研究非典型阿尔茨海默病纵向临床衰退的异质性及神经解剖学关联。
Investigating Heterogeneity and Neuroanatomic Correlates of Longitudinal Clinical Decline in Atypical Alzheimer Disease.
作者信息
Whitwell Jennifer L, Martin Peter R, Graff-Radford Jonathan, Machulda Mary M, Sintini Irene, Buciuc Marina, Senjem Matthew L, Schwarz Christopher G, Botha Hugo, Carrasquillo Minerva M, Ertekin-Taner Nilufer, Lowe Val J, Jack Clifford R, Josephs Keith A
机构信息
From the Departments of Radiology (J.W., I.S., M.L.S., C.G.S., V.J.L., C.R.J.), Quantitative Health Sciences (P.R.M.), Neurology (J.G.-R., M.B., H.B., K.A.J.), Psychiatry and Psychology (M.M.), and Information Technology (M.L.S.), Mayo Clinic, Rochester, MN; and Department of Neuroscience (M.M.C., N.E.-T.), Mayo Clinic, Jacksonville, FL.
出版信息
Neurology. 2022 Jun 13;98(24):e2436-e2445. doi: 10.1212/WNL.0000000000200336.
BACKGROUND AND OBJECTIVES
The aims of this work were to compare rates of longitudinal change in neurologic and neuropsychological test performance between the logopenic progressive aphasia (LPA) and posterior cortical atrophy (PCA) variants of atypical Alzheimer disease (AD) and to use unbiased principal component analysis to assess heterogeneity in patterns of change and relationships to demographics and concurrent brain atrophy.
METHODS
Patients with PCA or LPA who were positive for amyloid and tau AD biomarkers and had undergone serial neurologic and neuropsychological assessments and structural MRI were identified. Rates of change in 13 clinical measures were compared between groups in a case-control design, and principal component analysis was used to assess patterns of clinical change unbiased by clinical phenotype. Components were correlated with rates of regional brain atrophy with tensor-based morphometry.
RESULTS
Twenty-eight patients with PCA and 27 patients with LPA were identified. Those with LPA showed worse baseline performance and faster rates of decline in naming, repetition, and working memory, as well as faster rates of decline in verbal episodic memory, compared to those with PCA. Conversely, patients with PCA showed worse baseline performance in tests of visuospatial and perceptual function and on the Clinical Dementia Rating Scale and faster rates of decline in visuoperceptual function compared to those with LPA. Principal component analysis showed that patterns of clinical decline were highly heterogeneous across the cohort, with 10 principal components required to explain >90% of the variance. The first principal component reflected overall severity, with higher scores in LPA than PCA reflecting faster decline in LPA, and was related to left temporoparietal atrophy. The second and third principal components were not related to clinical phenotype but showed some relationship to regional atrophy. No relationships were identified between the principal components and age, sex, disease duration, amyloid PET findings, or apolipoprotein genotype.
DISCUSSION
Longitudinal patterns of clinical decline differ between LPA and PCA but are heterogeneous and related to different patterns of topographic spread. PCA is associated with a more slowly progressive course than LPA.
背景与目的
本研究旨在比较非典型阿尔茨海默病（AD）的语言流畅性进行性失语（LPA）和后皮质萎缩（PCA）变体之间神经学和神经心理学测试表现的纵向变化率，并使用无偏主成分分析来评估变化模式的异质性以及与人口统计学和同时期脑萎缩的关系。
方法
识别出淀粉样蛋白和tau AD生物标志物呈阳性、接受过系列神经学和神经心理学评估以及结构MRI检查的PCA或LPA患者。采用病例对照设计比较两组间13项临床指标的变化率，并使用主成分分析来评估不受临床表型影响的临床变化模式。通过基于张量的形态测量法将各成分与区域脑萎缩率进行相关性分析。
结果
共识别出28例PCA患者和27例LPA患者。与PCA患者相比，LPA患者在命名、复述和工作记忆方面的基线表现更差，下降速度更快，在言语情景记忆方面的下降速度也更快。相反，与LPA患者相比，PCA患者在视觉空间和感知功能测试以及临床痴呆评定量表上的基线表现更差，视觉感知功能下降速度更快。主成分分析表明，整个队列的临床衰退模式高度异质，需要10个主成分来解释>90%的方差。第一个主成分反映总体严重程度，LPA中的得分高于PCA，反映出LPA中衰退更快，且与左侧颞顶叶萎缩有关。第二和第三个主成分与临床表型无关，但与区域萎缩有一定关系。未发现主成分与年龄、性别、病程、淀粉样蛋白PET结果或载脂蛋白基因型之间存在关联。
讨论
LPA和PCA的临床衰退纵向模式不同，但具有异质性，且与不同的地形扩散模式有关。与LPA相比，PCA的病程进展更缓慢。
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