Pharmacotherapy for behavioural manifestations in frontotemporal dementia: An expert consensus from the European Reference Network for Rare Neurological Diseases (ERN-RND).

Background And Purpose: Frontotemporal dementia (FTD) is a neurodegenerative disorder characterized by pervasive personality and behavioural disturbances with severe impact on patients and caregivers. In current clinical practice, treatment is based on nonpharmacological and pharmacological approaches. Unfortunately, trial-based evidence supporting symptomatic pharmacological treatment for the behavioural disturbances in FTD is scarce despite the significant burden this poses on the patients and caregivers.

[Cortico-basal syndrome and cortico-basal degeneration: From the clinical diagnosis to the lesional substrate for an adapted care].

Cortico-basal degeneration is a relatively uncommon cause of degenerative parkinsonism in the elderly. From a clinical point of view, it manifests as a cortico-basal syndrome (CBS), featuring a highly asymmetrical akinetic-rigid syndrome, dystonia, myoclonus and cognitive-behavioral impairment with predominant apraxia. Other clinical phenotypes are possible, including variants with mainly language or behavioral impairment, or with axial, symmetrical parkinsonism resembling progressive supranuclear palsy (PSP).

Assessment of Mendelian and risk-factor genes in Alzheimer disease: A prospective nationwide clinical utility study and recommendations for genetic screening.

Purpose: To assess the likely pathogenic/pathogenic (LP/P) variants rates in Mendelian dementia genes and the moderate-to-strong risk factors rates in patients with Alzheimer disease (AD).

Methods: We included 700 patients in a prospective study and performed exome sequencing. A panel of 28 Mendelian and 6 risk-factor genes was interpreted and returned to patients.

Evaluation of MRI-based machine learning approaches for computer-aided diagnosis of dementia in a clinical data warehouse.

A variety of algorithms have been proposed for computer-aided diagnosis of dementia from anatomical brain MRI. These approaches achieve high accuracy when applied to research data sets but their performance on real-life clinical routine data has not been evaluated yet. The aim of this work was to study the performance of such approaches on clinical routine data, based on a hospital data warehouse, and to compare the results to those obtained on a research data set.

Atypical White Matter Hyperintensities Markedly Impact Plasma Neurofilament Light Chain Variability in GRN Patients.

GRN mutations, causing frontotemporal dementia, can be associated with atypical white matter hyperintensities (WMH). We hypothesized that the presence of WMH may impact neurofilament light chain (NfL) levels, markers of neuroaxonal damage. We analyzed plasma NfL in 20 GRN patients and studied their association to visually-scored WMH burden.

Plasma lysosphingolipids in GRN-related diseases: Monitoring lysosomal dysfunction to track disease progression.

GRN mutations are among the main genetic causes of frontotemporal dementia (FTD). Considering the progranulin involvement in lysosomal homeostasis, we aimed to evaluate if plasma lysosphingolipids (lysoSPL) are increased in GRN mutation carriers, and whether they might represent relevant fluid-based biomarkers in GRN-related diseases. We analyzed four lysoSPL levels in plasmas of 131 GRN carriers and 142 non-carriers, including healthy controls and patients with frontotemporal dementias (FTD) carrying a C9orf72 expansion or without any mutation.

Behavioural disinhibition in frontotemporal dementia investigated within an ecological framework.

Disinhibition is a core symptom in behavioural variant frontotemporal dementia (bvFTD) particularly affecting the daily lives of both patients and caregivers. Yet, characterisation of inhibition disorders is still unclear and management options of these disorders are limited. Questionnaires currently used to investigate behavioural disinhibition do not differentiate between several subtypes of disinhibition, encompass observation biases and lack of ecological validity.

MicroRNA signatures in genetic frontotemporal dementia and amyotrophic lateral sclerosis.

Objective: MicroRNAs are promising biomarkers of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), but discrepant results between studies have so far hampered their use in clinical trials. We aim to assess all previously identified circulating microRNA signatures as potential biomarkers of genetic FTD and/or ALS, using homogeneous, independent validation cohorts of C9orf72 and GRN mutation carriers.

Methods: 104 individuals carrying a C9orf72 or a GRN mutation, along with 31 controls, were recruited through the French research network on FTD/ALS.

Brain Metabolic Profile in Presymptomatic Carriers Throughout a 5-Year Follow-up.

Background And Objectives: variants are a frequent cause of familial frontotemporal dementia (FTD). Monitoring disease progression in asymptomatic carriers of genetic variants is a major challenge in delivering preventative therapies before clinical onset. This study aimed to assess the usefulness of fluorodeoxyglucose (FDG)-PET in identifying metabolic changes in presymptomatic carriers (PS-+) and to trace their longitudinal progression.

Disease Progression Score Estimation From Multimodal Imaging and MicroRNA Data Using Supervised Variational Autoencoders.

Frontotemporal dementia and amyotrophic lateral sclerosis are rare neurodegenerative diseases with no effective treatment. The development of biomarkers allowing an accurate assessment of disease progression is crucial for evaluating new therapies. Concretely, neuroimaging and transcriptomic (microRNA) data have been shown useful in tracking their progression.

An ecological approach to identify distinct neural correlates of disinhibition in frontotemporal dementia.

Disinhibition is a core symptom of many neurodegenerative diseases, particularly frontotemporal dementia, and is a major cause of stress for caregivers. While a distinction between behavioural and cognitive disinhibition is common, an operational definition of behavioural disinhibition is still missing. Furthermore, conventional assessment of behavioural disinhibition, based on questionnaires completed by the caregivers, often lacks ecological validity.

How can we define the presymptomatic C9orf72 disease in 2022? An overview on the current definitions of preclinical and prodromal phases.

Repeat expansions in C9orf72 gene are the main genetic cause of frontotemporal dementia, amyotrophic lateral sclerosis and related phenotypes. With the advent of disease-modifying treatments, the presymptomatic disease phase is getting increasing interest as an ideal time window in which innovant therapeutic approaches could be administered. Recommendations issued from international study groups distinguish between a preclinical disease stage, during which lesions accumulate in absence of any symptoms or signs, and a prodromal stage, marked by the appearance the first subtle cognitive, behavioral, psychiatric and motor signs, before the full-blown disease.

Plasma NfL levels and longitudinal change rates in and -associated diseases: from tailored references to clinical applications.

Objective: Neurofilament light chain (NfL) is a promising biomarker in genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). We evaluated plasma neurofilament light chain (pNfL) levels in controls, and their longitudinal trajectories in and cohorts from presymptomatic to clinical stages.

Methods: We analysed pNfL using Single Molecule Array (SiMoA) in 668 samples (352 baseline and 316 follow-up) of and patients, presymptomatic carriers (PS) and controls aged between 21 and 83.

Primary Progressive Aphasia Associated With Mutations: New Insights Into the Nonamyloid Logopenic Variant.

Objective: To determine relative frequencies and linguistic profiles of primary progressive aphasia (PPA) variants associated with (progranulin) mutations and to study their neuroanatomic correlates.

Methods: Patients with PPA carrying mutations (PPA-) were selected among a national prospective research cohort of 1,696 patients with frontotemporal dementia, including 235 patients with PPA. All patients with amyloid-positive CSF biomarkers were excluded.

Use of Backward Walking Speed to Screen Dynamic Balance and Mobility Deficits in Older Adults Living Independently in the Community.

Background And Purpose: Older adults who live independently in the community are higher functioning and routinely ambulate in the community. Unrestricted community ambulation increases the likelihood of encountering precarious situations challenging balance. Sufficient dynamic balance is necessary to avoid falls.

Clinical Update on C9orf72: Frontotemporal Dementia, Amyotrophic Lateral Sclerosis, and Beyond.

The identification of C9orf72 gene has led to important scientific progresses and has considerably changed our clinical practice. However, a decade after C9orf72 discovery, some important clinical questions remain unsolved. The reliable cutoff for the pathogenic repeat number and the implication of intermediate alleles in frontotemporal dementia, amyotrophic lateral sclerosis, or in other diseases are still uncertain.

Psychological Distress in a Sample of Adult Italian Patients Affected by Vocal Nodules and Muscle-Tension Dysphonia: Preliminary Results.

Objectives: To evaluate the correlation between voice disorders and psychological distress, in terms of anxiety, stress, and depression, in a sample of adult Italian patients and to compare our results with those obtained in a group of adult healthy controls matched by age, sex, geographic distribution, and occupation.

Methods: This prospective-controlled study included 100 adults with Vocal nodules (VN) and Muscle Tension Dysphonia (MTD1), aged between 18 and 65 years, as Experimental Group (EG) and 100 age-matched subjects without any voice disorders as a Control Group (CG). All patients in the EG underwent a phoniatric evaluation, including the administration of the Voice Handicap Index (VHI) and laryngeal examination.

Plasma microRNA signature in presymptomatic and symptomatic subjects with -associated frontotemporal dementia and amyotrophic lateral sclerosis.

Objective: To identify potential biomarkers of preclinical and clinical progression in chromosome 9 open reading frame 72 gene (-associated disease by assessing the expression levels of plasma microRNAs (miRNAs) in patients and presymptomatic carriers.

Methods: The PREV-DEMALS study is a prospective study including 22 patients, 45 presymptomatic mutation carriers and 43 controls. We assessed the expression levels of 2576 miRNAs, among which 589 were above noise level, in plasma samples of all participants using RNA sequencing.

The Rise of the GRN C157KfsX97 Mutation in Southern Italy: Going Back to the Fall of the Western Roman Empire.

Background: Frontotemporal lobar degeneration (FTLD) designates a group of neurodegenerative diseases with remarkable clinical, pathological, and genetic heterogeneity. Mutations in progranulin gene (GRN) are among the most common causes of familial FTLD. The GRN C157KfsX97 mutation is the most frequent mutation occurring in Southern Italy and has been already described in a previous work.