Clinical, anatomical and pathological features in the three variants of primary progressive aphasia : a review

Primary progressive aphasias (PPA) are neurodegenerative diseases clinically characterized by an early and relatively isolated language impairment. Three main clinical variants, namely the nonfluent/agrammatic variant (nfvPPA), the semantic variant (svPPA), and the logopenic variant (lvPPA) have been described, each with specific linguistic/cognitive deficits, corresponding anatomical and most probable pathological features. Since the discovery and the development of diagnostic criteria for the PPA variants by the experts in the field, significant progress has been made in the understanding of these diseases. This review aims to provide an overview of the literature on each of the PPA variant in terms of their clinical, anatomical and pathological features, with a specific focus on recent findings. In terms of clinical advancements, recent studies have allowed a better characterization and differentiation of PPA patients based on both their linguistic and non-linguistic profiles. In terms of neuroimaging, techniques such as diffusion imaging and resting-state fMRI have allowed a deeper understanding of the impact of PPA on structural and functional connectivity alterations beyond the well-defined pattern of regional gray matter atrophy. Finally, in terms of pathology, despite significant advances, clinico-pathological correspondence in PPA remains far from absolute. Nonetheless, the improved characterization of PPA has the potential to have a positive impact on the management of patients. Improved reliability of diagnoses and the development of reliable in vivo biomarkers for underlying neuropathology will also be increasingly important in the future as trials for etiology-specific treatments become available

Atrophy in Alzheimer’s disease and semantic dementia : an ALE meta-analysis of voxel-based morphometry studies

Background/Objectives: Alzheimer’s disease (AD) and semantic dementia (SD) have distinct episodic memory profiles despite the hippocampal atrophy that characterizes both diseases. The aim of this study was to delineate the pattern of gray matter (GM) atrophy associated with AD and SD as well as any differences in these patterns by pooling together the results of previous voxel-based morphometry (VBM) studies. Methods/Overview: We conducted a meta-analysis of VBM studies that investigated GM atrophy in AD patients versus controls (CTRLs) and in SD patients versus CTRLs using the activation likelihood estimation (ALE) approach. Our systematic review allowed us to identify 63 VBM studies. Results: The results confirmed that in addition to the classical cortical pattern of atrophy involving posterior medial and lateral regions in AD and the anterior lateral temporal lobes in SD, both AD and SD patients are characterized by bilateral atrophy of the hippocampus. Furthermore, in SD, the hippocampal atrophy was limited to the anterior portion of the hippocampus, while in AD, both the anterior and posterior parts of the hippocampus exhibited atrophy. When we compared the foci identified in the studies that compared AD patients versus CTRLs with those identified in the studies that compared SD patients versus CTRLs, we observed that the atrophy in the posterior hippocampus and precuneus was more severe in AD. Conclusion: These results support theories that propose that the deficits observed in AD result from damage to the episodic memory network, which involves the posterior hippocampus and posterior medial brain regions. However, sparing of the posterior hippocampus in SD could explain the absence of episodic memory deficits in this population

The neural correlates of verbal and nonverbal semantic processing deficits in neurodegenerative disease

Objective—To investigate the neural correlates of verbal and non-verbal semantic processing in neurodegenerative disease. Background—Semantic memory is often impaired in neurodegenerative disease. Neuropsychological and functional neuroimaging studies suggest that the semantic processing of verbal and non-verbal stimuli may depend on partially distinct brain networks. Methods—We examined this possibility using voxel-based morphometry to correlate performance on verbal and non-verbal versions of a semantic association task with regional gray matter atrophy in 144 individuals with a variety of neurodegenerative diseases. Results—Results showed that, regardless of stimulus type, semantic processing correlated with atrophy in both temporal lobes. In addition, material-specific correlations were found in left temporal regions for verbal stimuli and the right fusiform gyrus for non-verbal stimuli. Conclusions—These results provide evidence for a differential role of the left and right hemispheres in the extraction of semantic information from verbal and pictorial representations. Areas in the right inferior temporal lobe may be necessary to access structural descriptions of visually presented object

Connected speech features from picture description in Alzheimer's disease: a systematic review

The language changes that occur over the course of Alzheimer’s disease (AD) can impact communication abilities and have profound functional consequences. Picture description tasks can be used to approximate everyday communication abilities of AD patients. As various methods and variables have been studied over the years, current knowledge about the most affected features of AD discourse in the context of picture descriptions is difficult to summarize. This systematic review aims to provide researchers with an overview of the most common areas of impairment in AD discourse as they appear in picture description tasks. Based on the 44 articles fulfilling inclusion criteria, our findings reflect a multidimensional pattern of changes in the production (speech rate), syntactic (length of utterance), lexical (word-frequency and use of pronouns), fluency (repetitions and word-finding difficulties), semantic (information units), and discourse (efficiency) domains. We discuss our findings in the light of current research and point to potential scientific and clinical uses of picture description tasks in the context of AD

Task-induced functional connectivity of picture naming in healthy aging : the impacts of age and task complexity

The topological organization of the brain, governed by the capacity of brain regions to synchronize their activity, allows for cost-effective performance during everyday cognitive activity. Functional connectivity is an fMRI method deemed task-specific and demand-dependent. Although the brain undergoes significant changes during healthy aging, conceptual knowledge and word-production accuracy are generally preserved. The exploration of task-induced functional connectivity patterns during active picture naming may thus provide additional information about healthy functional cerebral mechanisms that are specifically adapted to the cognitive activity at hand. The goal of this study is to assess and describe age-related differences in functional connectivity during an overt picture-naming task, as well as to compare age-related differences under complex task demand, defined by lexical frequency. Results suggest both age-specific and task-specific mechanisms. In the context of preserved behavioral performance in a picture-naming task, older adults show a complex array of differences in functional connectivity architecture, including both increases and decreases. In brief, there is increased segregation and specialization of regions that are classically assigned to naming processes. Results also expand on previous word-production studies and suggest that motor regions are particularly subject to age-related differences. This study also provides the first indication that intrinsic task demand, as manipulated by lexical frequency, interacts little with the relationship between age and functional connectivity. Together, these findings confirm the value of task-induced functional connectivity analysis in revealing the brain organization that subserves task performance during healthy aging

Aging and language : maintenance of morphological representations in older adults

Studies employing primed lexical decision tasks have revealed morphological facilitation effects in children and young adults. It is unknown if this effect is preserved or diminished in older adults. In fact, only few studies have investigated age-related changes in morphological processing and results are inconsistent across studies. To address this issue, we investigated inflection morphology compared to orthographic and semantic processing in young and older adults. Twenty-six adults aged 60–85 and 22 younger adults aged 19–28 participated. We probed verb recognition using a sandwich-masked primed lexical decision paradigm. We investigated lexical decision using different prime presentation times (PPTs) (33, 66, and 150 ms), and prime types with priming conditions involving orthographic (e.g., cassis—CASSE ‘blackcurrant—break’), regular inflection morphological (cassait—CASSE ‘broke—break’), and semantic primes (brise—CASSE ‘break—break’) and their controls, while measuring response accuracy and reaction times. Response accuracy analyses revealed that older participants performed at ceiling on the lexical decision task, and that accuracy levels were higher compared to young adults. Reaction-time data revealed effects of age group, priming condition, and an interaction of age group and morphological priming, but no PPT effects. Both young and older adults presented a significant facilitation effect (reduced reaction times) in the orthographic and morphological priming conditions. No semantic effects were observed in either group. Younger adults also showed a significantly stronger morphological priming effect, while older adults showed no difference between orthographic and morphological priming when comparing priming magnitudes. These findings suggest (1) that regular inflectional morphological processing benefits lexical access in younger French adults, confirming studies in other languages, and (2) that this advantage is reduced at older ages

Single and Multiple Domain Amnestic MCI: two sides of the same coin?

Background. Amnestic Mild Cognitive Impairment (aMCI) is considered a transition stage between normal aging and Alzheimer's disease (AD). Two main clinical subtypes of aMCI have been identified: 1) aMCI single domain (aMCI-SD), with isolated episodic memory impairments, and 2) aMCI multiple domain (aMCI-MD), with episodic memory impairments and deficits in one or more other cognitive domains. Aims.To map the pattern of gray matter (GM) atrophy associated with aMCI-SD, aMCIMD and mild AD. Methods. A group of aMCI-SD, aMCI-MD characterized by executive function disorders, mild AD patients and cognitively unimpaired age-matched subjects underwent a comprehensive neuropsychological assessment and a high-definition MR brain scan. Voxel-based morphometry (VBM) analysis was used to characterize the GM tissue loss in each patient group, and the common pattern of GM atrophy in aMCI-SD and aMCIMD. Results. The results revealed that aMCI-SD and aMCI-MD are characterized by a common pattern of GM atrophy within the medial temporal cortex, predisposing to AD and correlating with the severity of verbal memory symptoms. Moreover, the pattern of GM atrophy observed in aMCI-SD, aMCI-MD and mild AD revealed that, from an anatomical point of view, these three clinical syndromes could represent three severity points along the continuum between normal aging and AD

Treatment-induced neuroplasticity after anomia therapy in post-stroke aphasia : a systematic review of neuroimaging studies

We systematically reviewed the literature on neural changes following anomia treatment post-stroke. We conducted electronic searches of CINAHL, Cochrane Trials, Embase, Ovid MEDLINE, MEDLINE-in-Process and PsycINFO databases; two independent raters assessed all abstracts and full texts. Accepted studies reported original data on adults with post-stroke aphasia, who received behavioural treatment for anomia, and magnetic resonance brain imaging (MRI) pre- and post-treatment. Search results yielded 2481 citations; 33 studies were accepted. Most studies employed functional MRI and the quality of reporting neuroimaging methodology was variable, particularly for pre-processing steps and statistical analyses. The most methodologically robust data were synthesized, focusing on pre- versus post-treatment contrasts. Studies more commonly reported increases (versus decreases) in activation following naming therapy, primarily in the left supramarginal gyrus, and left/bilateral precunei. Our findings highlight the methodological heterogeneity across MRI studies, and the paucity of robust evidence demonstrating direct links between brain and behaviour in anomia rehabilitation

Visual and auditory perceptual strength norms for 3,596 French nouns and their relationship with other psycholinguistic variables

Perceptual experience plays a critical role in the conceptual representation of words. Higher levels of semantic variables such as imageability, concreteness, and sensory experience are generally associated with faster and more accurate word processing. Nevertheless, these variables tend to be assessed mostly on the basis of visual experience. This underestimates the potential contributions of other perceptual modalities. Accordingly, recent evidence has stressed the importance of providing modality-specific perceptual strength norms. In the present study, we developed French Canadian norms of visual and auditory perceptual strength (i.e., the modalities that have major impact on word processing) for 3,596 nouns. We then explored the relationship between these newly developed variables and other lexical, orthographic, and semantic variables. Finally, we demonstrated the contributions of visual and auditory perceptual strength ratings to visual word processing beyond those of other semantic variables related to perceptual experience (e.g., concreteness, imageability, and sensory experience ratings). The ratings developed in this study are a meaningful contribution toward the implementation of new studies that will shed further light on the interaction between linguistic, semantic, and perceptual systems

Differential involvement of the anterior temporal lobes in famous people semantics

The ability to recognize a famous person occurs through semantic memory. Previous neuroimaging studies have shown that the anterior temporal lobes (ATLs) are involved in the recognition of famous people. However, it is still a matter of debate whether the semantic processing of names or pictures of famous people has an impact on the activation of ATLs. The aim of this study was to explore the pattern of activation associated with a semantic processing of famous people based on face and written name stimuli. Fifteen healthy young individuals participated in our fMRI study, in which they were asked to perform a semantic categorization judgment task, based on profession, of visually presented pictures, and names of famous people. Neuroimaging findings showed a common pattern of activation for faces and names mainly involving the inferior frontal regions, the posterior temporal lobe, the visual cortex, and the ATLs. We found that the comparison names vs. pictures lead to significant activation in the anterior superior temporal gyrus. On the other hand, faces vs. names seemed associated with increased activation in the medial ATL. Moreover, our results demonstrated that the functional connectivity network anchored to the medial ATL, compared to the anterior STG, is more connected to the bilateral occipital lobe and fusiform gyrus that are regions implicated in the visual system and visual processing of faces. This study provides critical evidence of the differential involvement of ATL regions in semantics of famous people