Frederic Sampedro

Hospital de la Santa Creu i Sant Pau

Background: Cognitive decline in Parkinson's disease (PD) is a highly prevalent condition with no effective treatment. Cortical atrophy is thought to promote its development but to design optimal therapeutic approaches in this clinical setting we need to understand the physiopathological mechanisms leading to this disorder. Objective: To charact...

Diffusion tensor imaging (DTI) allows the quantification of water diffusivity within the cerebral cortex. Alterations in cortical mean diffusivity (MD) have been suggested to reflect microstructural damage. Interestingly, microstructural changes can be detected in the absence of macrostructural alterations such as cortical thinning or gray matter v...

Striatal dopamine transporter (DAT) uptake assessment through I¹²³-Ioflupane Single-Pphoton Emission Computed Tomography (SPECT) provides valuable information about the dopaminergic denervation occurring in Parkinson's disease (PD). However, little is known about the clinical or biological relevance of extrastriatal DAT uptake in PD. Here, from the...

Introduction Cognitive impairment and dementia are highly prevalent non-motor complications in Parkinson's disease (PD) with deleterious consequences for patients and caregivers. With no treatment currently available, finding and validating minimally-invasive biomarkers of neurodegeneration in this population represents an urgent need for clinical...

Background: The C allele of the rs11136000 genetic variant of the clusterin gene has been associated with increased risk of Alzheimer's disease. However, a comprehensive characterization of the role of this genetic variant in early cognitive deterioration in PD is lacking. Methods: Using the Parkinson's Progression Markers Initiative database, w...

Background Minor hallucinations in Parkinson's disease are associated with connectivity changes in attentional networks and increased risk of structured hallucinations. However, the clinical translation of these abnormalities in attention processes is not well-defined, and commonly used neuropsychological tests are not able to detect significant de...

Background Patients with Huntington’s disease (HD) exhibit a variable predominance of cognitive, behavioral and motor symptoms. A specific instrument focusing on the impact of cognitive impairment in HD over functional capacity is lacking. Objective To address the need for a brief and specifically developed HD questionnaire able to capture functio...

Background and purpose: Reduced facial expression of emotions is a very frequent symptom of Parkinson's disease (PD) and has been considered part of the motor features of the disease. However, the neural correlates of hypomimia and the relationship between hypomimia and other non-motor symptoms of PD are poorly understood. Methods: The clinical...

Background: Huntington's disease (HD) is a neurodegenerative disorder characterized by cognitive, motor, and neuropsychiatric manifestations. Oxytocin is a neuropeptide studied for its role as a neuromodulator regulating multiple behaviors linked to social cognition. Genetic variation of oxytocin receptor (OXTR) might interact in the etiology and...

Although there is evidence that chemotherapy can have side effects on metabolism and brain function, there are few studies on the occurrence of these side effects with immunotherapy. The present study was conducted to assess whether brain metabolic changes occur in patients with malignant melanoma under immunotherapy. Thirty-nine patients after sur...

Background: Cognitive dysfunction is a disabling complication in Parkinson's disease (PD). Accuracy of diagnosis of mild cognitive impairment in PD (PD-MCI) depends on the tests performed, which limits results generalization. Blood-based biomarkers could provide additional objective information for PD-MCI diagnosis and progression. Blood neurofila...

Background: Apathy represents a core neuropsychiatric symptom in Parkinson's disease (PD). As there is currently no established effective treatment for apathy in PD, further investigating the biological origin of this symptom is needed to design novel therapeutic strategies. Among the multiple neurotransmitter alterations that have been associated...

Mild cognitive impairment in Parkinson’s disease (PD-MCI) is associated with consistent structural and functional brain changes. Whether different approaches for diagnosing PD-MCI are equivalent in their neural correlates is presently unknown. We aimed to profile the neuroimaging changes associated with the two endorsed methods of diagnosing PD-MCI...

Purpose Huntington’s disease (HD) is a monogenic neurodegenerative disease with no effective treatment currently available. The pathological hallmark of HD is the aggregation of mutant huntingtin in the medium spiny neurons of the striatum, leading to severe subcortical atrophy. Cortical degeneration also occurs in HD from its very early stages, al...

Background Blood homocysteine appears to be increased in Parkinson's disease (PD) and may play a role in the development and progression of this disorder. However, the specific contribution of abnormal homocysteine levels to cortical degeneration in PD remains elusive. Objective To characterize the cortical structural correlates of homocysteine le...

Background: Huntington's disease is a neurodegenerative disorder characterized by clinical alterations in the motor, behavioral, and cognitive domains. However, the structure and disruptions to large-scale brain cognitive networks have not yet been established. Objective: We aimed to profile changes in large-scale cognitive networks in premanife...

Female Huntington’s disease (HD) patients have consistently shown a faster clinical worsening than male, but the underlying mechanisms responsible for this observation remain unknown. Here, we describe how sex modifies the impact of neurodegeneration on brain atrophy and clinical severity in HD. Cerebrospinal fluid neurofilament light chain (NfL) l...

Objectives: Previous imaging studies in patients with borderline personality disorder (BPD) have detected functional brain dysfunctions. Mindfulness training may improve the symptoms of BPD, although the neural mechanisms involved remain poorly understood. This study had several key aims: 1) to investigate the role of right anterior insula (rAI) f...

Although previous imaging studies in borderline personality disorder (BPD) have found brain abnormalities, the results have been inconsistent. This study aimed to investigate structural brain abnormalities using voxel-based morphometry (VBM) and cortical thickness (Cth) analyses in a large sample of patients with BPD. Additionally, we aimed to dete...

Background: Arithmetic word-problem solving depends on the interaction of several cognitive processes that may be affected early in the disease in gene-mutation carriers for Huntington's disease (HD). Objective: Our goal was to examine the pattern of performance of arithmetic tasks in premanifest and manifest HD, and to examine correlations betw...

Background The mechanisms through which kappa opioid receptor (KOR) agonists induce psychotomimetic effects are largely unknown, although the modulation of this receptor has attracted attention for its clinical use. In this work, we characterize the neuropharmacological effects of salvinorin-A, a highly selective KOR agonist. Methods Changes in mu...

Background Although several progressive supranuclear palsy (PSP) phenotypes have recently been described, studies identifying cognitive and neuropsychiatric differences between them are lacking. Methods An extensive battery of cognitive and behavioural assessments was administered to 63 PSP patients, 25 PD patients with similar sociodemographic cha...

Dopamine-replacing therapies are an effective treatment for the motor aspects of Parkinson's disease. However, its precise effect over the cognitive resting-state networks is not clear; whether dopaminergic treatment normalizes their functional connectivity-as in other networks- and the links with cognitive decline are presently unknown. We recruit...

Background: Empathy is a multidimensional construct and a key component of social cognition. In Huntington's disease (HD), little is known regarding the phenomenology and the neural correlates of cognitive and affective empathy, and regarding how empathic deficits interact with other behavioral and cognitive manifestations. Objective: To explore...

Aim To determine if there are differences in terms of neurophysiology and neurocognitive functioning a group of type 1 diabetes (T1D) patients in terms of hypoglycaemia awareness. Methods 27 patients with T1D were classified according to Clarke score as having impaired awareness of hypoglycaemia (IAH; n=11) or normal awareness to hypoglycaemia (NA...

Hallucinations in Parkinson’s disease (PD) are disturbing and frequent non-motor symptoms and constitute a major risk factor for psychosis and dementia. We report a robotics-based approach applying conflicting sensorimotor stimulation, enabling the induction of presence hallucinations (PHs) and the characterization of a subgroup of patients with PD...

Objectives To explore and quantify systematically the ocular abnormal movements present in progressive supranuclear palsy (PSP) from the early stages, to assess the ability of this standardized examination in the differential diagnosis of PSP from Parkinson’s disease (PD), and to compare in more detail oculomotor disturbances between PSP variants....

Introduction Huntington’s disease is a severe neurodegenerative disorder with no effective treatment. Minimally-invasive biomarkers such as blood neurofilament light chain (NfL) in HD are therefore needed to quantitatively characterize neuronal loss. NfL levels in HD are known to correlate with disease progression and striatal atrophy, but whether...

Treatment-resistant auditory verbal hallucinations (TRAVH) are a relatively prevalent and devastating symptom in patients with schizophrenia (SCZ). Even though their pathological mechanisms are poorly understood, they seem to differ from those underlying non-hallucinating SCZ. In this study, we characterise structural brain changes in SCZ patients...

In Huntington’s disease (HD), irritability and aggressive behavior represent highly prevalent and disabling neuropsychiatric symptoms. However, their structural brain correlates have not been extensively explored. Here, we rated the severity of irritability and aggression (IAs) using the Problem Behaviors Assessment for HD (PBA-s) in 31 early HD pa...

The original version of this article unfortunately contained a mistake.

Context Type 1 Diabetes (T1D) is associated with an increased risk of cognitive decline, where severe hypoglycaemia (SH) and impaired awareness of hypoglycaemia (IAH) may play a role. While there is evidence of a possible association between IAH and brain damage, the potential brain changes remain poorly characterized by magnetic resonance imaging...

Background and purpose Well‐structured hallucinations in Parkinson’s disease (PD) are associated with poor prognosis and dementia. However, the predictive value of minor psychotic phenomena in cognitive deterioration is not well known. Cross‐sectional studies have shown that PD patients with minor hallucinations have more severe cortical atrophy th...

About 20% of type 1 diabetes (T1D) patients have impaired awareness of hypoglycemia (IAH). IAH represents a risk factor for severe and recurrent hypoglycemic events, which can lead to brain damage. As no effective treatments are currently available to prevent IAH in this population, characterizing the set of brain alterations associated with IAH ma...

Background: Huntington's disease (HD) is a fatal genetic neurodegenerative disorder with no effective treatment currently available. Progressive basal ganglia and whole-brain atrophy and concurrent cognitive deterioration are prototypical aspects of HD. However, the specific patterns of brain atrophy underlying cognitive impairment of different se...

Background Impulse control disorders (ICD) are a common and disrupting complication of Parkinson’s disease (PD) treatment. Although their relationship with dopaminergic activity is well studied, their brain metabolic correlates are mostly unknown. Methods In this work we studied brain metabolism using brain ¹⁸F-FDG-PET. We performed a case-control...

Introduction Impaired awareness of hypoglycemia (IAH) is a common complication in patients with type-1 diabetes (T1D). IAH is a major risk factor for severe hypoglycemic events, leading to adverse clinical consequences and cerebral damage. Non-invasive, cost-effective, and logistically efficient biomarkers for this condition have not been validated...

Hallucinations in Parkinson's disease (PD) are one of the most disturbing non-motor symptoms, affect half of the patients, and constitute a major risk factor for adverse clinical outcomes such as psychosis and dementia. Here we report a robotics-based approach, enabling the induction of a specific clinically-relevant hallucination (presence halluci...

Background Cognitive impairment is an essential feature of Huntington’s disease (HD) and dementia is a predictable outcome in all patients. However, validated instruments to assess global cognitive performance in the field of HD are lacking.Objectives We aimed to explore the utility of the Parkinson’s disease-Cognitive Rating Scale (PD-CRS) for the...

Deep brain stimulation (DBS) has been found to be effective in treatment resistant neurological and psychiatric disorders. So far there has been only one completed trial in schizophrenia, in which seven treatment resistant patients received DBS in the subgenual anterior cingulate cortex (sgACC, N = 4) or the nucleus accumbens (NAc, N = 3); four met...

Introduction: Memory alterations are common in Parkinson’s disease (PD) patients but the mechanisms involved in these deficits remain poorly understood. The study aims to explore the profile of episodic memory deficits in non-demented early PD patients. Methods: We obtained neurological, cognitive and behavioral data from 114 PD patients and 41 he...

Background Impulsivity is an aspect of personality and a major component of multiple neuropsychiatric conditions. In Parkinson’s disease, it has been associated with the expression of impulse control disorders, a highly prevalent non‐motor complication. Even though multiple tests of impulsivity have been used in this context, the impact of test cho...

We have discovered an error in the Table in our article “Depression as a Risk Factor for Impulse Control Disorders in Parkinson Disease.” The Table contains a typographical error. In the column headed “PD-Not Depressed,” the number of women should be 101 (not 104). The associated percentages and statistics were based on the correct number and there...

Objective: We aimed to investigate the relationship between cerebrospinal fluid levels (CSF) of amyloid precursor protein (APP)-derived peptides related to the amyloidogenic pathway, cortical thickness, neuropsychological performance, and cortical gene expression profiles in frontotemporal lobar degeneration (FTLD)-related syndromes, Alzheimer's d...

Progressive striatal atrophy has long been considered the pathological hallmark of Huntington’s disease (HD), but is it now recognized that malfunction and degeneration of posterior-cortical territories are also prominent characteristics of the disease. The limited knowledge about the functional impact of these posterior-cortical changes could be p...

Cognitive impairment and dementia in Parkinson's disease (PD) are highly disabling non-motor symptoms with no effective treatment currently available. As cortical degeneration is thought to be involved in the development of these comorbidities, novel imaging biomarkers capable of detecting early cortical deterioration are needed. Recently, an incre...

Background and purpose: Huntington disease is a devastating genetic neurodegenerative disorder for which no effective treatment is yet available. Although progressive striatal atrophy is its pathologic hallmark, concomitant cortical deterioration is assumed to occur, but it is poorly characterized. Our objective was to study the loss of cortical i...

Objectives: To longitudinally evaluate the role of depression in the development of impulse control disorders (ICD) in Parkinson's disease (PD) patients. Methods: Using data from the Parkinson's Progression Markers Initiative (PPMI) we included PD patients without ICD at baseline according to the Questionnaire for Impulsive-Compulsive Disorders...

Objective: To determine the cutoffs that optimized the agreement between 18 F-Florbetapir positron emission tomography (PET) and Aβ1-42, Aβ1-40, tTau, pTau and their ratios measured in cerebrospinal fluid (CSF) on the LUMIPULSE G600II instrument, we quantified the levels of these four biomarkers in 94 CSF samples from participants of the Sant Pau...

The brain-derived neurotrophic factor (BDNF) val66met polymorphism has been suggested to modulate cognitive deterioration in Parkinson's disease (PD). In particular, the val/val genotype has been recently suggested to increase the risk of cognitive decline in this population. However, to date, little is known about the underlying brain alterations...

Purpose Huntington’s disease (HD) is a fatal neurodegenerative disorder with no effective treatment currently available. Although the pathological hallmark of HD is massive striatal atrophy, it has been suggested that cortical deterioration may concomitantly occur and play a major role in the patient’s functional independence. Our objective was to...

Cognitive decline is a major disabling feature in Parkinson's disease (PD). Multimodal imaging studies have shown functional disruption in neurocognitive networks related to cognitive impairment. However, it remains unknown whether these changes are related to gray matter loss, or whether they outline network vulnerability in the early stages of co...

Objective: Because patients homozygous for Huntington disease (HD) receive the gain-of-function mutation in a double dose, one would expect a more toxic effect in homozygotes than in heterozygotes. Our aim was to investigate the phenotypic differences between homozygotes with both alleles ≥36 CAG repeats and heterozygotes with 1 allele ≥36 CAG rep...

The COMT Val¹⁵⁸Met polymorphism has recently been identified as a predictor for cognitive decline in Parkinson’s disease (PD). However, it remains unknown whether an early brain structural compromise could be involved in this clinical association. Here, in a cohort of 120 cognitively preserved de novo PD patients from the Parkinson’s Progression Ma...

Background Minor hallucinations and well‐structured hallucinations are considered in the severity continuum of the psychotic spectrum associated with Parkinson's disease. Although their chronological relationship is largely unknown, the spatial patterns of brain atrophy in these 2 forms of hallucinations partially overlap, suggesting they share sim...

The role of cerebrospinal fluid (CSF) biomarkers such as CSF α-synuclein and CSF tau in predicting cognitive decline in Parkinson's disease (PD) continues to be inconsistent. Here, using a cohort of de novo PD patients with preserved cognition from the Parkinson's Progression Markers Initiative (PPMI), we show that the SNCA rs356181 single nucleoti...

Objective: Normalization to an appropriate reference region in F-FDG PET imaging may enhance diagnostic performance in Huntington disease (HD). We aimed to identify stable brain areas that could be used to model neurometabolic degeneration in HD correlating imaging (SUVrvalues at the basal ganglia [BBGG]) and clinical parameters (disease burden sc...

Introduction: Bilingualism exerts neuroprotective effects against neurodegeneration. In Huntington's disease (HD), the systems involved in bilingual control show early compromise, but the effect of bilingualism on the course of HD is unknown. Methods: We addressed the impact of livelong use of bilingualism on the clinical features, brain structu...

The MAPT H1 haplotype has been identified as a predictor of cognitive decline in Parkinson's disease (PD). However, its underlying pathological mechanisms have not been fully established. In this work, using a cohort of 120 de novo PD patients with preserved cognition from the Parkinson's Progression Markers Initiative (PPMI) database, we found tha...

Background Apathy is the most prevalent and characteristic neuropsychiatric feature of Huntington's disease. Congruent with the main early pathological changes, apathy is primarily associated with subcortical damage in frontal‐striatal circuits. However, little is known about its precise subserving mechanisms and the contribution of regions other t...

Apathy is a common but poorly understood neuropsychiatric disturbance in Parkinson’s disease (PD). In a recent study using event-related brain potentials we demonstrated impaired reward processing and compromised mesocortico-limbic pathways in PD patients with clinical symptoms of apathy. Here we aimed to further investigate the involvement of rewa...

Background: Ayahuasca is a plant tea containing the psychedelic 5-HT2A agonist N,N-dimethyltryptamine and harmala monoamine-oxidase inhibitors. Acute administration leads to neurophysiological modifications in brain regions of the default mode network, purportedly through a glutamatergic mechanism. Post-acutely, ayahuasca potentiates mindfulness ca...