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Association between normal tension glaucoma and the risk of Alzheimer’s disease: a nationwide population-based cohort study in Taiwan
  1. Yu-Yen Chen1,2,
  2. Yun-Ju Lai2,3,4,
  3. Yung-Feng Yen2,5,
  4. Ying-Cheng Shen1,
  5. Chun-Yuan Wang1,
  6. Chiao-Ying Liang1,
  7. Keng-Hung Lin1,
  8. Lir-Wan Fan6
  1. 1 Department of Ophthalmology, Taichung Veterans General Hospital, Taichung, Taiwan
  2. 2 School of Medicine, National Yang-Ming University, Taipei, Taiwan
  3. 3 Division of Endocrinology and Metabolism, Department of Internal Medicine, Puli Branch of Taichung Veterans General Hospital, Nantou, Taiwan
  4. 4 Department of Exercise Health Science, National Taiwan University of Sport, Taichung, Taiwan
  5. 5 Section of Infectious Diseases, Taipei City Hospital, Taipei, Taiwan
  6. 6 Department of Pediatrics; Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA
  1. Correspondence to Dr Yu-Yen Chen;{at}


Objectives To investigate a possible association between normal tension glaucoma (NTG) and an increased risk of developing Alzheimer’s disease (AD).

Design Retrospective cohort study.

Setting NTG group and the comparison group were retrieved from the whole population of the Taiwan National Health Insurance Research Database from 1 January 2001 to 31 December 2013.

Participants A total of 15 317 subjects with NTG were enrolled in the NTG group, and 61 268 age-matched and gender-matched subjects without glaucoma were enrolled in the comparison group.

Primary and secondary outcome measures Kaplan-Meier curves were generated to compare the cumulative hazard of AD between the two groups. A multivariable Cox regression analysis was used to estimate the adjusted hazard ratios (HRs) of AD, adjusted for diabetes, hypertension, hyperlipidaemia, coronary artery disease and stroke. Furthermore, risk factors for developing AD among the NTG group were investigated.

Results The mean age of the cohort was 62.1±12.5 years. Patients with NTG had significantly higher proportions of diabetes, hypertension, hyperlipidaemia, coronary artery disease and stroke than the comparisons. Patients with NTG had a significantly higher cumulative hazard for AD than the comparisons (p<0.0001). In the multivariable Cox regression after adjustment for confounders, the NTG group had a significantly higher risk of AD (adjusted HR 1.52; 95% CI 1.41 to 1.63). Moreover, in the NTG group, when we compared the effects of different types of glaucoma eye drops, none of the eye drops used were significant risk factors or protective factors for AD.

Conclusions People with NTG are at a significantly greater risk of developing AD compared with individuals without glaucoma. Among patients with NTG, none of the glaucoma eye drops used significantly changed the risk of subsequent AD.

  • normal tension glaucoma
  • alzheimer’s disease
  • risk factors
  • national health insurance research database
  • cohort study

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  • Contributors Conceptualisation: Y-YC, Y-JL, Y-FY, Y-CS and L-WF; formal analysis: Y-YC, Y-JL, C-YW and L-WF; investigation: Y-YC, C-YW, C-YL, K-HL and L-WF; methodology: Y-YC, Y-JL, Y-FY and Y-CS; Validation: Y-YC, Y-FY and K-HL; writing the original draft: Y-YC and L-WF.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval This study has been approved by the institutional review board of National Yang-Ming University (2015A018).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Data are available from the National Health Insurance Research Database (NHIRD) published by Taiwan National Health Insurance (NHI) Bureau. The data used in this study cannot be made available in the manuscript, the supplemental files or in a public repository due to the Personal Information Protection Act executed by Taiwan’s government, starting from 2012. Requests for data can be sent as a formal proposal to the NHIRD ( or by email to wt.gro.irhn@drihn.