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Incident traumatic spinal cord injury and risk of Alzheimer’s disease and related dementia: longitudinal case and control cohort study

Spinal Cord (2024)Cite this article

Subjects

Abstract

Study design

Retrospective case/control longitudinal cohort study

Objectives

Prevalent traumatic spinal cord injury (TSCI) is associated with Alzheimer’s disease and related dementia (ADRD). We examined the hazard ratio for ADRD after incident TSCI and hypothesized that ADRD hazard is greater among adults with incident TSCI compared with their matched control of adults without TSCI.

Setting

Using 2010–2020 U.S. national private administrative claims data, we identified adults aged 45 years and older with probable (likely and highly likely) incident TSCI (n = 657). Our controls included one-to-ten matched cohort of people without TSCI (n = 6553).

Methods

We applied Cox survival models and adjusted them for age, sex, years of living with certain chronic conditions, exposure to six classes of prescribed medications, and neighborhood characteristics of place of residence. Hazard ratios were used to compare the results within a 4-year follow-up.

Results

Our fully adjusted model without any interaction showed that incident TSCI increased the risk for ADRD (HR = 1.30; 95% CI, 1.01–1.67). People aged 45–64 with incident TSCI were at high risk for ADRD (HR = 5.14; 95% CI, 2.27–11.67) and no significant risk after age 65 (HR = 1.20; 95% CI, .92–1.55). Our sensitivity analyses confirmed a higher hazard ratio for ADRD after incident TSCI at 45–64 years of age compared with the matched controls.

Conclusions

TSCI is associated with a higher hazard of ADRD. This study informs the need to update clinical guidelines for cognitive screening after TSCI to address the heightened risk of cognitive decline and to shed light on the causality between TSCI and ADRD.

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Fig. 1: Monthly exposure to six classes of medications among cases and controls.
Fig. 2: Unadjusted ADRD rates and Kaplan–Meier curves among cases and controls.

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Data availability

The data that support the findings of this study are available from OptumInsight but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of OptumInsight.

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Acknowledgements

Authors acknowledge Liz Katz for her assistance in editing the manuscript.

Funding

This research was developed under a grant from the Craig Neilsen Foundation (Grant Application # 721097) and the Department of Defence (Grant Application# W81XWH2110751).

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Authors and Affiliations

  1. Department of Family Medicine, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA

    Paul Lin & Elham Mahmoudi

  2. Institute for Healthcare Policy and Innovation, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA

    Paul Lin, Neil Kamdar, Christine Cigolle & Elham Mahmoudi

  3. Department of Physical Medicine and Rehabilitation, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA

    Gianna M. Rodriguez & Denise Tate

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  1. Paul Lin
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  2. Neil Kamdar
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  6. Elham Mahmoudi
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Contributions

PL conducted the data analysis and drafted and revised the data and methods sections. NK revised the manuscript. JR validated the cohort selection and revised the manuscript. CC assisted in cohort selection and revised the manuscript. DT revised the manuscript. EM designed the study, wrote the research design, and drafted and revised the manuscript.

Corresponding author

Correspondence to Elham Mahmoudi.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

This research project used human data in agreement with the Declaration of Helsinki. Since we used secondary de-identified data, receiving informed consent was not applicable. The study was deemed exempt from our Institutional Review Board approval (IRB#HUM00192830) because administrative claims data are de-identified for research purposes.

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Lin, P., Kamdar, N., Rodriguez, G.M. et al. Incident traumatic spinal cord injury and risk of Alzheimer’s disease and related dementia: longitudinal case and control cohort study. Spinal Cord (2024). https://doi.org/10.1038/s41393-024-01009-1

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