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A multi-state model based reanalysis of the Framingham Heart Study: Is dementia incidence really declining?

  • NEURO-EPIDEMIOLOGY
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Abstract

Recent research by Satizabal and colleagues using data from the Framingham Heart Study demonstrated a linear decline in dementia incidence since the 1970s. The aim of this study is to re-examine these findings, given concerns that bias resulted from failure to account for the probability of acquiring dementia between the last dementia-free observation and death. This analysis included 5118 persons 60+ years of age, and determined the 5-year dementia incidence during four non-overlapping epochs. In addition to a replication using Cox proportional hazards, we applied separate Cox models (given unequal hazards across epochs) and a Spline-based penalized likelihood approach based on the illness-death multi-state model. In addition, we present a simulation study demonstrating the bias associated with the use of standard survival models. The simulation showed that estimates of disease incidence derived from the multi-state model-based approach were consistent with the true disease incidence, whereas Cox regression ‘censoring’ observations at death or at last observation consistently underestimated it. Using the Framingham data, the 5-year age- and sex-adjusted cumulative hazard rates for dementia as derived from the multi-state model-based approach were 3.84, 2.66, 3.29 and 3.13 per 100 persons in epochs 1, 2, 3 and 4 respectively. The findings do not support the conclusion that dementia incidence has declined in the Framingham Heart Study over the given time period. Previous findings of a decline may have been an artefact resulting from improper treatment of those cases in which death precluded the observation of dementia onset.

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Acknowledgements

This manuscript was prepared using the FRAMCOHORT and FRAMOFFSPRING Research Materials obtained from the NHLBI Biologic Specimen and Data Repository Information Coordinating Center and does not necessarily reflect the opinions or views of the FRAMCOHORT, FRAMOFFSPRING or the NHLBI. We would like to thank Renee Marie Kingma for assistance in constructing the analysis data sets.

Funding

This work was supported by the German Research Foundation (Grant No. DFG SCHU 756/12). The funding agreement ensured the authors’ independence in designing the study, collecting, analyzing, and interpreting the data, writing of the manuscript, and in the decision to submit the manuscript for publication.

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Authors and Affiliations

  1. Institute for Prevention and Cancer Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Elsässerstrasse 2, 79110, Freiburg, Germany

    Nadine Binder & James Balmford

  2. Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Stefan-Meier-Strasse 26, 79104, Freiburg, Germany

    James Balmford & Martin Schumacher

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  1. Nadine Binder
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  2. James Balmford
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  3. Martin Schumacher
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Correspondence to Nadine Binder.

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Binder, N., Balmford, J. & Schumacher, M. A multi-state model based reanalysis of the Framingham Heart Study: Is dementia incidence really declining?. Eur J Epidemiol 34, 1075–1083 (2019). https://doi.org/10.1007/s10654-019-00567-6

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  • DOI: https://doi.org/10.1007/s10654-019-00567-6

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