The Cognitive decline in Older Patients with End stage renal disease (COPE) study – rationale and design

Abstract

Background: Older patients with end stage renal disease (ESRD) are at increased risk for cognitive decline, but detailed studies of the magnitude of cognitive decline on dialysis or comprehensive conservative management (CCM) are lacking and the underlying pathophysiological mechanisms have poorly been studied.

Objectives: To describe the rationale and design of the COPE study. Study objectives are as follows. Firstly, to examine the severity of cognitive impairment in older patients reaching ESRD before dialysis and the rate of decline after dialysis or CCM initiation. Secondly, to study the association of blood biomarkers for microvascular damage and MRI derived measurements of small vessel disease with the rate of cognitive decline. Thirdly, to examine to what extent cardiac function is related to brain structure and perfusion in patients reaching ESRD. Finally, to study the association of cognitive and functional capacity with quality of life in pre-dialysis patients, as well as after dialysis or CCM initiation.

Study design and methods: The COPE study is a prospective, multicenter cohort study in the Netherlands, including prevalent and incident pre-dialysis patients ≥65 years old with eGFR ≤20 ml/min/1.73 m², awaiting either dialysis or CCM initiation. At baseline extensive data is collected including a comprehensive geriatric assessment and laboratory tests. Brain and cardiac MRI for analysis of structural and functional abnormalities are performed at baseline and repeated following therapy change. All other measurements are repeated annually during four years of follow up, including an extra evaluation six months after initiation of dialysis.

Conclusions: Knowledge of the magnitude of cognitive decline and its underlying pathophysiological mechanism, as well as its impact on functionality and quality of life can eventually help to postulate an algorithm for well balanced decision making in treatment strategies in older patients reaching ESRD.

Clinical trial registration: The COPE study is registered on www.ccmo.nl (number: NL46389.058.13).

Keywords:

• Cognition
• ESRD
• dialysis
• small vessel disease

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Declaration of funding

This study was supported by a grant of Roche Nederland BV. The sponsor did not play a role in the preparation this article.

Author contributions: M.H.K. and N.B.-B. contributed equally to the preparation of the article. M.B., S.P.M., N.B.-B., T.J.R. and A.G. were responsible for the design of the study, and contributed significantly to the content of the article. M.A.B, M.J.O., L.J.M.K. and S.H. were responsible for the design of the MRI protocol, and revised the article critically with regard to both the MRI part and the entire study protocol. H.B. is actively involved in the study protocol and contributed intellectually to the content of the paper. All authors agree to be accountable for all aspects of the work.

Declaration of financial/other relationships

M.B. has disclosed that she has received research funding from Roche, and served as an advisor for Amgen, Baxter and Roche. The Institute for Evidence-Based Medicine in Old Age (S.P.M.) is funded by the Dutch Ministry of Health and Welfare and supported by “ZonMW” (project number 62700.3002). N.B.-B., M.H.K., A.G., T.J.R., S.H., M.A.B., M.J.O., L.J.M.K., H.B. and S.P.M. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgements

There is no further involvement of any company with this article in any way. The authors declare that they have no relevant competing interests with respect to the contents of this article.

All authors reviewed and approved the final version of the article.

No assistance in the preparation of this article is to be declared.