The Precision Neurology development process implements systems theory with system biology and neurophysiology in a parallel, bidirectional research path: a combined hypothesis-driven investigation of systems dysfunction within distinct molecular, cellular and large-scale neural network systems in both animal models as well as through tests for the usefulness of these candidate dynamic systems biomarkers in different diseases and subgroups at different stages of pathophysiological progression. This translational research path is paralleled by an “omics”-based, hypothesis-free, exploratory research pathway, which will collect multimodal data from progressing asymptomatic, preclinical and clinical neurodegenerative disease (ND) populations, within the wide continuous biological and clinical spectrum of ND, applying high-throughput and high-content technologies combined with powerful computational and statistical modeling tools, aimed at identifying novel dysfunctional systems and predictive marker signatures associated with ND. The goals are to identify common biological denominators or differentiating classifiers across the continuum of ND during detectable stages of pathophysiological progression, characterize systems-based intermediate endophenotypes, validate multi-modal novel diagnostic systems biomarkers, and advance clinical intervention trial designs by utilizing systems-based intermediate endophenotypes and candidate surrogate markers. Achieving these goals is key to the ultimate development of early and effective individualized treatment of ND, such as Alzheimer’s disease (AD). The Alzheimer Precision Medicine Initiative (APMI) and cohort program (APMI-CP), as well as the Paris based core of the Sorbonne University Clinical Research Group “Alzheimer Precision Medicine” (GRC-APM) were recently launched to facilitate the passageway from conventional clinical diagnostic and drug development towards breakthrough innovation based on the investigation of the comprehensive biological nature of aging individuals. The APMI movement is gaining momentum to systematically apply both systems neurophysiology and systems biology in exploratory translational neuroscience research on ND.
After intense scientific exploration and more than a decade of failed trials, Alzheimer's disease (AD) remains a fatal global epidemic. A traditional research and drug development paradigm continues to target heterogeneous late-stage clinically phenotyped patients with single 'magic bullet' drugs. Here, we propose that it is time for a paradigm shift towards the implementation of precision medicine (PM) for enhanced risk screening, detection, treatment, and prevention of AD. The overarching structure of how PM for AD can be achieved will be provided through the convergence of breakthrough technological advances, including big data science, systems biology, genomic sequencing, blood-based biomarkers, integrated disease modeling and P4 medicine. It is hypothesized that deconstructing AD into multiple genetic and biological subsets existing within this heterogeneous target population will provide an effective PM strategy for treating individual patients with the specific agent(s) that are likely to work best based on the specific individual biological make-up. The Alzheimer's Precision Medicine Initiative (APMI) is an international collaboration of leading interdisciplinary clinicians and scientists devoted towards the implementation of PM in Neurology, Psychiatry and Neuroscience. It is hypothesized that successful realization of PM in AD and other neurodegenerative diseases will result in breakthrough therapies, such as in oncology, with optimized safety profiles, better responder rates and treatment responses, particularly through biomarker-guided early preclinical disease-stage clinical trials.
Background Stroke is a leading cause of death and disability worldwide. According to the Iranian Ministry of Medical Health and Education, out of 100,000 stroke incidents in the country, 25,000 lead to death. Thus, identifying risk factors of stroke can help healthcare providers to establish prevention strategies. This study was conducted to investigate the prevalence of stroke risk factors and their distribution based on stroke subtypes in Sayad Shirazi Hospital, Gorgan, Northeastern Iran. Material and Methods A retrospective hospital-based study was conducted at Sayad Shirazi Hospital in Gorgan, the only referral university hospital for stroke patients in Gorgan city. All medical records with a diagnosis of stroke were identified based on the International Classification of Diseases, Revision 10, from August 23, 2015, to August 22, 2016. A valid and reliable data gathering form was used to capture data about demographics, diagnostics, lifestyle, risk factors, and medical history. Results Out of 375 cases, two-thirds were marked with ischemic stroke with mean ages (standard deviation) of 66.4 (14.2) for men and 64.6 (14.2) for women. The relationship between stroke subtypes and age groups (P=0.008) and hospital outcome (P=0.0001) was significant. Multiple regression analysis showed that hypertension (Exp. (B) =1.755, P=0.037), diabetes mellitus (Exp. (B) =0.532, P=0.021), and dyslipidemia (Exp. (B) =2.325, P=0.004) significantly increased the risk of ischemic stroke. Conclusion Overall, hypertension, diabetes mellitus, and dyslipidemia were the major risk factors of stroke in Gorgan. Establishment of stroke registry (population- or hospital-based) for the province is recommended.
Our findings suggest that cognitively intact older men compared with women have higher resilience to pathophysiological processes of Alzheimer's disease.
Development of ADO as an open ADO is a first attempt to organize information related to Alzheimer's disease in a formalized, structured manner. We demonstrate that ADO is able to capture both established and scattered knowledge existing in scientific text.
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