Estado prenatal de los ácidos grasos durante la gestación

L'embaràs implica nombrosos canvis fisiològics en la dona i requereix cobrir unes necessitats nutricionals especials per a la mare i per al fetus. L'estat nutricional matern dels àcids grassos (AG), concretament els AG essencials i AG poliinsaturats n-3 com DHA i EPA, juga un paper important tant per a ella com per a la seva descendència. Durant l’etapa de l'embaràs s'ha vist que és necessària una elevada quantitat d’AG materns per a satisfer les demandes fetals. Per això, és important mantenir uns nivells sèrics òptims d’AG en la mare que facilitin el seu pas a través de la placenta. No obstant, el nombre d’estudis que realitzin un seguiment de les concentracions d’AG durant tot el període de l'embaràs és molt limitat en la bibliografia actual. L'objectiu principal d’aquest estudi és determinar l'estat nutricional d’AG en l’embarassada al llarg de tota la gestació. El projecte ECLIPSIS-ÁG és un estudi observacional longitudinal multicèntric realitzat en 793 dones embarassades sanes d'una regió Mediterrània del sur de Catalunya en el qual es va analitzar un perfil ampli d’AG en sèrum mitjançant tècniques cromatogràfiques. Es van mesurar les concentracions sèriques dels AG i es van establir els seus intervals de referència (IR) en el primer (T1) i tercer (T3) trimestre de gestació. Les concentracions d’AG van variar del T1 al T3 (AG saturats, monoinsaturats i poliinsaturats n-6 van augmentar, i els derivats d’AG essencials (AA, EPA i DHA) van disminuir). Aquests canvis es van veure influenciats per determinats factors materns (socioeconòmics i d'estil de vida)El embarazo implica numerosos cambios fisiológicos en la mujer e impone necesidades nutricionales especiales tanto para ella como para el feto. El estado nutricional materno de los ácidos grasos (AG) juega un papel importante para ella y su descendencia, concretamente los AG esenciales y AG poliinsaturados n-3 como DHA y EPA. Durante el transcurso del embarazo, se ha visto que es necesaria una elevada cantidad de AG maternos para satisfacer las demandas fetales. Por ello, es importante mantener unos niveles séricos óptimos de AG para facilitar su paso a través de la placenta durante el embarazo. Sin embargo, existen pocos estudios en la bibliografía que realicen un seguimiento de las concentraciones de AG durante todo el embarazo. El objetivo principal del estudio es determinar el estado nutricional de AG en la mujer embarazada a lo largo de su gestación. El proyecto ECLIPSES-ÁG es un estudio observacional longitudinal multicéntrico realizado en 793 mujeres embarazadas sanas de una región Mediterránea del sur de Cataluña en el que se analizó un perfil amplio de AG en suero mediante técnicas cromatográficas. Se midieron las concentraciones séricas de los AG y se establecieron sus intervalos de referencia (IR) en el primer (T1) y tercer (T3) trimestre de gestación. Las concentraciones de AG variaron de T1 a T3 (AG saturados, monoinsaturados y poliinsaturados n-6 aumentaron, y los derivados de AG esenciales (AA, EPA y DHA) disminuyeron). Estos cambios se vieron influenciados por determinados factores maternos (socioeconómicos y de estilo de vida).Pregnancy induces many physiological changes in women and requires special nutritional needs for both the woman and the foetus. The maternal nutritional status of fatty acids (FA) plays an important role for her and her offspring, specifically essential FA and n-3 polyunsaturated FA such as DHA and EPA. During the course of pregnancy, it has been shown that a high amount of maternal FA is necessary to support fetal demands. Therefore, it is important to maintain optimal serum levels of FA to facilitate their transfer across the placenta during pregnancy. However, there are few studies that monitor FA concentrations throughout pregnancy. The main objective of this study is to determine the FA nutritional status of pregnant women throughout pregnancy. The ECLIPSES-ÁG project is a multicenter longitudinal observational study conducted in 793 healthy pregnant women from a Mediterranean region of southern Catalonia in which a large serum FA profile was analyzed using chromatographic techniques. Serum concentrations of FAs were measured and their reference ranges (RR) were established in the first (T1) and third (T3) trimester of gestation. The concentrations of FA varied from T1 to T3 (saturated, monounsaturated and n-6 polyunsaturated FA increased, and FA derived from essential FA (AA, EPA and DHA) decreased). These changes were influenced by certain maternal factors (socio-economic and lifestyle). The proposed FA levels seem to be a useful tool to assess the degree of FA adequacy in pregnant women and to make dietary interventions based on specific maternal factor

Social Representation of Dementia: An Analysis of 5,792 Consecutive Cases Evaluated in a Memory Clinic

Abstract. Background: Different interpretations of cognitive impairment and dementia due to differences in health structures, such as cultural differences could affect the diagnosis and treatment of the condition. it is reasonable to expect that the social and family impact of the disease and coping strategies will differ among societies. Objective: The general aim of this study is to understand the social representations of dementia, its associated practices, and the effects they imply. Methods: People diagnosed with clinical dementia and their families were assessed from 2005 to 2015 in the memory clinic of the Fundacio ́ ACE, Institut Catala` de Neurocie`ncies Aplicades in Barcelona, Spain. Results: 9,898 people were examined and 5,792 were diagnosed with dementia. For those with a caregiver (71%), the decision-making fell on the person with dementia in 16.2% of the cases; and for those without a caregiver, in 26.4% of the cases the family did not perceive the deficits as a disease, which led to multiple risk situations (74.6%). Conclusions: The recognition of dementia as part of aging is common among families. Consequently, risk situations may arise and diagnosis and access to treatment may be delayed. The incorporation of a social appraisal to the diagnostic process is a necessity to evaluate these situations

Exploring APOE genotype effects on Alzheimer's disease risk and amyloid β burden in individuals with subjective cognitive decline: The FundacioACE Healthy Brain Initiative (FACEHBI) study baseline results

Introduction: Subjective cognitive decline (SCD) has been proposed as a potential preclinical stage of Alzheimer's disease (AD). Nevertheless, the genetic and biomarker profiles of SCD individuals remain mostly unexplored. Methods: We evaluated apolipoprotein E (APOE) ε4's effect in the risk of presenting SCD, using the Fundacio ACE Healthy Brain Initiative (FACEHBI) SCD cohort and Spanish controls, and performed a meta-analysis addressing the same question. We assessed the relationship between APOE dosage and brain amyloid burden in the FACEHBI SCD and Alzheimer's Disease Neuroimaging Initiative cohorts. Results: Analysis of the FACEHBI cohort and the meta-analysis demonstrated SCD individuals presented higher allelic frequencies of APOE ε4 with respect to controls. APOE dosage explained 9% (FACEHBI cohort) and 11% (FACEHBI and Alzheimer's Disease Neuroimaging Initiative cohorts) of the variance of cerebral amyloid levels. Discussion: The FACEHBI sample presents APOE ε4 enrichment, suggesting that a pool of AD patients is nested in our sample. Cerebral amyloid levels are partially explained by the APOE allele dosage, suggesting that other genetic or epigenetic factors are involved in this AD endophenotype

Neuropsychiatric profiles and conversion to dementia in mild cognitive impairment, a latent class analysis

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER)Altres ajuts: Generalitat de Catalunya. Programa CERCAAltres ajuts: Instituto de Salud Carlos III (CIBERSAM i CIBERNED)Altres ajuts: Fundació "La Caixa"Altres ajuts: Grífols SA (GR@ACE project)Neuropsychiatric symptoms (NPS) have been recently addressed as risk factors of conversion to Alzheimer's disease (AD) and other dementia types in patients diagnosed with Mild Cognitive Impairment (MCI). Our aim was to determine profiles based on the prominent NPS in MCI patients and to explore the predictive value of these profiles on conversion to specific types of dementia. A total of 2137 MCI patients monitored in a memory clinic were included in the study. Four NPS profiles emerged (classes), which were defined by preeminent symptoms: Irritability, Apathy, Anxiety/Depression and Asymptomatic. Irritability and Apathy were predictors of conversion to dementia (HR = 1.43 and 1.56, respectively). Anxiety/depression class showed no risk effect of conversion when compared to Asymptomatic class. Irritability class appeared as the most discriminant neuropsychiatric condition to identify non-AD converters (i.e., frontotemporal dementia, vascular dementia, Parkinson's disease and dementia with Lewy Bodies). The findings revealed that consistent subgroups of MCI patients could be identified among comorbid basal NPS. The preeminent NPS showed to behave differentially on conversion to dementia, beyond AD. Therefore, NPS should be used as early diagnosis facilitators, and should also guide clinicians to detect patients with different illness trajectories in the progression of MCI

Social Representation of Dementia : An Analysis of 5,792 Consecutive Cases Evaluated in a Memory Clinic

Background: Different interpretations of cognitive impairment and dementia due to differences in health structures, such as cultural differences could affect the diagnosis and treatment of the condition. it is reasonable to expect that the social and family impact of the disease and coping strategies will differ among societies. Objective: The general aim of this study is to understand the social representations of dementia, its associated practices, and the effects they imply. Methods: People diagnosed with clinical dementia and their families were assessed from 2005 to 2015 in the memory clinic of the Fundació ACE, Institut Català de Neurociències Aplicades in Barcelona, Spain. Results: 9,898 people were examined and 5,792 were diagnosed with dementia. For those with a caregiver (71%), the decision-making fell on the person with dementia in 16.2% of the cases; and for those without a caregiver, in 26.4% of the cases the family did not perceive the deficits as a disease, which led to multiple risk situations (74.6%). Conclusions: The recognition of dementia as part of aging is common among families. Consequently, risk situations may arise and diagnosis and access to treatment may be delayed. The incorporation of a social appraisal to the diagnostic process is a necessity to evaluate these situations

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks : The GR@ACE project

Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele