Association between open-angle glaucoma and Alzheimer’s disease in Sweden: a long-term population-based follow-up study

Keywords: Alzheimer’s disease, open-angle glaucoma, normal-tension glaucoma, dementia, epidemiology, risk factor


Background: Open-angle glaucoma (OAG) and Alzheimer’s disease (AD) are two age-related neurodegenerative diseases of significant public health importance. Epidemiological studies have indicated that there might be an association between the disorders.

Methods: Predictors of AD, including mixed and unspecified dementia, were analysed in a cohort of 712 residents aged 65–74 years, examined in a population survey in the rural district of Tierp, Sweden, from 1984 to 1986. To expand the sample size, 821 people were recruited by means of glaucoma case records established at the Eye Department in Tierp from 1978 to 2007. In this way, the cohort comprised 1,533 people, representing more than 21,000 person-years at risk. Medical records were reviewed to identify subjects diagnosed with dementia. Those with a follow-up duration shorter than 2 years were excluded.

Results: By the conclusion of the study, in August 2020, 307 subjects had received a diagnosis of AD, including mixed and unspecified dementia. Of these cases, 55 were affected with definite OAG at baseline. Higher age and ischemic heart disease were the only predictors of AD identified. In multivariate analysis, adjusting for age, participation in the population survey and competing events, no association was found between OAG and AD (hazard ratio 1.08; 95% confidence interval: 0.80–1.47).

Conclusion: In this long-term follow-up study of subjects aged 65–74 years old in Sweden, OAG was not associated with AD.


Download data is not yet available.


  1. Selkoe DJ. Alzheimer’s disease: genes, proteins and therapy. Physiol Rev. 2001;81:741–66. doi: 10.1152/physrev.2001.81.2.741

  2. Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA. 1997;278:1349–56. doi: 10.1001/jama.1997.03550160069041

  3. Ekström C. Risk factors for incident open-angle glaucoma: A population-based 20-year follow-up study. Acta Ophthalmol. 2012;90:316–21. doi: 10.1111/j.1755–3768.2010.01943.x

  4. McKinnon SJ. Glaucoma: ocular Alzheimer’s disease? Front Biosci. 2003;8:1140–56. doi: 10.2741/1172

  5. Hinton DR, Sadun AA, Blanks JC, Miller CA. Optic-nerve degeneration in Alzheimer’s disease. N Engl J Med. 1986;315:485–7. doi: 10.1056/NEJM198608213150804

  6. Blanks JC, Hinton DR, Sadun AA, Miller CA. Retinal ganglion cell degeneration in Alzheimer’s disease. Brain Res. 1989;501:364–72. doi: 10.1016/0006–8993(89)90653–7

  7. Wostyn P, Audenaert K, De Deyn PP. Alzheimer´s disease and glaucoma: is there a causal relationship? Br J Ophthalmol. 2009;93:1557–9. doi: 10.1136/bjo.2008.148064

  8. Berdahl JP, Allingham RR, Johnson DH. Cerebrospinal fluid pressure is decreased in primary open-angle glaucoma. Ophthalmology. 2008;115:763–8. doi: 10.1016/j.ophtha.2008.01.013

  9. Bayer AU, Ferrari F, Erb C. High occurrence rate of glaucoma among patients with Alzheimer’s disease. Euro Neurol. 2002;47:165–8. doi: 10.1159/000047976

  10. Tamura H, Kawakami H, Kanamoto T, Yokoyama T, Sasaki K, Izumi Y, et al. High frequency of open-angle glaucoma in Japanese patients with Alzheimer’s disease. J Neurol Sci. 2006;246:79–83. doi: 10.1016/j.jns.2006.02.009

  11. Helmer C, Malet F, Rougier M-B, Schweitzer C, Colin J, Delyfer M-N, et al. Is there a link between open-angle glaucoma and dementia?: the Three-City-Alienor cohort. Ann Neurol. 2013;74:171–9. doi: 10.1002/ana.23926

  12. Lin I-C, Wang Y-H, Wang T-J, Wang I-J, Shen Y-D, Chi N-F, et al. Glaucoma, Alzheimer’s disease, and Parkinson’s disease: an 8-year population-based follow-up study. PLoS One. 2014;9:e108938. doi: 10.1371/journal.pone.0108938

  13. Lai S-W, Lin C-L, Liao K-F. Glaucoma may be a non-memory manifestation of Alzheimer’s disease in older people. Int Psychoger. 2017;29:1535–41. doi: 10.1017/S1041610217000801

  14. Chen Y-Y, Lai Y-J, Yen Y-F, Shen Y-C, Wang C-Y, Liang C-Y, et al. Association between normal tension glaucoma and the risk of Alzheimer’s disease: a nationwide population-based cohort study in Taiwan. BMJ Open. 2018;8:e022987. doi: 10.1136/bmjopen-2018-022987

  15. Mullany S, Xiao L, Qassim A, Marshall H, Gharahkhani P, MacGregor S, et al. Normal-tension glaucoma is associated with cognitive impairment. Br J Ophthalmol. 2021;0:1–5. doi: 10.1136/bjophthalmol–2020–317461

  16. Kessing LV, Lopez AG, Andersen PK, Kessing SV. No increased risk of developing Alzheimer’s disease in patients with glaucoma. J Glaucoma. 2007;16:47–51. doi: 1097/IJG.0b013e31802b3527

  17. Ou Y, Grossman DS, Lee PP, Sloan FA. Glaucoma, Alzheimer’s disease and other dementia: a longitudinal analysis. Ophthal Epidemiol. 2012;19:285–92. doi: 10.3109/09286586.2011.649228

  18. Keenan TDL, Goldacre R, Goldacre MJ. Associations between primary open angle glaucoma, Alzheimer’s disease and vascular dementia: record linkage study. Br J Ophthalmol. 2015;99:524–7. doi: 10.1136/bjophthalmol-2014-305863

  19. Lee CS, Larsson EB, Gibbons LE, Lee AY, McCurry SM, Bowen JD, et al. Associations between recent and established ophthalmic conditions and risk of Alzheimer’s disease. Alzheimers Dement. 2019;15:34–41. doi: 10.1016/j.jalz.2018.06.2856

  20. Ong SY, Cheung CY, Li X, Lamoureux E, Ikram MK, Ding J, et al. Visual impairment, age-related eye diseases, and cognitive function. The Singapore Malay Eye Study. Arch Ophthalmol. 2012;130:895–900. doi: 10.1001/archophthalmol.2012.152

  21. Ekström C, Kilander L. Open-angle glaucoma and Alzheimer’s disease: a population-based 30-year follow-up study. Acta Ophthalmol. 2017;95:e157–8. doi: 10.1111/aos.13243

  22. Ekström C. Prevalence of open-angle glaucoma in central Sweden. The Tierp Glaucoma Survey. Acta Ophthalmol Scand. 1996;74:107–12. doi: 10.1111/j.1600–0420.1996.tb00052.x

  23. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging–Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:263–9. doi: 10.1016/j.jalz.2011.03.005

  24. Foster PJ, Buhrmann R, Quigley HA, Johnson GJ. The definition and classification of glaucoma in prevalence surveys. Br J Ophthalmol. 2002;86:238–42. doi: 10.1136/bjo.86.2.238

  25. Rothman KJ, Greenland S, Lash TL. Modern epidemiology. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2008, pp. 106–7.

  26. Xu X-H, Zou J-Y, Geng W, Wang A-Y. Association between glaucoma and the risk of Alzheimer’s disease: a systematic review of observational studies. Acta Ophthalmol. 2019;97:665–71. doi: 10.1111/aos.14114

  27. Ekström C, Haglund B. Chronic open-angle glaucoma and advanced visual field defects in a defined population. Acta Ophthalmol. 1991;69:574–80. doi: 10.1111/j.1755–3768.1991.tb04842.x

  28. Bach-Holm D, Kessing SV, Mogensen U, Forman JL, Andersen PK, Kessing LV. Normal tension glaucoma and Alzheimer’s disease: comorbidity? Acta Ophthalmol. 2012;90:683–5. doi: 10.1111/j.1755–3768.2011.02125.x

  29. Lee SH, Kim GA, Lee W, Bae HW, Seong GJ, Kim CY. Vascular and metabolic comorbidities in open-angle glaucoma with low- and high-teen intraocular pressure: a cross-sectional study from South Korea. Acta Ophthalmol. 2017;95:e563–74. doi: 10.1111/aos.13487

  30. Rönnemaa E, Zethelius B, Lannfelt L, Kilander L. Vascular risk factors and dementia: 40-year follow-up of a populations-based cohort. Dement Geriatr Cogn Disord. 2011;31:460–6. doi: 10.1159/000330020

  31. Rothman KJ. Epidemiology. An introduction. 2nd ed. Oxford: Oxford University Press; 2012, pp. 133–6.

  32. Lobo A, Launer LJ, Fratiglioni L, Andersen K, Di Carlo A, Breteler MM, et al. Prevalence of dementia and major subtypes in Europe: a collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology. 2000;54: S4–9.

  33. SveDem. [updated 20 February 2019]. Available from: [cited 10 February 2021].

How to Cite
Ekström, C., Puhto, I., & Kilander, L. (2021). Association between open-angle glaucoma and Alzheimer’s disease in Sweden: a long-term population-based follow-up study. Upsala Journal of Medical Sciences, 126(1).
Original Articles