Felix Bermejo Pareja - Academia.edu (original) (raw)
Papers by Felix Bermejo Pareja
JMIR Research Protocols, 2019
Background: The Neurological Disorders in Central Spain, second survey (NEDICES-2) is a populatio... more Background: The Neurological Disorders in Central Spain, second survey (NEDICES-2) is a population-based, closed-cohort study that will include over 8000 subjects aged ≥55 years. It will also include a biobank. Objective: The objective of this study was to evaluate all major aspects of the NEDICES-2 (methods, database, screening instruments, and questionnaires, as well as interexpert rating of the neurological diagnoses) in each one of the planned areas (all of them in central Spain) and to test the possibility of obtaining biological samples from each participant. Methods: A selection of patients and participants of the planned NEDICES-2 underwent face-to-face interviews including a comprehensive questionnaire on demographics, current medications, medical conditions, and lifestyle habits. Biological samples (blood, saliva, urine, and hair) were also obtained. Furthermore, every participant was examined by a neurologist.
Revista de Neurología, 2006
Objetivos. Conocer el numero de reclamaciones que recibe el Servicio de Neurologia en un ano, y r... more Objetivos. Conocer el numero de reclamaciones que recibe el Servicio de Neurologia en un ano, y realizar un analisis cualitativo, asi como revisar la gestion llevada a cabo para dar respuesta a los pacientes. Materiales y metodos. Estudio retrospectivo de reclamaciones de los pacientes al Servicio de Neurologia durante el ano 2004, mediante la informacion suministrada por el Servicio de Atencion al Paciente. Los indicadores de calidad utilizados para evaluar la gestion llevada a acabo fueron: porcentaje de reclamaciones respondidas < 30 dias desde su recepcion y porcentaje de reclamaciones solucionadas. Resultados. Se recibieron 183 reclamaciones: 1/478 ingresos hospitalarios (0,21%), 71/43.841 consultas medicas (0,16%), 110/5.522 estudios neurofisiologicos (2%), y 3 de otro origen. El 90,2% de todas las reclamaciones tenia relacion con las listas de espera; un 3,3% a causa de problemas de trato personal, y el resto se debia a otras causas. El 86,3% de las reclamaciones quedo solucionado, el 10,2% se denego y el resto fue orientado o se archivo. El 77,5% de las reclamaciones se atendio en menos de 30 dias (parametro de calidad); la demora media fue de 21,3 dias (desviacion estandar: 11,3). Conclusiones. Presentamos una tasa baja de reclamaciones, aunque se debe mejorar tanto cuantitativamente, como en la gestion de estas. No existen practicamente datos publicados de estos aspectos de la gestion clinica neurologica.
Revista de Neurología, 2008
Revista de Neurología, 2008
Revista de Neurología, 2011
Current Alzheimer Research, 2017
Objective: The association between higher education and increased mortality in Alzheimer's diseas... more Objective: The association between higher education and increased mortality in Alzheimer's disease (AD) is controversial. Further it is unknown whether education predicts survival in all dementia subtypes. We assessed mortality rates and death causes of persons with dementia compared to participants without dementia. Methods: Participants derive from the Neurological Disorders in Central Spain, a prospective population-based cohort study of older adults. We compared 269 persons with dementia to 2944 participants without dementia. We carried out Cox regression models to predict the risk of mortality dependent on the educational attainment adjusting for covariates. Reasons of death were obtained from the National Population Register. Results: During a median follow-up of 5.4 years, 400 individuals died (171 with dementia, 229 without dementia). Among the participants with dementia, those with higher educational attainment had an increased risk of death than those with lower education; the adjusted hazard ratio (HRa) was 1.40 (95% confidence interval [CI], 1.01 to 1.94). When the analysis was restricted to patients with AD the HRa increased to 1.51 (95% CI = 1.01-2.24). By contrast, educational attainment was not associated with increased mortality among participants without dementia (HRa = 0.92, 95% CI = 0.71-1.20, p = 0.55), whereas education did not influence mortality in QD. Conclusion: Our findings suggest that high educational attainment is associated with increased mortality risk in people with dementia. This observation implies that neuropathology is more advanced in patients with higher education at any level of clinical severity, leading these individuals to an earlier death after diagnosis.
Current Alzheimer Research, 2015
Frontiers in Cellular Neuroscience, 2015
Megalin or low-density lipoprotein receptor-related protein-2 is a member of the low-density lipo... more Megalin or low-density lipoprotein receptor-related protein-2 is a member of the low-density lipoprotein receptor family, which has been linked to Alzheimer's disease (AD) by clearing brain amyloid β-peptide (Aβ) across the blood-cerebrospinal fluid barrier at the choroid plexus. Here, we found a soluble form of megalin secreted from choroid plexus epithelial cells. Soluble megalin levels were also localized in the human cerebrospinal fluid (CSF), being reduced in AD patients. We have also shown that soluble megalin binding to Aβ is decreased in the CSF of AD patients, suggesting that decreased sequestration of Aβ in the CSF could be associated with defective clearance of Aβ and an increase of brain Aβ levels. Thus, therapies, which increase megalin expression, at the choroid plexus and/or enhance circulating soluble megalin hold potential to control brain Aβ-related pathologies in AD.
Journal of Alzheimer's disease : JAD, 2010
In this study, we analyzed the economic impact of one-year healthcare and non-healthcare resource... more In this study, we analyzed the economic impact of one-year healthcare and non-healthcare resources utilization by patients with dementia of Alzheimer's disease (AD) under usual medical practice in Spain. A one-year, prospective, naturalistic, multicenter cohort study was designed to recruit patients with mild, moderate to severe, and severe AD according to Clinical Dementia Rating scale: the ECO study. Healthcare resources (medical visits, drugs and concomitant treatments, complementary and diagnostic tests, institutionalization and use of home-nursing facilities) and non-healthcare resources (inventory materials, consumables, professional and non-professional caregivers' time for care and supervision) were recorded and valued at 2006 prices. A total of 560 patients with possible/probable AD by DSM-IV-NINCDS-ADRDA criteria were included in the study: 68% women, 77 +/- 6 years old, 29% treatment naïve. Monthly average cost per patient was 1,425.73 euro, and increased 10.08% a...
Medicine - Programa de Formación Médica Continuada Acreditado, 2003
Se revisa la demencia vascular, y se analizan brevemente, la demencia en la enfermedad de Parkins... more Se revisa la demencia vascular, y se analizan brevemente, la demencia en la enfermedad de Parkinson, la enfermedad de Creutzfeldt-Jakob y otras enfermedades prionicas, y algunas demencias secundarias y metabolicas.
Tremor and other hyperkinetic movements (New York, N.Y.), 2012
Essential tremor (ET) is the most common tremor disorder. ET has classically been viewed as a ben... more Essential tremor (ET) is the most common tremor disorder. ET has classically been viewed as a benign monosymptomatic condition. Yet over the past 10 years, a growing body of evidence indicates that this is a progressive condition that is clinically heterogeneous, and may be associated with a variety of different features. Large epidemiological studies such as the Neurological Disorders of Central Spain (NEDICES), a longitudinal, population-based survey, have contributed significantly to the changing view of the disease. Our aim is to review some of the main results of NEDICES within the larger framework of the epidemiology of ET. Data for this review were gathered from all our articles published up to October 2011 regarding NEDICES study and "Essential Tremor". We have published 18 articles up to October 2011. The prevalence, incidence, and mortality of ET were analyzed in this cohort. In addition, ET was found to be associated with increased frailty and low morale, as wel...
Journal of Alzheimer's disease : JAD, 2014
The purpose of this review is to assess the extent to which dementia is omitted as a cause of dea... more The purpose of this review is to assess the extent to which dementia is omitted as a cause of death from the death certificates of patients with dementia. A systematic literature search was performed to identify population-based cohort studies in which all participants were examined or screened for symptoms of dementia with a validated instrument followed by confirmation of any suspected cases with a clinical examination (two-phase investigation). Data were extracted in a standardized manner and assessed through the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative. Seven studies met the selection criteria. These were from the Americas (5 articles: 2 from Canada, 2 from the US, and 1 from Brazil) and Europe (2 articles: 1 from the UK and 1 from Spain). Each met at least 83% of the STROBE criteria. The reporting of dementia on death certificates was poor in these 7 studies, ranging from 7.2%-41.8%. Respiratory or circulatory-related problems wer...
Tremor and other hyperkinetic movements (New York, N.Y.), 2014
Our aim was to assess the diagnostic agreement among the neurologists in the Neurological Disorde... more Our aim was to assess the diagnostic agreement among the neurologists in the Neurological Disorders in Central Spain 2 (NEDICES-2) study; these neurologists were assigning diagnoses of essential tremor (ET) vs. no ET. Clinical histories and standardized video-taped neurological examinations of 26 individuals (11 ET, seven Parkinson's disease, three diagnostically unclear, four normal, one with a tremor disorder other than ET) were provided to seven consultant neurologists, six neurology residents, and five neurology research fellows (18 neurologists total). For each of the 26 individuals, neurologists were asked to assign a diagnosis of "ET" or "no ET" using diagnostic criteria proposed by the Movement Disorders Society (MDS). Inter-rater agreement was assessed both with percent concordance and non-weighted κ statistics. Overall κ was 0.61 (substantial agreement), with no differences between consultant neurologists (κ = 0.60), neurology residents (κ = 0.61),…
Neurobiology of Aging, 2010
One of the possible mechanisms involved in -amyloid (A)-induced neuronal damage is blood-cerebr... more One of the possible mechanisms involved in -amyloid (A)-induced neuronal damage is blood-cerebrospinal fluid barrier dysfunction. Recently, we have demonstrated that Alzheimer patients have an elevated expression of A in the choroid plexus (CP), where it could impair the physiological functions of CP epithelium. We investigated whether these alterations were mediated by mitochondrial dysfunction, a common early pathomechanism in Alzheimer's disease. Our main observations were: high A levels; increased nitric oxide levels; impairment of the activity and assembly of mitochondrial respiratory chain complexes I and IV; and a significant increase in reactive oxygen species and caspase expression in CP epithelial cells treated with A. Our results also demonstrate a direct relationship between A toxicity, increased expression of matrix metalloproteinase-9, and blood-cerebrospinal fluid barrier disruption. We propose a sequence of pathological steps that link A accumulation in CP epithelium with an enhanced nitric oxide production, mitochondrial dysfunction, and up-regulation of matrix metalloproteinase-9, which ultimately lead to cell death, and probably to CSF barrier dysfunction.
Neuroepidemiology, 2009
Background: Recent interest in antihypertensive agents, especially calcium channel blockers, has ... more Background: Recent interest in antihypertensive agents, especially calcium channel blockers, has been sparked by the notion that these medications may be neuroprotective. A modest literature, with mixed results, has examined whether these medications might lower the odds or risk of Parkinson’s disease (PD) or dementia. There are no data for essential tremor (ET). Objective: To examine the association between antihypertensive use (defined broadly and by individual subclasses) and ET, PD and dementia. For each disorder, we used cross-sectional data (association with prevalent disease) and prospective data (association with incident disease). Methods: Prospective population-based study in Spain enrolling 5,278 participants at baseline. Results: Use of antihypertensive medications (aside from β-blockers) was similar in prevalent ET cases and controls. Baseline use of antihypertensive agents was not associated with reduced risk of incident ET. Antihypertensive medication use was not asso...
Neuroepidemiology, 2007
In a population-based sample, we determined whether a larger proportion of essential tremor (ET) ... more In a population-based sample, we determined whether a larger proportion of essential tremor (ET) cases reported hearing impairment compared with controls. Ninety-six (38.7%) of 248 ET cases versus 1,371 (29.4%) of 4,669 controls (p = 0.002) reported hearing impairment. In a logistic regression analysis adjusted for age, gender, educational level, depressive symptoms, and dementia, participants who reported hearing impairment were 30% more likely to suffer from ET than were controls (odds ratio 1.3; 95% confidence interval 1.01–1.7; p = 0.04). ET seemed to be associated with reported hearing impairment. The basis for this finding, which has been noted in several studies, deserves further exploration.
Neurocase, 2010
Mirrored-self misidentification, often referred as the &amp;amp;amp;amp;amp;amp;amp;amp;a... more Mirrored-self misidentification, often referred as the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;mirror sign&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;, is a delusion characterized by the inability to recognize one&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s own reflected image, often associated with the intact capacity to recognize others in the mirror. It has been described mainly in moderate or severe dementia, especially Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease. In the few reported cases without global cognitive impairment, right hemispheric and frontal dysfunctions have been described. We report a 90-year-old man with abrupt onset of the mirror sign after a minor right hemispheric ischemic stroke. Neuropsychological testing revealed preserved cognitive capacities, except for mild to moderate impairment of visuospatial skills, suggesting right hemisphere dysfunction. Neuroimaging showed a small right dorsolateral frontal infarct, and bifrontal encephalomalacia, consistent with a past history of head trauma. Scattered ischemic white matter lesions in posterior periventricular regions were also seen. It seems that the mirror sign is a multifactorial phenomenon that usually requires right hemispheric dysfunction (perceptual abnormalities, loss of familiarity) and frontal damage (loss of judgement and inability to correct wrong beliefs). The right frontal dorsolateral prefrontal cortex seems to have a crucial role in self-recognition.
Neurobiology of Disease, 2009
Accumulation of amyloid-beta (Abeta) peptides is thought to be a critical event in the pathology ... more Accumulation of amyloid-beta (Abeta) peptides is thought to be a critical event in the pathology of Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD), because they induce multiple neurotoxic effects, including mitochondrial dysfunction and apoptotic cell death. Therefore the reduction of Abeta is considered a primary therapeutic target. Gelsolin, an Abeta binding protein, has been shown to inhibit apoptosis, although the underlying mechanism is unclear. To clarify these effects, we manipulated cytoplasmic gelsolin levels through viral-directed overexpression in the brain of APP/Ps1 transgenic mice. We observed that gelsolin reduces brain Abeta burden in the APP/Ps1 mice, possibly by enhancing Abeta clearance via megalin. The reduction in brain Abeta levels was accompanied by an inhibition of nitric oxide production and cell death, not only in the choroid plexus but also in the cerebral cortex. Notably, overexpressed gelsolin restored the impaired mitochondrial activity in the APP/Ps1 mice, resulting in the increase of cytochrome c oxidase activity. By contrast, RNA interference to block gelsolin expression, confirmed that cytoplasmic gelsolin acts as a modulator of brain Abeta levels and its neurotoxic effects. We conclude that gelsolin might prevent brain amyloidosis and Abeta-induced apoptotic mitochondrial changes. These findings make cytoplasmic gelsolin a potential therapeutic strategy in AD.
Neurobiology of Aging, 2011
Insulin-like growth factor I (IGF-I), a neuroprotective factor with a wide spectrum of actions in... more Insulin-like growth factor I (IGF-I), a neuroprotective factor with a wide spectrum of actions in the adult brain, is involved in the pathogenesis of Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD). Circulating levels of IGF-I change in AD patients and are implicated in the clearance of brain amyloid beta (Aβ) complexes. To investigate this hypothesis, we screened the IGF-I gene for various well known single nucleotide polymorphisms (SNPs) covering % of the gene variability in a population of 2352 individuals. Genetic analysis indicated different distribution of genotypes of 1 single nucleotide polymorphism, and 1 extended haplotype in the AD population compared with healthy control subjects. In particular, the frequency of rs972936 GG genotype was significantly greater in AD patients than in control subjects (63% vs. 55%). The rs972936 GG genotype was associated with an increased risk for disease, independently of apolipoprotein E genotype, and with enhanced circulating levels of IGF-I. These findings suggest that polymorphisms within the IGF-I gene could infer greater risk for AD through their effect on IGF-I levels, and confirm the physiological role IGF-I in the pathogenesis of AD.
JMIR Research Protocols, 2019
Background: The Neurological Disorders in Central Spain, second survey (NEDICES-2) is a populatio... more Background: The Neurological Disorders in Central Spain, second survey (NEDICES-2) is a population-based, closed-cohort study that will include over 8000 subjects aged ≥55 years. It will also include a biobank. Objective: The objective of this study was to evaluate all major aspects of the NEDICES-2 (methods, database, screening instruments, and questionnaires, as well as interexpert rating of the neurological diagnoses) in each one of the planned areas (all of them in central Spain) and to test the possibility of obtaining biological samples from each participant. Methods: A selection of patients and participants of the planned NEDICES-2 underwent face-to-face interviews including a comprehensive questionnaire on demographics, current medications, medical conditions, and lifestyle habits. Biological samples (blood, saliva, urine, and hair) were also obtained. Furthermore, every participant was examined by a neurologist.
Revista de Neurología, 2006
Objetivos. Conocer el numero de reclamaciones que recibe el Servicio de Neurologia en un ano, y r... more Objetivos. Conocer el numero de reclamaciones que recibe el Servicio de Neurologia en un ano, y realizar un analisis cualitativo, asi como revisar la gestion llevada a cabo para dar respuesta a los pacientes. Materiales y metodos. Estudio retrospectivo de reclamaciones de los pacientes al Servicio de Neurologia durante el ano 2004, mediante la informacion suministrada por el Servicio de Atencion al Paciente. Los indicadores de calidad utilizados para evaluar la gestion llevada a acabo fueron: porcentaje de reclamaciones respondidas < 30 dias desde su recepcion y porcentaje de reclamaciones solucionadas. Resultados. Se recibieron 183 reclamaciones: 1/478 ingresos hospitalarios (0,21%), 71/43.841 consultas medicas (0,16%), 110/5.522 estudios neurofisiologicos (2%), y 3 de otro origen. El 90,2% de todas las reclamaciones tenia relacion con las listas de espera; un 3,3% a causa de problemas de trato personal, y el resto se debia a otras causas. El 86,3% de las reclamaciones quedo solucionado, el 10,2% se denego y el resto fue orientado o se archivo. El 77,5% de las reclamaciones se atendio en menos de 30 dias (parametro de calidad); la demora media fue de 21,3 dias (desviacion estandar: 11,3). Conclusiones. Presentamos una tasa baja de reclamaciones, aunque se debe mejorar tanto cuantitativamente, como en la gestion de estas. No existen practicamente datos publicados de estos aspectos de la gestion clinica neurologica.
Revista de Neurología, 2008
Revista de Neurología, 2008
Revista de Neurología, 2011
Current Alzheimer Research, 2017
Objective: The association between higher education and increased mortality in Alzheimer's diseas... more Objective: The association between higher education and increased mortality in Alzheimer's disease (AD) is controversial. Further it is unknown whether education predicts survival in all dementia subtypes. We assessed mortality rates and death causes of persons with dementia compared to participants without dementia. Methods: Participants derive from the Neurological Disorders in Central Spain, a prospective population-based cohort study of older adults. We compared 269 persons with dementia to 2944 participants without dementia. We carried out Cox regression models to predict the risk of mortality dependent on the educational attainment adjusting for covariates. Reasons of death were obtained from the National Population Register. Results: During a median follow-up of 5.4 years, 400 individuals died (171 with dementia, 229 without dementia). Among the participants with dementia, those with higher educational attainment had an increased risk of death than those with lower education; the adjusted hazard ratio (HRa) was 1.40 (95% confidence interval [CI], 1.01 to 1.94). When the analysis was restricted to patients with AD the HRa increased to 1.51 (95% CI = 1.01-2.24). By contrast, educational attainment was not associated with increased mortality among participants without dementia (HRa = 0.92, 95% CI = 0.71-1.20, p = 0.55), whereas education did not influence mortality in QD. Conclusion: Our findings suggest that high educational attainment is associated with increased mortality risk in people with dementia. This observation implies that neuropathology is more advanced in patients with higher education at any level of clinical severity, leading these individuals to an earlier death after diagnosis.
Current Alzheimer Research, 2015
Frontiers in Cellular Neuroscience, 2015
Megalin or low-density lipoprotein receptor-related protein-2 is a member of the low-density lipo... more Megalin or low-density lipoprotein receptor-related protein-2 is a member of the low-density lipoprotein receptor family, which has been linked to Alzheimer's disease (AD) by clearing brain amyloid β-peptide (Aβ) across the blood-cerebrospinal fluid barrier at the choroid plexus. Here, we found a soluble form of megalin secreted from choroid plexus epithelial cells. Soluble megalin levels were also localized in the human cerebrospinal fluid (CSF), being reduced in AD patients. We have also shown that soluble megalin binding to Aβ is decreased in the CSF of AD patients, suggesting that decreased sequestration of Aβ in the CSF could be associated with defective clearance of Aβ and an increase of brain Aβ levels. Thus, therapies, which increase megalin expression, at the choroid plexus and/or enhance circulating soluble megalin hold potential to control brain Aβ-related pathologies in AD.
Journal of Alzheimer's disease : JAD, 2010
In this study, we analyzed the economic impact of one-year healthcare and non-healthcare resource... more In this study, we analyzed the economic impact of one-year healthcare and non-healthcare resources utilization by patients with dementia of Alzheimer's disease (AD) under usual medical practice in Spain. A one-year, prospective, naturalistic, multicenter cohort study was designed to recruit patients with mild, moderate to severe, and severe AD according to Clinical Dementia Rating scale: the ECO study. Healthcare resources (medical visits, drugs and concomitant treatments, complementary and diagnostic tests, institutionalization and use of home-nursing facilities) and non-healthcare resources (inventory materials, consumables, professional and non-professional caregivers' time for care and supervision) were recorded and valued at 2006 prices. A total of 560 patients with possible/probable AD by DSM-IV-NINCDS-ADRDA criteria were included in the study: 68% women, 77 +/- 6 years old, 29% treatment naïve. Monthly average cost per patient was 1,425.73 euro, and increased 10.08% a...
Medicine - Programa de Formación Médica Continuada Acreditado, 2003
Se revisa la demencia vascular, y se analizan brevemente, la demencia en la enfermedad de Parkins... more Se revisa la demencia vascular, y se analizan brevemente, la demencia en la enfermedad de Parkinson, la enfermedad de Creutzfeldt-Jakob y otras enfermedades prionicas, y algunas demencias secundarias y metabolicas.
Tremor and other hyperkinetic movements (New York, N.Y.), 2012
Essential tremor (ET) is the most common tremor disorder. ET has classically been viewed as a ben... more Essential tremor (ET) is the most common tremor disorder. ET has classically been viewed as a benign monosymptomatic condition. Yet over the past 10 years, a growing body of evidence indicates that this is a progressive condition that is clinically heterogeneous, and may be associated with a variety of different features. Large epidemiological studies such as the Neurological Disorders of Central Spain (NEDICES), a longitudinal, population-based survey, have contributed significantly to the changing view of the disease. Our aim is to review some of the main results of NEDICES within the larger framework of the epidemiology of ET. Data for this review were gathered from all our articles published up to October 2011 regarding NEDICES study and "Essential Tremor". We have published 18 articles up to October 2011. The prevalence, incidence, and mortality of ET were analyzed in this cohort. In addition, ET was found to be associated with increased frailty and low morale, as wel...
Journal of Alzheimer's disease : JAD, 2014
The purpose of this review is to assess the extent to which dementia is omitted as a cause of dea... more The purpose of this review is to assess the extent to which dementia is omitted as a cause of death from the death certificates of patients with dementia. A systematic literature search was performed to identify population-based cohort studies in which all participants were examined or screened for symptoms of dementia with a validated instrument followed by confirmation of any suspected cases with a clinical examination (two-phase investigation). Data were extracted in a standardized manner and assessed through the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative. Seven studies met the selection criteria. These were from the Americas (5 articles: 2 from Canada, 2 from the US, and 1 from Brazil) and Europe (2 articles: 1 from the UK and 1 from Spain). Each met at least 83% of the STROBE criteria. The reporting of dementia on death certificates was poor in these 7 studies, ranging from 7.2%-41.8%. Respiratory or circulatory-related problems wer...
Tremor and other hyperkinetic movements (New York, N.Y.), 2014
Our aim was to assess the diagnostic agreement among the neurologists in the Neurological Disorde... more Our aim was to assess the diagnostic agreement among the neurologists in the Neurological Disorders in Central Spain 2 (NEDICES-2) study; these neurologists were assigning diagnoses of essential tremor (ET) vs. no ET. Clinical histories and standardized video-taped neurological examinations of 26 individuals (11 ET, seven Parkinson's disease, three diagnostically unclear, four normal, one with a tremor disorder other than ET) were provided to seven consultant neurologists, six neurology residents, and five neurology research fellows (18 neurologists total). For each of the 26 individuals, neurologists were asked to assign a diagnosis of "ET" or "no ET" using diagnostic criteria proposed by the Movement Disorders Society (MDS). Inter-rater agreement was assessed both with percent concordance and non-weighted κ statistics. Overall κ was 0.61 (substantial agreement), with no differences between consultant neurologists (κ = 0.60), neurology residents (κ = 0.61),…
Neurobiology of Aging, 2010
One of the possible mechanisms involved in -amyloid (A)-induced neuronal damage is blood-cerebr... more One of the possible mechanisms involved in -amyloid (A)-induced neuronal damage is blood-cerebrospinal fluid barrier dysfunction. Recently, we have demonstrated that Alzheimer patients have an elevated expression of A in the choroid plexus (CP), where it could impair the physiological functions of CP epithelium. We investigated whether these alterations were mediated by mitochondrial dysfunction, a common early pathomechanism in Alzheimer's disease. Our main observations were: high A levels; increased nitric oxide levels; impairment of the activity and assembly of mitochondrial respiratory chain complexes I and IV; and a significant increase in reactive oxygen species and caspase expression in CP epithelial cells treated with A. Our results also demonstrate a direct relationship between A toxicity, increased expression of matrix metalloproteinase-9, and blood-cerebrospinal fluid barrier disruption. We propose a sequence of pathological steps that link A accumulation in CP epithelium with an enhanced nitric oxide production, mitochondrial dysfunction, and up-regulation of matrix metalloproteinase-9, which ultimately lead to cell death, and probably to CSF barrier dysfunction.
Neuroepidemiology, 2009
Background: Recent interest in antihypertensive agents, especially calcium channel blockers, has ... more Background: Recent interest in antihypertensive agents, especially calcium channel blockers, has been sparked by the notion that these medications may be neuroprotective. A modest literature, with mixed results, has examined whether these medications might lower the odds or risk of Parkinson’s disease (PD) or dementia. There are no data for essential tremor (ET). Objective: To examine the association between antihypertensive use (defined broadly and by individual subclasses) and ET, PD and dementia. For each disorder, we used cross-sectional data (association with prevalent disease) and prospective data (association with incident disease). Methods: Prospective population-based study in Spain enrolling 5,278 participants at baseline. Results: Use of antihypertensive medications (aside from β-blockers) was similar in prevalent ET cases and controls. Baseline use of antihypertensive agents was not associated with reduced risk of incident ET. Antihypertensive medication use was not asso...
Neuroepidemiology, 2007
In a population-based sample, we determined whether a larger proportion of essential tremor (ET) ... more In a population-based sample, we determined whether a larger proportion of essential tremor (ET) cases reported hearing impairment compared with controls. Ninety-six (38.7%) of 248 ET cases versus 1,371 (29.4%) of 4,669 controls (p = 0.002) reported hearing impairment. In a logistic regression analysis adjusted for age, gender, educational level, depressive symptoms, and dementia, participants who reported hearing impairment were 30% more likely to suffer from ET than were controls (odds ratio 1.3; 95% confidence interval 1.01–1.7; p = 0.04). ET seemed to be associated with reported hearing impairment. The basis for this finding, which has been noted in several studies, deserves further exploration.
Neurocase, 2010
Mirrored-self misidentification, often referred as the &amp;amp;amp;amp;amp;amp;amp;amp;a... more Mirrored-self misidentification, often referred as the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;mirror sign&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;, is a delusion characterized by the inability to recognize one&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s own reflected image, often associated with the intact capacity to recognize others in the mirror. It has been described mainly in moderate or severe dementia, especially Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease. In the few reported cases without global cognitive impairment, right hemispheric and frontal dysfunctions have been described. We report a 90-year-old man with abrupt onset of the mirror sign after a minor right hemispheric ischemic stroke. Neuropsychological testing revealed preserved cognitive capacities, except for mild to moderate impairment of visuospatial skills, suggesting right hemisphere dysfunction. Neuroimaging showed a small right dorsolateral frontal infarct, and bifrontal encephalomalacia, consistent with a past history of head trauma. Scattered ischemic white matter lesions in posterior periventricular regions were also seen. It seems that the mirror sign is a multifactorial phenomenon that usually requires right hemispheric dysfunction (perceptual abnormalities, loss of familiarity) and frontal damage (loss of judgement and inability to correct wrong beliefs). The right frontal dorsolateral prefrontal cortex seems to have a crucial role in self-recognition.
Neurobiology of Disease, 2009
Accumulation of amyloid-beta (Abeta) peptides is thought to be a critical event in the pathology ... more Accumulation of amyloid-beta (Abeta) peptides is thought to be a critical event in the pathology of Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD), because they induce multiple neurotoxic effects, including mitochondrial dysfunction and apoptotic cell death. Therefore the reduction of Abeta is considered a primary therapeutic target. Gelsolin, an Abeta binding protein, has been shown to inhibit apoptosis, although the underlying mechanism is unclear. To clarify these effects, we manipulated cytoplasmic gelsolin levels through viral-directed overexpression in the brain of APP/Ps1 transgenic mice. We observed that gelsolin reduces brain Abeta burden in the APP/Ps1 mice, possibly by enhancing Abeta clearance via megalin. The reduction in brain Abeta levels was accompanied by an inhibition of nitric oxide production and cell death, not only in the choroid plexus but also in the cerebral cortex. Notably, overexpressed gelsolin restored the impaired mitochondrial activity in the APP/Ps1 mice, resulting in the increase of cytochrome c oxidase activity. By contrast, RNA interference to block gelsolin expression, confirmed that cytoplasmic gelsolin acts as a modulator of brain Abeta levels and its neurotoxic effects. We conclude that gelsolin might prevent brain amyloidosis and Abeta-induced apoptotic mitochondrial changes. These findings make cytoplasmic gelsolin a potential therapeutic strategy in AD.
Neurobiology of Aging, 2011
Insulin-like growth factor I (IGF-I), a neuroprotective factor with a wide spectrum of actions in... more Insulin-like growth factor I (IGF-I), a neuroprotective factor with a wide spectrum of actions in the adult brain, is involved in the pathogenesis of Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD). Circulating levels of IGF-I change in AD patients and are implicated in the clearance of brain amyloid beta (Aβ) complexes. To investigate this hypothesis, we screened the IGF-I gene for various well known single nucleotide polymorphisms (SNPs) covering % of the gene variability in a population of 2352 individuals. Genetic analysis indicated different distribution of genotypes of 1 single nucleotide polymorphism, and 1 extended haplotype in the AD population compared with healthy control subjects. In particular, the frequency of rs972936 GG genotype was significantly greater in AD patients than in control subjects (63% vs. 55%). The rs972936 GG genotype was associated with an increased risk for disease, independently of apolipoprotein E genotype, and with enhanced circulating levels of IGF-I. These findings suggest that polymorphisms within the IGF-I gene could infer greater risk for AD through their effect on IGF-I levels, and confirm the physiological role IGF-I in the pathogenesis of AD.