Institute Catala Of Neurociencies Aplicades

Barcelona, Spain

Institute Catala Of Neurociencies Aplicades

Barcelona, Spain

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Espinosa A.,Institute Catala Of Neurociencies Aplicades | Alegret M.,Institute Catala Of Neurociencies Aplicades | Valero S.,Institute Catala Of Neurociencies Aplicades | Valero S.,Autonomous University of Barcelona | And 9 more authors.
Journal of Alzheimer's Disease | Year: 2013

The most recent studies about mild cognitive impairment (MCI) are focused on the search for factors that make patients more vulnerable to conversion to dementia, mainly Alzheimer's disease (AD). The aim of this study was to determine which neuropsychological test performances, including episodic memory profiles, and genetic risk factors (APOE ε4) better predict early conversion to dementia among the four MCI subtypes. Data from 550 MCI patients were analyzed for the purpose of this study and were classified according to Petersen's criteria (2004), and also taking into account the absence (probable MCI) or presence (possible MCI) of comorbidities that could explain cognitive deficits. MCI cases were divided into Probable amnestic (Pr-aMCI) (n = 115), probable non-amnestic (Pr-naMCI) (n = 37), possible amnestic (Pss-aMCI) (n = 234), and possible non-amnestic (Pss-naMCI) (n = 164), single or multiple domain. In the whole MCI sample, regression analysis showed that low performances on Orientation, Verbal Delayed Recall of the Word List Learning test from WMS-III, and Luria's Clock test were associated with conversion to dementia, independently of APOE ε4 allele. Cox proportional-hazards showed that the Probable MCI subtype, presence of storage memory impairment, multiple domain condition, and presence of at least one ε4 allele increased the risk of conversion to dementia. Multivariate survival and Kapplan-Meier analyses showed that the Pr-aMCI with storage memory impairment had the most and closest risk of conversion to dementia. In conclusion, the Pr-aMCI subset of patients had 8.5 times more risk of converting to dementia than the Pss-naMCI group, who displayed the slowest conversion rate to dementia. © 2013 - IOS Press and the authors. All rights reserved.

Moreno-Grau S.,Institute Catala Of Neurociencies Aplicades | Ruiz A.,Institute Catala Of Neurociencies Aplicades
Expert Reviews in Molecular Medicine | Year: 2016

Genetic characterization of individuals at risk of Alzheimer's disease (AD), i.e. people having amyloid deposits in the brain without symptoms, people suffering from subjective cognitive decline (SCD) or mild cognitive impairment (MCI), has spurred the interests of researchers. However, their pre-dementia genetic profile remains mostly unexplored. In this study, we reviewed the loci related to phenotypes of AD, MCI and SCD from literature and performed the first meta-analyses evaluating the role of apolipoprotein E (APOE) in the risk of conversion from a healthy status to MCI and SCD. For AD dementia risk, an increased number of loci have been identified; to date, 28 genes have been associated with Late Onset AD. In MCI syndrome, APOE is confirmed as a pheno-conversion factor leading from MCI to AD, and clusterin is a promising candidate. Additionally, our meta-analyses revealed APOE as genetic risk factor to convert from a healthy status to MCI [OR = 1.849 (1.587–2.153); P = 2.80 × 10−15] and to a lesser extent from healthy status to SCD [OR = 1.151 (1.015–1.304); P = 0.028]. Thus, we believe that genetic studies in longitudinal SCD and MCI series may provide new therapeutic targets and improve the existing knowledge of AD. This type of studies must be completed on healthy subjects to better understand the natural disease resistance to brain insults and neurodegeneration. Copyright © Cambridge University Press 2016

Lovestone S.,University of Oxford | Boada M.,Institute Catala Of Neurociencies Aplicades | Dubois B.,University Pierre and Marie Curie | Hull M.,Center for Geriatric Medicine Freiburg | And 7 more authors.
Journal of Alzheimer's Disease | Year: 2015

Background: The ARGO study was a phase II, double-blind, placebo controlled, four parallel arm trial of tideglusib in Alzheimer's disease (AD). Objective: To prove the clinical efficacy of an inhibitor of glycogen synthase kinase-3 (GSK-3), in AD. Methods: Mild to moderate (Mini-Mental State Examination (MMSE) score, 14-26) AD patients on cholinesterase inhibitor and/or memantine treatment were administered tideglusib or placebo for 26 weeks. The ADAS-cog15 was the primary efficacy measure; function, cognition, behavior, and quality of life were assessed as secondary measures; cerebral atrophy in MRI and the levels of tau, amyloid-β, and BACE1 in cerebrospinal fluid (CSF) were exploratory endpoints. Results: 306 AD patients were randomized to active (1000 mg QD: n = 86, 1000 mg QOD: n = 90, and 500 mg QD: n = 50) or placebo (n = 85) in 55 sites in four European countries. There were no statistically significant differences between either active and placebo arms in the efficacy variables. However, BACE1 in CSF significantly decreased with treatment in a small subgroup of patients. Participants with mild AD in the 500 mg QD group showed significant responses on ADAS-cog15, MMSE, and word fluency. Diarrhea (14-18% in active, 11% placebo) and dose-dependent, mild to moderate, and fully reversible transaminase increase (9-16% in active, 3.5% placebo) were the most frequent adverse events. Conclusions: Short term (26 weeks) tideglusib was acceptably safe but produced no clinical benefit in this trial. However, given the non-linear dose response, especially in mildly affected patients, further dose finding studies in early disease stages and for longer duration are warranted to examine GSK-3 inhibition in AD patients. © 2015 - IOS Press and the authors.

Introduction and aims. Results from a pilot study and its 2-year extension (IG0502) performed on patients with mild or moderate Alzheimer's disease revealed a tendency towards clinical stabilization after a plasmapheresis program with plasma exchange with therapeutic albumin Human Albumin Grifols® 5%. Plasma levels of Aß40 and Aß42 presented a saw-tooth pattern associated to plasma exchanges. These findings encouraged a new randomized, controlled, parallel, blind study (IG0602) to confirm our previous working hypotheses, i.e. that Aß40 and Aß42 concentrations in plasma were modified pre- and post plasmapheresis with Human Albumin Grifols® 5% and, in the clinical area, that the cognitive capabilities of patients could be stabilized or even improved. Other aims of the study were focused on neuroimaging evaluation of structural and functional changes in the brain the by means of magnetic resonance and single-photon emission computerised tomography. Results. Preliminary results from the randomized study carried out after a follow-up of one year of the first 29 patients (80% of the recruited) show a clear difference between the treated and the control groups with regard to the levels of Aß40, both in plasma and in cerebrospinal fluid, that are associated with the plasma exchanges. This pattern is not so evident for Aß42. Regarding cognitive performance, the treated group scored better than the control group after the period study, according to the evaluation performed by using the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-Cog nitive (ADAS-Cog) tests. Conclusions. These preliminary results suggest that plasmapheresis with plasma exchange with Human Albumin Grifols® 5% may have a promising future as a treatment of mild-moderate Alzheimer's disease. © 2010 Revista de Neurología.

Rodriguez-Gomez O.,Institute Catala Of Neurociencies Aplicades | Palacio-Lacambra M.E.,Institute Catala Of Neurociencies Aplicades | Palasi A.,Institute Catala Of Neurociencies Aplicades | Palasi A.,Hospital Universitari Of La Vall Dhebro | And 2 more authors.
Journal of Alzheimer's Disease | Year: 2014

The incidence of dementia is rapidly increasing in developed countries due to social and demographic changes. This trend is expected to worsen in the coming decades, with the number of cases possibly even tripling in the next 25 years. Therefore Alzheimer's disease (AD) prevention is becoming a global health priority. Our knowledge of the pathophysiological process leading to the development of pathological brain lesions that characterize AD has increased exponentially in recent years. However, the phenotypic expression of AD not only depends on the development of senile plaques and neurofibrillary tangles but other factors also play a role. Thus, over the last few decades, epidemiological studies have revealed several risk factors for developing AD, such as vascular or lifestyle related factors. Having the current knowledge on AD, two different strategies have been developed for the prevention of AD: one is based on primary prevention by acting on modifiable risk factors, the other is a pathophysiology-driven approach aimed to identify individuals in a preclinical stage of the disease and treating them with drugs purporting to act on molecular targets of the amyloid cascade. Several promising trials with these approaches are currently ongoing and results are expected in the next few years. The intrinsic limitations in the design of preventive trials should be overcome through a global effort involving healthy population, healthcare professionals, governments, industry, and scientific institutions. This exertion will be more than compensated if we can make AD a preventable disease. © 2014 - IOS Press and the authors. All rights reserved.

Alegret M.,Institute Catala Of Neurociencies Aplicades | Espinosa A.,Institute Catala Of Neurociencies Aplicades | Vinyes-Junque G.,Institute Catala Of Neurociencies Aplicades | Valero S.,Institute Catala Of Neurociencies Aplicades | And 6 more authors.
Journal of Clinical and Experimental Neuropsychology | Year: 2012

There is an increasing need for standardized assessment of cognition in older patients that is relatively brief, easy to administer, and has normative data adjusted for age and educational attainment. We tested 332 literate, cognitively normal, Spanish persons older than 49 years from the Memory Clinic of Fundació ACE, Institut Català de Neurociències Aplicades (Barcelona, Spain) with measures of cognitive information processing speed, orientation, attention, verbal learning and memory, language, visuoperception, praxis, and executive functions. Several of the tests were affected by age, education, and/or gender, but the language of administration (i.e., Spanish or Catalan) did not affect the test scores. Standardized scores and percentile ranks were calculated for each age and/or education group for use by clinical neuropsychologists. © 2012 Psychology Press, an imprint of the Taylor & Francis Group, an Informa business.

Rodriguez-Gomez O.,Institute Catala Of Neurociencies Aplicades | Abdelnour C.,Institute Catala Of Neurociencies Aplicades | Jessen F.,German Center for Neurodegenerative Diseases | Valero S.,Autonomous University of Barcelona | Boada M.,Institute Catala Of Neurociencies Aplicades
Journal of Alzheimer's Disease | Year: 2015

Subjective cognitive decline (SCD) has been proposed as a marker of neurodegeneration in cognitively normal elderly. This idea is supported by the growing evidence that SCD is associated with Alzheimer's disease (AD) biomarkers and increases the risk of future cognitive impairment. Nevertheless, this evidence is not complete, since other studies have not found these associations. This discrepancy could have a methodological basis. It is well known that across the broad spectrum of degenerative disease from healthy controls to dementia, the research setting affects key characteristics of the sample such as age, educational level, or family history of dementia. However, virtually no studies have specifically tested the influence of sampling and recruitment methods in SCD research. Population-based samples are less biased and therefore they probably are more suitable for the study of memory complaints as a symptom at the population level. On the other hand, the memory clinic setting could introduce a set of biases that make these patients more likely to develop cognitive impairment. Thus, memory clinic would be the most cost-effective context in which to study the phenomenology of SCD due to AD and eventually recruit patients for secondary prevention trials. However, this general hypothesis needs to be tested. Studies that compare samples of patients with SCD from different settings are necessary. Sometimes it is difficult for patients with subtle forms of cognitive impairment to access specialized diagnostic centers. Based in our experience we state that Open House type initiatives may be useful for attracting these individuals to memory clinics. © 2015 - IOS Press and the authors. All rights reserved.

PubMed | Alzheimer Center Educational, University of Pittsburgh, Autonomous University of Barcelona and Institute Catala Of Neurociencies Aplicades
Type: Journal Article | Journal: Journal of Alzheimer's disease : JAD | Year: 2016

The existing pharmacological treatments for Alzheimers disease (AD) can only slow the progression of symptoms or delay admission to long-term care facilities. The beneficial effects of non-drug treatments are poorly studied.To describe the effects of an Integrated Psychostimulation Program (IPP) in patients with mild-moderate AD treated with acetylcholinesterase inhibitors; and to identify factors related to greater benefit of the IPP.206 patients (mean age=75.9 years; MMSE=19.6) were evaluated before starting the IPP and 3, 6, 9, and 12 months later. Measures included: Mini-Mental State Examination (MMSE), Cognitive Subscale of Alzheimers Disease Assessment Scale (ADAS-Cog), Rapid Disability Rating Scale (RDRS-2), and Neuropsychiatric Inventory Questionnaire (NPI-Q).Patients remained cognitively stable (MMSE/ADAS-Cog) for more than 6 months and significantly worsened at 9-month and 12-month follow-ups, without clinically significant functional changes (RDRS-2) or psychiatric symptoms(NPI-Q). The mean annual change on MMSE and ADAS-Cog were 2.06 and 3.56 points, respectively, lower than the annual decline demonstrated previously in similar patients (2.4 and 4.5, respectively). 42.7% of patients maintained or improved global cognitive scores between baseline and 12-month follow-up. The patients who maintained cognitive functions were older than those who did not (77.5 versus 74.7 years).The IPP may be an effective treatment to maintain cognition, functionality, and psychiatric symptoms in AD patients pharmacologically treated, and older age seems to increase beneficial effects of IPP.

PubMed | Grifols, Howard University, Institute Catala Of Neurociencies Aplicades, Hospital General Universitario Gregorio Maranon and 4 more.
Type: Journal Article | Journal: Journal of Alzheimer's disease : JAD | Year: 2016

Studies conducted in animal models and humans suggest the presence of a dynamic equilibrium of amyloid- (A) peptide between cerebrospinal fluid (CSF) and plasma compartments.To determine whether plasma exchange (PE) with albumin replacement was able to modify A concentrations in CSF and plasma as well as to improve cognition in patients with mild-moderate Alzheimers disease (AD).In a multicenter, randomized, patient- and rater-blind, controlled, parallel-group, phase II study, 42 AD patients were assigned (1:1) to PE treatment or control (sham) groups. Treated patients received a maximum of 18 PE with 5% albumin (Albutein, Grifols) with three different schedules: two PE/weekly (three weeks), one PE/weekly (six weeks), and one PE/bi- weekly (12 weeks), plus a six-month follow-up period. Plasma and CSF A1-40 and A1-42 levels, as well as cognitive, functional, and behavioral measures were determined.CSF A1-42 levels after the last PE compared to baseline were marginally higher in PE-treated group versus controls (adjusted means of variation: 75.3 versus -45.5pg/mL; 95% CI: -19.8, 170.5 versus 135.1, 44.2; p=0.072). Plasma A1-42 levels were lower in the PE-treated group after each treatment period (p<0.05). Plasma A1-40 levels showed a saw-tooth pattern variation associated with PE. PE-treated patients scored better in the Boston Naming Test and Semantic Verbal Fluency (p<0.05) throughout the study. Neuropsychiatric Inventory scores were higher in controls during the PE phase (p<0.05).PE with human albumin modified CSF and plasma A1-42 levels. Patients treated with PE showed improvement in memory and language functions, which persisted after PE was discontinued.

PubMed | University of Kassel, Institute Catala Of Neurociencies Aplicades, Alzheimer Center, University of Strasbourg and 4 more.
Type: Journal Article | Journal: Movement disorders : official journal of the Movement Disorder Society | Year: 2016

Alzheimers disease pathologies are common in dementia with Lewy bodies, but their clinical relevance is not clear. CSF biomarkers amyloid beta 1-42, total tau, and tau phosphorylated at threonine 181 reflect Alzheimers disease neuropathology antemortem. In PD, low CSF amyloid beta 1-42 predict long-term cognitive decline, but little is known about these biomarkers as predictors for cognitive decline in Lewy body dementia. The aim of this study was to assess whether Alzheimers disease CSF biomarkers predict cognitive decline in Lewy body dementia.From a large European dementia with Lewy bodies multicenter study, we analyzed baseline Alzheimers disease CSF biomarkers and serial MMSE (baseline and 1- and 2-year follow-up) in 100 patients with Lewy body dementia. Linear mixed-effects analyses, adjusted for sex, age, baseline MMSE, and education, were performed to model the association between CSF biomarkers and rate of cognitive decline measured with MMSE. An Alzheimers disease CSF profile was defined as pathological amyloid beta 1-42 plus pathological total tau or phosphorylated tau.The Alzheimers disease CSF profile, and pathological levels of amyloid beta 1-42, were associated with a more rapid decline in MMSE (2.2 [P < 0.05] and 2.9 points difference [P < 0.01], respectively). Higher total tau values showed a trend toward association without statistical significance (2.0 points difference; P = 0.064), whereas phosphorylated tau was not associated with decline.Reduced levels of CSF amyloid beta 1-42 were associated with more rapid cognitive decline in Lewy body dementia patients. Future prospective studies should include larger samples, centralized CSF analyses, longer follow-up, and biomarker-pathology correlation. 2016 International Parkinson and Movement Disorder Society.

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