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Principal Investigator  
Principal Investigator's Name: Andreas Engvig
Institution: Oslo University Hospital
Department: Department of Endocrinology, Morbid Obesity and Pr
Proposed Analysis: 1) Frailty is emerging as an independent risk factor for dementia. A Frailty Index (FI) was recently validated in the ADNI2-cohort (1). Still, the relationship between frailty and AD-conversion has not been studied in ADNI. We aim to compute a FI for ADNI1, and study its relationship with AD-conversion using Cox proportional hazards modeling. 2) The optimal way to compute an FI is unknown. Furthermore, current practices of FI-estimation is related to bias and may be suboptimal (2). We aim to use ADNI data to compare AD-conversion in MCI-patients living with or without frailty – as estimated by an FI – with MCI-patient subgroups identified by a dimensionality reduction technique combined with hierarchical clustering of the same health items used for estimation of the FI. We expect that the data-driven clustering approach will lead to improved prediction of AD-conversion compared with the conventional expert-generated FI. Next, we aim to use the variable weighting identified by hierarchical clustering to prune the original FI - creating a data-driven FI – and compare its predictive ability in terms of AD-conversion with the original, expert-generated FI. We believe the proposed analyses will better illuminate the relationship between indices of frailty and risk of dementia. References 1. Canevelli, M., Arisi, I., Bacigalupo, I., Arighi, A., Galimberti, D., Vanacore, N., D’Onofrio, M., Cesari, M., Bruno, G., 2021. Biomarkers and phenotypic expression in Alzheimer’s disease: exploring the contribution of frailty in the Alzheimer’s Disease Neuroimaging Initiative. GeroScience 43, 1039–1051.. doi:10.1007/s11357-020-00293-y 2) Chao YS, Wu HC, Wu CJ, Chen WC. Index or illusion: The case of frailty indices in the Health and Retirement Study. PLoS One. 2018;13(7):e0197859. Published 2018 Jul 18. doi:10.1371/journal.pone.0197859
Additional Investigators  
Investigator's Name: Luigi Maglanoc
Proposed Analysis: Dr. Maglanoc is a data scientist with a Ph. D. in cognitive neuroscience and will lead the subject clustering analyses
Investigator's Name: Karl Trygve Kalleberg
Proposed Analysis: Dr. Kalleberg will lead processing and analysis of DNA methylation data
Investigator's Name: Esten Høyland Leonardsen
Proposed Analysis: Mr. Leonardsen will perform processing and analysis of brain age according to a validated procedure
Investigator's Name: Lars Tjelta Westlye
Proposed Analysis: Conceptualization, supervision, overall analysis, and writing of draft