Clinical and cortical trajectories in non-fluent primary progressive aphasia and Alzheimer's disease: A role for emotion processing.

Objectives: To examine the clinical trajectories and neural correlates of cognitive and emotion processing changes in the non-fluent/agrammatic (nfvPPA) and the logopenic (lvPPA) variants of primary progressive aphasia (PPA).

Design: Observational case-control longitudinal cohort study.

Setting: Research clinic of frontotemporal dementia.

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.

Rationale and Design of the "DIagnostic and Prognostic Precision Algorithm for behavioral variant Frontotemporal Dementia" (DIPPA-FTD) Study: A Study Aiming to Distinguish Early Stage Sporadic FTD from Late-Onset Primary Psychiatric Disorders.

Background: The behavioral variant of frontotemporal dementia (bvFTD) is very heterogeneous in pathology, genetics, and disease course. Unlike Alzheimer's disease, reliable biomarkers are lacking and sporadic bvFTD is often misdiagnosed as a primary psychiatric disorder (PPD) due to overlapping clinical features. Current efforts to characterize and improve diagnostics are centered on the minority of genetic cases.

Disrupted myelin lipid metabolism differentiates frontotemporal dementia caused by GRN and C9orf72 gene mutations.

Heterozygous mutations in the GRN gene and hexanucleotide repeat expansions in C9orf72 are the two most common genetic causes of Frontotemporal Dementia (FTD) with TDP-43 protein inclusions. The triggers for neurodegeneration in FTD with GRN (FTD-GRN) or C9orf72 (FTD-C9orf72) gene abnormalities are unknown, although evidence from mouse and cell culture models suggests that GRN mutations disrupt lysosomal lipid catabolism. To determine how brain lipid metabolism is affected in familial FTD with TDP-43 inclusions, and how this is related to myelin and lysosomal markers, we undertook comprehensive lipidomic analysis, enzyme activity assays, and western blotting on grey and white matter samples from the heavily-affected frontal lobe and less-affected parietal lobe of FTD-GRN cases, FTD-C9orf72 cases, and age-matched neurologically-normal controls.

Cerebellar integrity and contributions to cognition in C9orf72-mediated frontotemporal dementia.

Background: The GGGGCC hexanucleotide repeat expansion in the non-coding region of the chromosome 9 open reading frame 72 gene (C9orf72) is the most common genetic cause of familial frontotemporal dementia (FTD). This study aims to clarify the patterns of cerebellar atrophy in FTD patients with and without a C9orf72 repeat expansion compared with healthy controls and determine whether associations between cerebellar atrophy and cognition differ between patient groups.

Methods: Thirty C9orf72 repeat expansion-positive FTD patients, 30 C9orf72 repeat expansion-negative FTD patients, and 30 age-, sex-, and education-matched healthy controls underwent brain MRI and cognitive assessments.

Examining the presence and nature of delusions in Alzheimer's disease and frontotemporal dementia syndromes.

Objectives: Abnormal beliefs and delusions have been reported in some people with dementia, however, the prevalence of delusions, and their neurocognitive basis has been underexplored. This study aimed to examine the presence, severity, content and neural correlates of delusions in a large, well-characterised cohort of dementia patients using a transdiagnostic, cross-sectional approach.

Methods: Four-hundred and eighty-seven people with dementia were recruited: 102 Alzheimer's disease, 136 behavioural-variant frontotemporal dementia, 154 primary progressive aphasia, 29 motor neurone disease, 46 corticobasal syndrome, 20 progressive supranuclear palsy.

The effects of the COVID-19 pandemic on neuropsychiatric symptoms in dementia and carer mental health: an international multicentre study.

As a global health emergency, the rapid spread of the novel coronavirus disease (COVID-19) led to the implementation of widespread restrictions (e.g., quarantine, physical/social distancing measures).

Differences in Sex Distribution Between Genetic and Sporadic Frontotemporal Dementia.

Background: Reported sex distributions differ between frontotemporal dementia (FTD) cohorts. Possible explanations are the evolving clinical criteria of FTD and its subtypes and the discovery of FTD causal genetic mutations that has resulted in varying demographics.

Objective: Our aim was to determine the sex distribution of sporadic and genetic FTD cases and its subtypes in an international cohort.

Brain changes underlying progression of speech motor programming impairment.

Aquired apraxia of speech is a disorder that impairs speech production, despite intact peripheral neuromotor function. Its pathomechanism remains to be established. Neurodegenerative lesion models provide an unequalled opportunity to explore the neural correlates of apraxia of speech, which is present in a subset of patients diagnosed with non-semantic variants of primary progressive aphasia.

Qualitative Deficits in Verbal Fluency in Parkinson's Disease with Mild Cognitive Impairment: A Clinical and Neuroimaging Study.

Background: Mild cognitive impairment (MCI) in Parkinson's disease (PD) is considered a risk factor for PD with dementia (PDD). Verbal fluency tasks are widely used to assess executive function in PDD. However, in cases of PD with MCI (PD-MCI), the relative diagnostic accuracy of different qualitative verbal fluency measures and their related neural mechanisms remain unknown.

Neural correlates of disturbance in the sense of agency in schizophrenia: An fMRI study using the 'enfacement' paradigm.

An altered sense of self-awareness and agency has been proposed to underlie symptoms of schizophrenia. In this study, we used the enfacement illusion paradigm - in which perception of another person's face leads to changes in perception of one's own peri-personal space - to examine the brain correlates of the sense of agency and its potential disruption in schizophrenia. Thirty-three schizophrenic patients and 27 healthy controls underwent fMRI scanning during performance of a task designed to elicit the enfacement illusion.

Clinical and Biological Correlates of White Matter Hyperintensities in Patients With Behavioral-Variant Frontotemporal Dementia and Alzheimer Disease.

Objective: To test the hypothesis that white matter hyperintensities (WMH) in behavioral-variant frontotemporal dementia (bvFTD) and Alzheimer disease (AD) are associated with disease variables such as disease severity, cortical atrophy, and cognition, we conducted a cross-sectional brain MRI study with volumetric and voxel-wise analyses.

Methods: A total of 129 patients (64 bvFTD, 65 AD) and 66 controls underwent high-resolution brain MRI and clinical and neuropsychological examination. Genetic screening was conducted in 124 cases (54 bvFTD, 44 AD, 26 controls) and postmortem pathology was available in 18 cases (13 bvFTD, 5 AD).

Cerebellar contributions to cognition in corticobasal syndrome and progressive supranuclear palsy.

Mounting evidence suggests an association between cerebellar atrophy and cognitive impairment in the main frontotemporal dementia syndromes. In contrast, whether cerebellar atrophy is present in the motor syndromes associated with frontotemporal lobar degeneration (corticobasal syndrome and progressive supranuclear palsy) and the extent of its contribution to their cognitive profile remain poorly understood. The current study aimed to comprehensively chart profiles of cognitive impairment in relation to cerebellar atrophy in 49 dementia patients (corticobasal syndrome = 33; progressive supranuclear palsy = 16) compared to 33 age-, sex- and education-matched healthy controls.

Interactions between decision-making and emotion in behavioral-variant frontotemporal dementia and Alzheimer's disease.

Negative and positive emotions are known to shape decision-making toward more or less impulsive responses, respectively. Decision-making and emotion processing are underpinned by shared brain regions including the ventromedial prefrontal cortex (vmPFC) and the amygdala. How these processes interact at the behavioral and brain levels is still unclear.

Cerebellar structural connectivity and contributions to cognition in frontotemporal dementias.

Frontotemporal dementia (FTD) is a heterogeneous group of neurodegenerative brain disorders, primarily affecting the frontal and/or temporal lobes. Three main subtypes are recognised, each with distinct clinical and cognitive profiles: behavioural-variant FTD (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA). Subtype-specific cerebellar grey matter atrophy has been associated with cognitive dysfunction in FTD; however, the extent and severity of structural abnormalities in the cerebro-cerebellar circuits in these disorders has not been investigated.

Robust automated computational approach for classifying frontotemporal neurodegeneration: Multimodal/multicenter neuroimaging.

Introduction: Timely diagnosis of behavioral variant frontotemporal dementia (bvFTD) remains challenging because it depends on clinical expertise and potentially ambiguous diagnostic guidelines. Recent recommendations highlight the role of multimodal neuroimaging and machine learning methods as complementary tools to address this problem.

Methods: We developed an automatic, cross-center, multimodal computational approach for robust classification of patients with bvFTD and healthy controls.

Neural networks associated with body composition in frontotemporal dementia.

Background: Frontotemporal dementia (FTD) is associated with complex changes in eating behavior and metabolism, which potentially affect disease pathogenesis and survival. It is currently not known if body composition changes and changes in fat deposition also exist in FTD, the relationship of these changes in eating behavior and appetite, and whether these changes are centrally mediated.

Methods: Body composition was measured in 28 people with behavioral-variant frontotemporal dementia (bvFTD), 16 with Alzheimer's disease (AD), and 19 healthy controls, using dual energy x-ray absorptiometry.

The Cerebellum in Frontotemporal Dementia: a Meta-Analysis of Neuroimaging Studies.

Frontotemporal dementia (FTD) is a neurodegenerative brain disorder primarily affecting the frontal and/or temporal lobes. Three main subtypes have been recognized: behavioural-variant FTD (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA), each of which has a distinct clinical and cognitive profile. Although the role of the cerebellum in cognition is increasingly accepted, knowledge of cerebellar changes across neuroimaging modalities and their contribution to behavioural and cognitive changes in FTD syndromes is currently scant.

Correlates of anomia in non-semantic variants of primary progressive aphasia converge over time.

To track neural correlates of naming performance with disease progression, we estimated key areas affected in nonfluent/agrammatic (nfvPPA) and logopenic (lvPPA) primary progressive aphasia variants over time and changes in naming correlates over time. Twenty-nine non-semantic PPA participants (17 nfvPPA and 12 lvPPA) were selected based upon current diagnostic criteria and PiB-PET status and conducted a confrontation-naming task and a structural MRI. Linear mixed-effect models implemented in FreeSurfer were used for tracking cortical thickness and epicenters of atrophy over time.

How Does Eye Movement Desensitization and Reprocessing Therapy Work? A Systematic Review on Suggested Mechanisms of Action.

Eye movement desensitization and reprocessing [EMDR] is an innovative, evidence-based and effective psychotherapy for post-traumatic stress disorder [PTSD]. As with other psychotherapies, the effectiveness of EMDR contrasts with a limited knowledge of its underlying mechanism of action. In its relatively short life as a therapeutic option, EMDR has not been without controversy, in particular regarding the role of the bilateral stimulation as an active component of the therapy.

Cerebellar atrophy and its contribution to cognition in frontotemporal dementias.

Objective: Increasing evidence suggests that cerebellar damage impacts on cognitive functions. Frontotemporal dementias (FTDs) are neurodegenerative brain conditions, primarily affecting the frontal and/or temporal lobe. Three main phenotypes are recognized, each with a distinct clinical and cognitive profile: behavioral-variant FTD (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA).

Loss of white matter connections after severe traumatic brain injury (TBI) and its relationship to social cognition.

Adults with severe traumatic brain injury (TBI) often suffer poor social cognition. Social cognition is complex, requiring verbal, non-verbal, auditory, visual and affective input and integration. While damage to focal temporal and frontal areas has been implicated in disorders of social cognition after TBI, the role of white matter pathology has not been examined.

Multimodal Brain Changes in First-Episode Mania: A Voxel-Based Morphometry, Functional Magnetic Resonance Imaging, and Connectivity Study.

Background: Brain structural and functional changes in bipolar disorder (BD) are well-established findings, but it is uncertain whether these changes are already present in first episode mania (FEM).

Methods: We compared 31 FEM subjects, with 31 healthy individuals matched for age, sex, and premorbid IQ. Whole-brain voxel-wise morphometry, functional magnetic resonance imaging during the n-back task, and a functional connectivity analysis were performed.