Primary Non-fluent Aphasia Research Articles

Longitudinal volumetric changes in amygdala subregions in frontotemporal dementia.

Amygdala atrophy has been found in frontotemporal dementia (FTD), yet the specific changes of its subregions across different FTD phenotypes remain unclear. The aim of this study was to investigate the volumetric alterations of the amygdala subregions in FTD phenotypes and how they evolve with disease progression. Patients clinically diagnosed with behavioral variant FTD (bvFTD) (n = 20), semantic dementia (SD) (n = 20), primary nonfluent aphasia (PNFA) (n = 20), Alzheimer's disease (AD) (n = 20), and 20 matched healthy controls underwent whole brain structural MRI. The patient groups were followed up annually for up to 3.5years. Amygdala nuclei were segmented using FreeSurfer, corrected by total intracranial volumes, and grouped into the basolateral, superficial, and centromedial subregions. Linear mixed effects models were applied to identify changes in amygdala subregional volumes over time. At baseline, bvFTD, SD, and AD displayed global amygdala volume reduction, whereas amygdala volume appeared to be preserved in PNFA. Asymmetrical amygdala atrophy (left > right) was most pronounced in SD. Longitudinally, SD and PNFA showed greater rates of annual decline in the right basolateral and superficial subregions compared to bvFTD and AD. The findings provide comprehensive insights into the differential impact of FTD pathology on amygdala subregions, revealing distinct atrophy patterns that evolve over disease progression. The characterization of amygdala subregional involvement in FTD and their potential role as biomarkers carry substantial clinical implications.

Contrasting longitudinal changes in amygdala integrity in early Alzheimer’s disease and frontotemporal dementia subtypes

AbstractBackgroundThe amygdala is a complex and heavily connected subcortical brain structure. It plays a central role in regulating social, emotional and cognitive processes. Amygdala atrophy has been previously reported in Alzheimer’s disease (AD) and in frontotemporal dementia (FTD), although the findings are inconsistent. In addition, the trajectories of atrophy progression over time are unclear. The aim of this study was to determine the structural changes of the amygdala in early AD and FTD and map their changes over time.MethodPatients clinically diagnosed with amnestic AD (n = 20) or with FTD (behavioural variant FTD (bvFTD) = 20; semantic dementia (SD) = 20, primary nonfluent aphasia (PNFA) = 20), and 20 matched healthy controls (HC) completed whole brain structural MRI annually across multiple time points. Automated regional parcellation of the amygdala into three subregions was performed with FreeSurfer 7.1.1 using the T1‐weighted images. Linear mixed effects models were applied to identify changes in amygdala volumes over time.ResultAt baseline, bvFTD, SD and AD, but not PNFA, displayed significant overall amygdala volume loss compared with HC. Atrophy was most severe and asymmetrical (Left > Right) in SD. No subregional differences emerged across the clinical groups. Longitudinal analyses revealed a significantly greater amygdalar atrophy rate overall in all patient groups compared with HC. The greatest volume reduction was found in the right amygdala, which was significantly most pronounced in SD, across all subregions. In contrast, only the AD and PNFA groups showed a significant change over time in the left amygdala.ConclusionThese findings identified global amygdala changes in AD and FTD. Importantly, these changes have a different time and location signature depending on the disease. In FTD, they occur early and more severely in SD and bvFTD, but later in PNFA. In AD, atrophy seems to take a more protracted course. In all groups, the right amygdala was affected later than the left. These findings have implications for the diagnosis and monitoring of these dementias. Future analyses will examine the relations of these alterations in amygdala integrity with social cognition and emotion regulation, functions known to be variably compromised in AD and FTD.

Ventricular features as reliable differentiators between bvFTD and other dementias

IntroductionLateral ventricles are reliable and sensitive indicators of brain atrophy and disease progression in behavioral variant frontotemporal dementia (bvFTD). We aimed to investigate whether an automated tool using ventricular features could improve diagnostic accuracy in bvFTD across neurodegenerative diseases. MethodsUsing 678 subjects −69 bvFTD, 38 semantic variant, 37 primary non-fluent aphasia, 218 amyloid + mild cognitive impairment, 74 amyloid + Alzheimer’s Dementia and 242 normal controls- with a total of 2750 timepoints, lateral ventricles were segmented and differences in ventricular features were assessed between bvFTD, normal controls and other dementia cohorts. ResultsVentricular antero-posterior ratio (APR) was the only feature that was significantly different and increased faster in bvFTD compared to all other cohorts. We achieved a 10-fold cross-validation accuracy of 80% (77% sensitivity, 82% specificity) in differentiating bvFTD from all other cohorts with other ventricular features (i.e., total ventricular volume and left–right lateral ventricle ratios), and 76% accuracy using only the single APR feature. DiscussionVentricular features, particularly the APR, might be reliable and easy-to-implement markers for bvFTD diagnosis. We have made our ventricle feature estimation and bvFTD diagnostic tool publicly available, allowing application of our model in other studies.

Reader response: The underacknowledged PPA-ALS: A unique clinicopathologic subtype with strong heritability.

In their article, Tan et al.1 highlighted the association between primary nonfluent aphasia (nfvPPA), the semantic subtype of primary progresssive aphasia (PPA), and amyotrophic lateral sclerosis (ALS), which may also be hereditary.

Adaptation and validation of the Cantonese Sydney Language Battery for assessment of language deficits in patients with primary progressive aphasia in Hong Kong

Adaptation and validation of the Cantonese Sydney Language Battery for assessment of language deficits in patients with primary progressive aphasia in Hong Kong

Odor identification in frontotemporal lobar degeneration subtypes.

Odor identification impairment is a feature of several neurodegenerative disorders. Although neurodegenerative changes in the frontotemporal lobar degeneration (FTLD) subtypes involve areas important for olfactory processing, data on olfactory function in these patients are limited. An 18-item, multiple-choice odor identification test developed at our memory clinic, the Motol Hospital smell test, was administered to 9 patients with behavioral variant frontotemporal dementia, 13 patients with the language variants, primary nonfluent aphasia (n = 7) and semantic dementia (n = 6), and 8 patients with progressive supranuclear palsy. Compared to the control group (n = 15), all FTLD subgroups showed significant impairment of odor identification (P < .05). The differences between the FTLD subgroups were not significant. No correlation between odor identification and neuropsychological tests results was found. Our data suggest that odor identification impairment is a symptom common to FTLD syndromes, and it seems to be based on olfactory structure damage rather than cognitive decline.

Clinical phenotypes and genetic biomarkers of FTLD

Frontotemporal lobar degeneration (FTLD) is the most frequent neurodegenerative disorder with a presenile onset. It presents with a spectrum of clinical manifestations, ranging from behavioural and executive impairment to language disorders and motor dysfunction. New diagnostic criteria identified two main cognitive syndromes: behavioural variant frontotemporal dementia (bvFTD) and primary progressive aphasia (PPA). Regarding bvFTD, new criteria that include the use of biomarkers have been proposed. According to them, bvFTD can be classified in "possible" (clinical features only), "probable" (inclusion of imaging biomarkers) and "definite" (in the presence o f a known causal mutation or at autopsy). Concerning autosomal dominant mutations, microtubule associated protein tau gene mutations have been the first ones identified and are generally associated with early onset bvFTD phenotype. More recently, progranulin gene mutations were recognized in association with familial form of FTLD. In addition, other genes are linked to rare cases of familial FTLD, primarily the newly discovered C9ORF72 hexanucleotide expansion repeats. As regards PPA, new consensus criteria identify three syndromes: primary non-fluent aphasia, semantic variant of PPA and logopenic aphasia, which seems to be associated, in the majority of cases, with underlying Alzheimer's disease pathology. In this review, new criteria, including MRI, cerebrospinal fluid and genetic biomarkers, will be presented and discussed.

Primary Progressive Non-Fluent Aphasia: A Case Study

A case study of a 65 year old man is described with an eight-year history of progressive primary non-fluent aphasia accompanied by agrammatism, phonemic paraphasias and mild spelling dysgraphia.His naming ability, however, has remained at an exceptionally high level and there has been no evidence of impairment of word or sentence comprehension. Non-verbal skills and memory functions have also been preserved within the range of his very high premorbid level of abilities.Single photon emission computed tomography was consistent with bifrontal hypoperfusion.We argue that the selective language deficits in this patient are characteristic of dynamic aphasia and of other speech disturbances which are also known to be associated with left frontal lesions. The possible underlying pathology is discussed in the context of known degenerative disorders.