RbAp48 Protein Is a Critical Component of GPR158/OCN Signaling and Ameliorates Age-Related Memory Loss

Precisely deciphering the molecular mechanisms of age-related memory loss is crucial to create appropriate therapeutic interventions. We have previously shown that the histone-binding protein RbAp48/Rbbp4 is a molecular determinant of Age-Related Memory Loss. By exploring how this protein regulates the genomic landscape of the hippocampal circuit, we find that RbAp48 controls the expression of BDNF and GPR158 proteins, both critical components of osteocalcin (OCN) signaling in the mouse hippocampus. We show that inhibition of RbAp48 in the hippocampal formation inhibits OCN’s beneficial functions in cognition and causes deficits in discrimination memory. In turn, disruption of OCN/GPR158 signaling leads to the downregulation of RbAp48 protein, mimicking the discrimination memory deficits observed in the aged hippocampus. We also show that activation of the OCN/GPR158 pathway increases the expression of RbAp48 in the aged dentate gyrus and rescues age-related memory loss

Clinical Neuropsychology as a Specialist Profession in European Health Care : Developing a Benchmark for Training Standards and Competencies Using the Europsy Model?

The prevalence and negative impact of brain disorders are increasing. Clinical Neuropsychology is a specialty dedicated to understanding brain-behavior relationships, applying such knowledge to the assessment of cognitive, affective, and behavioral functioning associated with brain disorders, and designing and implementing effective treatments. The need for services goes beyond neurological diseases and has increased in areas of neurodevelopmental and psychiatric conditions, among others. In Europe, a great deal of variability exists in the education and training of Clinical Neuropsychologists. Training models include master's programs, continuing education courses, doctoral programs, and/or post-doctoral specialization depending on the country, with no common framework of requirements, although patients' needs demand equal competencies across Europe. In the past 5 years, the Standing Committee on Clinical Neuropsychology of the European Federation of Psychologists' Association has conducted a series of surveys and interviews with experts in the field representing 30 European countries. The information, along with information from the existing literature, is used in presenting an overview of current and relevant topics related to policy and guidelines in the training and competencies in Clinical Neuropsychology. An option for the way forward is the EuroPsy Specialist Certificate, which is currently offered in Work and Organizational Psychology, and in psychotherapy. It builds upon the basic certificate and complements national standards without overriding them. General principles can be found that can set the basis for a common, solid, and comprehensive specialty education/training, sharpening the Neuropsychologists' competencies across Europe. The requirements in Clinical Neuropsychology should be comparable to those for the existing specialty areas in the EuroPsy model. Despite the perceived challenges, developing a specialist certificate appears a step forward for the development of Clinical Neuropsychology. Recommendations are proposed toward a shared framework of competencies by the means of a common level of education/training for the professionals in Europe. Benchmarking training standards and competencies across Europe has the potential of providing protection against unqualified and ethically questionable practice, creating transparency, raising the general European standard, and promoting mobility of both Clinical Neuropsychologists and patients in Europe, for the benefit of the professional field and the population.Peer reviewe

Core Competencies in Clinical Neuropsychology as a Training Model in Europe

The multitude of training models and curricula for the specialty of clinical neuropsychology around the world has led to organized activities to develop a framework of core competencies to ensure sufficient expertise among entry-level professionals in the field. The Standing Committee on Clinical Neuropsychology of the European Federation of Psychologists' Associations is currently working toward developing a specialty certification in clinical neuropsychology to establish a cross-national standard against which to measure levels of equivalency and uniformity in competence and service provision among professionals in the field. Through structured interviews with experts from 28 European countries, we explored potential areas of core competency. Specifically, questions pertained to the perceived importance of a series of foundational, functional, and other competencies, as well as current training standards and practices, and optimal standards. Our findings revealed considerable agreement (about three quarters and above) on academic and clinical training, despite varied actual training requirements currently, with fewer respondents relegating importance to training in teaching, supervision, and research (a little over half), and even fewer to skills related to management, administration, and advocacy (fewer than half). European expert clinical neuropsychologists were in agreement with previous studies (including those conducted in the United States, Australia, and other countries) regarding the importance of sound theoretical and clinical training but management, administrative, and advocacy skills were not central to their perspective of a competent specialist in clinical neuropsychology. Establishing a specialty certificate in clinical neuropsychology based on core competencies may enable mobility of clinical neuropsychologists across Europe, and, perhaps, provide an impetus for countries with limited criteria to reconsider their training requirements and harmonize their standards with others.Peer reviewe

European Clinical Neuropsychology : Role in Healthcare and Access to Neuropsychological Services

This study analyzed aspects of the work of clinical neuropsychologists across Europe. There are no published comparisons between European countries regarding the nature of clinical neuropsychologists' work. Forty-one national psychological and neuropsychological societies were approached, of which 31 (76%) responded. Data from seven countries with less than 10 neuropsychologists were excluded. A license is required to practice clinical neuropsychology in 50% of the countries. Clinical neuropsychologists work independently in 62.5%. Diagnostic/assessment work is the most frequently reported activity (54%). Most neuropsychologists work in public hospitals, followed by health centers. Adult neuropsychology was the most frequent area of activity. Services in public institutions are covered by public entities (45.8%), or by a combination of patient funds and public entities (29.2%) and only 4.2% by the patient; whereas services in private institutions are covered by the patient (26.1%) and the combination of patient, public entities (21.7%) or patient and private entities (17.4%). The data suggest that the number of neuropsychologists working across European countries is considerably low in comparison to other medical professionals. The results of the survey identified similar aspects of neuropsychologists' work, despite variations in terms of reimbursement and mechanisms, reflecting economic and healthcare differences. Estimates on the number of clinical neuropsychologists suggest insufficient access to neuropsychological services.Peer reviewe

Sleep and subjective cognitive decline in cognitively healthy elderly: Results from two cohorts

Subjective cognitive decline may reflect a dementia prodrome or modifiable risk factor such as sleep disturbance. What is the association between sleep and subjective cognitive decline? Cross-sectional design, from two studies of older adults: the WHICAP in the USA and the HELIAD in Greece. A total of 1,576 WHICAP and 1,456 HELIAD participants, without mild cognitive impairment, dementia or severe depression/anxiety, were included. Participants were mostly women, with 12 (WHICAP) and 8 (HELIAD) mean years of education. Sleep problems were estimated using the Sleep Scale from the Medical Outcomes Study. Subjective cognitive decline was assessed using a structured complaint questionnaire that queries for subjective memory and other cognitive symptoms. Multinomial or logistic regression models were used to examine whether sleep problems were associated with complaints about general cognition, memory, naming, orientation and calculations. Age, sex, education, sleep medication, use of medications affecting cognition, co-morbidities, depression and anxiety were used as co-variates. Objective cognition was also estimated by summarizing neuropsychological performance into composite z-scores. Sleep problems were associated with two or more complaints: WHICAP: β = 1.93 (95% confidence interval: 1.59–2.34), p ≤ .0001; HELIAD: β = 1.48 (95% confidence interval: 1.20–1.83), p ≤ .0001. Sleep problems were associated with complaints in all the cognitive subcategories, except orientation for the WHICAP. The associations were noted regardless of objective cognition. At any given level of objective cognition, sleep disturbance is accompanied by subjective cognitive impairment. The replicability in two ethnically, genetically and culturally different cohorts adds validity to our results. The results have implications for the correlates, and potential aetiology of subjective cognitive decline, which should be considered in the assessment and treatment of older adults with cognitive complaints

Sex differences in dementia risk and risk factors: Individual‐participant data analysis using 21 cohorts across six continents from the COSMIC consortium

Introduction: Sex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno‐regional groups. Methods: A total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta‐analysis. Sex‐specific hazard ratios (HRs), and women‐to‐men ratio of hazard ratios (RHRs) for associations between RFs and all‐cause dementia were derived from mixed‐effect Cox models. Results: Incident dementia occurred in 2089 (66% women) participants over 4.6 years (median). Women had higher dementia risk (HR, 1.12 [1.02, 1.23]) than men, particularly in low‐ and lower‐middle‐income economies. Associations between longer education and former alcohol use with dementia risk (RHR, 1.01 [1.00, 1.03] per year, and 0.55 [0.38, 0.79], respectively) were stronger for men than women; otherwise, there were no discernible sex differences in other RFs. Discussion: Dementia risk was higher in women than men, with possible variations by country‐level income settings, but most RFs appear to work similarly in women and men

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