Background Monitoring frailty indicators in elderly people is recommended to identify those who could benefit from disability prevention programs. To contribute to the understanding of the development of frailty in the elderly, we have created the FREEDOM-LNA cohort constituting an observational study of ageing in general population. Here, we described the characteristics of a cohort of elderly subjects who are followed for determination of frailty and loss of independence trajectories. Results The cohort was composed of 1085 subjects in advanced age (mean: 83.7 ± 6.0 years) and of women in majority (68.3%). Cardiovascular risk factors were present in 88.4% of subjects. Abnormal musculoskeletal signs were reported in 44.0% and neurologic signs in 31.9%. There were 44.8% of subjects at risk of malnutrition (MNA <24) and 73.3% (668/911) at risk of mobility-related disability (SPPB ≤9); 39% (384/973) of subjects had impaired cognitive function (MMSE< 24, adjusted on education) and 49.0% (397/810) had signs of depression (GDS >9); 31.8% (240/753) were frail and 58.3% were pre-frail. Most subjects had at least one disability in ADL (66.9%) and IADL (85.1%). The SMAF indicated a loss of independence in 59.6%. Overall, 59.9% of subjects could not stay at home without at least some help. Consequently, a medical consultation was proposed in 68.2 and 42.1% social supports. Conclusions A large part of this cohort was frail or pre-frail and presented signs of loss of independence, which may be explained by multiple factors including impaired health status, poor physical performance, cognition, isolation, depression, or nutrition. This cohort will help to determine factors that adversely influence the trajectory of physical frailty over time.

Background Independence is related to the aging process. Loss of independence is defined as the inability to make decisions and participate in activities of daily living (ADLs). Independence is related to physical, psychological, biological, and socioeconomic factors. An enhanced understanding of older people’s independence trajectories and associated risk factors would enable the develop early intervention strategies. Methods Independence trajectory analysis was performed on patients identified in the Unité de Prévention de Suivi et d’Analyse du Vieillissement (UPSAV) database. UPSAV cohort is a prospective observational study. Participants were 221 community-dwelling persons aged ≥75 years followed for 24 months between July 2011–November 2013 and benefits from a prevention strategy. Data were collected prospectively using a questionnaire. Independence was assessed using the “Functional Autonomy Measurement System (Système de Mesure de l’Autonomie Fonctionnelle (SMAF))”. Group-based trajectory modeling (GBTM) was performed to identify independence trajectories, and the results were compared with those of k-means and hierarchical ascending classifications. A multinomial logistic regression was performed to identify predictive factors of the independence trajectory. Results Three distinct trajectories of independence were identified including a “Stable functional autonomy (SFA) trajectory” (53% of patients), a “Stable then decline functional autonomy decline (SDFA) trajectory” (33% of patients) and a “Constantly functional autonomy decline (CFAD) trajectory” (14% of patients). Not being a member of an association, and previous fall were significantly associated of a SDFA trajectory (P < 0.01). Absence of financial and human assistance, no hobbies, and cognitive disorder were significantly associated with a CFAD trajectory (P < 0.01). Previous occupation and multiple pathologies were predictive factors of both declining trajectories SDFA and CFAD. Conclusions Community-living older persons exhibit distinct independence trajectories and the predictive factors. The evidence from this study suggests that the prevention and screening for the loss of independence of the older adults should be anticipated to maintaining autonomy.

1315 AK2 deficiency is responsible for Reticular Dysgenesis (RD), a rare form of human Severe Combined Immunodeficiency which is characterized by the absence of blood neutrophils and T lymphocytes. AK2 which is located in the mitochondria interspace, plays an important role in energy metabolism and in efficient energy transfer through conversion of ADP into ATP and AMP and regulation of cellular adenine nucleotides homeostasis. We modelled the RD pathology using a lentiviral-mediated RNA interference strategy to knock-down AK2 expression. Human CD34+ progenitors invalidated for AK2 are deeply affected in their proliferative ability during the process of T-cell differentiation. Between 3 to 7 days after initiation of T-cell differentiation on the OP9-Delta1 stroma, we observed an increased cell apoptosis through disruption of the mitochondrial membrane potential, associated with a 2-fold decreased in the percentage of proliferative cells. In the presence of shAK2, the apparition of CD7+ T-cell precursors was profoundly reduced - as compared to the shControl - showing that the process of differentiation itself was affected. We also demonstrated that AK2 knock-down inhibits neutrophil differentiation using both G-CSF-mediated differentiation of CD34+ progenitors and ATRA-mediated differentiation of the HL60 cell line. In the HL60 system, we showed that the survival defect induced by the shAK2 could be rescued by expression of the anti-apoptotic protein Bcl-2, while this latter was not sufficient to restore a normal differentiation process. These data suggest a novel mechanism in which AK2 regulates not only the process of differentiation but also survival and proliferation of hematopoietic cell lineages. Disclosures: No relevant conflicts of interest to declare.

While the needs of dependent seniors needs are important in Nursing Home (NH), the medical resources are low in residences located in a medical desert. Access to care in these NH is very unequal and can result in a loss of chance for residents who are immediately transferred to emergency with a risk of iatrogeny or inappropriate hospitalization. Objective: We aim to find new models of care organization to optimize management of elderly in NH thanks to new technologies Artificial Intelligence (AI) associated to telemedicine. Method: Intel@Care is a 3 steps program planned over 5 years : 1- faisability study : Intel@Med-Faisa (2019-2020); 2- proof of concept : Intel@Med-POC with socio-environmental study (2020-2022); 3- efficiency study with medico-economic assessment Intel@Med-Efficiency (2022-2024). Results: Intel@Med-Faisa : 18 residents were included in 2 NHs; 20 additional diagnoses were created to adapt the Artificial Intelligence algorithm to the clinical characteristics of the elderly. Intel@Med-POC: (study in progress): 306 residents to be included to validate development of evidence-based decision tool to help physician to make decisions to manage healthcare interventions, verify the acceptability of the new care organization. A medico-economic study is also conducted. Perspectives : This program aims to secure the use of this tool by professionals and to identify the obstacles and levers about use, perception and find an economic model for the deployment on the territory. In parallel, a clinical research will be conducted in order to adapt this organization to elderly people living at home in medical desert areas.