Papers by Glòria Martí Andrés
Revista De Neurologia, 2015
Introduccion. El natalizumab es un farmaco utilizado en la esclerosis multiple (EM), cuyo princip... more Introduccion. El natalizumab es un farmaco utilizado en la esclerosis multiple (EM), cuyo principal efecto adverso es el desarrollo de una leucoencefalopatia multifocal progresiva (LMP). Como esta es potencialmente mortal o discapacitante, el tratamiento debe suspenderse inmediatamente ante su sospecha, teniendo en cuenta el posible desarrollo posterior de un sindrome de reconstitucion inmune o rebrote de la EM. Caso clinico. Se describe un caso de LMP, inicialmente asintomatico, en el contexto del tratamiento con natalizumab en una paciente con EM. Como factores de riesgo se determinaron titulos altos de anticuerpos contra el virus John Cunningham (VJC) y mas de dos anos de tratamiento. La reaccion en cadena de la polimerasa para el VJC en el liquido cefalorraquideo resulto negativa en dos determinaciones. El periodo entre el diagnostico radiologico y el inicio de la clinica fue de dos meses. Durante el curso de la enfermedad, la paciente desarrollo un sindrome inflamatorio de reconstitucion inmune y rebrotes de su EM. Presento una buena respuesta tras el inicio de tratamiento con fingolimod, una vez estabilizada la LMP. Conclusion. Este caso ilustra la importancia de una estrecha vigilancia clinicorradiologica en pacientes con EM tratados con natalizumab, sobre todo cuando presentan factores de riesgo para el desarrollo de LMP, asi como su potencial incidencia en la supervivencia y estado funcional final.
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Springer eBooks, Nov 11, 2021
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Springer eBooks, Nov 11, 2021
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Alzheimer's Research & Therapy, Jul 22, 2022
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European Journal of Neurology, Jan 12, 2023
Background and purposeAlthough sporadic Creutzfeldt–Jakob disease (sCJD) is a rare cause of demen... more Background and purposeAlthough sporadic Creutzfeldt–Jakob disease (sCJD) is a rare cause of dementia, it is critical to understand its functional networks as the prion protein spread throughout the brain may share similar mechanisms with other more common neurodegenerative disorders. In this study, the metabolic brain network associated with sCJD was investigated and its internal network organization was explored.MethodsWe explored 2‐[18F]fluoro‐2‐deoxy‐d‐glucose positron emission tomography (FDG‐PET) brain scans of 29 sCJD patients, 56 normal controls (NCs) and 46 other dementia patients from two independent centers. sCJD‐related pattern (CJDRP) was identified in a cohort of 16 pathologically proven sCJD patients and 16 age‐matched NCs using scaled subprofile modeling/principal component analysis and was prospectively validated in an independent cohort of 13 sCJD patients and 20 NCs. The pattern's specificity was tested on other dementia patients and its clinical relevance by clinical correlations. The pattern's internal organization was further studied using graph theory methods.ResultsThe CJDRP was characterized by relative hypometabolism in the bilateral caudate, thalami, middle and superior frontal gyri, parietal lobe and posterior cingulum in association with relative hypermetabolism in the hippocampi, parahippocampal gyri and cerebellum. The pattern's expression significantly discriminated sCJD from NCs and other dementia patients (p < 0.005; receiver operating characteristic analysis CJD vs. NCs area under the curve [AUC] 0.90–0.96, sCJD vs. Alzheimer's disease AUC 0.78, sCJD vs. behavioral variant of frontotemporal dementia AUC 0.84). The pattern's expression significantly correlated with cognitive, functional decline and disease duration. The metabolic connectivity analysis revealed inefficient information transfer with specific network reorganization.ConclusionsThe CJDRP is a robust metabolic biomarker of sCJD. Due to its excellent clinical correlations it has the potential to monitor disease in emerging disease‐modifying trials.
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Brain Sciences, Oct 11, 2019
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Acta neuropathologica communications, Apr 8, 2021
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Journal of Alzheimer's Disease, May 2, 2023
Background: Subjective cognitive decline (SCD) may represent a preclinical stage of Alzheimer’s d... more Background: Subjective cognitive decline (SCD) may represent a preclinical stage of Alzheimer’s disease (AD). Predicting progression of SCD patients is of great importance in AD-related research but remains a challenge. Objective: To develop and implement an ensemble machine learning (ML) algorithm to identify SCD subjects at risk of conversion to mild cognitive impairment (MCI) or AD. Methods: Ninety-nine SCD patients were included. Thirty-two progressed to MCI/AD, while 67 remained stable. To minimize the effect of class imbalance, both classes were balanced, and sensitivity was taken as evaluation metric. Bagging and boosting ML models were developed by using socio-demographic and clinical information, Mini-Mental State Examination and Geriatric Depression Scale (GDS) scores (feature-set 1a); socio-demographic characteristics and neuropsychological tests scores (feature-set 1b) and regional magnetic resonance imaging grey matter volumes (feature-set 2). The most relevant variables were combined to find the best model. Results: Good prediction performances were obtained with feature-sets 1a and 2. The most relevant variables (variable importance exceeding 20%) were: Age, GDS, and grey matter volumes measured in four cortical regions of interests. Their combination provided the optimal classification performance (highest sensitivity and specificity) ensemble ML model, Extreme Gradient Boosting with over-sampling of the minority class, with performance metrics: sensitivity = 1.00, specificity = 0.92 and area-under-the-curve = 0.96. The median values based on fifty random train/test splits were sensitivity = 0.83 (interquartile range (IQR) = 0.17), specificity = 0.77 (IQR = 0.23) and area-under-the-curve = 0.75 (IQR = 0.11). Conclusion: A high-performance algorithm that could be translatable into practice was able to predict SCD conversion to MCI/AD by using only six predictive variables.
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Springer eBooks, 2019
Parkinson’s disease (PD) is a complex neurodegenerative disorder. It is characterized by a combin... more Parkinson’s disease (PD) is a complex neurodegenerative disorder. It is characterized by a combination of motor and nonmotor symptoms that gradually appear as consequence of the selective loss of dopaminergic neurons in the substantia nigra pars compacta and the presence of Lewy bodies and dystrophic neurites, two abnormal structures composed by misfolded α-synuclein. Recent evidences suggest that the toxicity caused by α-synuclein relies on its oligomerization, which precedes the formation of the large α-synuclein aggregates. Several important contributions have been made in the PD field during recent years. However, an early and accurate diagnosis, together with the availability of disease-modifying therapies, still represents a major unmet need. The emergence of nanotechnology has provided new systems like ultra-sensitive biosensors that are able to detect PD-related biomarkers in complex but more accessible biological fluids, and novel MRI agents for contrast enhancement in imaging applications. Nanotechnology could also revolutionize the PD therapeutic pipeline, which is currently focused on the relief of motor symptoms. To date, the efficacy of nanotechnology in PD treatment has been supported by a large number of preclinical studies that have encapsulated different drugs in a wide range of nanoscale delivery systems such as nanoparticles, liposomes, exosomes, and quantum dots. In this chapter, we provide an overview of recent advances in the application of nanomedicine to both the diagnosis and treatment of PD. The main challenges anticipated, future perspectives, and the possibility of transferring these studies to future clinical trials are also discussed.
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Scientific Reports, 2020
The study was aimed at analysing the frequency of impulse control disorders (ICDs) and compulsive... more The study was aimed at analysing the frequency of impulse control disorders (ICDs) and compulsive behaviours (CBs) in patients with Parkinson’s disease (PD) and in control subjects (CS) as well as the relationship between ICDs/CBs and motor, nonmotor features and dopaminergic treatment in PD patients. Data came from COPPADIS-2015, an observational, descriptive, nationwide (Spain) study. We used the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) for ICD/CB screening. The association between demographic data and ICDs/CBs was analyzed in both groups. In PD, this relationship was evaluated using clinical features and treatment-related data. As result, 613 PD patients (mean age 62.47 ± 9.09 years, 59.87% men) and 179 CS (mean age 60.84 ± 8.33 years, 47.48% men) were included. ICDs and CBs were more frequent in PD (ICDs 12.7% vs. 1.6%, p < 0.001; CBs 7.18% vs. 1.67%, p = 0.01). PD patients had more frequent previous ICDs his...
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European Journal of Neurology, 2020
Background and purposeThe objective of this study was to analyze the relationship between motor c... more Background and purposeThe objective of this study was to analyze the relationship between motor complications and non‐motor symptom (NMS) burden in a population of patients with Parkinson’s disease (PD) and also in a subgroup of patients with early PD.MethodsPatients with PD from the COPPADIS cohort were included in this cross‐sectional study. NMS burden was defined according to the Non‐Motor Symptoms Scale (NMSS) total score. Unified Parkinson’s Disease Rating Scale (UPDRS) part IV was used to establish motor complication types and their severity. Patients with ≤5 years of symptoms from onset were included as patients with early PD.ResultsOf 690 patients with PD (62.6 ± 8.9 years old, 60.1% males), 33.9% and 18.1% presented motor fluctuations and dyskinesia, respectively. The NMS total score was higher in patients with motor fluctuations (59.2 ± 43.1 vs. 38.3 ± 33.1; P < 0.0001) and dyskinesia (63.5 ± 40.7 vs. 41.4 ± 36.3; P < 0.0001). In a multiple linear regression model an...
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Nanobiotechnology in Neurodegenerative Diseases, 2019
Parkinson’s disease (PD) is a complex neurodegenerative disorder. It is characterized by a combin... more Parkinson’s disease (PD) is a complex neurodegenerative disorder. It is characterized by a combination of motor and nonmotor symptoms that gradually appear as consequence of the selective loss of dopaminergic neurons in the substantia nigra pars compacta and the presence of Lewy bodies and dystrophic neurites, two abnormal structures composed by misfolded α-synuclein. Recent evidences suggest that the toxicity caused by α-synuclein relies on its oligomerization, which precedes the formation of the large α-synuclein aggregates. Several important contributions have been made in the PD field during recent years. However, an early and accurate diagnosis, together with the availability of disease-modifying therapies, still represents a major unmet need. The emergence of nanotechnology has provided new systems like ultra-sensitive biosensors that are able to detect PD-related biomarkers in complex but more accessible biological fluids, and novel MRI agents for contrast enhancement in imaging applications. Nanotechnology could also revolutionize the PD therapeutic pipeline, which is currently focused on the relief of motor symptoms. To date, the efficacy of nanotechnology in PD treatment has been supported by a large number of preclinical studies that have encapsulated different drugs in a wide range of nanoscale delivery systems such as nanoparticles, liposomes, exosomes, and quantum dots. In this chapter, we provide an overview of recent advances in the application of nanomedicine to both the diagnosis and treatment of PD. The main challenges anticipated, future perspectives, and the possibility of transferring these studies to future clinical trials are also discussed.
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Annals of Neurology, 2019
ObjectiveAlzheimer disease (AD) is the leading cause of dementia, and although its etiology remai... more ObjectiveAlzheimer disease (AD) is the leading cause of dementia, and although its etiology remains unclear, it seems that type 2 diabetes mellitus (T2DM) and other prediabetic states of insulin resistance could contribute to the appearance of sporadic AD. As such, we have assessed whether tau and β‐amyloid (Aβ) deposits might be present in pancreatic tissue of subjects with AD, and whether amylin, an amyloidogenic protein deposited in the pancreas of T2DM patients, might accumulate in the brain of AD patients.MethodsWe studied pancreatic and brain tissue from 48 individuals with no neuropathological alterations and from 87 subjects diagnosed with AD. We examined Aβ and tau accumulation in the pancreas as well as that of amylin in the brain. Moreover, we performed proximity ligation assays to ascertain whether tau and/or Aβ interact with amylin in either the pancreas or brain of these subjects.ResultsCytoplasmic tau and Aβ protein deposits were detected in pancreatic β cells of subj...
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Parkinsonism & Related Disorders, 2019
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Acta Neuropathologica Communications, 2021
Protein misfolding diseases refer to a variety of disorders that develop as a consequence of the ... more Protein misfolding diseases refer to a variety of disorders that develop as a consequence of the misfolding of proteins in various organs. The etiologies of Parkinson’s and Alzheimer’s disease remain unclear, but it seems that type two diabetes and other prediabetic states could contribute to the appearance of the sporadic forms of these diseases. In addition to amylin deposition, other amyloidogenic proteins implicated in the pathophysiology of neurodegenerative diseases could have important roles in the pathogenesis of this disease. As we have previously demonstrated the presence of α-synuclein deposits in the pancreas of patients with synucleinopathies, as well as tau and Aβ deposits in the pancreatic tissue of Alzheimer’s disease patients, we studied the immunoreactivity of amylin, tau and α-synuclein in the pancreas of 138 subjects with neurodegenerative diseases or type two diabetes and assessed whether the pancreatic β-cells of these subjects present cooccurrence of misfolded...
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npj Parkinson's Disease, 2021
Quality of life (QOL) plays an important role in independent living in Parkinson’s disease (PD) p... more Quality of life (QOL) plays an important role in independent living in Parkinson’s disease (PD) patients, being crucial to know what factors impact QoL throughout the course of the disease. Here we identified predictors of QoL impairment in PD patients from a Spanish cohort. PD patients recruited from 35 centers of Spain from the COPPADIS cohort from January 2016, to November 2017, were followed up during 2 years. Health-related QoL (HRQoL) and global QoL (GQoL) were assessed with the 39-item Parkinson’s disease Questionnaire (PDQ-39) and the EUROHIS-QOL 8-item index (EUROHIS-QOL8), respectively, at baseline (V0) and at 24 months ± 1 month (V2). Clinically significant QoL impairment was defined as presenting an increase (PDQ-39SI) or decrement (EUROHIS-QOL8) at V2 ≥ 10% of the score at baseline (V0). A comparison with a control group was conducted for GQoL. GQoL did not change significantly in PD patients (N = 507; p = 0.686) or in the control group (N = 119; p = 0.192). The mean PD...
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Nanobiotechnology in Neurodegenerative Diseases, 2019
Parkinson’s disease (PD) is a complex neurodegenerative disorder. It is characterized by a combin... more Parkinson’s disease (PD) is a complex neurodegenerative disorder. It is characterized by a combination of motor and nonmotor symptoms that gradually appear as consequence of the selective loss of dopaminergic neurons in the substantia nigra pars compacta and the presence of Lewy bodies and dystrophic neurites, two abnormal structures composed by misfolded α-synuclein. Recent evidences suggest that the toxicity caused by α-synuclein relies on its oligomerization, which precedes the formation of the large α-synuclein aggregates. Several important contributions have been made in the PD field during recent years. However, an early and accurate diagnosis, together with the availability of disease-modifying therapies, still represents a major unmet need. The emergence of nanotechnology has provided new systems like ultra-sensitive biosensors that are able to detect PD-related biomarkers in complex but more accessible biological fluids, and novel MRI agents for contrast enhancement in imag...
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Expert opinion on pharmacotherapy, 2017
Parkinson's disease (PD) is a progressive neurodegenerative disease. The currently available ... more Parkinson's disease (PD) is a progressive neurodegenerative disease. The currently available treatment options only have a symptomatic effect. With disease progression almost all antiparkinsonian pharmacological classes are tried, but the gold standard of pharmacological management is still L-dopa. Various strategies can be used to raise the dopaminergic tone. Catechol-O-methyltransferase (COMT) inhibitors attain this goal by decreasing L-dopa peripheral metabolism. Areas covered: Opicapone (Ongentys®) is a new COMT inhibitor developed to fulfill the need for more potent, safer and longer acting COMT inhibitors. This review puts into context opicapone's indications, its chemical and preclinical data, the pharmacodynamics and pharmacokinetic characteristics, and the efficacy and safety results delivered by clinical trials. Expert opinion: Opicapone is an efficacious COMT inhibitor. Its proprieties make it adequate for a once-a-day oral dose regimen. It has proved to reduce th...
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Revista de neurologia, Jan 16, 2015
Natalizumab is a drug used in multiple sclerosis (MS) and its main side effect is the development... more Natalizumab is a drug used in multiple sclerosis (MS) and its main side effect is the development of progressive multifocal leukoencephalopathy (PML). Since this is potentially fatal or disabling, treatment must be stopped immediately if it is suspected, taking into account the possible later development of immune reconstitution syndrome or renewed exacerbation of MS. We report a case of initially asymptomatic PML within the context of treatment with natalizumab in a female patient with MS. High antibody titers to the John Cunningham virus (JCV) and over two years' treatment were established as risk factors. The polymerase chain reaction for the JCV in cerebrospinal fluid was negative in two determinations. The interval between the radiological diagnosis and the onset of the clinical features was two months. During the course of the disease, the patient developed immune reconstitution inflammatory syndrome and relapses, or renewed exacerbation, of her MS. She responded well afte...
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Journal of Alzheimer's Disease
Background: Subjective cognitive decline (SCD) may represent a preclinical stage of Alzheimer’s d... more Background: Subjective cognitive decline (SCD) may represent a preclinical stage of Alzheimer’s disease (AD). Predicting progression of SCD patients is of great importance in AD-related research but remains a challenge. Objective: To develop and implement an ensemble machine learning (ML) algorithm to identify SCD subjects at risk of conversion to mild cognitive impairment (MCI) or AD. Methods: Ninety-nine SCD patients were included. Thirty-two progressed to MCI/AD, while 67 remained stable. To minimize the effect of class imbalance, both classes were balanced, and sensitivity was taken as evaluation metric. Bagging and boosting ML models were developed by using socio-demographic and clinical information, Mini-Mental State Examination and Geriatric Depression Scale (GDS) scores (feature-set 1a); socio-demographic characteristics and neuropsychological tests scores (feature-set 1b) and regional magnetic resonance imaging grey matter volumes (feature-set 2). The most relevant variable...
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Papers by Glòria Martí Andrés