MNI-FTD templates, unbiased average templates of frontotemporal dementia variants.
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ABSTRACT:
SUBMITTER: Dadar M
PROVIDER: S-EPMC8385071 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Purpose'Phenocopy' frontotemporal dementia (phFTD) patients may clinically mimic the behavioral variant of FTD (bvFTD), but do not show functional decline or abnormalities upon visual inspection of routine neuroimaging. We aimed to identify abnormalities in gray matter (GM) volume and perfusion in phFTD and to assess whether phFTD belongs to the FTD spectrum. We compared phFTD patients with both healthy controls and bvFTD patients.Materials & methodsSeven phFTD and 11 bvFTD patients, and 20 age-matched controls underwent structural T1-weighted magnetic resonance imaging (MRI) and 3D pseudo-continuous arterial spin labeling (pCASL) at 3T. Normalized GM (nGM) volumes and perfusion, corrected for partial volume effects, were quantified regionally as well as in the entire supratentorial cortex, and compared between groups taking into account potential confounding effects of gender and scanner.ResultsPhFTD patients showed cortical atrophy, most prominently in the right temporal lobe. Apart from this regional atrophy, GM volume was generally not different from either controls or from bvFTD. BvFTD however showed extensive frontotemporal atrophy. Perfusion was increased in the left prefrontal cortex compared to bvFTD and to a lesser extent to controls.ConclusionPhFTD and bvFTD show overlapping cortical structural abnormalities indicating a continuum of changes especially in the frontotemporal regions. Together with functional changes suggestive of a compensatory response to incipient pathology in the left prefrontal regions, these findings are the first to support a possible neuropathological etiology of phFTD and suggest that phFTD may be a neurodegenerative disease on the FTD spectrum.
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Project description:Parkinson's disease (PD) is a complex neurodegenerative disorder affecting regions such as the substantia nigra (SN), red nucleus (RN) and locus coeruleus (LC). Processing MRI data from patients with PD requires anatomical structural references for spatial normalization and structural segmentation. Extending our previous work, we present multi-contrast unbiased MRI templates using nine 3T MRI modalities: T1w, T2*w, T1-T2* fusion, R2*, T2w, PDw, fluid-attenuated inversion recovery (FLAIR), susceptibility-weighted imaging, and neuromelanin-sensitive MRI (NM). One mm isotropic voxel size templates were created, along with 0.5 mm isotropic whole brain templates and 0.3 mm isotropic templates of the midbrain. All templates were created from 126 PD patients (44 female; ages=40–87), and 17 healthy controls (13 female; ages=39–84), except the NM template, which was created from 85 PD patients and 13 controls, respectively. The dataset is available on the NIST MNI Repository via the following link: http://nist.mni.mcgill.ca/multi-contrast-pd126-and-ctrl17-templates/. The data is also available on NITRC at the following link: https://www.nitrc.org/projects/pd126/.
| S-EPMC10197003 | biostudies-literature
Project description:Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disorder of motor neurons in adults, with a median survival of 3-5 years after appearance of symptoms, and with no curative treatment currently available. Frontotemporal dementia (FTD) is also an adult-onset neurodegenerative disease, displaying not only clinical overlap with ALS, but also significant similarities at genetic and pathologic levels. Apart from the progressive loss of neurons and the accumulation of protein inclusions in certain cells and tissues, both disorders are characterized by chronic inflammation mediated by activated microglia and astrocytes, with an early and critical impact of neurodegeneration along the disease course. Despite the progress made in the last two decades in our knowledge around these disorders, the underlying molecular mechanisms of such non-cell autonomous neuronal loss still need to be clarified. In particular, immune signaling kinases are currently thought to have a key role in determining the neuroprotective or neurodegenerative nature of the central and peripheral immune states in health and disease. This review provides a comprehensive and updated view of the proposed mechanisms, therapeutic potential, and ongoing clinical trials of immune-related kinases that have been linked to ALS and/or FTD, by covering the more established TBK1, RIPK1/3, RACK I, and EPHA4 kinases, as well as other emerging players in ALS and FTD immune signaling.
| S-EPMC8707599 | biostudies-literature
Project description:The non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) and semantic variant (svPPA) of frontotemporal dementia (FTD) are neurodegenerative diseases. Previous works have shown alterations of fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor images (DTIs). This manuscript is aimed at using DTI images to build a global tractography and to identify atrophy patterns of white matter in each variant. Twenty patients with svPPA, 20 patients with nfvPPA, 26 patients with behavioral variant of FTD (bvFTD) and, 33 controls were included. An analysis based on the connectivity of structural networks showed changes in FA and MD in svPPA and nfvPPA with respect to bvFTD. Much damage in the internal networks of the left temporal lobe was found in svPPA patients; in contrast, patients with nfvPPA showed atrophy in networks from the basal ganglia to motor and premotor areas. Those findings support the dual stream model of speech and language.
| S-EPMC6716200 | biostudies-literature
Project description:Most neuropsychiatric symptoms (NPS) common in frontotemporal dementia (FTD) are currently not part of the Neuropsychiatric Inventory (NPI). We piloted an FTD Module that included eight extra items to be used in conjunction with the NPI. Caregivers of patients with behavioural variant FTD (n = 49), primary progressive aphasia (PPA; n = 52), Alzheimer's dementia (AD; n = 41), psychiatric disorders (n = 18), presymptomatic mutation carriers (n = 58) and controls (n = 58) completed the NPI and FTD Module. We investigated (concurrent and construct) validity, factor structure and internal consistency of the NPI and FTD Module. We performed group comparisons on item prevalence, mean item and total NPI and NPI with FTD Module scores, and multinomial logistic regression to determine its classification abilities. We extracted four components, together explaining 64.1% of the total variance, of which the largest indicated the underlying dimension 'frontal-behavioural symptoms'. Whilst apathy (original NPI) occurred most frequently in AD, logopenic and non-fluent variant PPA, the most common NPS in behavioural variant FTD and semantic variant PPA were loss of sympathy/empathy and poor response to social/emotional cues (part of FTD Module). Patients with primary psychiatric disorders and behavioural variant FTD showed the most severe behavioural problems on both the NPI as well as the NPI with FTD Module. The NPI with FTD Module correctly classified more FTD patients than the NPI alone. By quantifying common NPS in FTD the NPI with FTD Module has large diagnostic potential. Future studies should investigate whether it can also prove a useful addition to the NPI in therapeutic trials.
| S-EPMC10129920 | biostudies-literature
Project description:IntroductionFrontotemporal dementia (FTD) is considered to be part of a continuum with amyotrophic lateral sclerosis (ALS). Many genes are associated with both ALS and FTD. Yet, many genes associated with ALS have not been shown to cause FTD. We aimed to study a Portuguese cohort of FTD patients, searching for variants in genes associated with both FTD and/or ALS.MethodsWe included 57 thoroughly characterized index FTD patients from our memory clinic, who were not carriers of pathogenic variants in GRN, MAPT or C9orf72. We performed exome sequencing and 1) prioritized potential FTD and ALS causing variants by using Exomiser to annotate and filter results; and 2) looked specifically at rare variability in genes associated with FTD (excluding GRN, MAPT and C9ORF72) and/or ALS.ResultsWe identified 13 rare missense variants in 10 patients (three patients had two variants) in the following genes: FUS, OPTN, CCNF, DCTN1, TREM2, ERBB4, ANG, CHRNA4, CHRNB4 and SETX. We found an additional frameshift variant on GLT8D1 in one patient. One variant (ERBB4 p.Arg1112His) gathered enough evidence to be classified as likely pathogenic by the ACMG criteria.DiscussionWe report, for the first time, an expanded study of genes known to cause FTD-ALS, in the Portuguese population. Potentially pathogenic variants in ERBB4, FUS, SETX, ANG, CHRNA4 and CHRNB4 were identified in FTD patients. These findings provide additional evidence for the potential role of rare variability in ALS-associated genes in FTD, expanding the genetic spectrum between the two diseases.
| S-EPMC9300853 | biostudies-literature
Project description:(1) Background: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders with an overlap in clinical presentation and neuropathology. Common and differential mechanisms leading to protein expression changes and neurodegeneration in ALS and FTD were studied trough a deep neuroproteome mapping of the spinal cord. (2) Methods: A liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of the spinal cord from ALS-TAR DNA-binding protein 43 (TDP-43) subjects, ubiquitin-positive frontotemporal lobar degeneration (FTLD-U) subjects and controls without neurodegenerative disease was performed. (3) Results: 281 differentially expressed proteins were detected among ALS versus controls, while 52 proteins were dysregulated among FTLD-U versus controls. Thirty-three differential proteins were shared between both syndromes. The resulting data was subjected to network-driven proteomics analysis, revealing mitochondrial dysfunction and metabolic impairment, both for ALS and FTLD-U that could be validated through the confirmation of expression levels changes of the Prohibitin (PHB) complex. (4) Conclusions: ALS-TDP-43 and FTLD-U share molecular and functional alterations, although part of the proteostatic impairment is region- and disease-specific. We have confirmed the involvement of specific proteins previously associated with ALS (Galectin 2 (LGALS3), Transthyretin (TTR), Protein S100-A6 (S100A6), and Protein S100-A11 (S100A11)) and have shown the involvement of proteins not previously described in the ALS context (Methanethiol oxidase (SELENBP1), Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN-1), Calcyclin-binding protein (CACYBP) and Rho-associated protein kinase 2 (ROCK2)).
| S-EPMC6337647 | biostudies-literature
Project description:Progranulin (GRN) mutations are a major cause of frontotemporal dementia (FTD); the spectrum of clinical phenotypes of FTD is much more extensive than previously reported. The frequency and locations of GRN mutations in Chinese patients with FTD remain uncertain. We performed cDNA sequencing in one sporadic male patient who initially presented FTD symptoms. Brain magnetic resonance imaging (MRI) and positron emission computed tomography/computed tomography (PET/CT) were applied to further confirm the diagnosis of FTD from this patient. Cellular apoptosis and survival test were performed to identify the function of GRN. We identified one novel missense GRN mutation (c.1498G>A, p.V500I) in this patient, who initially presented typical behavioral-variant frontotemporal dementia (bvFTD) features but then presented progressive supranuclear palsy (PSP) clinical characteristics 5 years after onset. Besides, WT GRN protein showed an adequate trophic stimulus to preserve the survival of SH-SY5Y cells in the medium free of serum, while GRN mutation (c.1498G>A, p.V500I) may impair the ability of supporting cell survival. This study owns significant implications for genetic counseling and clinical heterogeneity. We illustrate the fact that FTD presenting features of bvFTD and PSP in one patient could be considered as a specific phenotype in patients with GRN mutations. GRN p.V500I led to the neuronal degeneration in vitro; this finding provides a significant evidence that this mutation may be a new causative mutation in patients with FTD.
| S-EPMC8460311 | biostudies-literature
Project description:IntroductionTrials to test disease-modifying treatments for frontotemporal dementia are eagerly awaited and sensitive instruments to assess potential treatment effects are increasingly urgent, yet lacking thus far. We aimed to identify gene-specific instruments assessing clinical onset and disease progression by comparing cognitive functioning between bvFTD patients across genetic mutations.MethodsWe examined differences in 7 cognitive domains between bvFTD patients with GRN (n = 20), MAPT (n = 29) or C9orf72 (n = 31) mutations, and non-carriers (n = 24), and described longitudinal (M = 22.6 months, SD = 16.6) data in a subsample (n = 27).ResultsPatients showed overall cognitive impairment, except memory recall, working memory and visuoconstruction. GRN patients performed lower on executive function (mean difference - 2.1; 95%CI - 4.1 to - 0.5) compared to MAPT and lower on attention compared to MAPT (mean difference - 2.5; 95%CI - 4.7 to - 0.3) and C9orf72 (mean difference - 2.4; 95%CI - 4.5 to - 0.3). Only MAPT patients were impaired on delayed recall (mean difference - 1.4; 95%CI - 2.1 to - 0.7). GRN patients declined rapidly on attention and memory, MAPT declined in confrontation naming, whereas C9orf72 patients were globally impaired but remained relatively stable over time on all cognitive domains.DiscussionThis study shows gene-specific cognitive profiles in bvFTD, which underlines the value of neuropsychological tests as outcome measures in upcoming trials for genetic bvFTD.
| S-EPMC7293665 | biostudies-literature
Project description:Semantic (svPPA) and nonfluent (nfvPPA) variants of primary progressive aphasia (PPA) have recently been associated with distinct patterns of white matter and functional network alterations in left frontoinsular and anterior temporal regions, respectively. Little information exists, however, about the topological characteristics of gray matter covariance networks in these two PPA variants. In the present study, we used a graph theory approach to describe the structural covariance network organization in 34 patients with svPPA, 34 patients with nfvPPA and 110 healthy controls. All participants underwent a 3 T structural MRI. Next, we used cortical thickness values and subcortical volumes to define subject-specific connectivity networks. Patients with svPPA and nfvPPA were characterized by higher values of normalized characteristic path length compared with controls. Moreover, svPPA patients had lower values of normalized clustering coefficient relative to healthy controls. At a regional level, patients with svPPA showed a reduced connectivity and impaired information processing in temporal and limbic brain areas relative to controls and nfvPPA patients. By contrast, local network changes in patients with nfvPPA were focused on frontal brain regions such as the pars opercularis and the middle frontal cortex. Of note, a predominance of local metric changes was observed in the left hemisphere in both nfvPPA and svPPA brain networks. Taken together, these findings provide new evidences of a suboptimal topological organization of the structural covariance networks in svPPA and nfvPPA patients. Moreover, we further confirm that distinct patterns of structural network alterations are related to neurodegenerative mechanisms underlying each PPA variant.
| S-EPMC9107413 | biostudies-literature