Studies suggest a link between blindness, age-related macular degeneration (AMD), and dementia risk, but whether this stems from AMD pathology or blindness remains unclear. This study examines the relationship between AMD and dementia.
Objective
To evaluate the association between AMD and 5-year dementia risk in non-blind patients.
Methods
This retrospective cohort study used TriNetX to compare non-blind patients with exudative AMD (n = 35,021) and non-exudative AMD (n = 96,809) to those without AMD (n = 1,801,879) for five-year dementia risk. Blind (n = 90,615) and non-blind (n = 800,737) patients were compared. Cohorts were propensity-matched for confounding factors.
Results
Non-blind AMD patients had decreased Alzheimer's disease risk, while blindness showed a strong positive association. Exudative AMD had HR of 0.84 (95% CI = [0.72, 0.97]), non-exudative AMD had HR of 0.95 (95% CI = [0.87, 1.04]), but blindness increased Alzheimer's disease risk (95% HR = 1.29, CI = [1.17, 1.41]).
Conclusions
These findings suggest that previously reported associations between AMD and dementia may be partially mediated by visual impairment. The modest reduction in dementia risk in non-blind AMD patients may reflect differences in healthcare utilization or treatment exposure among AMD patients.
NicholsESteinmetzJDVollsetSE, et al.Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019. Lancet Public Health2022; 7: e105–e125.
2.
BourneRSteinmetzJDFlaxmanS, et al.Trends in prevalence of blindness and distance and near vision impairment over 30 years: an analysis for the Global Burden of Disease Study. Lancet Glob Health2021; 9: e130–e143.
GoodmanRALochnerKAThambisettyM, et al.Prevalence of dementia subtypes in U.S. Medicare fee-for-service beneficiaries, 2011-2013. Alzheimers Dement2017; 13: 28–37.
5.
AzargoonjahromiA. The duality of amyloid-β: its role in normal and Alzheimer’s disease states. Mol Brain2024; 17: 44.
6.
PorsteinssonAPIsaacsonRSKnoxS, et al.Diagnosis of early Alzheimer’s disease: clinical practice in 2021. J Prev Alzheimers Dis2021; 8: 371–386.
7.
KilleenOJZhouYEhrlichJR. Objectively measured visual impairment and dementia prevalence in older adults in the US. JAMA Ophthalmol2023; 141: 786–790.
8.
ZhuZShiDLiaoH, et al.Visual impairment and risk of dementia: the UK Biobank study. Am J Ophthalmol2022; 235: 7–14.
9.
PaikJSHaMJungYH, et al.Low vision and the risk of dementia: a nationwide population-based cohort study. Sci Rep2020; 10: 9109.
10.
LittlejohnsTJHayatSLubenR, et al.Visual impairment and risk of dementia in 2 population-based prospective cohorts: UK Biobank and EPIC-Norfolk. J Gerontol A Biol Sci Med Sci2022; 77: 697–704.
11.
HwangPHLongstreth JrWTThielkeSM, et al.Ophthalmic conditions associated with dementia risk: the Cardiovascular Health Study. Alzheimers Dement2021; 17: 1442–1451.
12.
XiongZLiXYangD, et al.The association between cataract and incidence of cognitive impairment in older adults: a systematic review and meta-analysis. Behav Brain Res2023; 450: 114455.
13.
MitchellPLiewGGopinathB, et al.Age-related macular degeneration. Lancet2018; 392: 1147–1159.
14.
FurtadoJMJonasJBTapplyI, et al.Global estimates on the number of people blind or visually impaired by age-related macular degeneration: a meta-analysis from 2000 to 2020. Eye2024; 38: 2070–2082.
15.
FernandesARZielińskaASanchez-LopezE, et al.Exudative versus nonexudative age-related macular degeneration: physiopathology and treatment options. Int J Mol Sci2022; 23: 2592.
16.
RozziniLRivaMGhilardiN, et al.Cognitive dysfunction and age-related macular degeneration. Am J Alzheimers Dis Other Demen2014; 29: 256–262.
17.
TsaiDCChenSJHuangCC, et al.Age-related macular degeneration and risk of degenerative dementia among the elderly in Taiwan: a population-based cohort study. Ophthalmology2015; 122: 2327–2335.e2.
18.
KlaverCCWOttAHofmanA, et al.Is age-related maculopathy associated with Alzheimer's disease?: the Rotterdam Study. Am J Epidemiol1999; 150: 963–968.
19.
KeenanTDGoldacreRGoldacreMJ. Associations between age-related macular degeneration, Alzheimer disease, and dementia: record linkage study of hospital admissions. JAMA Ophthalmol2014; 132: 63–68.
20.
LeeCSLarsonEBGibbonsLE, et al.Associations between recent and established ophthalmic conditions and risk of Alzheimer's disease. Alzheimers Dement2019; 15: 34–41.
21.
ChoiSJahngWJParkSM, et al.Association of age-related macular degeneration on Alzheimer or Parkinson disease: a retrospective cohort study. Am J Ophthalmol2020; 210: 41–47.
22.
WenLYWanLLaiJN, et al.Increased risk of Alzheimer's disease among patients with age-related macular degeneration: a nationwide population-based study. PLoS One2021; 16: e0250440.
23.
ShangXZhuZHuangY, et al.Associations of ophthalmic and systemic conditions with incident dementia in the UK Biobank. Br J Ophthalmol2023; 107: 275–282.
24.
HwangGLeeSHLeeDY, et al.Age-related eye diseases and subsequent risk of mental disorders in older adults: a real-world multicenter study. J Affect Disord2025; 375: 306–315.
25.
SonKYChoiYJKimB, et al.Association between age-related macular degeneration with visual disability and risk of dementia: a nationwide cohort study. J Am Med Dir Assoc2025; 26: 105392.
26.
AgrawalNAfzalMKhanNH, et al.The role of VEGF in vascular dementia: impact of aging and cellular senescence. Biogerontology2025; 26: 77.
27.
ZhangMZhangZLiH, et al.Blockage of VEGF function by bevacizumab alleviates early-stage cerebrovascular dysfunction and improves cognitive function in a mouse model of Alzheimer’s disease. Transl Neurodegener2024; 13: 1.
28.
SKRManzSN. Brain health assessment in macular degeneration patients undergoing intravitreal anti-vascular endothelial growth factor injections (The BHAM Study): an interim analysis. Retina2021; 41: 1748–1753.
29.
ChewEYClemonsTSanGiovanniJP, et al.The age-related eye disease study 2 (AREDS2): study design and baseline characteristics (AREDS2 report number 1). Ophthalmology2012; 119: 2282–2289.
30.
The Age-Related Eye Disease Study 2 (AREDS2) Research Group. Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression: AREDS2 report no. 3. JAMA Ophthalmol2014; 132: 142–149.
31.
KeenanTDLAgrónEChewEY. Dietary nutrient intake and cognitive function in the Age-Related Eye Disease Studies 1 and 2. Alzheimers Dement2023; 19: 4311–4324.
32.
LiJAbdel-AalESM. Dietary lutein and cognitive function in adults: a meta-analysis of randomized controlled trials. Molecules2021; 26: 5794.
33.
Lanyau-DomínguezYMacías-MatosCLlibre-RodríguezJdeJ, et al.Levels of vitamins and homocysteine in older adults with Alzheimer disease or mild cognitive impairment in Cuba. MEDICC Rev2021; 22: 40–47.
34.
BeydounMABeydounHAFanelli-KuczmarskiMT, et al.Association of serum antioxidant vitamins and carotenoids with incident Alzheimer disease and all-cause dementia among US adults. Neurology2022; 98: e2150–e2162.
35.
ChewEYClemonsTEAgrónE, et al.Effect of omega-3 fatty acids, lutein/zeaxanthin, or other nutrient supplementation on cognitive function: the AREDS2 randomized clinical trial. JAMA2015; 314: 791–801.
36.
del-CuraMPJimeno AnayaLSastre IbáñezM, et al.Adherence and awareness of patients with age-related macular degeneration to AREDS 2 recommended nutritional supplements. J Nutr Gerontol Geriatr2025; 44: 123–132.
37.
AlghamdiAKeeganDConnellP, et al.Adherence of patients with age-related macular degeneration to AREDS 2-recommended nutritional supplements. Ir J Med Sci2023; 192: 3163–3167.
38.
JeongYWooSJ. Compliance with the Recommended Age-related Eye Disease Study 2 Supplementation among Korean age-related macular degeneration patients. J Retin2022; 7: 121–126.
39.
YuJJMillerJMLJohnsonMW, et al.Cost analysis and adherence of over-the-counter supplements to the AREDS2 protocol. Graefes Arch Clin Exp Ophthalmol2023; 261: 37–39.
40.
LiYAndrewNLaHoodBR. Evidence-based vitamin supplements for age-related macular degeneration: an analysis of available products. Clin Exp Optom2022; 105: 836–841.
41.
ReinDBWittenbornJSBurke-ConteZ, et al.Prevalence of age-related macular degeneration in the US in 2019. JAMA Ophthalmol2022; 140: 1202–1208.
42.
LissJLSeleri AssunçãoSCummingsJ, et al.Practical recommendations for timely, accurate diagnosis of symptomatic Alzheimer’s disease (MCI and dementia) in primary care: a review and synthesis. J Intern Med2021; 290: 310–334.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
