Wightman, H., Quinn, T. J. , Mair, F. S. , Lewsey, J. , McAllister, D. A. and Hanlon, P. (2023) Frailty in randomised controlled trials for dementia or mild cognitive impairment measured via the frailty index: prevalence and prediction of serious adverse events and attrition. Alzheimer's Research and Therapy, 15, 110. (doi: 10.1186/s13195-023-01260-3) (PMID:37312157) (PMCID:PMC10262528)
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Abstract
Background: Frailty and dementia have a bidirectional relationship. However, frailty is rarely reported in clinical trials for dementia and mild cognitive impairment (MCI) which limits assessment of trial applicability. This study aimed to use a frailty index (FI)—a cumulative deficit model of frailty—to measure frailty using individual participant data (IPD) from clinical trials for MCI and dementia. Moreover, the study aimed to quantify the prevalence of frailty and its association with serious adverse events (SAEs) and trial attrition. Methods: We analysed IPD from dementia (n = 1) and MCI (n = 2) trials. An FI comprising physical deficits was created for each trial using baseline IPD. Poisson and logistic regression were used to examine associations with SAEs and attrition, respectively. Estimates were pooled in random effects meta-analysis. Analyses were repeated using an FI incorporating cognitive as well as physical deficits, and results compared. Results: Frailty could be estimated in all trial participants. The mean physical FI was 0.14 (SD 0.06) and 0.14 (SD 0.06) in the MCI trials and 0.24 (SD 0.08) in the dementia trial. Frailty prevalence (FI > 0.24) was 6.9%/7.6% in MCI trials and 48.6% in the dementia trial. After including cognitive deficits, the prevalence was similar in MCI (6.1% and 6.7%) but higher in dementia (75.4%). The 99th percentile of FI (0.31 and 0.30 in MCI, 0.44 in dementia) was lower than in most general population studies. Frailty was associated with SAEs: physical FI IRR = 1.60 [1.40, 1.82]; physical/cognitive FI IRR = 1.64 [1.42, 1.88]. In a meta-analysis of all three trials, the estimated association between frailty and trial attrition included the null (physical FI OR = 1.17 [0.92, 1.48]; physical/cognitive FI OR = 1.16 [0.92, 1.46]), although higher frailty index values were associated with attrition in the dementia trial. Conclusion: Measuring frailty from baseline IPD in dementia and MCI trials is feasible. Those living with more severe frailty may be under-represented. Frailty is associated with SAEs. Including only physical deficits may underestimate frailty in dementia. Frailty can and should be measured in future and existing trials for dementia and MCI, and efforts should be made to facilitate inclusion of people living with frailty.
| Item Type: | Articles |
|---|---|
| Additional Information: | David McAllister is funded via an Intermediate Clinical Fellowship and Beit Fellowship from the Wellcome Trust, who also supported other costs related to this project such as data access costs and database licences (201492/Z/16/Z). Peter Hanlon is funded through a Clinical Research Training Fellowship from the Medical Research Council (Grant reference: MR/S021949/1). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | McAllister, Professor David and Hanlon, Dr Peter and Quinn, Professor Terry and Wightman, Ms Heather and Lewsey, Professor Jim and Mair, Professor Frances |
| Authors: | Wightman, H., Quinn, T. J., Mair, F. S., Lewsey, J., McAllister, D. A., and Hanlon, P. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > General Practice and Primary Care College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Health Economics and Health Technology Assessment |
| Journal Name: | Alzheimer's Research and Therapy |
| Publisher: | BioMed Central |
| ISSN: | 1758-9193 |
| ISSN (Online): | 1758-9193 |
| Copyright Holders: | Copyright © 2023 The Authors |
| First Published: | First published in Alzheimer's Research and Therapy 15: 110 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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