Loss of Insight in Syndromes Associated with Frontotemporal Lobar Degeneration: Clinical and Imaging Features.

Objectives: The present study aims to assess the prevalence, associated clinical symptoms, longitudinal changes, and imaging correlates of Loss of Insight (LOI), which is still unexplored in syndromes associated with Frontotemporal Lobar Degeneration (FTLD).

Design: Retrospective longitudinal cohort study, from Oct 2009 to Feb 2023.

Setting: Tertiary Frontotemporal Dementia research clinic.

Plasma p-tau and neurofilament/p-tau ratio in differentiating Alzheimer's disease from syndromes associated with frontotemporal lobar degeneration.

Introduction: Plasma-based biomarkers have shown promise for clinical implementation, but their accuracy in differentiating Alzheimer's disease (AD) from syndromes associated with frontotemporal lobar degeneration (FTLD) has yet to be fully investigated. This study assessed the potential of plasma biomarkers for differential diagnosis.

Methods: This cohort study included 374 participants (96 AD, 278 FTLD).

Impaired spatial dynamic functional network connectivity and neurophysiological correlates in functional hemiparesis.

The present study investigated spatial dynamic functional network connectivity (dFNC) in patients with functional hemiparesis (i.e., functional stroke mimics, FSM).

Clinical trial eligibility in PSP: Population representativeness and potential criteria adjustment based on PSP-NET findings.

Background: Progressive Supranuclear Palsy (PSP) is a rare, heterogeneous neurodegenerative disease for which no treatment is currently available. In the context of clinical trials, the representativeness of the included patients is crucial for the generalizability of the results. Herein, we present results from a multicenter perspective study to identify the most restrictive criteria for patient selection and to assess the representativeness of eligible patients.

The detection of GRN mutation carriers by progranulin blood protein levels from finger-stick collection.

Introduction: Heterozygous mutations in the progranulin gene (GRN) leading to decreased progranulin levels are one of the most frequent causes of inherited frontotemporal dementia (FTD). We evaluated progranulin levels in dried blood spots from capillary finger-stick collection (DBS).

Methods: Paired venous Ethylenediaminetetraacetic acid (EDTA) plasma and DBS samples were collected from each participant with or without pathogenic GRN mutations.

Association of Changes in Cerebral and Hypothalamic Structure With Sleep Dysfunction in Patients With Genetic Frontotemporal Dementia.

Background And Objectives: Sleep dysfunction is common in patients with neurodegenerative disorders; however, its neural underpinnings remain poorly characterized in genetic frontotemporal dementia (FTD). Hypothalamic nuclei important for sleep regulation may be related to this dysfunction. Thus, we examined changes in hypothalamic structure across the lifespan in patients with genetic FTD and whether these changes related to sleep dysfunction.

Association of Initial Side of Brain Atrophy With Clinical Features and Disease Progression in Patients With Frontotemporal Dementia.

Background And Objectives: Pathogenic variants in the gene cause frontotemporal dementia (FTD-) with marked brain asymmetry. This study aims to assess whether the disease progression of FTD- depends on the initial side of the atrophy. We also investigated the potential use of brain asymmetry as a biomarker of the disease.

Frontoparietal network integrity supports cognitive function in pre-symptomatic frontotemporal dementia: Multimodal analysis of brain function, structure, and perfusion.

Introduction: Genetic mutation carriers of frontotemporal dementia can remain cognitively well despite neurodegeneration. A better understanding of brain structural, perfusion, and functional patterns in the pre-symptomatic stage could inform accurate staging and potential mechanisms.

Methods: We included 207 pre-symptomatic genetic mutation carriers and 188 relatives without mutations.

The role of parvalbumin interneuron dysfunction across neurodegenerative dementias.

Parvalbumin-positive (PV+) basket neurons are fast-spiking, non-adapting inhibitory interneurons whose oscillatory activity is essential for regulating cortical excitation/inhibition balance. Their dysfunction results in cortical hyperexcitability and gamma rhythm disruption, which have recently gained substantial traction as contributing factors as well as potential therapeutic targets for the treatment of Alzheimer's Disease (AD). Recent evidence indicates that PV+ cells are also impaired in Frontotemporal Dementia (FTD) and Dementia with Lewy bodies (DLB).

Frequency and Longitudinal Course of Behavioral and Neuropsychiatric Symptoms in Participants With Genetic Frontotemporal Dementia.

Background And Objectives: Behavioral and neuropsychiatric symptoms are frequent in patients with genetic frontotemporal dementia (FTD). We aimed to describe behavioral and neuropsychiatric phenotypes in genetic FTD, quantify their temporal association, and investigate their regional association with brain atrophy.

Methods: We analyzed data of pathogenic variant carriers in the chromosome 9 open reading frame 72 (), progranulin (), or microtubule-associated protein tau () gene from the Genetic Frontotemporal dementia Initiative cohort study that enrolls both symptomatic pathogenic variant carriers and first-degree relatives of known carriers.

Predictors of Care Home Admission and Survival Rate in Patients With Syndromes Associated With Frontotemporal Lobar Degeneration in Europe.

Background And Objectives: Data on care home admission and survival rates of patients with syndromes associated with frontotemporal lobar degeneration (FTLD) are limited. However, their estimation is essential to plan trials and assess the efficacy of intervention. Population-based registers provide unique samples for this estimate.

Local functional connectivity abnormalities in mild cognitive impairment and Alzheimer's disease: A meta-analytic investigation using minimum Bayes factor activation likelihood estimation.

Functional magnetic resonance imaging research employing regional homogeneity (ReHo) analysis has uncovered aberrant local brain connectivity in individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD) in comparison with healthy controls. However, the precise localization, extent, and possible overlap of these aberrations are still not fully understood. To bridge this gap, we applied a novel meta-analytic and Bayesian method (minimum Bayes Factor Activation Likelihood Estimation, mBF-ALE) for a systematic exploration of local functional connectivity alterations in MCI and AD brains.

Inflammatory plasma profile in genetic symptomatic and presymptomatic Frontotemporal Dementia - A GENFI study.

Background: Inflammation has been proposed as a crucial player in neurodegeneration, including Frontotemporal Dementia (FTD). A few studies on sporadic FTD lead to inconclusive results, whereas large studies on genetic FTD are lacking. The aim of this study is to determine cytokine and chemokine plasma circulating levels in a large cohort of genetic FTD, collected within the GENetic Frontotemporal dementia Initiative (GENFI).

Alpha tACS Improves Cognition and Modulates Neurotransmission in Dementia with Lewy Bodies.

Background: Dementia with Lewy bodies (DLB) is characterized by a marked shift of electroencephalographic (EEG) power and dominant rhythm, from the α toward the θ frequency range. Transcranial alternate current stimulation (tACS) is a non-invasive brain stimulation technique that allows entrainment of cerebral oscillations at desired frequencies.

Objectives: Our goal is to evaluate the effects of occipital α-tACS on cognitive functions and neurophysiological measures in patients with DLB.

Long Non-Coding RNA Profile in Genetic Symptomatic and Presymptomatic Frontotemporal Dementia: A GENFI Study.

Background: Long non-coding RNAs (lncRNAs) play crucial roles in gene regulation and are implicated in neurodegenerative diseases, including frontotemporal dementia (FTD). However, their expression patterns and potential as biomarkers in genetic FTD involving Chromosome 9 Open Reading Frame (C9ORF72), Microtubule Associated Protein Tau (MAPT), and Progranulin (GRN) genes are not well understood.

Objective: This study aimed to profile the expression levels of lncRNAs in peripheral blood mononuclear cells collected within the GENetic Frontotemporal dementia Initiative (GENFI).

Impaired glymphatic system in genetic frontotemporal dementia: a GENFI study.

The glymphatic system is an emerging target in neurodegenerative disorders. Here, we investigated the activity of the glymphatic system in genetic frontotemporal dementia with a diffusion-based technique called diffusion tensor image analysis along the perivascular space. We investigated 291 subjects with symptomatic or presymptomatic frontotemporal dementia (112 with [] expansion, 119 with [] mutations and 60 with [] mutations) and 83 non-carriers (including 50 young and 33 old non-carriers).

Unveiling New Genetic Variants Associated with Age at Onset in Alzheimer's Disease and Frontotemporal Lobar Degeneration Due to Repeat Expansions.

Alzheimer's disease (AD) and Frontotemporal lobar degeneration (FTLD) represent the most common forms of neurodegenerative dementias with a highly phenotypic variability. Herein, we investigated the role of genetic variants related to the immune system and inflammation as genetic modulators in AD and related dementias. In patients with sporadic AD/FTLD (n = 300) and / mutation carriers (n = 80), we performed a targeted sequencing of 50 genes belonging to the immune system and inflammation, selected based on their high expression in brain regions and low tolerance to genetic variation.

Plasma biomarkers increase diagnostic confidence in patients with Alzheimer's disease or frontotemporal lobar degeneration.

Background: The recent development of techniques to assess plasma biomarkers has changed the way the research community envisions the future of diagnosis and management of Alzheimer's disease (AD) and other neurodegenerative disorders. This work aims to provide real world evidence on the clinical impact of plasma biomarkers in an academic tertiary care center.

Methods: Anonymized clinical reports of patients diagnosed with AD or Frontotemporal Lobar Degeneration with available plasma biomarkers (Aβ, Aβ/Aβ, p-tau, p-tau, NfL, GFAP) were independently assessed by two neurologists who expressed diagnosis and diagnostic confidence three times: (T0) at baseline based on the information collected during the first visit, (T1) after plasma biomarkers, and (T2) after traditional biomarkers (when available).