Neurodevelopmental Vulnerability in Alzheimer's Disease and Frontotemporal Dementia.

Background: Neurodevelopmental disorders (NDDs) may influence the course of Alzheimer's disease (AD) and frontotemporal dementia (FTD). However, prior studies have focused on specific pairs of NDDs and variants of AD/FTD. Adopting a dimensional approach to NDDs and considering the heterogeneity of AD/FTD, we investigated the association between a neurodevelopmental vulnerability (DV) and the clinical presentation and age at onset of AD/FTD.

Soluble SorLA in CSF, a novel biomarker to explore disrupted trafficking of SorLA protein in Alzheimer disease.

Background: The SorLA protein, encoded by the Sortilin-related receptor 1 (SORL1) gene, is a major player in Alzheimer's disease (AD) pathophysiology. Functional studies demonstrated that SorLA deficiency results in increased production of Aβ peptide, and thus a higher risk of AD. SorLA can be subject to proteolytic shedding at the cell surface, leading to the release of the soluble ectodomain of the protein (sSorLA) in the extracellular space.

Safety and efficacy of long-term gantenerumab treatment in dominantly inherited Alzheimer's disease: an open-label extension of the phase 2/3 multicentre, randomised, double-blind, placebo-controlled platform DIAN-TU trial.

Background: Amyloid plaque removal by monoclonal antibody therapies slows clinical progression in symptomatic Alzheimer's disease; however, the potential for delaying the onset of clinical symptoms in asymptomatic people is unknown. The Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) is an ongoing platform trial assessing the safety and efficacy of multiple investigational products in participants with dominantly inherited Alzheimer's disease (DIAD). Based on findings of amyloid removal and downstream biological effects from the gantenerumab group of the platform trial, we continued a 3-year open-label extension (OLE) study to assess the safety and efficacy of long-term treatment with high doses of gantenerumab.

Safety and efficacy of long-term gantenerumab treatment in dominantly inherited Alzheimer's disease: an open label extension of the phase 2/3 multicentre, randomised, double-blind, placebo-controlled platform DIAN-TU Trial.

Background: Amyloid-plaque removal by monoclonal antibody therapies slows clinical progression in symptomatic Alzheimer's disease; however, the potential for delaying the onset of clinical symptoms in asymptomatic people is unknown. The Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) is an ongoing platform trial assessing the safety and efficacy of multiple investigational products in participants with dominantly inherited Alzheimer's disease (DIAD) caused by mutations. On the basis of findings of amyloid removal and downstream biological effects from the gantenerumab arm of the platform trial, we continued a 3-year open-label extension (OLE) study to assess the safety and efficacy of long-term treatment with high doses of gantenerumab.

Factors behind poor cognitive outcome following a thalamic stroke.

Background: Thalamic strokes produce neurological, cognitive, and behavioral symptoms depending on the thalamic nuclei involved. While traditionally associated with severe cognitive deficits, recent studies suggest more modest impairments. This study aims to identify the factors that influence the severity of cognitive impairment following thalamic stroke.

An insight from the default mode network in patients with amnesia following left thalamic infarction involving the mediodorsal nucleus and mammillothalamic tract.

The role of the medial part of the thalamus, and in particular the mediodorsal nucleus (MD) and the mammillothalamic tract (MTT), in memory has long been studied, but their contribution remains unclear. While the main functional hypothesis regarding the MTT focuses on memory, some authors postulate that the MD plays a supervisory executive role (indirectly affecting memory retrieval) due to its dense structural connectivity with the prefrontal cortex (PFC). Recently, it has been proposed that the MD, MTT and PFC form part of the DMN the default mode network (DMN).

Galantamine combined with cognitive rehabilitation on post-stroke cognitive impairment: a proof-of-concept study.

Purpose: We conducted a proof-of-concept study to evaluate the effects of galantamine treatment versus placebo combined to cognitive rehabilitation (CR) after stroke.

Materials And Methods: In this 12-week, double blinded, randomized, controlled trial, patients were assigned to either combined approach of galantamine and CR (G-CR) or placebo and CR (P-CR). Primary outcome was the proportion of patients who crossed over from vascular cognitive disorder (VCD) to no-VCD at 12 weeks.

Prevalence and characteristics of vascular cognitive impairment in a European cohort of adult patients with Moyamoya angiopathy.

Introduction: Moyamoya angiopathy (MMA) is associated with a high risk of stroke, but it is also increasingly recognized as leading to cognitive impairment. The aim of this study was to determine the prevalence, nature, and severity of vascular cognitive impairment no dementia (VCIND) in adults with MMA and to identify clinical and imaging factors associated with VCIND.

Methods: We conducted a retrospective study of consecutive adult patients with MMA followed in two tertiary hospitals (Toulouse and Paris Lariboisiere).

Can neurodevelopmental disorders influence the course of neurodegenerative diseases? A scoping review.

This scoping review aims at giving an overview of the possible influence of neurodevelopmental disorders (NDDs) on cognitive-behavioral neurodegenerative diseases (CBNDs). Based on the PRISMA-ScR checklist, it details the methods of NDDs screening, the identified NDDs-CBNDs associations, as well as the criteria and types of association. The last literature search was performed in June 2023.

Translocator protein (TSPO) genotype does not change cerebrospinal fluid levels of glial activation, axonal and synaptic damage markers in early Alzheimer's disease.

Background: PET imaging of the translocator protein (TSPO) is used to assess in vivo brain inflammation. One of the main methodological issues with this method is the allelic dependence of the radiotracer affinity. In Alzheimer's disease (AD), previous studies have shown similar clinical and patho-biological profiles between TSPO genetic subgroups.

Downstream Biomarker Effects of Gantenerumab or Solanezumab in Dominantly Inherited Alzheimer Disease: The DIAN-TU-001 Randomized Clinical Trial.

Importance: Effects of antiamyloid agents, targeting either fibrillar or soluble monomeric amyloid peptides, on downstream biomarkers in cerebrospinal fluid (CSF) and plasma are largely unknown in dominantly inherited Alzheimer disease (DIAD).

Objective: To investigate longitudinal biomarker changes of synaptic dysfunction, neuroinflammation, and neurodegeneration in individuals with DIAD who are receiving antiamyloid treatment.

Design, Setting, And Participants: From 2012 to 2019, the Dominantly Inherited Alzheimer Network Trial Unit (DIAN-TU-001) study, a double-blind, placebo-controlled, randomized clinical trial, investigated gantenerumab and solanezumab in DIAD.

Robust thalamic nuclei segmentation from T1-weighted MRI using polynomial intensity transformation.

Accurate segmentation of thalamic nuclei, crucial for understanding their role in healthy cognition and in pathologies, is challenging to achieve on standard T1-weighted (T1w) magnetic resonance imaging (MRI) due to poor image contrast. White-matter-nulled (WMn) MRI sequences improve intrathalamic contrast but are not part of clinical protocols or extant databases. In this study, we introduce histogram-based polynomial synthesis (HIPS), a fast preprocessing transform step that synthesizes WMn-like image contrast from standard T1w MRI using a polynomial approximation for intensity transformation.

MRI hypoperfusion as a determinant of cognitive impairment in adults with Moyamoya angiopathy.

Introduction: In Moyamoya angiopathy (MMA), mechanisms underlying cognitive impairment remain debated. We aimed to assess the association of cognitive impairment with the degree and the topography of cerebral hypoperfusion in MMA.

Methods: A retrospective analysis of neuropsychological and perfusion MRI data from adults with MMA was performed.

Robust thalamic nuclei segmentation from T1-weighted MRI using polynomial intensity transformation.

Accurate segmentation of thalamic nuclei, crucial for understanding their role in healthy cognition and in pathologies, is challenging to achieve on standard T1-weighted (T1w) magnetic resonance imaging (MRI) due to poor image contrast. White-matter-nulled (WMn) MRI sequences improve intrathalamic contrast but are not part of clinical protocols or extant databases. In this study, we introduce histogram-based polynomial synthesis (HIPS), a fast preprocessing transform step that synthesizes WMn-like image contrast from standard T1w MRI using a polynomial approximation for intensity transformation.

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.

The long-term impact of irradiation on functional connectivity in brain circuits involved in memory processes after pediatric posterior fossa tumor.

Purpose: Memory is one of the main specific cognitive domains impaired with attention and processing speed after a pediatric brain tumor. This work explored the long-term impact of radiotherapy in children with posterior fossa tumor (PFT) on brain connectivity in neural circuits involved in memory using resting-state functional magnetic resonance imaging (rs-fMRI).

Methods: A total of 20 irradiated and 15 non-irradiated PFT survivors, and 21 healthy controls, prospectively included in the IMPALA study (NCT04324450), performed memory tests assessing episodic, procedural, and working memories and were subjected to an rs-fMRI.

Effects of sociodemographic and player characteristics on baseline cognitive performance in 1000 rugby players: A retrospective 8-year follow-up study.

Objectives: To analyze the effects of sociodemographic and player characteristics on the Sport Concussion Assessment Tool and neuropsychological scores over 8 years in a large sample of rugby players.

Design: An 8-year retrospective study of preseason clinical assessments of professional rugby players and players enrolled in training academies at professional clubs.

Methods: The Sport Concussion Assessment Tool-3 or -5, Trail Making Test and Digit Symbol Substitution Test were administered prior to the start of the competition season for each player.

Clinical heterogeneity of neuro-inflammatory PET profiles in early Alzheimer's disease.

The relationship between neuroinflammation and cognition remains uncertain in early Alzheimer's disease (AD). We performed a cross-sectional study to assess how neuroinflammation is related to cognition using TSPO PET imaging and a multi-domain neuropsychological assessment. A standard uptake value ratio (SUVR) analysis was performed to measure [F]-DPA-714 binding using the cerebellar cortex or the whole brain as a (pseudo)reference region.

Expressive Prosody in Patients With Focal Anterior Temporal Neurodegeneration.

Background And Objectives: Progressive focal anterior temporal lobe (ATL) neurodegeneration has been historically called semantic dementia. More recently, semantic variant primary progressive aphasia (svPPA) and semantic behavioral variant frontotemporal dementia (sbvFTD) have been linked with predominant left and right ATL neurodegeneration, respectively. Nonetheless, clinical tools for an accurate diagnosis of sbvFTD are still lacking.