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Abstract：
OBJECTIVE: Alzheimer disease (AD) spans heterogeneous typical and atypical phenotypes. Posterior cortical atrophy (PCA) is a striking example, characterized by prominent impairment in visual and other posterior functions in contrast to typical, amnestic AD. The primary study objective was to establish how the similarities and differences of cognition and brain volumes within AD and PCA (and by extension other AD variants) can be conceptualized as systematic variations across a transdiagnostic, graded multidimensional space.
METHODS: This was a cross-sectional, single-center, observational, cohort study performed at the National Hospital for Neurology & Neurosurgery, London, United Kingdom. Data were collected from a cohort of patients with PCA and AD, matched for age, disease duration, and Mini-Mental State Examination (MMSE) scores. There were 2 sets of outcome measures: (1) scores on a neuropsychological battery containing 22 tests spanning visuoperceptual and visuospatial processing, episodic memory, language, executive functions, calculation, and visuospatial processing and (2) measures extracted from high-resolution T1-weighted volumetric MRI scans. Principal component analysis was used to extract the transdiagnostic dimensions of phenotypical variation from the detailed neuropsychological data. Voxel-based morphometry was used to examine associations between the PCA-derived clinical phenotypes and the structural measures.
RESULTS: We enrolled 93 participants with PCA (mean: age = 59.9 years, MMSE = 21.2; 59/93 female) and 58 AD participants (mean: age = 57.1 years, MMSE = 19.7; 22/58 female). The principal component analysis for PCA (sample adequacy confirmed: Kaiser-Meyer-Olkin = 0.865) extracted 3 dimensions accounting for 61.0% of variance in patients\' performance, reflecting general cognitive impairment, visuoperceptual deficits, and visuospatial impairments. Plotting AD cases into the PCA-derived multidimensional space, and vice versa, revealed graded, overlapping variations between cases along these dimensions, with no evidence for categorical-like patient clustering. Similarly, the relationship between brain volumes and scores on the extracted dimensions was overlapping for PCA and AD cases.
CONCLUSIONS: These results provide evidence supporting a reconceptualization of clinical and radiologic variation in these heterogenous AD phenotypes as being along shared phenotypic continua spanning PCA and AD, arising from systematic graded variations within a transdiagnostic, multidimensional neurocognitive geometry.
METHODS: This was a cross-sectional, single-center, observational, cohort study performed at the National Hospital for Neurology & Neurosurgery, London, United Kingdom. Data were collected from a cohort of patients with PCA and AD, matched for age, disease duration, and Mini-Mental State Examination (MMSE) scores. There were 2 sets of outcome measures: (1) scores on a neuropsychological battery containing 22 tests spanning visuoperceptual and visuospatial processing, episodic memory, language, executive functions, calculation, and visuospatial processing and (2) measures extracted from high-resolution T1-weighted volumetric MRI scans. Principal component analysis was used to extract the transdiagnostic dimensions of phenotypical variation from the detailed neuropsychological data. Voxel-based morphometry was used to examine associations between the PCA-derived clinical phenotypes and the structural measures.
RESULTS: We enrolled 93 participants with PCA (mean: age = 59.9 years, MMSE = 21.2; 59/93 female) and 58 AD participants (mean: age = 57.1 years, MMSE = 19.7; 22/58 female). The principal component analysis for PCA (sample adequacy confirmed: Kaiser-Meyer-Olkin = 0.865) extracted 3 dimensions accounting for 61.0% of variance in patients\' performance, reflecting general cognitive impairment, visuoperceptual deficits, and visuospatial impairments. Plotting AD cases into the PCA-derived multidimensional space, and vice versa, revealed graded, overlapping variations between cases along these dimensions, with no evidence for categorical-like patient clustering. Similarly, the relationship between brain volumes and scores on the extracted dimensions was overlapping for PCA and AD cases.
CONCLUSIONS: These results provide evidence supporting a reconceptualization of clinical and radiologic variation in these heterogenous AD phenotypes as being along shared phenotypic continua spanning PCA and AD, arising from systematic graded variations within a transdiagnostic, multidimensional neurocognitive geometry.
摘要：
目的：阿尔茨海默病（AD）跨越异质性典型和非典型表型。后皮质萎缩（PCA）是一个突出的例子，与典型的相比，其特征是视觉和其他后部功能明显受损，失忆的AD.主要研究目标是确定AD和PCA（以及其他AD变体）中认知和脑容量的相似性和差异如何被概念化为跨诊断的系统变化。分级多维空间。
方法：这是一个横截面，单中心,观察,在国家神经病学和神经外科医院进行的队列研究，伦敦,联合王国。数据来自一组PCA和AD患者，年龄相匹配，疾病持续时间,和迷你精神状态检查（MMSE）成绩。有2组结果指标：（1）神经心理学测验的得分，其中包含22项涵盖视觉感知和视觉空间处理的测试，情景记忆,语言,执行功能，计算,和视觉空间处理以及（2）从高分辨率T1加权体积MRI扫描中提取的度量。主成分分析用于从详细的神经心理学数据中提取表型变异的诊断维度。基于体素的形态计量学用于检查PCA衍生的临床表型与结构测量之间的关联。
结果：我们招募了93名PCA参与者（平均年龄：59.9岁，MMSE=21.2；59/93女性）和58名AD参与者（平均年龄：57.1岁，MMSE=19.7；22/58女性）。PCA的主成分分析（样本充分性证实：Kaiser-Meyer-Olkin=0.865）提取了3个维度，占患者表现方差的61.0%，反映一般认知障碍，视觉感知缺陷，和视觉空间损伤。将AD案例绘制到PCA派生的多维空间中，反之亦然,揭示分级，沿着这些维度的案例之间的重叠变化，没有证据表明类似分类的患者聚类。同样，PCA和AD病例的脑体积与提取维度评分之间的关系重叠.
结论：这些结果提供了证据，支持这些异质性AD表型的临床和放射学变异的重新概念化，因为它们沿着跨PCA和AD的共有表型连续性，起因于诊断中的系统分级变化，多维神经认知几何。
方法：这是一个横截面，单中心,观察,在国家神经病学和神经外科医院进行的队列研究，伦敦,联合王国。数据来自一组PCA和AD患者，年龄相匹配，疾病持续时间,和迷你精神状态检查（MMSE）成绩。有2组结果指标：（1）神经心理学测验的得分，其中包含22项涵盖视觉感知和视觉空间处理的测试，情景记忆,语言,执行功能，计算,和视觉空间处理以及（2）从高分辨率T1加权体积MRI扫描中提取的度量。主成分分析用于从详细的神经心理学数据中提取表型变异的诊断维度。基于体素的形态计量学用于检查PCA衍生的临床表型与结构测量之间的关联。
结果：我们招募了93名PCA参与者（平均年龄：59.9岁，MMSE=21.2；59/93女性）和58名AD参与者（平均年龄：57.1岁，MMSE=19.7；22/58女性）。PCA的主成分分析（样本充分性证实：Kaiser-Meyer-Olkin=0.865）提取了3个维度，占患者表现方差的61.0%，反映一般认知障碍，视觉感知缺陷，和视觉空间损伤。将AD案例绘制到PCA派生的多维空间中，反之亦然,揭示分级，沿着这些维度的案例之间的重叠变化，没有证据表明类似分类的患者聚类。同样，PCA和AD病例的脑体积与提取维度评分之间的关系重叠.
结论：这些结果提供了证据，支持这些异质性AD表型的临床和放射学变异的重新概念化，因为它们沿着跨PCA和AD的共有表型连续性，起因于诊断中的系统分级变化，多维神经认知几何。
