Publications by authors named "Pablo Mir"

Cortical hypometabolism on FDG-PET is a well-established neuroimaging biomarker of cognitive impairment in Parkinson's disease (PD), but its pathophysiologic origins are incompletely understood. Cholinergic basal forebrain (cBF) degeneration is a prominent pathological feature of PD-related cognitive impairment and may contribute to cortical hypometabolism through cholinergic denervation of cortical projection areas. Here, we investigated in-vivo associations between subregional cBF volumes on 3T-MRI, cortical hypometabolism on [F]FDG-PET, and cognitive deficits in a cohort of 95 PD participants with varying degrees of cognitive impairment.

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Article Synopsis
  • A study was conducted to investigate the X-chromosome's role in Alzheimer's Disease (AD), which had been overlooked in previous genome-wide association studies.
  • The research included 115,841 AD cases and 613,671 controls, considering different X-chromosome inactivation (XCI) states in females.
  • While no strong genetic risk factors for AD were found on the X-chromosome, seven significant loci were identified, suggesting areas for future research.
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Background And Purpose: Parkinson disease (PD) is a complex and heterogeneous neurodegenerative disorder with a broad spectrum of clinical manifestations, determined by a complex interplay of environmental and genetic factors. This study aimed to investigate genetic variants associated with PD and assess their impact on the disease phenotype through genotype-phenotype correlations.

Methods: We employed a targeted resequencing panel to analyze 27 genes linked to PD in a cohort of 1185 PD patients from southern Spain.

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Background: Limited information is available on patients' experience living with Huntington's disease (HD). The primary objective of this study was to assess the health-related quality of life and well being of patients with HD.

Methods: A non-interventional, cross-sectional study was conducted in 17 hospitals-based movement disorders units in Spain.

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Background: Alzheimer's disease (AD) has a high heritable component characteristic of complex diseases, yet many of the genetic risk factors remain unknown. We combined genome-wide association studies (GWAS) on amyloid endophenotypes measured in cerebrospinal fluid (CSF) and positron emission tomography (PET) as surrogates of amyloid pathology, which may be helpful to understand the underlying biology of the disease.

Methods: We performed a meta-analysis of GWAS of CSF Aβ42 and PET measures combining six independent cohorts (n=2,076).

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Background And Purpose: Peripheral inflammation is probably involved in the pathogenesis of progressive supranuclear palsy (PSP) and it may be a common feature with Parkinson's disease (PD). The peripheral immune profile in PSP remains unclear, as well as whether the inflammatory pathways differ from those in PD. The neutrophil-to-lymphocyte ratio (NLR) has been proven to be a well-established biomarker of systemic inflammation.

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Background: Levodopa-induced dyskinesia (LID) is a common adverse effect of levodopa, one of the main therapeutics used to treat the motor symptoms of Parkinson's disease (PD). Previous evidence suggests a connection between LID and a disruption of the dopaminergic system as well as genes implicated in PD, including GBA1 and LRRK2.

Objectives: Our goal was to investigate the effects of genetic variants on risk and time to LID.

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Importance: Functional movement disorders (FMDs) are frequent and disabling neurological disorders with a substantial socioeconomic impact. Few randomized studies have analyzed the effectiveness of combined physiotherapy and psychotherapy in patients' quality of life.

Objective: To assess the efficacy of multidisciplinary treatment (physiotherapy plus cognitive behavioral therapy) in FMDs.

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Although transcranial direct current stimulation constitutes a non-invasive neuromodulation technique with promising results in a great variety of applications, its clinical implementation is compromised by the high inter-subject variability reported. This study aims to analyze the inter-subject variability in electric fields (E-fields) over regions of the cortical motor network under two electrode montages: the classical C3Fp2 and an alternative P3F3, which confines more the E-field over this region.Computational models of the head of 98 healthy subjects were developed to simulate the E-field under both montages.

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The ATP10B gene has been proposed to play an important role in the development of early-onset Parkinson's disease (PD). Nevertheless, various studies have presented controversial conclusions regarding the involvement of this gene in PD. Here, we screened 1162 patients with PD, employing a targeted resequencing approach to investigate the putative relevance of this gene in a large independent cohort of these patients from southern Spain.

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Background: Levodopa-induced dyskinesias (LID) are frequent in Parkinson's disease (PD).

Objective: To analyze the change in the frequency of LID over time, identify LID related factors, and characterize how LID impact on patients' quality of life (QoL).

Patients And Methods: PD patients from the 5-year follow-up COPPADIS cohort were included.

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Article Synopsis
  • Multiple system atrophy (MSA) is a neurodegenerative disease that leads to symptoms like parkinsonism and ataxia, but its genetic causes are not well understood and treatment options are limited to supportive care.
  • A comprehensive study involving the whole genome sequencing of nearly 900 MSA patients and over 7,000 controls discovered four key genetic risk factors associated with the disease.
  • The research identified potential susceptibility genes and provided insights into how genetic variations influence gene expression in brain cells, offering a valuable resource for further studies on similar diseases.
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  • - Microglial dysfunction is linked to Alzheimer's disease (AD), with a focus on a variant affecting the SIRPβ1 receptor that regulates the clearance of amyloid-β (Aβ).
  • - The study found that a specific insertion in the SIRPβ1 gene alters protein function, increasing the risk of AD and affecting cognitive decline rates in patients with mild cognitive impairment.
  • - Results suggest that this SIRPβ1 variant could influence microglial responses to Aβ and may serve as a potential target for treatment strategies that involve the TREM2-TYROBP pathway.
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Background: Pathogenic variants in several genes have been linked to genetic forms of isolated or combined dystonia. The phenotypic and genetic spectrum and the frequency of pathogenic variants in these genes have not yet been fully elucidated, neither in patients with dystonia nor with other, sometimes co-occurring movement disorders such as Parkinson's disease (PD).

Objectives: To screen >2000 patients with dystonia or PD for rare variants in known dystonia-causing genes.

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Background: Deep brain stimulation (DBS) is a highly efficient, evidence-based therapy to alleviate symptoms and improve quality of life in movement disorders such as Parkinson's disease, essential tremor, and dystonia, which is also being applied in several psychiatric disorders, such as obsessive-compulsive disorder and depression, when they are otherwise resistant to therapy.

Summary: At present, DBS is clinically applied in the so-called open-loop approach, with fixed stimulation parameters, irrespective of the patients' clinical state(s). This approach ignores the brain states or feedback from the central nervous system or peripheral recordings, thus potentially limiting its efficacy and inducing side effects by stimulation of the targeted networks below or above the therapeutic level.

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Complex disorders are caused by a combination of genetic, environmental and lifestyle factors, and their prevalence can vary greatly across different populations. The extent to which genetic risk, as identified by Genome Wide Association Study (GWAS), correlates to disease prevalence in different populations has not been investigated systematically. Here, we studied 14 different complex disorders and explored whether polygenic risk scores (PRS) based on current GWAS correlate to disease prevalence within Europe and around the world.

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Background And Objective: Recently, we demonstrated that staging Parkinson's disease (PD) with a novel simple classification called MNCD, based on four axes (motor, non-motor, cognition, and dependency) and five stages, correlated with disease severity and patients' quality of life. Here, we analyzed the correlation of MNCD staging with PD caregiver's status.

Patients And Methods: Data from the baseline visit of PD patients and their principal caregiver recruited from 35 centers in Spain from the COPPADIS cohort from January 2016 to November 2017 were used to apply the MNCD total score (from 0 to 12) and MNCD stages (from 1 to 5) in this cross-sectional analysis.

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Background: Levodopa-induced dyskinesia (LID) is a common adverse effect of levodopa, one of the main therapeutics used to treat the motor symptoms of Parkinson's disease (PD). Previous evidence suggests a connection between LID and a disruption of the dopaminergic system as well as genes implicated in PD, including and .

Objectives: To investigate the effects of genetic variants on risk and time to LID.

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Article Synopsis
  • Parkinson's disease (PD) is a brain disorder affecting about 7 million people, with genetics playing a big role in some cases, especially in European people.
  • Most research has been done on people of European descent, leaving a gap in understanding how PD affects other groups.
  • To improve research and create new treatments, scientists have formed a global network of 59 research centers and developed tools like an online map to share information and resources with each other.
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  • Scientists studied over 176,000 people to see how certain genes might protect against Parkinson's disease (PD) and Alzheimer's disease (AD).
  • They found that specific types of a gene called HLA could help reduce the risk of these diseases and lower harmful proteins in the brain.
  • This suggests that our immune system might help protect us from PD and AD, which could lead to new treatments in the future.
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Background: The evaluation of motor impairment in Parkinson's disease (PD) is mainly assessed with the motor subdomain of the Unified Parkinson's Disease Rating scale (UPDRS part III) and, lately, with the MDS-UPDRS part III. To optimize efforts and special needs during specific circumstances in clinical practice, we sought to identify the most sensitive items to assess motor impairment in PD.

Methods: We included the COPPADIS-PD cohort and collected the UPDRS part III at baseline (V0), 12 months (V1), and 24 months (V2).

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