Clarifying the association of CSF Aβ, tau, BACE1, and neurogranin with AT(N) stages in Alzheimer disease.

Background: Current AT(N) stratification for Alzheimer's disease (AD) accounts for complex combinations of amyloid (A), tau proteinopathy (T) and neurodegeneration (N) signatures. Understanding the transition between these different stages is a major challenge, especially in view of the recent development of disease modifying therapy.

Methods: This is an observational study, CSF levels of Tau, pTau181, pTau217, Aβ38/40/42, sAPPα/β, BACE1 and neurogranin were measured in the BALTAZAR cohort of cognitively impaired patients and in the Alzheimer's Disease Neuroimaging Initiative (ADNI).

Association of caffeine consumption with cerebrospinal fluid biomarkers in mild cognitive impairment and Alzheimer's disease: A BALTAZAR cohort study.

Introduction: We investigated the link between habitual caffeine intake with memory impairments and cerebrospinal fluid (CSF) biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients.

Methods: MCI (N = 147) and AD (N = 116) patients of the Biomarker of AmyLoid pepTide and AlZheimer's diseAse Risk (BALTAZAR) cohort reported their caffeine intake at inclusion using a dedicated survey. Associations of caffeine consumption with memory impairments and CSF biomarkers (tau, p-tau181, amyloid beta 1-42 [Aβ], Aβ) were analyzed using logistic and analysis of covariance models.

Clinical value of plasma ALZpath pTau217 immunoassay for assessing mild cognitive impairment.

Background: Among plasma biomarkers for Alzheimer's disease (AD), pTau181 and pTau217 are the most promising. However, transition from research to routine clinical use will require confirmation of clinical performance in prospective cohorts and evaluation of cofounding factors.

Method: pTau181 and pTau217 were quantified using, Quanterix and ALZpath, SIMOA assays in the well-characterised prospective multicentre BALTAZAR (Biomarker of AmyLoid pepTide and AlZheimer's diseAse Risk) cohort of participants with mild cognitive impairment (MCI).

The free plasma amyloid Aβ/Aβ ratio predicts conversion to dementia for subjects with mild cognitive impairment with performance equivalent to that of the total plasma Aβ/Aβ ratio. The BALTAZAR study.

Background And Purpose: Blood-based biomarkers are a non-invasive solution to predict the risk of conversion of mild cognitive impairment (MCI) to dementia. The utility of free plasma amyloid peptides (not bound to plasma proteins and/or cells) as an early indicator of conversion to dementia is still debated, as the results of studies have been contradictory. In this context, we investigated whether plasma levels of the free amyloid peptides Aβ and Aβ and the free plasma Aβ/Aβ ratio are associated with the conversion of MCI to dementia, in particular AD, over three years of follow-up in a subgroup of the BALTAZAR cohort.

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.

Blood Neurofilament Levels Predict Cognitive Decline across the Alzheimer's Disease Continuum.

Neurofilament light chain (NfL) is a potential diagnostic and prognostic plasma biomarker for numerous neurological diseases including Alzheimer's disease (AD). In this study, we investigated the relationship between baseline plasma concentration of Nfl and Mild Cognitive Impairment in participants who did and did not have a clinically determined diagnosis of dementia by the end of the three-year study. Additionally, we explored the connection between baseline plasma concentration of NfL and AD dementia patients, considering their demographics, clinical features, and cognitive profiles.

Head-to-Head Comparison of Two Plasma Phospho-tau Assays in Predicting Conversion of Mild Cognitive Impairment to Dementia.

Background: Among blood biomarkers, phospho-tau181 (pTau181) is one of the most efficient in detecting Alzheimer disease across its continuum. However, transition from research to routine clinical use will require confirmation of clinical performance in prospective cohorts and evaluation of cofounding factors.

Methods: Here we tested the Lumipulse assay for plasma pTau181 in mild cognitive impairment (MCI) participants from the Baltazar prospective cohort.

Validation study of "Santé-Cerveau", a digital tool for early cognitive changes identification.

Background: There is a need for a reliable, easy-to-use, widely available, and validated tool for timely cognitive impairment identification. We created a computerized cognitive screening tool (Santé-Cerveau digital tool (SCD-T)) including validated questionnaires and the following neuropsychological tests: 5 Word Test (5-WT) for episodic memory, Trail Making Test (TMT) for executive functions, and a number coding test (NCT) adapted from the Digit Symbol Substitution Test for global intellectual efficiency. This study aimed to evaluate the performance of SCD-T to identify cognitive deficit and to determine its usability.

Plasma phosphorylated tau 181 predicts amyloid status and conversion to dementia stage dependent on renal function.

Objectives: Plasma P-tau181 is an increasingly established diagnostic marker for Alzheimer's disease (AD). Further validation in prospective cohorts is still needed, as well as the study of confounding factors that could influence its blood level.

Methods: This study is ancillary to the prospective multicentre Biomarker of AmyLoid pepTide and AlZheimer's diseAse Risk cohort that enrolled participants with mild cognitive impairment (MCI) who were examined for conversion to dementia for up to 3 years.

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.

Disentangling Clinical Profiles of Apathy in Behavioral Variant Frontotemporal Dementia.

Background: Apathy is highly frequent in behavioral variant frontotemporal dementia (bvFTD). It is presumed to involve different pathophysiological mechanisms and neuroanatomical regions.

Objective: We explored the hypothesis that subgroups showing distinct profiles of apathy and distinct patterns of atrophy within frontal lobes could be disentangled in bvFTD.

Functional connectivity correlates of reduced goal-directed behaviors in behavioural variant frontotemporal dementia.

We explored the resting state functional connectivity correlates of apathy assessed as a multidimensional construct, using behavioral metrics, in behavioral variant frontotemporal dementia (bvFTD). We recorded the behavior of 20 bvFTD patients and 16 healthy controls in a close-to-real-life situation including a free phase (FP-in which actions were self-initiated) and a guided phase (GP-in which initiation of actions was facilitated by external guidance). We investigated the activity time and walking episode features as quantifiers of apathy.

A temporal classification method based on behavior time series data in patients with behavioral variant of frontotemporal dementia and apathy.

Background Apathy is a common behavioral syndrome that occurs across neurological and psychiatric disorders. An influential theoretical framework defined apathy as the quantitative reduction of self-generated voluntary and purposeful behaviors. There is evidence in the literature of the multidimensional nature of apathy with cognitive, behavioral, and emotional dimensions.

Plasma amyloid beta predicts conversion to dementia in subjects with mild cognitive impairment: The BALTAZAR study.

Introduction: Blood-based biomarkers are the next challenge for Alzheimer's disease (AD) diagnosis and prognosis.

Methods: Mild cognitive impairment (MCI) participants (N = 485) of the BALTAZAR study, a large-scale longitudinal multicenter cohort, were followed-up for 3 years. A total of 165 of them converted to dementia (95% AD).

Subtle postoperative cognitive disorder in preclinical Alzheimer's disease.

Background: We examined the association between preclinical Alzheimer's disease (AD) and undergoing anesthesia and surgery ("surgery" henceforth) in a cohort of elderly individuals with a subjective cognitive decline (SCD).

Methods: Individuals with SCD (N = 268) were enrolled in a longitudinal follow-up study. Participants underwent comprehensive yearly cognitive evaluation for a period of 4 years.

A multimodal, longitudinal study of cognitive heterogeneity in early-onset Alzheimer's disease.

Background And Purpose: Alzheimer's disease (AD) is a heterogeneous pathology. Young patients with AD are particularly likely to have an atypical presentation. The objectives of the present cluster analysis were to determine whether patients with early-onset AD (EOAD) had several distinct cognitive profiles and to compare the resulting clusters with regard to clinical, neuroimaging, and laboratory characteristics.

The wide spectrum of COVID-19 neuropsychiatric complications within a multidisciplinary centre.

A variety of neuropsychiatric complications has been described in association with COVID-19 infection. Large scale studies presenting a wider picture of these complications and their relative frequency are lacking. The objective of our study was to describe the spectrum of neurological and psychiatric complications in patients with COVID-19 seen in a multidisciplinary hospital centre over 6 months.

Diabetes Mellitus and Cognition: Pathway Analysis in the MEMENTO Cohort.

Objective: To assess the role of biomarkers of Alzheimer disease (AD), neurodegeneration, and small vessel disease (SVD) as mediators in the association between diabetes mellitus and cognition.

Methods: The study sample was derived from MEMENTO, a cohort of French adults recruited in memory clinics and screened for either isolated subjective cognitive complaints or mild cognitive impairment. Diabetes was defined based on blood glucose assessment, use of antidiabetic agent, or self-report.

Frontotemporal dementia subtypes based on behavioral inhibition deficits.

Introduction: We aimed to investigate phenotypic heterogeneity in the behavioral variant of frontotemporal dementia (bvFTD) through assessment of inhibition deficits.

Methods: We assessed occurrences of 16 behavioral inhibition deficits from video recordings of 15 bvFTD patients (early stage) and 15 healthy controls (HC) in an ecological setting. We extracted dimensions of inhibition deficit and analyzed their correlations with cognitive and clinical measures.

Validation in French of the Montreal Cognitive Assessment 5-Minute, a brief cognitive screening test for phone administration.

Background: The prevalence of cognitive impairment and dementia is high and steadily increasing. Early detection of cognitive decline is crucial since some interventions can reduce the risk of progression to dementia. However, there is a lack of manageable scales for assessing cognitive functions outside specialized consultations.

The cerebral network of COVID-19-related encephalopathy: a longitudinal voxel-based 18F-FDG-PET study.

Purpose: Little is known about the neuronal substrates of neuropsychiatric symptoms associated with COVID-19 and their evolution during the course of the disease. We aimed at describing the longitudinal brain metabolic pattern in COVID-19-related encephalopathy using 18F-FDG-PET/CT.

Methods: Seven patients with variable clinical presentations of COVID-19-related encephalopathy were explored thrice with brain 18F-FDG-PET/CT, once in the acute phase, 1 month later and 6 months after COVID-19 onset.