Henderson Shalom K, Ramanan Siddharth, Rouse Matthew A, Cope Thomas E, Halai Ajay D, Patterson Karalyn E, Rowe James B, Lambon Ralph Matthew A
Medical Research Council (MRC) Cognition and Brain Sciences Unit, University of Cambridge, Cambridge CB2 7EF, UK.
Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0QQ, UK.
Brain Commun. 2024 Dec 21;7(1):fcae463. doi: 10.1093/braincomms/fcae463. eCollection 2025.
We investigated semantic cognition in the logopenic variant of primary progressive aphasia, including (i) the status of verbal and non-verbal semantic performance; and (ii) whether the semantic deficit reflects impaired semantic control. Our hypothesis that individuals with logopenic variant of primary progressive aphasia would exhibit semantic control impairments was motivated by the anatomical overlap between the temporoparietal atrophy typically associated with logopenic variant of primary progressive aphasia and lesions associated with post-stroke semantic aphasia and Wernicke's aphasia, which cause heteromodal semantic control impairments. We addressed the presence, type (semantic representation and semantic control; verbal and non-verbal), and progression of semantic deficits in logopenic variant of primary progressive aphasia. Since most people with logopenic variant of primary progressive aphasia have Alzheimer's disease pathology and are part of a broader multi-dimensional phenotype space encompassing Alzheimer's disease sub-types, we compared semantic performance in logopenic variant of primary progressive aphasia and typical amnestic Alzheimer's disease. Given the differences in lesion and atrophy patterns in semantic aphasia and Wernicke's aphasia versus semantic-dementia/semantic-variant primary progressive aphasia patients, our second aim was to examine atrophy patterns in people with logopenic variant of primary progressive aphasia and typical Alzheimer's disease compared to age-matched controls. Twenty-seven patients participated in the study. People were grouped into those meeting consensus criteria for logopenic variant of primary progressive aphasia ( = 10) and others who may have previously satisfied definitions of logopenic variant of primary progressive aphasia but had progressed with multi-domain cognitive impairments (herein referred to as 'logopenic variant of primary progressive aphasia+'; = 8). People with typical amnestic Alzheimer's disease ( = 9) were relatively preserved across verbal and non-verbal semantic assessments. Logopenic variant of primary progressive aphasia patients were impaired on both verbal and non-verbal semantic tasks and their impairments showed the hallmark characteristics of a semantic control deficit. Logopenic variant of primary progressive aphasia and logopenic variant of primary progressive aphasia + patients showed effects of varying semantic control demands, positive cueing effects, and correlated performance between semantic and executive tasks. Whole-brain voxel-based morphometry, comparing each of the patient groups to age-matched controls, revealed significantly reduced grey and white matter in the bilateral hippocampi and lateral temporal regions in typical Alzheimer's disease patients. The logopenic variant of primary progressive aphasia group exhibited an asymmetric pattern of reduced grey and white matter intensity in the language-dominant left hemisphere, including a significant portion of the lateral and medial temporal lobe. Logopenic variant of primary progressive aphasia + patients demonstrated reduced grey and white matter in the left temporal lobe extending sub-cortically, anteriorly and posteriorly, as well as right temporal involvement. Our findings could aid diagnostic sub-typing of primary progressive aphasia by adopting semantic control features and offer improved clinical characterization of logopenic variant of primary progressive aphasia in the trajectory of semantic decline.
我们研究了原发性进行性失语的言语流畅性变异型中的语义认知,包括:(i)言语和非言语语义表现的状况;以及(ii)语义缺陷是否反映了语义控制受损。我们的假设是,原发性进行性失语的言语流畅性变异型个体将表现出语义控制受损,这是由通常与原发性进行性失语的言语流畅性变异型相关的颞顶叶萎缩与中风后语义性失语和韦尼克失语相关的病变之间的解剖学重叠所驱动的,而后两者会导致异模态语义控制受损。我们探讨了原发性进行性失语的言语流畅性变异型中语义缺陷的存在、类型(语义表征和语义控制;言语和非言语)以及进展情况。由于大多数原发性进行性失语的言语流畅性变异型患者具有阿尔茨海默病病理特征,并且是包含阿尔茨海默病亚型的更广泛多维表型空间的一部分,我们比较了原发性进行性失语的言语流畅性变异型和典型遗忘型阿尔茨海默病的语义表现。鉴于语义性失语和韦尼克失语与语义性痴呆/语义变异型原发性进行性失语患者在病变和萎缩模式上的差异,我们的第二个目标是检查原发性进行性失语的言语流畅性变异型患者和典型阿尔茨海默病患者与年龄匹配对照组相比的萎缩模式。27名患者参与了该研究。人们被分为符合原发性进行性失语的言语流畅性变异型共识标准的患者(n = 10)和其他可能先前满足原发性进行性失语的言语流畅性变异型定义但已进展为多领域认知障碍的患者(在此称为“原发性进行性失语的言语流畅性变异型+”;n = 8)。典型遗忘型阿尔茨海默病患者(n = 9)在言语和非言语语义评估中相对保留。原发性进行性失语的言语流畅性变异型患者在言语和非言语语义任务上均受损,且其损伤表现出语义控制缺陷的标志性特征。原发性进行性失语的言语流畅性变异型和原发性进行性失语的言语流畅性变异型+患者表现出不同语义控制需求的影响、积极提示效应以及语义和执行任务之间的相关表现。基于体素的全脑形态测量,将每个患者组与年龄匹配的对照组进行比较,发现典型阿尔茨海默病患者双侧海马体和外侧颞叶的灰质和白质显著减少。原发性进行性失语的言语流畅性变异型组在语言优势半球左半球表现出灰质和白质强度降低的不对称模式,包括外侧和内侧颞叶的很大一部分。原发性进行性失语的言语流畅性变异型+患者表现出左颞叶灰质和白质减少,延伸至皮质下、前部和后部,以及右侧颞叶受累。我们的研究结果可通过采用语义控制特征辅助原发性进行性失语的诊断亚型划分,并在语义衰退轨迹中提供对原发性进行性失语的言语流畅性变异型更好的临床特征描述。