Jaume Olives

• Hospital Clínic de Barcelona

We used an untargeted mass spectrometric approach, tandem mass tag proteomics, for the identification of proteomic signatures in genetic frontotemporal dementia (FTD). A total of 238 cerebrospinal fluid (CSF) samples from the Genetic FTD Initiative were analyzed, including samples from 107 presymptomatic (44 C9orf72 , 38 GRN , and 25 MAPT ) and 55...

The glymphatic system is an emerging target in neurodegenerative disorders. Here, we investigated the activity of the glymphatic system in genetic frontotemporal dementia with a diffusion-based technique called diffusion tensor image analysis along the perivascular space. We investigated 291 subjects with symptomatic or presymptomatic frontotempora...

Background Plasma biomarkers reflecting the pathology of frontotemporal dementia would add significant value to clinical practice, to the design and implementation of treatment trials as well as our understanding of disease mechanisms. The aim of this study was to explore the levels of multiple plasma proteins in individuals from families with gene...

Biomarkers that can predict disease progression in individuals with genetic frontotemporal dementia are urgently needed. We aimed to identify whether baseline MRI-based grey and white matter abnormalities are associated with different clinical progression profiles in presymptomatic mutation carriers in the GENetic Frontotemporal dementia Initiative...

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...

Background Behavioural variant fronto-temporal dementia (bvFTD) is characterised by a progressive change in personality in association with atrophy of the frontal and temporal lobes. Whilst language impairment has been described in people with bvFTD, little is currently known about the extent or type of linguistic difficulties that occur, particula...

While frontotemporal dementia has been considered a neurodegenerative disease that starts in mid-life or later, it is now clearly established that cortical and subcortical volume loss is observed more than a decade prior to symptom onset and progresses with ageing. To test the hypothesis that genetic mutations causing frontotemporal dementia have n...

Background Clinical endpoints for upcoming therapeutic trials in frontotemporal dementia (FTD) are increasingly urgent. Cognitive composite scores are often used as endpoints but are lacking in genetic FTD. We aimed to create cognitive composite scores for genetic frontotemporal dementia (FTD) as well as recommendations for recruitment and duration...

Objective To investigate the optimal method of adding motor features to a clinical rating scale for frontotemporal dementia (FTD). Methods Eight hundred and thirty-two participants from the international multicentre Genetic FTD Initiative (GENFI) study were recruited: 522 mutation carriers (with C9orf72 , GRN and MAPT mutations) and 310 mutation-n...

Objectives: Early- and late-onset Alzheimer's disease (EOAD and LOAD) share the same neuropathological traits but show distinct cognitive features. We aimed to explore baseline and longitudinal outcomes of global and domain-specific cognitive function in a well characterized cohort of patients with a biomarker-based diagnosis. Methods: In this r...

Background Approximately a third of frontotemporal dementia (FTD) is genetic with mutations in three genes accounting for most of the inheritance: C9orf72 , GRN , and MAPT . Impaired synaptic health is a common mechanism in all three genetic variants, so developing fluid biomarkers of this process could be useful as a readout of cellular dysfunctio...

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...

Introduction A third of frontotemporal dementia (FTD) is caused by an autosomal-dominant genetic mutation in one of three genes: microtubule-associated protein tau ( MAPT ), chromosome 9 open reading frame 72 ( C9orf72 ) and progranulin ( GRN ). Prior studies of prodromal FTD have identified impaired executive function and social cognition early in...

INTRODUCTION: A third of frontotemporal dementia (FTD) is caused by an autosomal-dominant genetic mutation in one of three genes: microtubule-associated protein tau (MAPT), chromosome 9 open reading frame 72 (C9orf72) and progranulin (GRN). Prior studies of prodromal FTD have identified impaired executive function and social cognition early in the...

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...

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...

We studied a sample of cognitively unimpaired individuals, with and without subjective cognitive decline (SCD), in order to investigate accelerated long‐term forgetting (ALF) and to explore the relationships between objective and subjective cognitive performance and cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarkers. Fifty‐two individual...

Objective Progranulin-related frontotemporal dementia (FTD- GRN ) is a fast progressive disease. Modelling the cascade of multimodal biomarker changes aids in understanding the aetiology of this disease and enables monitoring of individual mutation carriers. In this cross-sectional study, we estimated the temporal cascade of biomarker changes for F...

Accelerated long‐term forgetting (ALF) refers to a rapid loss of information over days or weeks despite normal acquisition/encoding. Notwithstanding its potential relevance as a presymptomatic marker of cognitive dysfunction, no study has addressed the relationship between ALF and Alzheimer’s disease (AD) biomarkers. We examined ALF in APOE ɛ4 carr...

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 Progranulin related frontotemporal dementia (FTD‐ GRN ) is a fast progressive disorder, in which pathophysiological changes precede overt clinical symptoms in only a short time period. Modelling the cascade of multimodal biomarker changes aids in understanding the etiology of this disease, enables monitoring of individual mutation carrie...

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 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...

A key symptom of frontotemporal dementia (FTD) is difficulty interacting socially with others. Social cognition problems in FTD include impaired emotion processing and theory of mind difficulties, and whilst these have been studied extensively in sporadic FTD, few studies have investigated them in familial FTD. Facial Emotion Recognition (FER) and...

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...

Aim: To evaluate cognitive progression in the Alzheimer's disease (AD) continuum focusing on the influence of age [EA early onset (EOAD) vs. Late onset EA (LOAD)], as well as on the utility of total tau (t-tau), phosphorylated tau (p-tau) and Neurofilament light chain (NfL) as prognostic biomarkers. Material and methods: 211 subjects were included...

Background Exploring the relationship between Alzheimer’s disease (AD) biomarkers and subjective cognitive decline (SCD) is needed for better defining its clinical meaning in preclinical AD (preAD). Objective To assess the association between the Subjective Cognitive Decline Questionnaire (SCD-Q), gray matter (GM), and cerebrospinal fluid amyloid-...

Since the current neuropsychological assessments are not sensitive to subtle deficits that may be present in cognitively normal subjects with amyloid-β positivity, more accurate and efficient measures are needed. Our aim was to investigate the presence of subtle motor deficits in this population and its relationship with cerebrospinal fluid (CSF) a...

Mutations in the MAPT gene cause frontotemporal dementia with tau deposits. We report the novel p.P397S MAPT variant in eight subjects from five apparently nonrelated families suffering from frontotemporal dementia with autosomal dominant pattern of inheritance. In silico analysis reported conflicting evidence of pathogenicity. The segregation anal...

Background We investigated a sample of cognitively healthy subjects with normal Alzheimer’s disease (AD) cerebrospinal fluid (CSF) biomarker levels to identify the earliest variables related to longitudinal memory changes. Objective Employing a new highly demanding learning and memory test (the Ancient Farming Equipment Test; AFE-T), we aimed to i...

NIA-AA diagnostic criteria include volumetric or visual rating measures of hippocampal atrophy (HA) as a diagnostic biomarker of Alzheimer's disease (AD). We aimed to determine its utility as a diagnostic biomarker for early onset Alzheimer's disease (EOAD) by assessing Medial Temporal Atrophy (MTA) and hippocampal volume (HV) determination. MTA sc...

Background Several diagnostic biomarkers are currently available for its clinical use in early onset cognitive impairment. The decision of which biomarker is used in each patient depends on several factors such as its predictive value or tolerability. Methods Forty subjects with early onset cognitive complaints (<65 years): 26 with Alzheimer's dis...

Here we provide evidence for biological markers linked to cognitive aging highlighting the role of tau, which could be related with longitudinal memory decline even in healthy subjects. The development of new cognitive measures is crucial to test new disease modifying pharmacological strategies.