A systematic review and meta-analysis on the prevalence of dementia in europe. estimates from the highest-quality studies adopting the dsm iv diagnostic criteria

BACKGROUND: Dementia, including Alzheimer's disease (AD), is one of the most burdensome medical conditions. Usually, the reviews that aim at calculating the prevalence of dementia include estimates from studies without assessing their methodological quality. Alzheimer's Disease International (ADI) proposed a score to assess the methodological quality of population-based studies aimed at estimating the prevalence of dementia. During the last three years, the European Commission has funded three projects (Eurodem, EuroCoDe, and ALCOVE) in order to estimate the prevalence of dementia in Europe. OBJECTIVE: The aim of this study was to perform a systematic review and meta-analysis of data on the prevalence of dementia in Europe derived from studies that included only subjects with a diagnosis of dementia according to the DSM IV criteria, and that had a high quality score according to ADI criteria. METHODS: We considered the studies selected by the two projects EuroCoDe (1993-2007) and Alcove (2008-2011), and we performed a new bibliographic search. For the systematic review, we only selected the subset of articles that included subjects with a diagnosis of dementia according to the DSM IV criteria. The studies were qualitatively assessed using the ADI tool. RESULTS: The meta-analysis considered 9 studies that were carried out in Europe between 1993 and 2018 including a total of 18,263 participants, of which 2,137 were diagnosed with dementia. The prevalence rate standardized for age and sex resulted 7.1%. DISCUSSION: This is the first systematic review on the prevalence of dementia in Europe considering only high-quality studies adopting the same diagnostic criteria (i.e., DSM IV)

An estimate of attributable cases of alzheimer disease and vascular dementia due to modifiable risk factors. the impact of primary prevention in europe and in italy

Background: Up to 53.7% of all cases of dementia are assumed to be due to Alzheimer disease (AD), while 15.8% are considered to be due to vascular dementia (VaD). In Europe, about 3 million cases of AD could be due to 7 potentially modifiable risk factors: diabetes, midlife hypertension and/or obesity, physical inactivity, depression, smoking, and low educational level. Aims: To estimate the number of VaD cases in Europe and the number of AD and VaD cases in Italy attributable to these 7 potentially modifiable risk factors. Methods: Assuming the nonindependence of the 7 risk factors, the adjusted combined population attributable risk (PAR) was estimated for AD and VaD. Results: In Europe, adjusted combined PAR was 31.4% for AD and 37.8% for VaD. The total number of attributable cases was 3,033,000 for AD and 873,000 for VaD. In Italy, assuming a 20% reduction of the prevalence of each risk factor, adjusted combined PAR decreased from 45.2 to 38.9% for AD and from 53.1 to 46.6% for VaD, implying a 6.4 and 6.5% reduction in the prevalence of AD and VaD, respectively. Conclusion: A relevant reduction of AD and VaD cases in Europe and Italy could be obtained through primary prevention

Editorial: Dementia, Frailty and Aging

10.3389/fmed.2018.00168Frontiers in Medicine5MAY16

A Frailty Index based on clinical data to quantify mortality risk in dogs

Frailty is defined as a decline in an organism's physiological reserves resulting in increased vulnerability to stressors. In humans, a single continuous variable, the so-called Frailty Index (FI), can be obtained by multidimensionally assessing the biological complexity of an ageing organism. Here, we evaluate this variability in dogs and compare it to the data available for humans. In dogs, there was a moderate correlation between age and the FI, and the distribution of the FI increased with age. Deficit accumulation was strongly related to mortality. The effect of age, when combined with the FI, was negligible. No sex-related differences were evident. The FI could be considered in epidemiological studies and/or experimental trials to account for the potential confounding effects of the health status of individual dogs. The age-related deficit accumulation reported in dogs is similar to that demonstrated in humans. Therefore, dogs might represent an excellent model for human aging studies

Methodological Issues in the Clinical Validation of Biomarkers for Alzheimer's Disease : The Paradigmatic Example of CSF

The use of biomarkers is profoundly transforming medical research and practice. Their adoption has triggered major advancements in the field of Alzheimer's disease (AD) over the past years. For instance, the analysis of the cerebrospinal fluid (CSF) and neuroimaging changes indicative of neuronal loss and amyloid deposition has led to the understanding that AD is characterized by a long preclinical phase. It is also supporting the transition towards a biology-grounded framework and definition of the disease. Nevertheless, though sufficient evidence exists about the analytical validity (i.e., accuracy, reliability, and reproducibility) of the candidate AD biomarkers, their clinical validity (i.e., how well the test measures the clinical features, and the disease or treatment outcomes) and clinical utility (i.e., if and how the test improves the patient's outcomes, confirms/changes the diagnosis, identifies at-risk individuals, influences therapeutic choices) have not been fully proven. In the present review, some of the methodological issues and challenges that should be addressed in order to better appreciate the potential benefits and limitations of AD biomarkers are discussed. The ultimate goal is to stimulate a constructive discussion aimed at filling the existing gaps and more precisely defining the directions of future research. Specifically, four main aspects of the clinical validation process are addressed and applied to the most relevant CSF biomarkers: (1) the definition of reference values; (2) the identification of reference standards for the disease of interest (i.e., AD); (3) the inclusion within the diagnostic process; and (4) the statistical process supporting the whole framework

Use of biomarkers in ongoing research protocols on alzheimer’s disease

The present study aimed to describe and discuss the state of the art of biomarker use in ongoing Alzheimer’s disease (AD) research. A review of 222 ongoing phase 1, 2, 3, and 4 protocols registered in the clinicaltrials.gov database was performed. All the trials (i) enrolling subjects with clinical disturbances and/or preclinical diagnoses falling within the AD continuum; and (ii) testing the efficacy and/or safety/tolerability of a therapeutic intervention, were analyzed. The use of biomarkers of amyloid deposition, tau pathology, and neurodegeneration among the eligibility criteria and/or study outcomes was assessed. Overall, 58.2% of ongoing interventional studies on AD adopt candidate biomarkers. They are mostly adopted by studies at the preliminary stages of the drug development process to explore the safety profile of novel therapies, and to provide evidence of target engagement and disease-modifying properties. The biologically supported selection of participants is mostly based on biomarkers of amyloid deposition, whereas the use of biomarkers as study outcomes mostly relies on markers of neurodegeneration. Biomarkers play an important role in the design and conduction of research protocols targeting AD. Nevertheless, their clinical validity, utility, and cost-effectiveness in the “real world” remain to be clarified

The Management of Frailty: Barking Up the Wrong Tree

Frailty is today a hot topic in the scientific community and among clinicians. Geriatricians are no longer the only specialists discussing this age-related condition. Many medical disciplines (e.g., oncologists (1), cardiologists (2), neurologists (3), nephrologists (4), infectious disease specialists (5), pneumologists (6), anesthesiologists (7)) have finally started looking at this critical aspect in older persons, particularly impactful on prognosis and treatment modalities (e.g., (8, 9)). In the debate about this “novel” condition, it may sometimes happen that the word “frailty” is inappropriately used, suggesting a still incomplete understanding of the condition of interest. Some concepts seem difficult to get through, especially in those fields that are not used to the holistic approach and multidisciplinarity typical of geriatrics

A systematic review of the biological processes involved in deep-brain stimulation for parkinson’s disease: A focus on the potential disease-modifying effects

Deep-Brain Stimulation (DBS) is an important treatment option for the management of Parkinson’s disease (PD) and is a common symptomatic treatment. However, an increasing number of studies have examined the biological processes to assess if DBS can also modify the natural history of PD by acting on its pathophysiological mechanisms. Relevant literature published up to November 2020 was systematically searched on databases such as PubMed, ISI Web of Knowledge, Academic Search Index, and Science Citation Index. The following predefined inclusion criteria were applied to the full-text versions of the selected articles: I) recruiting and monitoring of PD subjects that were previously treated with DBS and ii) investigating the electrophysiological, biochemical, epigenetic, or neuroimaging effects of DBS. Studies focusing exclusively on motor and clinical changes were excluded. Reviews, case reports, studies on animal models, and computational studies were also not considered. Out of 2,960 records screened, 43 studies met the inclusion criteria. Only three studies described a potential disease-modifying effect of DBS. However, a wide heterogeneity was observed in the investigated biomarkers, and the design and methodological issues of several studies limited their ability to find potential disease-modifying features. Specifically, 60.4% of the trials followed-up subjects for no more than 1 year from the surgical intervention, and 67.4% observed patients with PD only once after DBS. Moreover, 64.2% of the studies enrolled late-stage PD patients. Most of the studies (88.4%) reported that DBS only had a symptomatic effect, with several of them showing some limitations in the study design and recruitment of patients. Further studies using shared biomarkers are encouraged to assess if and how DBS might affect the progression of PD. Based on the existing preclinical literature, prospective clinical trials examining the course of PD in early-stage patients are needed

An ontology-based approach for modelling and querying Alzheimer’s disease data

Background The recent advances in biotechnology and computer science have led to an ever-increasing availability of public biomedical data distributed in large databases worldwide. However, these data collections are far from being "standardized" so to be harmonized or even integrated, making it impossible to fully exploit the latest machine learning technologies for the analysis of data themselves. Hence, facing this huge flow of biomedical data is a challenging task for researchers and clinicians due to their complexity and high heterogeneity. This is the case of neurodegenerative diseases and the Alzheimer's Disease (AD) in whose context specialized data collections such as the one by the Alzheimer's Disease Neuroimaging Initiative (ADNI) are maintained.Methods Ontologies are controlled vocabularies that allow the semantics of data and their relationships in a given domain to be represented. They are often exploited to aid knowledge and data management in healthcare research. Computational Ontologies are the result of the combination of data management systems and traditional ontologies. Our approach is i) to define a computational ontology representing a logic-based formal conceptual model of the ADNI data collection and ii) to provide a means for populating the ontology with the actual data in the Alzheimer Disease Neuroimaging Initiative (ADNI). These two components make it possible to semantically query the ADNI database in order to support data extraction in a more intuitive manner.Results We developed: i) a detailed computational ontology for clinical multimodal datasets from the ADNI repository in order to simplify the access to these data; ii) a means for populating this ontology with the actual ADNI data. Such computational ontology immediately makes it possible to facilitate complex queries to the ADNI files, obtaining new diagnostic knowledge about Alzheimer's disease.Conclusions The proposed ontology will improve the access to the ADNI dataset, allowing queries to extract multivariate datasets to perform multidimensional and longitudinal statistical analyses. Moreover, the proposed ontology can be a candidate for supporting the design and implementation of new information systems for the collection and management of AD data and metadata, and for being a reference point for harmonizing or integrating data residing in different sources