Diagnostic accuracy of automated Lumipulse plasma pTau-217 in Alzheimer's disease: a real-world study.

Background And Objectives: This study evaluates the discriminative performance of the automated Lumipulse plasma pTau-217 compared to plasma pTau-181 and the Aβ42/Aβ40 ratio across cerebrospinal fluid (CSF) A/T classes and diagnostic groups within a memory-center-based population of cognitively impaired patients.

Methods: This cross-sectional study in a Memory Center enrolled 98 patients along the AD continuum or affected by other neurodegenerative disorders, stratified by CSF A/T status and clinical syndrome. Plasma pTau-217, pTau-181, and Aβ42/Aβ40 were measured using Lumipulse.

Analysis of individual alpha frequency in a large cohort from a tertiary memory center.

Background And Purpose: Precise and timely diagnosis is crucial for the optimal use of emerging disease-modifying treatments for Alzheimer disease (AD). Electroencephalography (EEG), which is noninvasive and cost-effective, can capture neural abnormalities linked to various dementias. This study explores the use of individual alpha frequency (IAF) derived from EEG as a diagnostic and prognostic tool in cognitively impaired patients.

Stepwise Functional Brain Architecture Correlates with Atrophy in Progressive Supranuclear Palsy.

Background: Stepwise functional connectivity (SFC) detects whole-brain functional couplings of a selected region of interest at increasing link-step topological distances.

Objective: This study applied SFC to test the hypothesis that stepwise architecture propagating from the disease epicenter would shape patterns of brain atrophy in patients with progressive supranuclear palsy-Richardson's syndrome (PSP-RS).

Methods: Thirty-six patients with PSP-RS and 44 age-matched healthy control subjects underwent brain magnetic resonance imaging on a 3-T scanner.

Association of APOE genotype and cerebrospinal fluid Aβ and tau biomarkers with cognitive and motor phenotype in amyotrophic lateral sclerosis.

Objective: Little is known about amyotrophic lateral sclerosis (ALS)-nonspecific cognitive deficits - most notably memory disturbance - and their biological underpinnings. We investigated the associations of the Alzheimer's disease (AD) genetic risk factor APOE and cerebrospinal fluid (CSF) biomarkers Aβ and tau proteins with cognitive and motor phenotype in ALS.

Methods: APOE haplotype was determined in 281 ALS patients; for 105 of these, CSF levels of Aβ42, Aβ40, total tau (T-tau), and phosphorylated tau (P-tau181) were quantified by chemiluminescence enzyme immunoassay (CLEIA).

Update on recent advances in amyotrophic lateral sclerosis.

In the last few years, our understanding of disease molecular mechanisms underpinning ALS has advanced greatly, allowing the first steps in translating into clinical practice novel research findings, including gene therapy approaches. Similarly, the recent advent of assistive technologies has greatly improved the possibility of a more personalized approach to supportive and symptomatic care, in the context of an increasingly complex multidisciplinary line of actions, which remains the cornerstone of ALS management. Against this rapidly growing background, here we provide an comprehensive update on the most recent studies that have contributed towards our understanding of ALS pathogenesis, the latest results from clinical trials as well as the future directions for improving the clinical management of ALS patients.

Clinical and neuroanatomical characterization of the semantic behavioral variant of frontotemporal dementia in a multicenter Italian cohort.

Background: Semantic behavioral variant frontotemporal dementia (sbvFTD) is a neurodegenerative condition presenting with specific behavioral and semantic derangements and predominant atrophy of the right anterior temporal lobe (ATL). The objective was to evaluate clinical, neuropsychological, neuroimaging, and genetic features of an Italian sbvFTD cohort, defined according to recently proposed guidelines, compared to semantic variant primary progressive aphasia (svPPA) and behavioral variant FTD (bvFTD) patients.

Methods: Fifteen sbvFTD, sixty-three bvFTD, and twenty-five svPPA patients and forty controls were enrolled.

Distinct neural signatures of pulvinar in C9orf72 amyotrophic lateral sclerosis mutation carriers and noncarriers.

Background And Purpose: Thalamic alterations have been reported as a major feature in presymptomatic and symptomatic patients carrying the C9orf72 mutation across the frontotemporal dementia-amyotrophic lateral sclerosis (ALS) spectrum. Specifically, the pulvinar, a high-order thalamic nucleus and timekeeper for large-scale cortical networks, has been hypothesized to be involved in C9orf72-related neurodegenerative diseases. We investigated whether pulvinar volume can be useful for differential diagnosis in ALS C9orf72 mutation carriers and noncarriers and how underlying functional connectivity changes affect this region.

Structural and Functional Brain Network Connectivity at Different King's Stages in Patients With Amyotrophic Lateral Sclerosis.

Background And Objectives: There is currently no validated disease-stage biomarker for amyotrophic lateral sclerosis (ALS). The identification of quantitative and reproducible markers of disease stratification in ALS is fundamental for study design definition and inclusion of homogenous patient cohorts into clinical trials. Our aim was to assess the rearrangements of structural and functional brain connectivity underlying the clinical stages of ALS, to suggest objective, reproducible measures provided by MRI connectomics mirroring disease staging.

The value of routine blood work-up in clinical stratification and prognosis of patients with amyotrophic lateral sclerosis.

Background: There is an unmet need in amyotrophic lateral sclerosis (ALS) to provide specific biomarkers for the disease. Due to their easy availability, we aimed to investigate whether routine blood parameters provide useful clues for phenotypic classification and disease prognosis.

Methods: We analyzed a large inpatient cohort of 836 ALS patients who underwent deep phenotyping with evaluation of the clinical and neurophysiological burden of upper (UMN) and lower (LMN) motor neuron signs.

Age-related vulnerability of the human brain connectome.

Multifactorial models integrating brain variables at multiple scales are warranted to investigate aging and its relationship with neurodegeneration. Our aim was to evaluate how aging affects functional connectivity of pivotal regions of the human brain connectome (i.e.

A novel mutation in an Italian patient with non-fluent variant of primary progressive aphasia at onset: a longitudinal case report.

Objectives: We report the clinical presentation and evolution of a case with a novel Progranulin gene () mutation and non-fluent language disturbances at onset.

Materials And Methods: A 60 year-old, white patient was followed due to a history of language disturbances. Eighteen months after onset, the patient underwent FDG positron emission tomography (PET), and at month 24 was hospitalized to perform neuropsychological evaluation, brain 3 T MRI, lumbar puncture for cerebrospinal fluid (CSF) analysis, and genotyping.

Functional Connectivity From Disease Epicenters in Frontotemporal Dementia.

Background And Objectives: MRI connectomics is an ideal tool to test a network-based model of pathologic propagation from a disease epicenter in neurodegenerative disorders. In this study, we used a novel graph theory-based MRI paradigm to explore functional connectivity reorganization, discerning between direct and indirect connections from disease epicenters, and its relationship with neurodegeneration across clinical presentations of the frontotemporal dementia (FTD) spectrum, including behavioral variant of FTD (bvFTD), nonfluent variant of primary progressive aphasia (nfvPPA), and semantic variant of primary progressive aphasia (svPPA).

Methods: In this observational cross-sectional study, disease epicenters were defined as the peaks of atrophy of a cohort of patients with high confidence of frontotemporal lobar degeneration pathology (Mayo Clinic).

Combining semi-quantitative rating and automated brain volumetry in MRI evaluation of patients with probable behavioural variant of fronto-temporal dementia: an added value for clinical practise?

Purpose: To evaluate the diagnostic value of combined semiquantitative and quantitative assessment of brain atrophy in the diagnostic workup of the behavioural-variant of frontotemporal dementia (bvFTD).

Methods: Three neuroradiologists defined brain atrophy grading and identified atrophy pattern suggestive of bvFTD on 3D-T1 brain MRI of 112 subjects using a semiquantitative rating scale (Kipps'). A quantitative atrophy assessment was performed using two different automated software (Quantib® ND and Icometrix®).

The human functional connectome in neurodegenerative diseases: relationship to pathology and clinical progression.

Introduction: Neurodegenerative diseases can be considered as 'disconnection syndromes,' in which a communication breakdown prompts cognitive or motor dysfunction. Mathematical models applied to functional resting-state MRI allow for the organization of the brain into nodes and edges, which interact to form the functional brain connectome.

Areas Covered: The authors discuss the recent applications of functional connectomics to neurodegenerative diseases, from preclinical diagnosis, to follow up along with the progressive changes in network organization, to the prediction of the progressive spread of neurodegeneration, to stratification of patients into prognostic groups, and to record responses to treatment.

Italian reference values and brain correlates of verbal fluency index - standard verbal fluency test - to assess executive dysfunction in ALS.

In amyotrophic lateral sclerosis (ALS), verbal fluency index (V) is used to investigate fluency accounting for motor impairment. This study has three aims: (1) to provide V reference values from a cohort of Italian healthy subjects; (2) to assess the ability of V reference values ( standard verbal fluency test [VFT]) in distinguishing ALS patients with and without executive dysfunction; and (3) to investigate the association between V and brain structural features of ALS patients. We included 180 healthy subjects and 157 ALS patients who underwent neuropsychological assessment, including VFT and V, and brain MRI.