Biomarkers of Age-Related Frailty and Frailty Related to Diseases: An Exploratory, Cross-Sectional Analysis from the MAPT Study.

BACKGROUND: Frailty may in most cases result from two main causes: the aging process (age-related frailty) and diseases (evolving chronic conditions or acute medical illnesses - disease-related frailty). The biological determinants characterizing these two main causes of frailty may be different. OBJECTIVES: The aim of this study is to compare the biological and neuroimaging profile of people without frailty, those with age-related frailty, and subjects with disease-related frailty in community-dwelling older adults. MATERIAL AND METHODS: We performed a secondary, cross-sectional analysis from the Multidomain Alzheimer Preventive Trial (MAPT). We included 1199 subjects without frailty throughout the 5-year follow-up, 82 subjects with incident age-related frailty, and 53 with incident disease-related frailty. Available blood biomarkers involved nutritional (eg, vitamin D, omega-3 fatty acids), inflammatory-related (IL-6, TNFR1, GDF15), neurodegenerative (eg, beta-amyloid, neurofilament light chain) and neuroimaging markers (MRI, Amyloid-PET). RESULTS: Although not statistically significant, the results of the unadjusted model showed increasing gradients for inflammatory markers (GDF15, TNFR1) and decreasing gradients for nutritional and neuroimaging markers (omega 3 index, hippocampal volume) from age-related frailty participants to individuals with disease-related frailty. Considering the linear models we observed higher GDF15 values in disease-related frailty group compared to age-related frailty individuals [ß = 242.8 (49.5, 436.2)]. We did not find any significant difference between subjects without frailty and those with age-related frailty. Subjects with disease-related frailty compared to subjects without frailty had lower values of DHA [ß = -2.42 (-4.76, -0.08)], Omega 3 Index [ß = -0.50 (-0.95, -0.06)] and hippocampal volume [ß = -0.22 (-0.42,-0.02)]. They also had higher values of GDF15 [ß = 246.1 (88.9, 403.4)] and TNFR1 [ß = 157.5 (7.8, 307.2)]. CONCLUSION: Age-related frailty and disease-related frailty may represent different degrees of frailty severity on a biological level. Further research is needed to identify biomarkers potentially able to distinguish these classifications of frailty.

Framework Implementation of the INSPIRE ICOPE-CARE Program in Collaboration with the World Health Organization (WHO) in the Occitania Region.

INTRODUCTION: Limiting the number of dependent older people in coming years will be a major economic and human challenge. In response, the World Health Organization (WHO) has developed the «Integrated Care for Older People (ICOPE)¼ approach. The aim of the ICOPE program is to enable as many people as possible to age in good health. To reach this objective, the WHO proposes to follow the trajectory of an individual's intrinsic capacity, which is the composite of all their physical and mental capacities and comprised of multiple domains including mobility, cognition, vitality / nutrition, psychological state, vision, hearing. OBJECTIVE: The main objective of the INSPIRE ICOPE-CARE program is to implement, in clinical practice at a large scale, the WHO ICOPE program in the Occitania region, in France, to promote healthy aging and maintain the autonomy of seniors using digital medicine. METHOD: The target population is independent seniors aged 60 years and over. To follow this population, the 6 domains of intrinsic capacity are systematically monitored with pre-established tools proposed by WHO especially STEP 1 which has been adapted in digital form to make remote and large-scale monitoring possible. Two tools were developed: the ICOPE MONITOR, an application, and the BOTFRAIL, a conversational robot. Both are connected to the Gerontopole frailty database. STEP 1 is performed every 4-6 months by professionals or seniors themselves. If a deterioration in one or more domains of intrinsic capacity is identified, an alert is generated by an algorithm which allows health professionals to quickly intervene. The operational implementation of the INSPIRE ICOPE-CARE program in Occitania is done by the network of Territorial Teams of Aging and Prevention of Dependency (ETVPD) which have more than 2,200 members composed of professionals in the medical, medico-social and social sectors. Targeted actions have started to deploy the use of STEP 1 by healthcare professionals (physicians, nurses, pharmacists,…) or different institutions like French National old age insurance fund (CNAV), complementary pension funds (CEDIP), Departmental Council of Haute Garonne, etc. Perspective: The INSPIRE ICOPE-CARE program draws significantly on numeric tools, e-health and digital medicine to facilitate communication and coordination between professionals and seniors. It seeks to screen and monitor 200,000 older people in Occitania region within 3 to 5 years and promote preventive actions. The French Presidential Plan Grand Age aims to largely implement the WHO ICOPE program in France following the experience of the INSPIRE ICOPE-CARE program in Occitania.

Integrated Care for Older People and the Implementation in the INSPIRE Care Cohort.

BACKGROUNDS: The World Health Organization has published the Integrated Care for Older People, ICOPE handbook Guidance on person-centred assessment and pathways in primary care. This is an integrated individual care tool focused on the individual and healthy ageing. The ICOPE tool proposes step by step, a screening, a fine assessment, the development of a personalized care plan, its implementation and follow up and finally the consideration of the caregivers and community. The new Geroscience field is focusing on preventing age-related diseases, and should now investigate with the ICOPE tool the optimal maintenance of intrinsic capacity (IC) through mobility, cognition, psychology, vitality, hearing and vision. This article aims to present this new tool and to presents its innovative implementation at the Toulouse University Hospital through the INSPIRE study. We believe that the ICOPE integrated care program will also be a pragmatic way to maintain cognitive functions and detect early Alzheimer. OBJECTIVES: The main objective of the INSPIRE study is to build a Bio-resource Research Platform for Healthy Ageing gathering biological, clinical and digital resources in order to identify markers of ageing, age-related diseases and IC evolution. The study will be also testing the implementation and follow up of the ICOPE tool. METHODS: The Inspire Platform will gather clinical data and bio-specimens from 1000 subjects in the Occitania Region, of different ages (from 30 years and over) over 10 years. Data will be collected annually. Using the ICOPE tool IC domains will be monitored every 4 months. Once IC decline is identified, participants will have a thorough clinical assessment and blood sampling to investigate the response of markers of ageing at the time of decline. The French ethic committee approved the study. RESULTS: The Inspire platform aims to develop an integrative approach to promote novel new technologies for the assessment and monitoring of functional capacities.

Formulation and evaluation of lactoferrin bioadhesive tablets.

For the treatment of chronic inflammation in the oral cavity, we attempted to develop bioadhesive tablets of bovine lactoferrin (B-LF) which has antibacterial properties and immune regulatory functions. B-LF tablets containing pectin, tamarind gum or carboxymethylcellulose (CMC) were prepared by direct compression. Tablets consisting of B-LF, pectin and xylitol passed through 60- or 100-mesh sieves were also prepared. The tablets containing CMC had insufficient bioadhesive force. Although the tablets containing tamarind gum showed the longest residence time in the oral cavity, an unpleasant taste gradually developed. The tablets containing pectin showed the highest value of bioadhesive force and the taste was acceptable. The characteristics of the B-LF tablets were improved by adding an appropriate amount of xylitol and using the ingredients sieved by a 100-mesh sieve. The therapeutic effect was evaluated by using rats with an ulcer on the oral mucosa. In the present study, swelling on the periphery of the ulcer was observed after administration of the B-LF tablets, and then the ulcer has reduced overall.