Juan D Gispert

Juan D Gispert
Barcelonabeta Brain Research Center · Neuroimaging

PhD

About

364
Publications
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Publications

Publications (364)
Article
Full-text available
PURPOSE: The aim of the present study was to evaluate the use of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) as a noninvasive strategy to assess the time course of inflammatory processes after inhalation of ZnO nanoparticles (NPs) in rats. PROCEDURES: Healthy, male Sprague-Dawley rats (n = 30) were divided in two groups of 15 animals each. Animals...
Article
Full-text available
The aim of the present study was to evaluate the use of 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) as a noninvasive strategy to assess the time course of inflammatory processes after inhalation of ZnO nanoparticles (NPs) in rats. Healthy, male Sprague-Dawley rats (n = 30) were divided in two groups of 15 animals each. Animals from one group (n...
Article
The investigation of resting-state functional connectivity (rsFC) in asymptomatic individuals at genetic risk for Alzheimer’s disease (AD) enables discovering the earliest brain alterations in preclinical stages of the disease. The APOE-ε4 variant is the major genetic risk factor for AD, and previous studies have reported rsFC abnormalities in carr...
Article
White matter hyperintensities (WMH) have a heterogeneous etiology, associated with both vascular risk factors and amyloidosis due to Alzheimer’s disease (AD). While spatial distribution of both amyloid and WM lesions carry important information for the underlying pathogenic mechanisms, the regional relationship between these two pathologies and the...
Article
Higher grey matter volumes/cortical thickness and fluorodeoxyglucose uptake have been consistently found in cognitively unimpaired individuals with abnormal Alzheimer's disease biomarkers compared with those with normal biomarkers. It has been hypothesized that such transient increases may be associated with neuroinflammatory mechanisms triggered i...
Article
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Background Despite its widespread use, the semi-quantitative standardized uptake value ratio (SUVR) may be biased compared with the distribution volume ratio (DVR). This bias may be partially explained by changes in cerebral blood flow (CBF) and is likely to be also dependent on the extent of the underlying amyloid-β (Aβ) burden. This study aimed t...
Article
Full-text available
Amyloid-β (Aβ) pathology is one of the earliest detectable brain changes in Alzheimer’s disease (AD) pathogenesis. The overall load and spatial distribution of brain Aβ can be determined in vivo using positron emission tomography (PET), for which three fluorine-18 labelled radiotracers have been approved for clinical use. In clinical practice, trai...
Article
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Amyloid (Aβ) pathology is the earliest detectable pathophysiological event along the Alzheimer’s continuum, which can be measured both in the cerebrospinal fluid (CSF) and by Positron Emission Tomography (PET). Yet, these biomarkers identify two distinct Aβ pools, reflecting the clearance of soluble Aβ as opposed to the presence of Aβ fibrils in th...
Article
Background and objectives Currently, amyloid-β (Aβ) staging models assume a single spatial-temporal progression of amyloid accumulation. We assessed evidence for Aβ accumulation subtypes by applying the data-driven Subtype and Stage Inference (SuStaIn) model to amyloid-PET data. Methods Amyloid-PET data of 3010 subjects were pooled from 6 cohorts...
Article
Purpose: A novel phantom-imaging platform, a set of software tools, for automated and high precision imaging of the American College of Radiology (ACR) PET phantom for PET/MR and PET/CT systems is proposed. Methods: The key feature of this platform is the vector graphics design which facilitates the automated measurement of the knife-edge respon...
Article
Full-text available
Amyloid (Aβ) pathology is the earliest detectable pathophysiological event along the Alzheimer's continuum, which can be measured both in the cerebrospinal fluid (CSF) and by Positron Emission Tomography (PET). Yet, these biomarkers identify two distinct Aβ pools, reflecting the clearance of soluble Aβ as opposed to the presence of Aβ fibrils in th...
Article
Full-text available
Background: Recognizing clinical manifestations heralding the development of Alzheimer's disease (AD)-related cognitive impairment could improve the identification of individuals at higher risk of AD who may benefit from potential prevention strategies targeting preclinical population. We aim to characterize the association of body weight change w...
Article
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Introduction: Harboring two copies of the apolipoprotein E (APOE) ε2 allele strongly protects against Alzheimer's disease (AD). However, the effect of this genotype on gray matter (GM) volume in cognitively unimpaired individuals has not yet been described. Methods: Multicenter brain magnetic resonance images (MRIs) from cognitively unimpaired ε...
Article
Telomere length (TL) is an objective biomarker of biological aging and it has been proposed to play a crucial role in Alzheimer's disease (AD) progression by impairing cognitive resilience. However, published studies show inconsistent results and a very limited number of studies have evaluated the role of TL in aging and midlife individuals. The ma...
Article
Obesity has been linked to brain atrophy and peripheral inflammation. However, the association between body mass index (BMI) and brain structure can be confounded by Alzheimer’s disease (AD) pathology‐related weight loss, and its association with neuroinflammation remains unknown. We explored associations of BMI with brain structure and biomarkers...
Article
Sleep disturbances are prevalent in Alzheimer’s disease (AD), with sleep quality having been reported to be already impaired at the preclinical stage of the disease. However, most results originate from studies with rather limited sample sizes. This research aimed to evaluate the association of subjective sleep measures with cerebrospinal fluid (CS...
Article
Atherosclerosis has been linked to cognitive decline in late life; however, the impact of cardiovascular risk factors (CVRFs) and subclinical atherosclerosis on brain metabolism at earlier stages remains unexplored. This study, aimed at determining the association between brain metabolism, subclinical atherosclerosis and CVRFs in midlife, included...
Article
Iron dyshomeostasis is involved in the pathophysiology of Alzheimer’s disease (AD). Magnetic resonance imaging (MRI) is sensitive to iron in the brain as its concentration decreases the intensity of T2‐weighted images. However, there is little evidence on how iron affects structural changes in the brain of cognitively unimpaired individuals at the...
Article
Anxiety and depression are more prevalent in women and caregivers and are associated with increased Alzheimer’s disease (AD) risk. We investigated multimodal predictors of increased anxiety/depression during the Covid19‐related confinement in cognitively unimpaired (CU) older adults with an increased risk for AD with a special focus on sex/gender....
Article
Evidence shows that APOE‐ε4 is associated with amyloid‐beta (Aβ) aggregation in the medial temporal lobe (MTL), a crucial region supporting episodic memory (EM), early in the AD continuum. However, the impact of Aβ aggregation in the MTL of cognitively unimpaired (CU) APOE‐ε4 carriers has not been explored. We determine whether abnormal Aβ in the M...
Article
There is growing evidence of sex differences in the association between Alzheimer’s disease (AD) biomarkers and cognition. However, few studies have examined the effect of sex on the associations between established AD risk factors and cognitive performance in clinically normal older adults. This study aimed to elucidate potential sex differences i...
Article
In a sample of cognitively unimpaired (CU) middle‐aged adults with family history (FH) of sporadic Alzheimer’s disease (AD), we (i) classified participants based on similarity patterns of expression in cerebrospinal fluid (CSF) biomarkers of AD, axonal damage, synaptic dysfunction, neuroinflammation, and glial response, and (ii) characterized the p...
Article
Cerebral beta‐amyloid (Aβ) deposition disrupts functional resting‐state connectivity in cognitively unimpaired (CU) individuals. However, only a few studies have investigated these associations using Aβ cerebrospinal fluid (CSF) markers. Moreover, the reorganization of functional brain networks across the progressive stages of preclinical Alzheimer...
Article
Subjective cognitive decline (SCD) is often related to affective symptoms and both predict cognitive decline. We investigated whether SCD status predicted higher anxiety/depression during the Covid19‐related confinement, along with amyloid positivity in cognitively unimpaired older adults. We included 205 participants from the ALFA+ study (Table 1)...
Article
Plasma biomarkers have demonstrated excellent agreement with established markers of amyloid‐β (Aβ) positivity (PET and CSF) to identify patients with symptomatic AD. However, their predictive capacity in cognitively unimpaired (CU) individuals is lower. In this work, we aimed at assessing whether structural MRI features could improve the capacity o...
Conference Paper
AMYPAD‐DPMS is a European, multicenter, prospective, interventional, randomized controlled study. It aims to assess clinical utility and cost‐effectiveness of amyloid‐PET. It recruited individuals with Subjective Cognitive Decline plus (SCD+), and syndromic diagnosis of Mild Cognitive Impairment (MCI) and dementia. Here, we describe the quantitativ...
Article
The Centiloid method enables direct quantitative comparison of amyloid‐PET scans acquired with different amyloid tracers. However, it does not explicitly model differences in image resolution which may have an impact on quantification, particularly in multicenter studies. This study evaluated the stability of the Centiloid scale with or without pos...
Article
Accurate quantitative measures of amyloid beta (Aβ) plaques are needed to identify individuals with subthreshold Aβ levels or for measuring small changes over time. To this end, dynamic or dual‐time‐window scanning protocols are required. Optimal pharmacokinetic models for quantifying Aβ burden using both [18F]flutemetamol and [18F]florbetaben dual...
Article
It is not clear whether neuroinflammation is a detrimental or a compensatory mechanism in Alzheimer’s disease (AD). Recent evidence suggests that increased levels of YKL40 are related to better memory performance in cognitively unimpaired older individuals with memory complaints. In this study, we aimed i) at replicating these previous findings and...
Article
The hippocampus is involved in several complex diseases which display sex differences in their prevalence. Therefore, it can be hypothesized that sex‐specific genetic vulnerability in hippocampal formation might partially explain these differences. The aim of this study was to investigate whether the genetic predisposition to several complex diseas...
Article
Several reports have described higher gray matter volumes and glucose consumption in cognitively unimpaired individuals with abnormal amyloid biomarkers, typically interpreted to be caused by inflammatory or compensatory mechanisms. In this study, we investigated structural and metabolic differences in cognitively unimpaired individuals with mismat...
Article
Amyloid burden staging models assume a single spatial‐temporal progression of amyloid accumulation across subjects, while disease heterogeneity suggests there might be subtypes with distinct trajectories. Here, we apply a data‐driven model which simultaneously resolves subtypes and stages (SuStaIn)1 to amyloid PET data to assess evidence for Aβ acc...
Article
Neuroimaging biomarkers in large‐scale multimodal studies have proven effective for early diagnosis. Image‐derived phenotypes (IDPs) are summary features derived from modalities such as magnetic resonance imaging (MRI). We provide an overview of the IDPs computed from the European Prevention of Alzheimer Dementia (EPAD) cohort study, a multi‐center...
Article
Multiple pathophysiological pathways are altered in the early stages of Alzheimer's disease (AD). The associations between these pathways and structural and metabolic brain changes are not clear. This study investigated associations between imaging neurodegeneration markers and cerebrospinal fluid (CSF) markers of amyloid‐β ([Aβ]; Aβ42/40) and tau...
Article
Background: Multicomponent interventions including diet, physical activity and cognitive training have shown great potential to prevent cognitive decline in individuals at risk of developing the clinical stages of Alzheimer's disease (AD). The PENSA study is a clinical trial focused on the prevention of cognitive decline in individuals with subjec...
Article
Perivascular spaces (PVS) have an important role in the elimination of metabolic waste from the brain. However, the relationship between enlarged PVS (ePVS) and risk factors or pathophysiological mechanisms involved in Alzheimer’s disease (AD) remains unknown. The aim of this study was to investigate the association between the ePVS, demographic an...
Article
CSF Aβ42 is thought to show AD‐related alterations earlier than amyloid‐β PET. Therefore, cognitively unimpaired (CU) individuals with abnormal CSF Aβ42 and normal amyloid‐β PET are believed to be in the earliest stages of the AD continuum. In this work, we sought to detect structural cerebral alterations in CU individuals with discordant status in...
Article
Structural MRI measurements can contribute to the prediction of amyloid pathology in cognitively unimpaired (CU) individuals. In this work, we aimed at studying the predictive capacity, robustness, and generalizability of ML techniques to predict amyloid‐β pathology in CU individuals, as well as identifying key brain regions contributing to this pr...
Article
Understanding the role of amyloid imaging in the earliest stages of Alzheimer’s Disease (AD) becomes increasingly relevant for secondary prevention. In this context, the AMYPAD Prognostic and Natural History Study (PNHS) is an open‐label, prospective, multi‐centre cohort study (http://amypad.eu/) to determine the value of quantitative amyloid PET i...
Article
Amyloid‐b (Ab) and tau exert a synergistic action on brain structure and function in cognitively unimpaired (CU) individuals. However, these two biomarkers have so far been investigated separately. Recently, it was proposed that the cerebrospinal fluid (CSF) phospho‐tau (pTau)/Ab42 ratio may represent a novel prognostic core biomarker, providing in...
Article
Gray matter network (GMN) disruptions correlate with amyloid burden in the earliest stages of Alzheimer’s Disease (AD) pathology in cognitively unimpaired individuals. However, it remains unknown if and how hyperphosphorylated tau (p‐tau) influences GMNs. Here, we investigated the relation between GMNs and cerebrospinal fluid (CSF) p‐tau181 levels...
Article
Full-text available
In recent decades, our understanding of the molecular changes involved in neurodegenerative diseases has been transformed. Single-cell RNA sequencing and single-nucleus RNA sequencing technologies have been applied to provide cellular and molecular details of the brain at the single-cell level. This has expanded our knowledge of the central nervous...
Article
Full-text available
Importance: Glial fibrillary acidic protein (GFAP) is a marker of reactive astrogliosis that increases in the cerebrospinal fluid (CSF) and blood of individuals with Alzheimer disease (AD). However, it is not known whether there are differences in blood GFAP levels across the entire AD continuum and whether its performance is similar to that of CS...
Preprint
Full-text available
The European Prevention of Alzheimer Dementia (EPAD) is a multi-center study that aims to characterize the preclinical and prodromal stages of Alzheimer’s Disease. The EPAD imaging dataset includes core (3D T1w, 3D FLAIR) and advanced (ASL, diffusion MRI, and resting-state fMRI) MRI sequences. Here, we give an overview of the semi-automatic multimo...
Article
Imaging genetic studies aim to test how genetic information influences brain structure and function by combining neuroimaging-based brain features and genetic data from the same individual. Most studies focus on individual correlation and association tests between genetic variants and a single measurement of the brain. Despite the great success of...
Article
Full-text available
Most people have a soundtrack of life, a set of special musical pieces closely linked to certain biographical experiences. Autobiographical memories (AM) and music listening (ML) involve complex mental processes ruled by differentiate brain networks. The aim of the paper was to determine the way both networks interact in linked occurrences. We perf...
Article
Full-text available
Objective To determine whether CSF synaptic biomarkers are altered in the early preclinical stage of the Alzheimer’s continuum and associated with Alzheimer’s disease (AD) risk factors, primary pathology, and neurodegeneration markers. Methods Cross-sectional study in the ALFA+ cohort, comprising middle-aged cognitively unimpaired participants. CS...
Article
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Background: Cognitive performance of a given individual should be interpreted in the context of reference standards obtained in cognitively healthy populations. Recent evidence has shown that removing asymptomatic individuals with biomarker evidence of Alzheimer's disease (AD) pathology from normative samples increases the sensitivity of norms to...
Article
Full-text available
Background Air quality contributes to incidence of Alzheimer’s disease (AD) although the underlying neurobiological mechanisms are unclear. This study was aimed to examine the association between air pollution and concentrations of cerebrospinal fluid (CSF) AD biomarkers and amyloid-β (Aβ) deposition. Participants and methods The sample included 15...
Preprint
Full-text available
Neurodegenerative and neuropsychiatric disorders (ND-NPs) are multifactorial, polygenic and complex behavioral phenotypes caused by brain abnormalities. Large-scale collaborative efforts have tried to identify the genetic architecture of these conditions. However, specific and shared underlying molecular pathobiology of brain illnesses is not clear...
Article
PURPOSE Radiation dose received by the neural stem cells of the hippocampus during whole-brain radiotherapy has been associated with neurocognitive decline. The key concern using hippocampal avoidance-prophylactic cranial irradiation (HA-PCI) in patients with small-cell lung cancer (SCLC) is the incidence of brain metastasis within the hippocampal...
Article
Full-text available
Background Perivascular spaces (PVS) have an important role in the elimination of metabolic waste from the brain. It has been hypothesized that the enlargement of PVS (ePVS) could be affected by pathophysiological mechanisms involved in Alzheimer’s disease (AD), such as abnormal levels of CSF biomarkers. However, the relationship between ePVS and t...
Article
Full-text available
Background Understanding the changes that occur in the transitional stage between absent and overt amyloid-β (Aβ) pathology within the Alzheimer’s continuum is crucial to develop therapeutic and preventive strategies. The objective of this study is to test whether cognitively unimpaired individuals with a low burden of Aβ pathology have a distinct...
Article
Full-text available
Introduction: Urban environmental exposures might contribute to the incidence of Alzheimer's disease (AD). Our aim was to identify structural brain imaging correlates of urban environmental exposures in cognitively unimpaired individuals at increased risk of AD. Methods: Two hundred twelve participants with brain scans and residing in Barcelona,...
Article
Full-text available
Purpose To examine associations between the APOE-ε2 and APOE-ε4 alleles and core Alzheimer’s disease (AD) pathological hallmarks as measured by amyloid-β (Aβ) and tau PET in older individuals without dementia. Methods We analyzed data from 462 ADNI participants without dementia who underwent Aβ ([ ¹⁸ F]florbetapir or [ ¹⁸ F]florbetaben) and tau ([...
Article
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Purpose To investigate the sensitivity of visual read (VR) to detect early amyloid pathology and the overall utility of regional VR. Methods [ ¹⁸ F]Flutemetamol PET images of 497 subjects (ALFA+ N = 352; ADC N = 145) were included. Scans were visually assessed according to product guidelines, recording the number of positive regions (0–5) and a fi...
Article
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Background [¹⁸F]flutemetamol PET scanning provides information on brain amyloid load and has been approved for routine clinical use based upon visual interpretation as either negative (equating to none or sparse amyloid plaques) or amyloid positive (equating to moderate or frequent plaques). Quantitation is however fundamental to the practice of nu...
Article
Full-text available
There is clear evidence that hippocampal subfield volumes have partly distinct genetic determinants associated with specific biological processes. The identification of genetic correlates of hippocampal subfield volumes may help to elucidate the mechanisms of neurologic diseases, as well as aging and neurodegenerative processes. However, despite th...
Article
Full-text available
This study investigated whether genetic factors involved in Alzheimer’s disease (AD) are associated with enlargement of Perivascular Spaces (ePVS) in the brain. A total of 680 participants with T2-weighted MRI scans and genetic information were acquired from the ALFA study. ePVS in the basal ganglia (BG) and the centrum semiovale (CS) were assessed...
Article
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Background: Detecting subtle-to-moderate biomarker changes such as those in amyloid PET imaging becomes increasingly relevant in the context of primary and secondary prevention of Alzheimer's disease (AD). This work aimed to determine if and when distribution volume ratio (DVR; derived from dynamic imaging) and regional quantitative values could i...
Article
Full-text available
Background: We classified non-demented European Prevention of Alzheimer's Dementia (EPAD) participants through the amyloid/tau/neurodegeneration (ATN) scheme and assessed their neuropsychological and imaging profiles. Materials and methods: From 1500 EPAD participants, 312 were excluded. Cerebrospinal fluid cut-offs of 1000 pg/mL for amyloid bet...
Article
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Background The number of APOE-ε4 alleles is a major nonmodifiable risk factor for sporadic Alzheimer disease (AD). There is increasing evidence on the benefits of dietary DHA (22:6n–3) before the onset of AD symptoms, particularly in APOE-ε4 carriers. Brain alterations in the preclinical stage can be detected by structural MRI. Objectives We aimed...
Experiment Findings
Full-text available
Recent decades have witnessed an increasing number of large to very large imaging studies, prominently in the field of neurodegenerative diseases. The datasets collected during these studies form essential resources for the research aiming at new biomarkers. Collecting, hosting, managing, processing, or reviewing those datasets is typically achieve...
Article
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Introduction: The association between cerebral amyloid-β accumulation and downstream CSF biomarkers is not fully understood, particularly in asymptomatic stages. Methods: In 318 cognitively unimpaired participants, we assessed the association between amyloid-β PET (Centiloid), and cerebrospinal fluid (CSF) biomarkers of several pathophysiologica...
Article
Full-text available
Neurofilament light chain (NfL) is an axonal protein that when measured in cerebrospinal fluid (CSF) serves as a biomarker of neurodegeneration. We aimed at investigating the association among CSF NfL, presence of Subjective Cognitive Decline (SCD) and hippocampal volume, and how CSF amyloid-β (Aβ) modifies these associations. We included 278 cogni...
Article
Full-text available
Optimal pharmacokinetic models for quantifying amyloid beta (Aβ) burden using both [¹⁸F]flutemetamol and [¹⁸F]florbetaben scans have previously been identified at a region of interest (ROI) level. The purpose of this study was to determine optimal quantitative methods for parametric analyses of [¹⁸F]flutemetamol and [¹⁸F]florbetaben scans. Forty-si...