In May 2012, a Sarcopenia Consensus Summit was convened by the Foundation of the National Institutes of Health (FNIH), National Institute of Aging (NIA), and the U.S. Food and Drug Administration (FDA); and co-sponsored by five pharmaceutical companies. At this summit, sarcopenia experts from around the world worked to develop agreement on a working definition of sarcopenia, building on the work of previous efforts to generate a consensus. With the ultimate goal of improving function and independence in individuals with sarcopenia, the Task Force focused its attention on people at greatly increased risk of muscle atrophy as a consequence of hip fracture. The rationale for looking at this population is that since hip fracture is a recognized condition, there is a clear regulatory path forward for developing interventions. Moreover, patients with hip fracture may provide an appropriate population to advance understanding of sarcopenia, for example helping to define diagnostic criteria, develop biomarkers, understand the mechanisms that underlie the age-related loss of muscle mass and strength, and identify endpoints for clinical trials that are reliable, objective, and clinically meaningful. Task Force members agreed that progress in treating sarcopenia will require strengthening of partnerships between academia, industry, and government agencies, and across continents to reach consensus on diagnostic criteria, optimization of clinical trials design, and identification of improved treatment and preventive strategies. In this report, the main results of the Task Force discussion are presented.
This is the final version of the article. Available from the publisher via the DOI in this record. ; Although mitochondrial dysfunction is a consistent feature of Alzheimer's disease in the brain and blood, the molecular mechanisms behind these phenomena are unknown. Here we have replicated our previous findings demonstrating reduced expression of nuclear-encoded oxidative phosphorylation (OXPHOS) subunits and subunits required for the translation of mitochondrial-encoded OXPHOS genes in blood from people with Alzheimer's disease and mild cognitive impairment. Interestingly this was accompanied by increased expression of some mitochondrial-encoded OXPHOS genes, namely those residing closest to the transcription start site of the polycistronic heavy chain mitochondrial transcript (MT-ND1, MT-ND2, MT-ATP6, MT-CO1, MT-CO2, MT-C03) and MT-ND6 transcribed from the light chain. Further we show that mitochondrial DNA copy number was unchanged suggesting no change in steady-state numbers of mitochondria. We suggest that an imbalance in nuclear and mitochondrial genome-encoded OXPHOS transcripts may drive a negative feedback loop reducing mitochondrial translation and compromising OXPHOS efficiency, which is likely to generate damaging reactive oxygen species. ; This work represents independent research part funded by the InnoMed (Innovative Medicines in Europe) an Integrated Project funded by the European Union of the Sixth Framework program priority FP6-2004-LIFESCIHEALTH-5, Alzheimer's Research UK, The John and Lucille van Geest Foundation, the Rosetrees Trust, the National Institute for Health Research (NIHR) Biomedical Research Centre and Dementia Unit at South London and Maudsley NHS Foundation Trust and King's College London and the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. A. H. receives support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement no115372, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007e2013) and EFPIA companies in kind contribution. R. D. is supported by awards to establish the Farr Institute of Health Informatics Research at UCL Partners, from the Medical Research Council, Arthritis Research UK, British Heart Foundation, Cancer Research UK, Chief Scientist Office, Economic and Social Research Council, Engineering and Physical Sciences Research Council, National Institute for Health Research, National Institute for Social Care and Health Research, and Wellcome Trust (grant MR/K006584/1)
Prevention of fragility fractures in older people has become a public health priority, although the most appropriate and cost-effective strategy remains unclear. In the present statement, the Interest Group on Falls and Fracture Prevention of the European Union Geriatric Medicine Society (EUGMS), in collaboration with the International Association of Gerontology and Geriatrics for the European Region (IAGG-ER), the European Union of Medical Specialists (EUMS), the International Osteoporosis Foundation - European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, outlines its views on the main points in the current debate in relation to the primary and secondary prevention of falls, the diagnosis and treatment of bone fragility, and the place of combined falls and fracture liaison services for fracture prevention in older people.
Prevention of fragility fractures in older people has become a public health priority, although the most appropriate and cost-effective strategy remains unclear. In the present statement, the Interest Group on Falls and Fracture Prevention of the European Union Geriatric Medicine Society (EUGMS), in collaboration with the International Association of Gerontology and Geriatrics for the European Region (IAGG-ER), the European Union of Medical Specialists (EUMS), the International Osteoporosis Foundation - European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, outlines its views on the main points in the current debate in relation to the primary and secondary prevention of falls, the diagnosis and treatment of bone fragility, and the place of combined falls and fracture liaison services for fracture prevention in older people.
Published ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Changes in brain amyloid burden have been shown to relate to Alzheimer's disease pathology, and are believed to precede the development of cognitive decline. There is thus a need for inexpensive and non-invasive screening methods that are able to accurately estimate brain amyloid burden as a marker of Alzheimer's disease. One potential method would involve using demographic information and measurements on plasma samples to establish biomarkers of brain amyloid burden; in this study data from the Alzheimer's Disease Neuroimaging Initiative was used to explore this possibility. Sixteen of the analytes on the Rules Based Medicine Human Discovery Multi-Analyte Profile 1.0 panel were found to associate with [(11)C]-PiB PET measurements. Some of these markers of brain amyloid burden were also found to associate with other AD related phenotypes. Thirteen of these markers of brain amyloid burden--c-peptide, fibrinogen, alpha-1-antitrypsin, pancreatic polypeptide, complement C3, vitronectin, cortisol, AXL receptor kinase, interleukin-3, interleukin-13, matrix metalloproteinase-9 total, apolipoprotein E and immunoglobulin E--were used along with co-variates in multiple linear regression, and were shown by cross-validation to explain >30% of the variance of brain amyloid burden. When a threshold was used to classify subjects as PiB positive, the regression model was found to predict actual PiB positive individuals with a sensitivity of 0.918 and a specificity of 0.545. The number of APOE [Symbol: see text] 4 alleles and plasma apolipoprotein E level were found to contribute most to this model, and the relationship between these variables and brain amyloid burden was explored. ; Alzheimer's Disease Neuroimaging Initiative (ADNI) ; Canadian Institutes of Health Research ; Foundation for the National Institutes of Health ; National Institutes of Health ; InnoMed, European Union of the Sixth Framework program ; National Institutes for Health Research Biomedical Research Centre for Mental Health at the South London and Maudsley National Health Service Foundation Trust ; Institute of Psychiatry, King's College London
Published ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't ; BACKGROUND: The study aimed to validate previously discovered plasma biomarkers associated with AD, using a design based on imaging measures as surrogate for disease severity and assess their prognostic value in predicting conversion to dementia. METHODS: Three multicenter cohorts of cognitively healthy elderly, mild cognitive impairment (MCI), and AD participants with standardized clinical assessments and structural neuroimaging measures were used. Twenty-six candidate proteins were quantified in 1148 subjects using multiplex (xMAP) assays. RESULTS: Sixteen proteins correlated with disease severity and cognitive decline. Strongest associations were in the MCI group with a panel of 10 proteins predicting progression to AD (accuracy 87%, sensitivity 85%, and specificity 88%). CONCLUSIONS: We have identified 10 plasma proteins strongly associated with disease severity and disease progression. Such markers may be useful for patient selection for clinical trials and assessment of patients with predisease subjective memory complaints. ; Medical Research Council (MRC) ; Alzheimer's Research UK ; The National Institute for Health Research (NIHR) Biomedical Research Centre ; Biomedical Research Unit for Dementia ; AddNeuroMed through the EU FP6 program ; Innovative Medicines Initiative Joint Undertaking under an EMIF grant ; European Union's Seventh Framework Programme (FP7/2007-2013)
Prevention of fragility fractures in older people has become a public health priority, although the most appropriate and cost-effective strategy remains unclear. In the present statement, the Interest Group on Falls and Fracture Prevention of the European Union Geriatric Medicine Society, in collaboration with the International Association of Gerontology and Geriatrics for the European Region, the European Union of Medical Specialists, and the International Osteoporosis Foundation-European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, outlines its views on the main points in the current debate in relation to the primary and secondary prevention of falls, the diagnosis and treatment of bone fragility, and the place of combined falls and fracture liaison services for fracture prevention in older people. ; Non peer reviewed
Published also in Aging Clinical and Experimental Research, Vol.28, No.4, WOS: 000379034800030 ; Prevention of fragility fractures in older people has become a public health priority, although the most appropriate and cost-effective strategy remains unclear. In the present statement, the Interest Group on Falls and Fracture Prevention of the European Union Geriatric Medicine Society (EUGMS), in collaboration with the International Association of Gerontology and Geriatrics for the European Region (IAGG-ER), the European Union of Medical Specialists (EUMS), the International Osteoporosis Foundation - European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, outlines its views on the main points in the current debate in relation to the primary and secondary prevention of falls, the diagnosis and treatment of bone fragility, and the place of combined falls and fracture liaison services for fracture prevention in older people. ; Peer reviewed
Published also in Aging Clinical and Experimental Research, Vol.28, No.4, WOS: 000379034800030 ; Prevention of fragility fractures in older people has become a public health priority, although the most appropriate and cost-effective strategy remains unclear. In the present statement, the Interest group on falls and fracture prevention of the European union geriatric medicine society (EUGMS), in collaboration with the International association of gerontology and geriatrics for the European region (IAGG-ER), the European union of medical specialists (EUMS), the Fragility fracture network (FFN), the International osteoporosis foundation (IOF) - European society for clinical and economic aspects of osteoporosis and osteoarthritis (ECCEO), outlines its views on the main points in the current debate in relation to the primary and secondary prevention of falls, the diagnosis and treatment of bone fragility, and the place of combined falls and fracture liaison services for fracture prevention in older people. (C) 2016 Published by Elsevier Masson SAS. ; Peer reviewed
