Neus Falgàs

• Neurologa at Hospital Clínic de Barcelona

Introduction Sleep disruption in Alzheimer’s disease (AD) is common, linked to cognitive decline, and a major cause of institutionalization. While AD is associated with increased daytime napping, nocturnal wakefulness, and disrupted rest-activity rhythms (RAR), differences between amnestic (amAD) and atypical (atypAD; non-amnestic presentation) phe...

INTRODUCTION We aimed to determine whether cognitively unimpaired (CU) amyloid‐ beta‐positive (Aβ+) individuals display decreased practice effects on serial neuropsychological testing. METHODS We included 209 CU participants from three research centers, 157 Aβ− controls and 52 Aβ+ individuals. Participants underwent neuropsychological assessment a...

Objectives Frontotemporal dementia (FTD) usually shows more asymmetric atrophy patterns than Alzheimer’s disease (AD). We aim to quantify this asymmetry to differentiate FTD, AD, and FTD subtypes. Methods We studied T1-MRI scans, including FTD (different phenotypes), AD, and healthy controls (CTR). We defined the Cortical Asymmetry Index (CAI) usi...

Plasma tau phosphorylated at threonine 181 (p-tau181) and 217 (p-tau217) have demonstrated high accuracy for Alzheimer’s disease (AD) diagnosis, defined by CSF/PET amyloid beta (Aβ) positivity, but most studies have been performed in research cohorts, limiting their generalizability. We studied plasma p-tau217 and p-tau181 for CSF Aβ status discrim...

Background Alzheimer’s Disease (AD) is associated with sleep disturbances. Moreover, individuals with sleep disturbances have been reported to have a higher risk for developing AD. The measurement of sleep behavior therefore opens the opportunity for a potential digital biomarker of AD. Method We modeled sleep patterns coming from the RADAR‐AD coh...

Background Although Alzheimer’s disease (AD) is a common cause of dementia, whether patients and caregivers have notions of its risk factors, behavioral aspects or care considerations is unclear. Therefore, our study aims to evaluate caregiver’s knowledge of AD by using the Alzheimer’s Disease Knowledge Scale (ADKS). Method The ADKS is a comprehen...

Background Brain Health (BH) perspectives and practices among health care professionals constitute a crucial piece of information for developing tailored initiatives to foster BH at the regional level. We aim to characterize knowledge and clinical practices associated with BH in Spanish neurologists by a cross‐sectional survey. Method An original...

Background Sleep‐wake alterations are common symptoms in Alzheimer’s Disease (AD) associated with faster cognitive decline. Noradrenaline dysfunction and neuroinflammation have been proposed as potential driving mechanisms. The ADIS project aims to study the relationship between sleep‐wake patterns, immune signatures (peripheral blood cytotoxic lym...

Background Alzheimer's disease (AD) features a complex interplay of factors influencing cognitive decline. While CSF and plasma biomarkers have widely demonstrated their diagnostic utility, whether they may add prognostic value remains unrevealed. With this longitudinal study we aim to address this knowledge gap by evaluating the predictive value o...

Background Alzheimer’s Disease (AD) is associated with sleep disturbances. Moreover, individuals with sleep disturbances have been reported to have a higher risk for developing AD. The measurement of sleep behavior therefore opens the opportunity for a potential digital biomarker of AD. Method We modeled sleep patterns coming from the RADAR‐AD coh...

Background Practice effects are a well‐known cognitive phenomenon that is reduced in patients with Alzheimer’s disease (AD). We aimed to investigate whether cognitively unimpaired (CU) individuals within the Alzheimer’s continuum (i.e., positive amyloid‐β biomarker) display decreased practice effects on serial neuropsychological testing. Methods W...

Background Neuromodulatory subcortical systems (NSS) are affected from the early stages of Alzheimer’s Disease (AD) by the accumulation of tau pathology. Increased tau burden within the subcortical nucleus that are in control of sleep and wake regulation may contribute to the breakdown of sleep‐wake patterns in AD. A recent postmortem study showed...

INTRODUCTION Early‐onset Alzheimer's disease (EOAD) shows a higher burden of neuropsychiatric symptoms than late‐onset Alzheimer's disease (LOAD). We aim to determine the differences in the severity of neuropsychiatric symptoms and locus coeruleus (LC) integrity between EOAD and LOAD accounting for disease stage. METHODS One hundred four subjects...

We aimed to characterize the cognitive profile of post-acute COVID-19 syndrome (PACS) patients with cognitive complaints, exploring the influence of biological and psychological factors. Participants with confirmed SARS-CoV-2 infection and cognitive complaints ≥ 8 weeks post-acute phase were included. A comprehensive neuropsychological battery (NPS...

This perspective offers an alternative to the amyloid hypothesis in the etiology of Alzheimer's disease (AD). We review evidence for a novel signaling mechanism based on a little‐known peptide, T14. T14 could drive neurodegeneration as an aberrantly activated process of plasticity selective to interconnecting subcortical nuclei, the isodendritic co...

Alzheimer’s disease has an increasing prevalence in the population world-wide, yet current diagnostic methods based on recommended biomarkers are only available in specialized clinics. Due to these circumstances, Alzheimer’s disease is usually diagnosed late, which contrasts with the currently available treatment options that are only effective for...

Introduction Differential diagnosis among subjects with Primary Progressive Aphasia (PPA) can be challenging. Structural MRI can support the clinical profile. Visual rating scales are a simple and reliable tool to assess brain atrophy in the clinical setting. The aims of the study were to establish to what extent the visual rating scales could be u...

Background: Frontotemporal dementia (FTD) patients usually show more asymmetric atrophy patterns than Alzheimer’s Disease (AD) patients. Here, we define the individual Cortical Asymmetry Index (CAI) and explore its diagnostic utility. Methods: We collected structural T1-MRI scans from 554 participants, including FTD (different phenotypes), AD, and...

Plasma biomarkers have emerged as promising tools for identifying amyloid beta (Aβ) pathology. Before implementation in routine clinical practice, confounding factors modifying their concentration beyond neurodegenerative diseases should be identified. We studied the association of a comprehensive list of demographics, comorbidities, medication and...

Background Despite previous studies establishing cognitive impairment as a major complaint in post‐acute COVID‐19 syndrome (PACS), a deeper understanding of the neuropsychological features and underlying causes is needed. We aimed to characterize the cognitive profile of patients affected with cognitive PACS and the influence of biological and psyc...

Background Little is known about the influence of age at onset (AAO) on plasma biomarkers and their use as prognostic biomarkers in Alzheimer’s disease (AD). Method We selected patients with AD diagnosis with available neuropsychological testing (NPS) at time of diagnosis and two years later, and plasma biomarkers at baseline. NPS battery included...

Background Neuropsychiatric symptoms, including sleep‐wake disturbances, are more common in Early‐onset Alzheimer’s disease (EOAD) than in Late‐onset AD (LOAD)( Falgàs, EurJNeurol2022 ). The pattern of tau‐related degeneration of wake and sleep‐promoting neurons determine sleep‐wake profiles in neurodegenerative disorders ( Oh, JAMANeurol2022 ). We...

Background Plasma Neurofilament light chain (pNfL) is a promising biomarker to discriminate Frontotemporal dementia (FTD) from other diagnoses such as Alzheimer’s disease (AD) or psychiatric disorders. Currently, the diagnostic criteria for FTD syndromes are structured hierarchically into “Possible”, “Probable” and “Definite” levels depending on th...

Background One of the clinical problems for biomarkers' clinical use is the ability to differentiate between Alzheimer’s disease (AD), frontotemporal dementia (FTD), and healthy subjects (CTR). This clearly challenges diagnosis and prognosis. We implemented a ML algorithm that provides individual probabilistic diagnoses for these dementias based on...

Background The diagnosis of early‐onset neurodegenerative dementias (<65 years) can represent a challenge due to their lower frequency respect to late‐onset dementias and atypical forms of presentation. Cognitive impairment has emerged as a frequent complaint after COVID‐19 infection. Method We retrospectively reviewed (2016‐2021) the demographic...

Background The application of blood‐based biomarkers for the identification of Alzheimer’s disease (AD) and the development of novel digital technologies as cognitive screening tests are critical to moving toward a reliable, more accessible early diagnosis. Our aim was to evaluate the diagnostic performance of a machine learning‐based cognitive ass...

Background Post‐acute Covid‐19 syndrome (PACS) frequently refers to cognitive complaints. It is not yet clear whether there is an association between cognitive symptoms with brain changes or neuropsychiatric symptoms. Our aims are 1) to study cross‐sectional and longitudinal MRI brain measures in a cohort of PACS and 2) their association with cogni...

Background Blood‐based biomarkers have recently emerged as minimally‐invasive, accessible and relatively inexpensive diagnostic and prognostic tools for people with cognitive impairment. Before being routinely implemented in clinical practice, the diagnostic performance of distinct commercially available assays should be studied in real‐world cohor...

Background Lewy Body Dementia (LBD) is the second most common neurodegenerative dementia. To date, no validated biochemical marker is available to support clinical diagnosis. The development of the Real‐Time Quaking‐Induced Conversion (RT‐QuIC) assay for detecting alpha‐synuclein (aSyn) seeds in biological samples can be a sensitive biomarker speci...

Background and objective Alzheimer’s disease (AD) and frontotemporal dementia (FTD) show different patterns of cortical thickness (CTh) loss compared with healthy controls (HC), even though there is relevant heterogeneity between individuals suffering from each of these diseases. Thus, we developed CTh models to study individual variability in AD,...

Background Neuroimaging and fluid biomarkers are used in clinics to differentiate frontotemporal dementia (FTD) from Alzheimer’s disease (AD) and other neurodegenerative and non-neurodegenerative disorders. We implemented a machine learning (ML) algorithm that provides individual probabilistic scores for these patients based on magnetic resonance i...

We aimed to characterize the cognitive profile of post-acute COVID-19 syndrome (PACS) patients with cognitive complaints, exploring the influence of biological and psychological factors. Participants with confirmed SARS-CoV-2 infection and cognitive complaints ≥ eight weeks post-acute phase were included. A comprehensive neuropsychological battery...

Background In healthy ageing, there is evidence of sex differences in vulnerability of hippocampal subfields to volume loss. However, this has not been investigated in early‐onset Alzheimer’s disease (<65 years; EOAD). Method We included 106 subjects: 62 EOAD (A+T+N+, MMSE>15) and 44 healthy controls (HC; A‐T‐N‐) that underwent lumbar puncture for...

Background Currently used biomarkers for the differential diagnosis of cognitive impairment are expensive and/or relatively invasive, limiting their availability to the general population. Blood protein biomarkers have showed promising results for screening, differential diagnosis, and prognosis. We aimed to study the diagnostic performance of plas...

Alzheimer’s disease (AD) is the most common cause of dementia worldwide. Increasing evidence points to the thalamus as an important hub in the clinical symptomatology of the disease, with the ‘limbic thalamus’ been described as especially vulnerable. In this work, we examined thalamic atrophy in early-onset AD (EOAD) and late-onset AD (LOAD) compar...

Introduction: Sleep-wake disturbances are a prominent feature of Alzheimer's disease (AD). Atypical (non-amnestic) AD syndromes have different patterns of cortical vulnerability to AD. We hypothesized that atypical AD also shows differential vulnerability in subcortical nuclei that will manifest as different patterns of sleep dysfunction. Methods...

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are common causes of dementia with partly overlapping, symptoms and brain signatures. There is a need to establish an accurate diagnosis and to obtain markers for disease tracking. We combined unsupervised and supervised machine learning to discriminate between AD and FTD using brain magnet...

The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau‐associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction and cortical lesions. Accumulating evidence supports the role of NSS dysfunction and d...

Early‐onset Alzheimer’s Disease presentations (EOAD, under 65) frequently present with atypical phenotypes and a more aggressive disease course with a higher burden of neuropsychiatric symptoms than late‐onset AD (LOAD). Current treatments for sleep and behavioral disturbances are still non‐specific, causing side effects (e.g., sedation, falls). Id...

Background: Assess how APOE genotype can differentially affect cortical and subcortical memory structures in biomarker-confirmed early and late-onset Alzheimer's Disease (EOAD-LOAD). Methods: Eighty-seven CSF biomarker-confirmed AD patients were classified according to their APOE genotype and age at onset. 28 were EOAD APOE4 carriers (+EOAD), 21...

Background and Objectives Blood-based biomarkers have emerged as minimally-invasive options for evaluating cognitive impairment. Most studies to date have assessed them in research cohorts, limiting their generalization to everyday clinical practice. We evaluated their diagnostic performance and clinical applicability in a prospective, real-world,...

Introduction: Sex is believed to drive heterogeneity in Alzheimer's disease (AD), although evidence in early-onset AD (<65 years, EOAD) is scarce. Methods: We included 62 EOAD patients and 44 healthy controls (HC) with cerebrospinal fluid (CSF) AD's core biomarkers and neurofilament light chain levels, neuropsychological assessment, and 3T-MRI....

Objectives To investigate the objective sleep influencers behind older adult responses to subjective sleep measures, in this case, the Pittsburgh Sleep Quality Index (PSQI). Based on previous literature, we hypothesized that SE would be associated with PSQI reported sleep disruption. Furthermore, because SOL increases progressively with age and it...

BackgroundMRI atrophy predicts cognitive status in AD. However, this relationship has not been investigated in early-onset AD (EOAD, < 65 years) patients with a biomarker-based diagnosis.Methods Forty eight EOAD (MMSE ≥ 15; A + T + N +) and forty two age-matched healthy controls (HC; A − T − N −) from a prospective cohort underwent full neuropsycho...

Importance: The accurate diagnosis of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) is hampered by imperfect clinical-pathological correlations. Objective: To assess and compare the diagnostic value of the magnetic resonance parkinsonism index (MRPI) and other magnetic resonance imaging-based measures of cerebral atrop...

Importance: Sleep disturbance is common among patients with neurodegenerative diseases. Examining the subcortical neuronal correlates of sleep disturbances is important to understanding the early-stage sleep neurodegenerative phenomena. Objectives: To examine the correlation between the number of important subcortical wake-promoting neurons and...

Background Cortical mean diffusivity is a novel imaging metric sensitive to early changes in neurodegenerative syndromes. Higher cortical mean diffusivity values reflect microstructural disorganization and have been proposed as a sensitive biomarker that might antedate macroscopic cortical changes. We aimed to test the hypothesis that cortical mean...

Background: The faster rates of cognitive decline and predominance of atypical forms in early-onset Alzheimer's Disease (EOAD) suggest that neuropsychiatric symptoms could be different in EOAD compared to late-onset AD (LOAD), however, prior studies based on non-biomarker diagnosed cohorts show discordant results. Our goal was to determine the pro...

Background The amyloid deposition (A) in the 2018 ATN classification of Alzheimer disease can be assessed by CSF Aβ 1‐42 or amyloid PET. Although the agreement between them is high, it is not exact. Method We selected patients from the Alzheimer’s disease and other cognitive disorders Unit at Hospital Clínic of Barcelona with available amyloid PET...

Background: The ongoing COVID-19 pandemic and related care policies have affected dementia patients. The characteristics of early-onset dementia (EOD, <65 years) patients in 2020 may provide insights on how to rearrange the provision of care. Method: We retrospectively reviewed, from 2016 to 2020, the demographic and clinical data of the new ref...

Background: Sleep-wake disturbances are a prominent feature in Alzheimer's Disease (AD), negatively impacting patients and caregivers' quality of life. Growing evidence suggests that sleep-wake dysregulation happens early in AD due to the AD-tau degeneration of the arousal system (i.e., locus coeruleus). However, whether the pattern of sleep-wake...

There is evidence longitudinal atrophy in posterior brain areas in early-onset Alzheimer’s disease (EOAD; aged<65years), but no studies have been conducted in an EOAD cohort with fluid biomarkers characterization. We used 3T-MRI and Freesurfer 6.0 to investigate cortical and subcortical gray matter loss at two years in 12 EOAD patients (A+T+N+) com...

Background There is an increasing awareness that sleep disturbances are a risk factor for dementia. Prior case-control studies suggested that brain grey matter (GM) changes involving cortical (i.e, prefrontal areas) and subcortical structures (i.e, putamen, thalamus) could be associated with insomnia status. However, it remains unclear whether ther...

Importance The presence of atrophy on magnetic resonance imaging can support the diagnosis of the behavioral variant of frontotemporal dementia (bvFTD), but reproducible measurements are lacking. Objective To assess the diagnostic and prognostic utility of 6 visual atrophy scales (VAS) and the Magnetic Resonance Parkinsonism Index (MRPI). Design,...

Although, the clinical variants of Alzheimer's disease (AD) show distinct patterns of cognitive and behavioral decline, disease progression, and neuropathological features, it is unclear if this clinical heterogeneity extends to sleep‐wake patterns. Sleep and wake disturbances are frequent in typical AD, often preceding memory loss and negatively i...

Background Early‐onset dementia (EOD; <65 years) raises both diagnostic and social/health care challenges. Services for dementia are often designed for the elderly and might have difficulties supplying EOD needs. Clinical and epidemiological data are needed for care planning. Method We aim to describe the demographic and the clinical characteristi...

Background ABCA7 gene (ATP‐binding cassette transporter A7) loss‐of‐function mutations are related to increased risk of suffering Alzheimer’s disease (AD). On the other hand, mutations in GRN (Progranulin) gene are causative of frontotemporal dementia (FTD). Methods The proband was a patient diagnosed from semantic variant of primary progressive a...

Background Early‐onset Alzheimer’s disease (EOAD, onset before 65 years), is the most common early‐onset neurodegenerative dementia. However, it still represents a diagnostic challenge especially when compared with late‐onset Alzheimer’s disease (LOAD). Our aim was to describe and compare the neuropsychological presentation at diagnosis and its pro...

Background There is an increasing awareness that sleep disturbances are a risk factor for dementia (Sindi, 2018). Prior case‐control studies have suggested that certain alterations in brain structure could be associated with insomnia status (Sexton, 2014; Grau‐Rivera, 2019). Specifically, they mainly described smaller cortical volumes in orbitofron...

Background Changes in functional connectivity (FC) networks have been extensively reported in late onset Alzheimer’s Disease (AD), being the default mode network (DMN) the key system to be affected. However, it remains unclear if FC in early‐onset AD (EOAD) would show a similar pattern than late onset AD. Method We studied 48 EOAD patients (mean a...

Background The behavioral variant of frontotemporal dementia (bvFTD) presents with variable patterns of cortical and subcortical atrophy on Magnetic Resonance Imaging (MRI). We aimed to assess the clinical utility of two reproducible measurements of cerebral atrophy (Harper's visual atrophy scale [HVAS], and the Magnetic Resonance Parkinsonism Inde...

Early-onset Alzheimer’s disease (EOAD) and frontotemporal dementia (FTD) have a high proportion of genetically determined cases. Next-generation sequencing technologies have triggered the discovery of new mutations and genetic variants in dementia causal genes. We performed whole-exome sequencing and selective analysis of known genes causative of E...

Prior studies have described distinct patterns of brain gray matter and white matter alterations in Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD), as well as differences in their cerebrospinal fluid (CSF) biomarkers profiles. We aim to investigate the relationship between early‐onset AD (EOAD) and FTLD structural alterations...

Background The diagnosis of incipient symptomatic stages of early-onset dementia is challenging. The magnetic resonance imaging (MRI) is an easy-access biomarker. Objective We aim to determine the distribution and diagnostic performance of the existing atrophy visual rating scales on MRI in initial stages of the most frequent neurodegenerative ear...

Introduction: Synaptic damage, axonal neurodegeneration, and neuroinflammation are common features in Alzheimer's disease (AD), frontotemporal dementia (FTD), and Creutzfeldt-Jakob disease (CJD). Methods: Unicentric cohort of 353 participants included healthy control (HC) subjects, AD continuum stages, genetic AD and FTD, and FTD and CJD. We mea...