - 0.62）以及区分PCA/早发性tAD与bv-FTD（PCARP的AUC = 1.00/0.91，EOtADRP的AUC = 0.73/0.62）。PCARP在检测两种表型的临床严重程度方面显示出巨大潜力，而EOtADRP仅在早发性tAD中有效。
结论
在表型鉴别方面，PCARP优于EOtADRP，在严重程度评估方面具有更好的潜力。
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