Agnès Pérez-Millan

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• Physicist and Neuroscience PhD
• Assistant Professor at Universitat Oberta de Catalunya

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...

Large neuroimaging datasets play a crucial role in longitudinal modelling and prediction of neurodegenerative diseases, as they provide the opportunity to study biomarker trajectories over time. Noteworthy, the availability of these large datasets coexists with a paradigm shift in the theoretical understanding of these diseases: while classical stu...

Background Autosomal dominant Alzheimer’s Disease (ADAD) represents around 0.5% of all AD cases, and is caused by mutations in PSEN1, PSEN2 and APP genes. Gene expression studies can be useful for unravelling the physiopathology of AD and identifying potential biomarkers. However, most studies are focused on late‐onset AD (LOAD), and mainly on brai...

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 and objectives: Pathogenic variants in the GRN gene cause frontotemporal dementia (FTD-GRN) with marked brain asymmetry. This study aims to assess whether the disease progression of FTD-GRN depends on the initial side of the atrophy. We also investigated the potential use of brain asymmetry as a biomarker of the disease. Methods: Retr...

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...

Wasteosomes (or corpora amylacea) are polyglucosan bodies that appear in the human brain with aging and in some neurodegenerative diseases, and have been suggested to have a potential role in a nervous system cleaning mechanism. Despite previous studies in several neurodegenerative disorders, their status in frontotemporal lobar degeneration (FTLD)...

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...

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 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 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...

INTRODUCTION Neuroinflammation is a major contributor to the progression of frontotemporal dementia (FTD). Galectin‐3 (Gal‐3), a microglial activation regulator, holds promise as a therapeutic target and potential biomarker. Our study aimed to investigate Gal‐3 levels in patients with FTD and assess its diagnostic potential. METHODS We examined Ga...

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...

Objective: Subtle decline in memory is thought to arise in the preclinical phase of Alzheimer’s disease (AD). However, detecting these initial cognitive difficulties cross-sectionally has been challenging, and the exact nature of the decline is still debated. Accelerated long-term forgetting (ALF) has been recently suggested as one of the earliest...

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...

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 objectivesThe C9orf72 expansion is the most common genetic cause of frontotemporal dementia (FTD) and/or motor neuron disease (MND). Corticospinal degeneration has been described in post-mortem neuropathological studies in these patients, especially in those with MND. We used MRI to analyze white matter (WM) volumes in presymptomatic...

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....

Linear mixed effects (LME) modelling under both frequentist and Bayesian frameworks can be used to study longitudinal trajectories. We studied the performance of both frameworks on different dataset configurations using hippocampal volumes from longitudinal MRI data across groups—healthy controls (HC), mild cognitive impairment (MCI) and Alzheimer’...

Sporadic early-onset Alzheimer’s disease (EOAD) and autosomal dominant Alzheimer’s disease (ADAD) provide the opportunity to investigate the physiopathological mechanisms in the absence of aging, present in late-onset forms. Frontotemporal dementia (FTD) causes early-onset dementia associated to tau or TDP43 protein deposits. A 15% of FTD cases are...

Linear Mixed Effects (LME) modelling under both frequentist and Bayesian frameworks have been suggested to study longitudinal trajectories. We studied the performance of both approaches on different dataset configurations using hippocampal volumes from longitudinal MRI data across groups - healthy controls (HC), mild cognitive impairment (MCI) and...

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...

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 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 Structural neuroimaging longitudinal studies in Alzheimer’s disease (AD) have consistently defined a “cortical signature” of gray matter loss. Apparently, early‐onset AD (EOAD) has a greater density of amyloid, a more generalized atrophy and a more aggressive evolution than late‐onset AD (LOAD). We hypothesize EOAD would show pronounced...

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...