Ramanan Siddharth, Roquet Daniel, Goldberg Zoë-Lee, Hodges John R, Piguet Olivier, Irish Muireann, Lambon Ralph Matthew A
The University of Sydney, Brain and Mind Centre, Sydney, NSW, Australia.
The University of Sydney, School of Psychology, Sydney, NSW, Australia.
Brain Commun. 2020 Oct 17;2(2):fcaa125. doi: 10.1093/braincomms/fcaa125. eCollection 2020.
Logopenic progressive aphasia is a neurodegenerative syndrome characterized by sentence repetition and naming difficulties arising from left-lateralized temporoparietal atrophy. Clinical descriptions of logopenic progressive aphasia largely concentrate on profiling language deficits, however, accumulating evidence points to the presence of cognitive deficits even on tasks with minimal language demands. Although non-linguistic cognitive deficits in logopenic progressive aphasia are thought to scale with disease severity, patients at discrete stages of language dysfunction display overlapping cognitive profiles, suggesting individual-level variation in cognitive performance, independent of primary language dysfunction. To address this issue, we used principal component analysis to decompose the individual-level variation in cognitive performance in 43 well-characterized logopenic progressive aphasia patients who underwent multi-domain neuropsychological assessments and structural neuroimaging. The principal component analysis solution revealed the presence of two, statistically independent factors, providing stable and clinically intuitive explanations for the majority of variance in cognitive performance in the syndrome. Factor 1 reflected 'speech production and verbal memory' deficits which typify logopenic progressive aphasia. Systematic variations were also confirmed on a second, orthogonal factor mainly comprising visuospatial and executive processes. Adopting a case-comparison approach, we further demonstrate that pairs of patients with comparable Factor 1 scores, regardless of their severity, diverge considerably on visuo-executive test performance, underscoring the inter-individual variability in cognitive profiles in comparably 'logopenic' patients. Whole-brain voxel-based morphometry analyses revealed that speech production and verbal memory factor scores correlated with left middle frontal gyrus, while visuospatial and executive factor scores were associated with grey matter intensity of right-lateralized temporoparietal, middle frontal regions and their underlying white matter connectivity. Importantly, logopenic progressive aphasia patients with poorer visuospatial and executive factor scores demonstrated greater right-lateralized temporoparietal and frontal atrophy. Our findings demonstrate the inherent variation in cognitive performance at an individual- and group-level in logopenic progressive aphasia, suggesting the presence of a genuine co-occurring cognitive impairment that is statistically independent of language function and disease severity.
语法缺失性进行性失语是一种神经退行性综合征，其特征是句子复述和命名困难，由左侧颞顶叶萎缩引起。语法缺失性进行性失语的临床描述主要集中在语言缺陷的描述上，然而，越来越多的证据表明，即使在语言要求极低的任务中也存在认知缺陷。虽然语法缺失性进行性失语中的非语言认知缺陷被认为与疾病严重程度相关，但处于不同语言功能阶段的患者表现出重叠的认知特征，这表明认知表现存在个体差异，与原发性语言功能障碍无关。为了解决这个问题，我们使用主成分分析来分解43名特征明确的语法缺失性进行性失语患者的认知表现的个体差异，这些患者接受了多领域神经心理学评估和结构神经影像学检查。主成分分析结果显示存在两个统计上独立的因素，为该综合征认知表现的大部分变异提供了稳定且临床直观的解释。因素1反映了典型的语法缺失性进行性失语的“言语产生和言语记忆”缺陷。在主要包括视觉空间和执行过程的第二个正交因素上也证实了系统变异。采用病例对照方法，我们进一步证明，具有可比因素1得分的患者对，无论其严重程度如何，在视觉执行测试表现上都有很大差异，这突出了在具有可比“语法缺失性”的患者中认知特征的个体间变异性。基于体素的全脑形态计量学分析表明，言语产生和言语记忆因素得分与左中额叶回相关，而视觉空间和执行因素得分与右侧颞顶叶、中额叶区域及其潜在白质连接的灰质强度相关。重要的是，视觉空间和执行因素得分较差的语法缺失性进行性失语患者表现出更大的右侧颞顶叶和额叶萎缩。我们的研究结果表明，语法缺失性进行性失语在个体和群体水平上认知表现存在内在差异，这表明存在一种真正同时出现的认知障碍，在统计学上独立于语言功能和疾病严重程度。
