Spinal cord injury and Alzheimer’s disease risk: a population-based, retrospective cohort study

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Study design

Propensity score-matched, retrospective cohort study.


To determine the risk of developing Alzheimer’s disease (AD) in patients with spinal cord injury (SCI).


The present study used Taiwan’s National Health Insurance Research Database.


A total of 9257 patients who had 2 ambulatory visits with a diagnosis of SCI in 2001 were included in the SCI group. The non-SCI group consisted of 37,028 propensity score-matched patients without a diagnosis of SCI. The cumulative incidence of AD was estimated for each of the two patient groups using the Kaplan–Meier method. Stratified Cox proportional hazard regression was then employed to assess the influence of SCI on the risk of AD.


During the follow-up period, 25 subjects in the SCI group and 57 in the non-SCI group developed AD. The cumulative incidence of AD in the SCI group was higher than in the non-SCI group (P = 0.0168); and the hazard ratio of AD for the SCI group, as compared to the non-SCI group, was 1.71 (95% CI 1.06–2.76, P = 0.0273).


This study suggests that patients with SCI have an increased risk of developing AD.

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  1. 1.

    Cummings JL, Isaacson RS, Schmitt FA, Velting DM. A practical algorithm for managing Alzheimer’s disease: what, when, and why? Ann Clin Transl Neurol. 2015;2:307–23.

  2. 2.

    Brettschneider J, Del Tredici K, Lee VM, Trojanowski JQ. Spreading of pathology in neurodegenerative diseases: a focus on human studies. Nat Rev Neurosci. 2015;16:109–20

  3. 3.

    Daneshvar DH, Goldstein LE, Kiernan PT, Stein TD, McKee AC. Post-traumatic neurodegeneration and chronic traumatic encephalopathy. Mol Cell Neurosci. 2015;66:81–90.

  4. 4.

    Collins JM, King AE, Woodhouse A, Kirkcaldie MT, Vickers JC. The effect of focal brain injury on beta-amyloid plaque deposition, inflammation and synapses in the APP/PS1 mouse model of Alzheimer’s disease. Exp Neurol. 2015;267:219–29.

  5. 5.

    Park E, Velumian AA, Fehlings MG. The role of excitotoxicity in secondary mechanisms of spinal cord injury: a review with an emphasis on the implications for white matter degeneration. J Neurotrauma. 2004;21:754–74.

  6. 6.

    Cornish R, Blumbergs PC, Manavis J, Scott G, Jones NR, Reilly PL. Topography and severity of axonal injury in human spinal cord trauma using amyloid precursor protein as a marker of axonal injury. Spine (Phila Pa 1976). 2000;25:1227–33.

  7. 7.

    Ahlgren S, Li GL, Olsson Y. Accumulation of beta-amyloid precursor protein and ubiquitin in axons after spinal cord trauma in humans: immunohistochemical observations on autopsy material. Acta Neuropathol. 1996;92:49–55.

  8. 8.

    Olsson Y, Ahlgren S, Farooque M, Holtz A, Li GL, Yu WR. Pathophysiology of spinal cord trauma: observations on vasogenic oedema and axonal injuries in human and experimental material. Neuropathol Appl Neurobiol. 1996;22:518–20.

  9. 9.

    Huang SW, Wang WT, Chou LC, Liou TH, Lin HW. Risk of dementia in patients with spinal cord injury: a nationwide population-based cohort study. J Neurotrauma. 2017;34:615–22.

  10. 10.

    Lin CW, Huang YP, Pan SL. Spinal cord injury is related to an increased risk of multiple sclerosis: a population-based, propensity score-matched, longitudinal follow-up study. J Neurotrauma. 2015;32:655–9.

  11. 11.

    Yeh TS, Huang YP, Wang HI, Pan SL. Spinal cord injury and Parkinson/‘s disease: a population-based, propensity score-matched, longitudinal follow-up study. Spinal Cord. 2016;54:1215–9.

  12. 12.

    D’Agostino RB Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med. 1998;17:2265–81.

  13. 13.

    Huang YP, Chen LS, Yen MF, Fann CY, Chiu YH, Chen HH, et al. Parkinson’s disease is related to an increased risk of ischemic stroke-a population-based propensity score-matched follow-up study. PLoS ONE. 2013;8:e68314.

  14. 14.

    Fox M, Knapp LA, Andrews PW, Fincher CL. Hygiene and the world distribution of Alzheimer’s disease: epidemiological evidence for a relationship between microbial environment and age-adjusted disease burden. Evol Med Public Health. 2013;2013:173–86.

  15. 15.

    Liu C, Hung Y, Chuang Y, Chen Y, Weng W, Liu J, et al. Incorporating development stratification of Taiwan townships into sampling design of large scale health interview survey (in Chinese). J Health Manag. 2006;4:1–22.

  16. 16.

    Parsons L. Performing a 1:N case-control match on propensity score. In: Proceedings of the Twenty-ninth Annual SAS Users Group International Conference: 9-12 May 2004; Montreal, Canada. North Carolina: SAS Institute Inc.

  17. 17.

    Austin PC. A critical appraisal of propensity-score matching in the medical literature between 1996 and 2003. Stat Med. 2008;27:2037–49.

  18. 18.

    Pajoohesh-Ganji A, Burns MP, Pal-Ghosh S, Tadvalkar G, Hokenbury NG, Stepp MA, et al. Inhibition of amyloid precursor protein secretases reduces recovery after spinal cord injury. Brain Res. 2014;1560:73–82.

  19. 19.

    Kobayashi S, Sasaki T, Katayama T, Hasegawa T, Nagano A, Sato K. Temporal-spatial expression of presenilin 1 and the production of amyloid-beta after acute spinal cord injury in adult rat. Neurochem Int. 2010;56:387–93.

  20. 20.

    De-Paula VJ, Radanovic M, Diniz BS, Forlenza OV. Alzheimer’s disease. Subcell Biochem. 2012;65:329–52.

  21. 21.

    Song HL, Shim S, Kim DH, Won SH, Joo S, Kim S, et al. beta-Amyloid is transmitted via neuronal connections along axonal membranes. Ann Neurol. 2014;75:88–97.

  22. 22.

    Pouw MH, Kwon BK, Verbeek MM, Vos PE, van Kampen A, Fisher CG, et al. Structural biomarkers in the cerebrospinal fluid within 24 h after a traumatic spinal cord injury: a descriptive analysis of 16 subjects. Spinal Cord. 2014;52:428–33.

  23. 23.

    Kwon BK, Stammers AM, Belanger LM, Bernardo A, Chan D, Bishop CM, et al. Cerebrospinal fluid inflammatory cytokines and biomarkers of injury severity in acute human spinal cord injury. J Neurotrauma. 2010;27:669–82.

  24. 24.

    Roerig A, Carlson R, Tipold A, Stein VM. Cerebrospinal fluid tau protein as a biomarker for severity of spinal cord injury in dogs with intervertebral disc herniation. Vet J. 2013;197:253–8.

  25. 25.

    Le MN, Kim W, Lee S, McKee AC, Hall GF. Multiple mechanisms of extracellular tau spreading in a non-transgenic tauopathy model. Am J Neurodegener Dis. 2012;1:316–33.

  26. 26.

    Hall GF, Patuto BA. Is tau ready for admission to the prion club? Prion. 2012;6:223–33.

  27. 27.

    Davies AL, Hayes KC, Dekaban GA. Clinical correlates of elevated serum concentrations of cytokines and autoantibodies in patients with spinal cord injury. Arch Phys Med Rehabil. 2007;88:1384–93.

  28. 28.

    Hayes KC, Hull TC, Delaney GA, Potter PJ, Sequeira KA, Campbell K, et al. Elevated serum titers of proinflammatory cytokines and CNS autoantibodies in patients with chronic spinal cord injury. J Neurotrauma. 2002;19:753–61.

  29. 29.

    Manns PJ, McCubbin JA, Williams DP. Fitness, inflammation, and the metabolic syndrome in men with paraplegia. Arch Phys Med Rehabil. 2005;86:1176–81.

  30. 30.

    Heneka MT, Carson MJ, Khoury JE, Landreth GE, Brosseron F, Feinstein DL, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 2015;14:388–405.

  31. 31.

    Pasqualetti G, Brooks DJ, Edison P. The role of neuroinflammation in dementias. Curr Neurol Neurosci Rep. 2015;15:531.

  32. 32.

    Fischer R, Maier O. Interrelation of Oxidative Stress and Inflammation in Neurodegenerative Disease: Role of TNF. Oxid Med Cell Longev. 2015;2015:610813.

  33. 33.

    Kyrkanides S, Tallents RH, Miller JN, Olschowka ME, Johnson R, Yang M, et al. Osteoarthritis accelerates and exacerbates Alzheimer’s disease pathology in mice. J Neuroinflammation. 2011;8:112.

  34. 34.

    Cunningham C, Wilcockson DC, Campion S, Lunnon K, Perry VH. Central and systemic endotoxin challenges exacerbate the local inflammatory response and increase neuronal death during chronic neurodegeneration. J Neurosci. 2005;25:9275–84.

  35. 35.

    Engelhart MJ, Geerlings MI, Meijer J, Kiliaan A, Ruitenberg A, van Swieten JC, et al. Inflammatory proteins in plasma and the risk of dementia: the rotterdam study. Arch Neurol. 2004;61:668–72.

  36. 36.

    Tan ZS, Beiser AS, Vasan RS, Roubenoff R, Dinarello CA, Harris TB, et al. Inflammatory markers and the risk of Alzheimer disease: the Framingham Study. Neurology. 2007;68:1902–8.

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This work was supported by the Department of Health, Executive Yuan, Republic of China [DOH93-TD-M-113-030, DOH94-TD-M-113-004, and DOH95-TD-M-113-002].

Author information

Author notes


    1. Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan

      • Tian-Shin Yeh
    2. Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan

      • Yu-Chun Ho
      •  & Shin-Liang Pan
    3. Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taipei, Taiwan

      • Cherng-Lan Hsu
    4. Department of Physical Medicine and Rehabilitation, National Taiwan University College of Medicine, Taipei, Taiwan

      • Shin-Liang Pan


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    Conflict of interest

    The authors declare that they have no competing interests.


    The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

    Corresponding author

    Correspondence to Shin-Liang Pan.