Suchergebnisse

Javier Mar,1–4 Arantzazu Arrospide,2–4 Myriam Soto-Gordoa,5 Álvaro Iruin,4,6 Mikel Tainta,7,8 Andrea Gabilondo,4,6 Lore Mar-Barrutia,9 Montserrat Calvo,10 Maider Mateos,10 Oliver Ibarrondo2,41Clinical Management Unit, OSI Alto Deba, Arrasate-Mondragón, España; 2AP-OSIs Gipuzkoa Research Unit, OSI Alto Deba, Arrasate-Mondragón, España; 3Economic Evaluation Department, Health Services Research on Chronic Patients Network (REDISSEC), Bilbao, Spain; 4Economic Evaluation Department, Biodonostia Health Research Institute, Donostia-San Sebastián, Spain; 5Departamento de Ingeniería de Organización, Mondragón Unibertsitatea, Arrasate-Mondragón, España; 6Psychiatry Service, Gipuzkoa Mental Health Network, Donostia-San Sebastián, España; 7Psychiatry Service, CITA Alzheimer Foundation, Donostia-San Sebastián, España; 8Neurology Service, OSI Goierri-Alto Urola, Zumárraga, España; 9Psychiatry Service, Hospital Bellvitge, Hospitalet de Llobregat, España; 10Health Department, Basque Government, Vitoria-Gasteiz, EspañaBackground: Dementia-related neuropsychiatric symptoms (NPS) are the main determinant of family stress and institutionalization of patients. This study aimed to identify inequalities by gender and socioeconomic status in the management of NPS in patients diagnosed with dementia.Methods: An observational study was carried out to study all the cases of dementia in the corporate database of the Basque Health Service (29,864 patients). The prescription of antipsychotics and antidepressants and admission to a nursing home were used to establish the presence of NPS. The socioeconomic status of individuals was classified by a deprivation index. Logistic regressions were used to identify drivers for drug prescriptions and institutionalization.Results: NPS are poorly recorded in the clinical databases (12%). Neuropsychiatric symptoms were severe enough in two thirds of patients with dementia to be treated with psychoactive medication. Institutionalization showed an increase from those who did not receive medication to those who had been prescribed antidepressants (OR: 1.546), antipsychotics (OR: 2.075) or both (OR: 2.741). The resulting inequalities were the increased prescription of antidepressant drugs in women and more nursing-home admissions for women who were the least socioeconomically deprived and men who were the most deprived.Conclusions: In large clinical databases, psychoactive drugs prescriptions can be useful to underscore the considerable burden of dementia-related NPS. Specific tools are needed to monitor social and health care programs targeted to dementia-related NPS from a population perspective. Programs aimed at reducing the family burden of care of dementia patients at home become the key elements in reducing inequalities in these patients' care. Socioeconomic status is the most important driver of inequality, and gender inequality may simply be hidden within the social environment. Integrated programs boosting the continuity of care are an objective for which compliance could be measured according to the NPS coding in the electronic health record.Keywords: neuropsychiatric symptoms, prevalence, dementia, antidepressant drugs, antipsychotic drugs, nursing home, inequalities, deprivation index

© 2020 – IOS Press and the authors. ; [Background]: Previous studies suggest that Dickkopf-1 (DKK1), an inhibitor of Wnt signaling, plays a role in amyloid-induced toxicity and hence Alzheimer's disease (AD). However, the effect of DKK1 expression on protein expression, and whether such proteins are altered in disease, is unknown. [Objective]: We aim to test whether DKK1 induced protein signature obtained in vitro were associated with markers of AD pathology as used in the amyloid/tau/neurodegeneration (ATN) framework as well as with clinical outcomes. [Methods]: We first overexpressed DKK1 in HEK293A cells and quantified 1,128 proteins in cell lysates using aptamer capture arrays (SomaScan) to obtain a protein signature induced by DKK1. We then used the same assay to measure the DKK1-signature proteins in human plasma in two large cohorts, EMIF (n = 785) and ANM (n = 677). [Results]: We identified a 100-protein signature induced by DKK1 in vitro. Subsets of proteins, along with age and apolipoprotein E ɛ4 genotype distinguished amyloid pathology (A + T–N–, A+T+N–, A+T–N+, and A+T+N+) from no AD pathology (A–T–N–) with an area under the curve of 0.72, 0.81, 0.88, and 0.85, respectively. Furthermore, we found that some signature proteins (e.g., Complement C3 and albumin) were associated with cognitive score and AD diagnosis in both cohorts. [Conclusions]: Our results add further evidence for a role of DKK regulation of Wnt signaling in AD and suggest that DKK1 induced signature proteins obtained in vitro could reflect theATNframework as well as predict disease severity and progression in vivo. ; This research was conducted as part of the EMIF-AD project which has received support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement n° 115372, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies' in-kind contribution. The DESCRIPA study was funded by the European Commission within the 5th framework program (QLRT-2001-2455). The EDAR study was funded by the European Commission within the 5th framework program (contract # 37670). The Leuven cohort was funded by the Stichting voor Alzheimer Onderzoek (grant numbers #11020, #13007 and #15005). The Lausanne cohort study was supported by a grant from the Swiss National Research Foundation to JP (SNF 320030_141179). RV is a senior clinical investigator of the Flemish Research Foundation (FWO). JS is currently an employee of UCB, Braine-l'Alleud, Belgium. The San Sebastian GAP study is partially funded by the Department of Health of the Basque Government (allocation 17.0.1.08.12.0000.2.454.01.41142.001.H). We acknowledge the contribution of the personnel of the Genomic Service Facility at the VIB-U Antwerp Center for Molecular Neurology. The research at VIB-CMN is funded in part by the University of Antwerp Research Fund. FB is supported by the NIHR biomedical research centre at UCLH. RD is supported by Health Data Research UK, the National Institute for Health Research (NIHR) Biomedical Research Centre at South London, Maudsley NHS Foundation Trust, King's College London and the NIHR University College London Hospitals Biomedical Research Centre. LS is funded by DPUK through MRC (grant no. MR/L023784/2) and the UK Medical Research Council Award to the University of Oxford (grant no. MC_PC_17215). Also support was received from the NIHR Biomedical Research Centre at Oxford Health NHS Foundation Trust.