Biological brain age prediction using machine learning on structural neuroimaging data: Multi-cohort validation against biomarkers of Alzheimer's disease and neurodegeneration stratified by sex

Brain-age can be inferred from structural neuroimaging and compared to chronological age (brain-age delta) as a marker of biological brain aging. Accelerated aging has been found in neurodegenerative disorders like Alzheimer's disease (AD), but its validation against markers of neurodegeneration and AD is lacking. Here, imaging-derived measures from the UK Biobank dataset (N=22,661) were used to predict brain-age in 2,314 cognitively unimpaired (CU) individuals at higher risk of AD and mild cognitive impaired (MCI) patients from four independent cohorts with available biomarker data: ALFA+, ADNI, EPAD, and OASIS. Brain-age delta was associated with abnormal amyloid-β, more advanced stages (AT) of AD pathology and APOE-ε4 status. Brain-age delta was positively associated with plasma neurofilament light, a marker of neurodegeneration, and sex differences in the brain effects of this marker were found. These results validate brain-age delta as a non-invasive marker of biological brain aging in non-demented individuals with abnormal levels of biomarkers of AD and axonal injury

Optimising Access Surgery in Senior Haemodialysis Patients (OASIS): study protocol for a multicentre randomised controlled trial

Introduction Current evidence on vascular access strategies for haemodialysis patients is based on observational studies that are at high risk of selection bias. For elderly patients, autologous arteriovenous fistulas that are typically created in usual care may not be the best option because a significant proportion of fistulas either fail to mature or remain unused. In addition, long-term complications associated with arteriovenous grafts and central venous catheters may be less relevant when considering the limited life expectancy of these patients. Therefore, we designed the Optimising Access Surgery in Senior Haemodialysis Patients (OASIS) trial to determine the best strategy for vascular access creation in elderly haemodialysis patients. Methods and analysis OASIS is a multicentre randomised controlled trial with an equal participant allocation in three treatment arms. Patients aged 70 years or older who are expected to initiate haemodialysis treatment in the next 6 months or who have started haemodialysis urgently with a catheter will be enrolled. To detect and exclude patients with an unusually long life expectancy, we will use a previously published mortality prediction model after external validation. Participants allocated to the usual care arm will be treated according to current guidelines on vascular access creation and will undergo fistula creation. Participants allocated to one of the two intervention arms will undergo graft placement or catheter insertion. The primary outcome is the number of access-related interventions required for each patient-year of haemodialysis treatment. We will enrol 195 patients to have sufficient statistical power to detect an absolute decrease of 0.80 interventions per year. Ethics and dissemination Because of clinical equipoise, we believe it is justified to randomly allocate elderly patients to the different vascular access strategies. The study was approved by an accredited medical ethics review committee. The results will be disseminated through peer-reviewed publications and will be implemented in clinical practice guidelines. Protocol version and date V.5, 25 February 2021.Clinical epidemiolog

OASIS STUDY: ACTIVITY PATTERNS OF OLDER ADULTS LIVING IN FIVE AGING IN PLACE COMMUNITIES

Abstract Background: The Oasis program is a model of aging-in-place that targets social connectedness, physical activity and nutritional wellness through member-driven programming. Oasis, first established in an apartment building in Kingston Ontario, has recently been expanded to 6 new communities across Ontario in a participatory action research study. The purpose of this poster is to describe the physical activity patterns of five unique Oasis communities (Original and 4 new) and explore the impact of personal, environmental, and Oasis program characteristics on these patterns. Methods: Participants were recruited from Oasis communities in 3 market-priced apartiments, 1 subsidized apartment, and 1 mobile-home park. Participants wore the ActivPAL3 activity monitor for 7 days. Mobility was measured using the Timed Up and Go. Programming was described by type (e.g. social, exercise, nutrition), frequency, and timing of programming. Results: Participants included 70 older adults aged 79.8(min 62, max 97), community mean age ranged from 66.2 – 83.5 years. TUG score 11.6(SD 4.9) (community range 10.5 to 13.7 s). Average daily step count was 5800(SD 2835) steps, with communities ranging from 4685 to 6472 steps/day. An average of 604(community range 236 – 1056) of steps were taken at a healthy pace(100 steps/min). Only 27% of participants took the recommended 7000 steps/day (with community rates ranging from 9.5% to 37.5%). Conclusions: Older adults within these aging in place communities demonstrated low to moderate levels of physical activity, with activity patterns differing across communities. Impact of community make up and characteristics on activity patterns will be presented.</jats:p

KEY DIMENSIONS OF OASIS, AN OLDER-ADULT DRIVEN MODEL OF AGING-IN-PLACE IN CANADA

Abstract Oasis Senior Supportive Living (Oasis) is an active aging-in-place model created by older adults in a naturally occurring retirement community, such as an apartment building. The program is member-driven so that participating older residents determine the programming and services that best address their needs. The first Oasis program was established in an apartment building in Kingston, Canada and has been running for more than ten years. Preliminary evaluations of the Oasis program demonstrate that its members report feeling more socially connected, are more physically active, and have increased nutrition as a result of participation. In-depth interviews were conducted with Oasis members and key program stakeholders to identify the core dimensions of the Oasis program that has led to its success in supporting active aging in place. Interviews were audio-recorded and transcribed verbatim. Thematic analysis was used to identify, analyze and report themes. Four themes emerged: (1) nutrition, social and physical activities as critical programming pillars; (2) the importance of active member participation and decision-making; (3) the need for onsite support to facilitate programming; and (4) Oasis as a family. These findings highlight the need for programming that is designed for and by older adults. Supporting older adults to come together and form community is key to healthy and active aging. Identification of these elements is critical to modelling Oasis in other community contexts. Oasis is currently being expanded to seven new communities across Ontario using a participatory action research approach.</jats:p

Biological brain age prediction using machine learning on structural neuroimaging data: Multi-cohort validation against biomarkers of Alzheimer's disease and neurodegeneration stratified by sex

Brain-age can be inferred from structural neuroimaging and compared to chronological age (brain-age delta) as a marker of biological brain aging. Accelerated aging has been found in neurodegenerative disorders like Alzheimer's disease (AD), but its validation against markers of neurodegeneration and AD is lacking. Here, imaging-derived measures from the UK Biobank dataset (N=22,661) were used to predict brain-age in 2,314 cognitively unimpaired (CU) individuals at higher risk of AD and mild cognitive impaired (MCI) patients from four independent cohorts with available biomarker data: ALFA+, ADNI, EPAD, and OASIS. Brain-age delta was associated with abnormal amyloid-β, more advanced stages (AT) of AD pathology and APOE-ε4 status. Brain-age delta was positively associated with plasma neurofilament light, a marker of neurodegeneration, and sex differences in the brain effects of this marker were found. These results validate brain-age delta as a non-invasive marker of biological brain aging in non-demented individuals with abnormal levels of biomarkers of AD and axonal injury.The project leading to these results has received funding from “la Caixa” Foundation (ID 100010434), under agreement LCF/PR/GN17/50300004 and the Alzheimer’s Association and an international anonymous charity foundation through the TriBEKa Imaging Platform project (TriBEKa-17–519007). Additional support has been received from the Universities and Research Secretariat, Ministry of Business and Knowledge of the Catalan Government under the grant no. 2017-SGR-892 and the Spanish Research Agency (AEI) under project PID2020-116907RB-I00 of the call MCIN/ AEI /10.13039/501100011033. FB is supported by the NIHR biomedical research center at UCLH. MSC receives funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Grant agreement No. 948677), the Instituto de Salud Carlos III (PI19/00155), and from a fellowship from ”la Caixa” Foundation (ID 100010434) and from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 847648 (LCF/BQ/PR21/11840004)