The Association between Vision Impairment and Incidence of Dementia and Cognitive Impairment

TopicThe magnitude and direction of the association between vision impairment and incident dementia and cognitive impairment in prospective cohort studies was estimated by systematic review and meta-analysis. The global burden of dementia associated with vision impairment then was estimated.Clinical RelevanceBecause a predominant proportion of vision impairment is preventable or treatable, investigating its association with dementia may help to identify an important modifiable factor for the prevention of dementia.MethodsA literature search was conducted using PubMed, Embase, Web of Science, and Google Scholar on September 15, 2020. Relative risks (RRs) were pooled using random-effects models and stratified analyses for subgroups representing different study characteristics. Publication bias was evaluated with funnel plots and the Egger test. The global burden of dementia associated with vision impairment was estimated based on the Global Burden of Disease Study data on the prevalence of dementia and vision impairment.ResultsIn the meta-analysis of 14 prospective cohort studies with 6 204 827 participants and 171 888 dementia patients, the pooled RR associated with vision impairment was 1.47 (95% confidence interval [CI], 1.36–1.60). In the meta-analysis of 12 prospective cohort studies with 45 313 participants and 13 350 patients with cognitive impairment, the pooled RR was 1.35 (95% CI, 1.28–1.41). Stratified analyses showed that the associations of vision impairment with incident dementia and cognitive impairment were similar across methods of vision assessment, length of follow-up, and study quality. The global number of people with dementia associated with moderate or severe vision impairment in 2016 was 2.1 million (80% uncertainty interval, 1.0–3.3 million), which accounted for 4.7% (95% CI, 2.3%–7.5%) of the global burden of dementia. Economic inequality was significant for the burden of dementia associated with vision impairment.DiscussionThe overall quality of the body evidence was low because of the observational design of the studies included in the analysis. Vision impairment is associated with an increased risk of both dementia and cognitive impairment in older adults. Screening and treating vision impairment, especially in low- and middle-income countries, may help to alleviate the global burden of dementia. The magnitude and direction of the association between vision impairment and incident dementia and cognitive impairment in prospective cohort studies was estimated by systematic review and meta-analysis. The global burden of dementia associated with vision impairment then was estimated. Because a predominant proportion of vision impairment is preventable or treatable, investigating its association with dementia may help to identify an important modifiable factor for the prevention of dementia. A literature search was conducted using PubMed, Embase, Web of Science, and Google Scholar on September 15, 2020. Relative risks (RRs) were pooled using random-effects models and stratified analyses for subgroups representing different study characteristics. Publication bias was evaluated with funnel plots and the Egger test. The global burden of dementia associated with vision impairment was estimated based on the Global Burden of Disease Study data on the prevalence of dementia and vision impairment. In the meta-analysis of 14 prospective cohort studies with 6 204 827 participants and 171 888 dementia patients, the pooled RR associated with vision impairment was 1.47 (95% confidence interval [CI], 1.36–1.60). In the meta-analysis of 12 prospective cohort studies with 45 313 participants and 13 350 patients with cognitive impairment, the pooled RR was 1.35 (95% CI, 1.28–1.41). Stratified analyses showed that the associations of vision impairment with incident dementia and cognitive impairment were similar across methods of vision assessment, length of follow-up, and study quality. The global number of people with dementia associated with moderate or severe vision impairment in 2016 was 2.1 million (80% uncertainty interval, 1.0–3.3 million), which accounted for 4.7% (95% CI, 2.3%–7.5%) of the global burden of dementia. Economic inequality was significant for the burden of dementia associated with vision impairment. The overall quality of the body evidence was low because of the observational design of the studies included in the analysis. Vision impairment is associated with an increased risk of both dementia and cognitive impairment in older adults. Screening and treating vision impairment, especially in low- and middle-income countries, may help to alleviate the global burden of dementia. In 2016, dementia was the fifth leading cause of death globally, accounting for 2.4 million deaths.1Nichols E. Szoeke C.E.I. Vollset S.E. et al.Global, regional, and national burden of Alzheimer’s disease and other dementias, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016.Lancet Neurol. 2019; 18: 88-106Abstract Full Text Full Text PDF PubMed Scopus (660) Google Scholar The global number of people living with dementia was 43.8 million in 20161Nichols E. Szoeke C.E.I. Vollset S.E. et al.Global, regional, and national burden of Alzheimer’s disease and other dementias, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016.Lancet Neurol. 2019; 18: 88-106Abstract Full Text Full Text PDF PubMed Scopus (660) Google Scholar and is estimated to reach 152 million by 2050.2Patterson C. World Alzheimer Report 2018. Alzheimer’s Disease International, London2018Google Scholar Since 2010, the economic burden of dementia has increased by 35% to $818 billion United States dollars in 2015 and is projected to rise to approximately $2 trillion United States dollars in 2030.3Wimo A. Guerchet M. Ali G.C. et al.The worldwide costs of dementia 2015 and comparisons with 2010.Alzheimers Dement. 2017; 13: 1-7Abstract Full Text Full Text PDF PubMed Scopus (481) Google Scholar Its significant mortality and morbidity represent a tremendous burden on health care and economic systems globally. Because mild cognitive impairment may precede the onset of more severe functional impairment by many years,4Rajan K.B. Wilson R.S. Weuve J. et al.Cognitive impairment 18 years before clinical diagnosis of Alzheimer disease dementia.Neurology. 2015; 85: 898-904Crossref PubMed Scopus (108) Google Scholar a potential preventative window exists during which the onset of clinical dementia may be delayed. Therefore, it is imperative to identify important modifiable risk factors amenable to intervention for the prevention of dementia and cognitive decline in a rapidly ageing global population.5Baumgart M. Snyder H.M. Carrillo M.C. et al.Summary of the evidence on modifiable risk factors for cognitive decline and dementia: a population-based perspective.Alzheimers Dement. 2015; 11: 718-726Abstract Full Text Full Text PDF PubMed Scopus (705) Google Scholar,6Livingston G. Huntley J. Sommerlad A. et al.Dementia prevention, intervention, and care: 2020 report of the Lancet Commission.Lancet. 2020; 396: 413-446Abstract Full Text Full Text PDF PubMed Scopus (823) Google Scholar Sensory impairment plays an important role in the development of dementia, with hearing loss in midlife identified as the leading risk factor of dementia globally.6Livingston G. Huntley J. Sommerlad A. et al.Dementia prevention, intervention, and care: 2020 report of the Lancet Commission.Lancet. 2020; 396: 413-446Abstract Full Text Full Text PDF PubMed Scopus (823) Google Scholar Vision as another form of the sensory stimulus also warrants scrutiny, given that a large proportion of vision impairment (80.0% in 2020) is preventable or treatable.7Adelson J. Bourne R. Briant P. et al.Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: the Right to Sight: an analysis for the Global Burden of Disease Study.Lancet Glob Health. 2021; (9(2):e144-e160.)Google Scholar Longitudinal studies have shown that vision impairment is associated with accelerated cognitive decline,8Anstey K.J. Luszcz M.A. Sanchez L. Two-year decline in vision but not hearing is associated with memory decline in very old adults in a population-based sample.Gerontology. 2001; 47: 289-293Crossref PubMed Scopus (97) Google Scholar, 9Reyes-Ortiz C.A. Kuo Y.F. DiNuzzo A.R. et al.Near vision impairment predicts cognitive decline: data from the Hispanic Established Populations for Epidemiologic Studies of the Elderly.J Am Geriatr Soc. 2005; 53: 681-686Crossref PubMed Scopus (106) Google Scholar, 10Sloan F.A. Ostermann J. Brown D.S. Lee P.P. Effects of changes in self-reported vision on cognitive, affective, and functional status and living arrangements among the elderly.Am J Ophthalmol. 2005; 140: 618-627Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar, 11Yamada Y. Denkinger M.D. Onder G. et al.Dual sensory impairment and cognitive decline: the results from the Shelter Study.J Gerontol A Biol Sci Med Sci. 2016; 71: 117-123Crossref PubMed Scopus (48) Google Scholar, 12Maharani A. Dawes P. Nazroo J. et al.Visual and hearing impairments are associated with cognitive decline in older people.Age Ageing. 2018; 47: 575-581Crossref PubMed Scopus (52) Google Scholar, 13Zheng D.D. Swenor B.K. Christ S.L. et al.Longitudinal associations between visual impairment and cognitive functioning: the Salisbury Eye Evaluation Study.JAMA Ophthalmol. 2018; 136: 989-995Crossref PubMed Scopus (58) Google Scholar, 14Valentijn S.A. van Boxtel M.P. van Hooren S.A. et al.Change in sensory functioning predicts change in cognitive functioning: results from a 6-year follow-up in the Maastricht Aging Study.J Am Geriatr Soc. 2005; 53: 374-380Crossref PubMed Scopus (224) Google Scholar and causes of vision impairment such as age-related macular degeneration and glaucoma also are linked to Alzheimer’s disease.15Tsai D.C. Chen S.J. Huang C.C. et al.Age-related macular degeneration and risk of degenerative dementia among the elderly in Taiwan: a population-based cohort study.Ophthalmology. 2015; 122: 2327-2335.e2Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar,16Chen Y.Y. Lai Y.J. Yen Y.F. 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; 8e022987Crossref PubMed Scopus (17) Google Scholar However, until 2016, only 1 prospective study had linked vision impairment to dementia. Since 2017, a growing number of prospective cohort studies have investigated the association of vision impairment with dementia, cognitive impairment, or both, but the results have been far from consistent.17Tran E.M. Stefanick M.L. Henderson V.W. et al.Association of visual impairment with risk of incident dementia in a Women’s Health Initiative population.JAMA Ophthalmol. 2020; 138: 1-10Crossref Scopus (17) Google Scholar, 18Naël V. Pérès K. Dartigues J.F. et al.Vision loss and 12-year risk of dementia in older adults: the 3C cohort study.Eur J Epidemiol. 2019; 34: 141-152Crossref PubMed Scopus (34) Google Scholar, 19Davies-Kershaw H.R. Hackett R.A. Cadar D. et al.Vision impairment and risk of dementia: findings from the English Longitudinal Study of Ageing.J Am Geriatr Soc. 2018; 66: 1823-1829Crossref PubMed Scopus (31) Google Scholar, 20Lee A.T.C. Richards M. Chan W.C. et al.Higher dementia incidence in older adults with poor visual acuity.J Gerontol A Biol Sci Med Sci. 2020; 75: 2162-2168Crossref PubMed Scopus (19) Google Scholar For example, a recent longitudinal study of 1061 women 66 to 84 years of age at baseline found that those with vision impairment at baseline were more than twice as likely to demonstrate dementia over 4 years than those without vision impairment.17Tran E.M. Stefanick M.L. Henderson V.W. et al.Association of visual impairment with risk of incident dementia in a Women’s Health Initiative population.JAMA Ophthalmol. 2020; 138: 1-10Crossref Scopus (17) Google Scholar In contrast, another longitudinal analysis of 1810 Black and White participants from the Health, Aging, and Body Composition Study 70 to 79 years of age at baseline reported that vision impairment was not associated significantly with incident dementia over 10 years (hazard ratio [HR], 1.26; 95% confidence [CI], 0.90–1.77).21Brenowitz W.D. Kaup A.R. Lin F.R. Yaffe K. Multiple sensory impairment is associated with increased risk of dementia among black and white older adults.J Gerontol A Biol Sci Med Sci. 2019; 74: 890-896Crossref PubMed Scopus (34) Google Scholar However, no published systematic reviews and meta-analyses have been conducted on this topic. With no known cure or treatment for dementia presently, it is imperative to identify a modifiable risk factor implicated in the development of dementia that may be a potential preventive target. Therefore, it is of great importance to perform a meta-analysis to summarize the direction and magnitude of the association between vision impairment and both incident dementia and cognitive impairment in prospective studies. The global burden of dementia associated with 12 modifiable risk factors (low education, hearing loss, traumatic brain injury, excessive alcohol consumption, obesity, hypertension, smoking, depression, diabetes, social isolation, physical inactivity, and air pollution) has been estimated by the 2020 report of the Lancet Dementia Commission.6Livingston G. Huntley J. Sommerlad A. et al.Dementia prevention, intervention, and care: 2020 report of the Lancet Commission.Lancet. 2020; 396: 413-446Abstract Full Text Full Text PDF PubMed Scopus (823) Google Scholar Also, investigators have significant interest in the estimation of other important modifiable risk factors such as vision impairment if vision impairment can be demonstrated to be associated with an increased risk of dementia in our meta-analysis. A systematic review and meta-analysis of the recently published prospective cohort studies was conducted to determine whether vision impairment was a predictor for the development of dementia and cognitive decline. The magnitude of this association and the global burden of dementia associated with vision impairment also were analyzed. We conducted a systematic review and meta-analysis according to the Systematic Reviews and Meta-analyses Guidelines.22Moher D. Liberati A. Tetzlaff J. Altman D.G. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.PLoS Med. 2009; 6e1000097Crossref PubMed Scopus (34710) Google Scholar This study is registered with the International Prospective Register of Systematic Reviews (PROSPERO) database (identifier, CRD42020198341). All prospective cohort studies reporting the association between vision impairment and dementia or cognitive impairment were included in the systematic review. The criteria for inclusion of studies in our meta-analysis included prospective design; quality score of more than 5; end points of dementia, Alzheimer’s disease, or cognitive impairment; presentation of quantitative point estimates (HRs, relative risks [RRs], or odds ratios) and variance of the estimates of the association between vision impairment and outcomes; and description of adjustment for potential confounders. Study quality was assessed independently by 2 members of the research team (X.S. and Z.Z.) using the Newcastle-Ottawa Scale,23Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses.Eur J Epidemiol. 2010; 25: 603-605Crossref PubMed Scopus (7276) Google Scholar which is the most frequently used quality tool for cohort studies.24Zeng X. Zhang Y. Kwong J.S. et al.The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline: a systematic review.J Evid Based Med. 2015; 8: 2-10Crossref PubMed Scopus (873) Google Scholar With regard to duplicate reports from the same study, the most recent publication or the publication with the largest sample size was selected. The primary and secondary outcomes were incident dementia and cognitive impairment during follow-up, respectively. Dementia is a neurocognitive disorder that is associated with a significant functional deficit in language, behavior, and cognition,25Rossor M. Collinge J. Fox N. et al.Dementia and cognitive impairment.in: Clarke C. Howard R. Rossor M. Shorvon S. Neurology: A Queen Square Textbook. Second ed. 2016: 289-336Crossref Scopus (4) Google Scholar whereas cognitive impairment is the prelude to dementia and is characterized by reports of memory symptoms, abnormal memory for age, and impairments in other cognitive domains such as executive function, language, orientation.26Petersen R.C. Smith G.E. Waring S.C. et al.Mild cognitive impairment: clinical characterization and outcome.Arch Neurol. 1999; 56: 303-308Crossref PubMed Scopus (6772) Google Scholar A literature search was conducted by 2 investigators (X.S. and Z.Z.) using PubMed, Embase, and Web of Science on September 15, 2020, using the keywords search strategy vision impairment combined with dementia, Alzheimer’s disease, cognitive impairment or cognition (the search strategy is detailed in Table S1, available at www.aaojournal.org). We also reviewed references cited by the included studies and citations of the included publications (Google Scholar) to retrieve other potentially relevant studies. The search was restricted to adults, but without language restriction. We also searched for eligible unpublished large-scale cohort studies and identified 7 cohort studies with relevant data. Access to unpublished data from 4 studies, the China Health and Retirement Longitudinal Study,27Zhao Y. Hu Y. Smith J.P. et al.Cohort profile: the China Health and Retirement Longitudinal Study (CHARLS).Int J Epidemiol. 2014; 43: 61-68Crossref PubMed Scopus (689) Google Scholar the Health and Retirement Study (HRS),28Sonnega A. Faul J.D. Ofstedal M.B. et al.Cohort profile: the Health and Retirement Study (HRS).Int J Epidemiol. 2014; 43: 576-585Crossref PubMed Scopus (624) Google Scholar the Mexican Health and Ageing Study,29Wong R. Michaels-Obregon A. Palloni A. Cohort profile: the Mexican Health and Aging Study (MHAS).Int J Epidemiol. 2017; 46: e2Crossref PubMed Scopus (110) Google Scholar and the UK Biobank,30Sudlow C. Gallacher J. Allen N. et al.UK Biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age.PLoS Med. 2015; 12e1001779Crossref PubMed Scopus (2262) Google Scholar were granted. The data were analyzed and incorporated in the meta-analysis (detailed methods can be seen in Supplemental Text, available at www.aaojournal.org). Two reviewers (X.S. and Z.Z.) independently screened the titles and abstracts of studies to identify articles relevant to vision impairment and dementia or cognitive impairment. The 2 team members also independently reviewed the full text of the remaining studies to assess the study design. Studies with a study design that did not meet the inclusion criteria were excluded. Finally, we assessed the quality of the remaining studies using the Newcastle-Ottawa Scale.23Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses.Eur J Epidemiol. 2010; 25: 603-605Crossref PubMed Scopus (7276) Google Scholar Discrepancies were solved by discussion and consensus. Two reviewers (X.S. and Z.Z.) independently extracted data into a customized database using a predefined data extraction sheet (Excel; Microsoft Corporation, Redmond, WA). Extracted data included first author name, publication year, cohort name, country where the study was conducted, the year during which baseline data were collected, follow-up duration, number of participants, gender, age at baseline, RRs, and 95% CIs for dementia and cognitive impairment associated with vision impairment, the methods used to assess vision impairment, and methods used to identify events. The overall certainty of the body evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. By this approach, the evidence can be graded as being of high, moderate, low, or very low quality; however, evidence derived from observational studies receive an initial grade of low.31Balshem H. Helfand M. Schünemann H.J. et al.GRADE guidelines: 3. Rating the quality of evidence.J Clin Epidemiol. 2011; 64: 401-406Abstract Full Text Full Text PDF PubMed Scopus (3545) Google Scholar Criteria for downrating the quality of evidence include risk of bias (low Newcastle-Ottawa Scale score),32Guyatt G.H. Oxman A.D. Vist G. et al.GRADE guidelines: 4. Rating the quality of evidence—study limitations (risk of bias).J Clin Epidemiol. 2011; 64: 407-415Abstract Full Text Full Text PDF PubMed Scopus (1512) Google Scholar imprecision (the 95% CI for risk estimates are wide or cross a minimally important difference of 10% for benefit or harm),33Guyatt G.H. Oxman A.D. Kunz R. et al.GRADE guidelines 6. Rating the quality of evidence—imprecision.J Clin Epidemiol. 2011; 64: 1283-1293Abstract Full Text Full Text PDF PubMed Scopus (1304) Google Scholar inconsistency (substantial unexplained interstudy heterogeneity, I2 > 50%),34Guyatt G.H. Oxman A.D. Kunz R. et al.GRADE guidelines: 7. Rating the quality of evidence—inconsistency.J Clin Epidemiol. 2011; 64: 1294-1302Abstract Full Text Full Text PDF PubMed Scopus (1135) Google Scholar indirectness (presence of factors that limit the generalizability of the results),35Guyatt G.H. Oxman A.D. Kunz R. et al.GRADE guidelines: 8. Rating the quality of evidence—indirectness.J Clin Epidemiol. 2011; 64: 1303-1310Abstract Full Text Full Text PDF PubMed Scopus (938) Google Scholar and publication bias (evidence of small-study effects). Scores for observational analyses can be upgraded for a large magnitude of effect (RR, ≥2 or ≤0.5), dose-response gradient, or attenuation by plausible confounding.36Guyatt G.H. Oxman A.D. Sultan S. et al.GRADE guidelines: 9. Rating up the quality of evidence.J Clin Epidemiol. 2011; 64: 1311-1316Abstract Full Text Full Text PDF PubMed Scopus (708) Google Scholar Pooled estimates across studies were obtained using random-effects meta-analysis, after log-transformation of the study-specific estimates. Study weights were calculated from the inverse of the variance of the log RR.37Woodward M. Epidemiology: Study Design and Data Analysis. Chapman and Hall/CRC, Roca Raton, FL2005Google Scholar For studies that reported RRs of dementia only for subgroups (such as moderate and severe vision impairment),18Naël V. Pérès K. Dartigues J.F. et al.Vision loss and 12-year risk of dementia in older adults: the 3C cohort study.Eur J Epidemiol. 2019; 34: 141-152Crossref PubMed Scopus (34) Google Scholar,20Lee A.T.C. Richards M. Chan W.C. et al.Higher dementia incidence in older adults with poor visual acuity.J Gerontol A Biol Sci Med Sci. 2020; 75: 2162-2168Crossref PubMed Scopus (19) Google Scholar,38Paik J.S. Ha M. Jung Y.H. et al.Low vision and the risk of dementia: a nationwide population-based cohort study.Sci Rep. 2020; 10: 9109Crossref PubMed Scopus (11) Google Scholar,39Maharani A. Dawes P. Nazroo J. et al.Associations between self-reported sensory impairment and risk of cognitive decline and impairment in the Health and Retirement Study cohort.J Gerontol B Psychol Sci Soc Sci. 2020; 75: 1230-1242Crossref PubMed Scopus (26) Google Scholar the pooled RR using random-effects models for the corresponding study was used in the meta-analysis. Risk estimates from the most fully adjusted models were used in the estimation of the pooled RR. Random-effects models taking into account both within-study and between-study variability were used to estimate pooled RRs for associations of vision impairment with incident dementia and cognitive impairment. Secondary analyses were conducted to examine whether the association of vision impairment with incident dementia and cognitive impairment differed across subgroups of important variables. Stratified analyses were performed for these variables: the length of follow-up, methods used to assess vision, geographical region, and study quality that were available in the included prospective studies. As a value for describing the proportion of the total variation in study estimates, I2 was used to test between-study heterogeneity (25%, 50%, and 75% for low, moderate, and high heterogeneity, respectively).40Higgins J.P. Thompson S.G. Quantifying heterogeneity in a meta-analysis.Stat Med. 2002; 21: 1539-1558Crossref PubMed Scopus (18940) Google Scholar Several commonly used methods—Egger’s test and funnel plots, trim and fill, as well as the calculation of pooled estimates of remaining studies by removing 1 study at a time—were applied to investigate publication bias. Publication bias for the primary analysis was assessed first using Egger’s test and funnel plots for asymmetry. Trim-and-fill analysis then was used to adjust RRs (95% CIs) for the presence of publication bias. A sensitivity analysis also was conducted to calculate the pooled estimates of remaining studies by removing 1 study at a time to determine whether the association was dependent on a particular study. Population-attributable risk (PAR) of incident dementia associated with vision impairment was computed for each country using the following formula:PAR%=p×(RR-1)p×(RR-1)+1×100 where p represents the proportion of vision impairment and RR represents the pooled RR for incident dementia associated with vision impairment based on our meta-analysis. The prevalence of vision impairment in 2015 for each country estimated by the Global Burden of Disease Study was used in the analysis.41Bourne R.R.A. Flaxman S.R. Braithwaite T. et al.Magnitude, temporal trends, and projections of the global prevalence of blindness and distance and near vision impairment: a systematic review and meta-analysis.Lancet Glob Health. 2017; 5: e888-e897Abstract Full Text Full Text PDF PubMed Scopus (987) Google Scholar The global burden of dementia associated with vision impairment as well as the burden for each country then was calculated. The number of people with dementia in 2016 for each country was based on the data estimated by the Global Burden of Disease Study in 2016.1Nichols E. Szoeke C.E.I. Vollset S.E. et al.Global, regional, and national burden of Alzheimer’s disease and other dementias, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016.Lancet Neurol. 2019; 18: 88-106Abstract Full Text Full Text PDF PubMed Scopus (660) Google Scholar The meta-analysis was performed with STATA software version 13.1 (StataCorp, College Station, TX). A total of 13 917 articles were identified, with 92 remaining after a review of the titles and abstracts. Only 38 prospective cohort studies (36 plus 2 additional studies retrieved through the citations or references) reported the association of vision impairment with incident dementia or cognitive impairment. These 38 articles, with the addition of the unpublished results of the China Health and Retirement Longitudinal Study, HRS, Mexican Health and Ageing Study, and the UK Biobank, were included in the systematic review (Fig 1). Seven cohort studies reporting only the association between vision impairment and cognitive decline and 11 investigating the association between causes of vision impairment (age-related macular degeneration, cataract, glaucoma, and diabetic retinopathy) and dementia or Alzheimer’s disease were excluded from the meta-analysis. Two studies were excluded from the meta-analysis because the quality score was 5 or less,42Heward J. Stone L. Paddick S.M. et al.A longitudinal study of cognitive decline in rural Tanzania: rates and potentially modifiable risk factors.Int Psychogeriatr. 2018; 30: 1333-1343Crossref PubMed Scopus (18) Google Scholar,43Michalowsky B. Hoffmann W. Kostev K. Association between hearing and vision impairment and risk of dementia: results of a case-control study based on secondary data.Front Aging Neurosci. 2019; 11: 363Crossref PubMed Scopus (12) Google Scholar and 22 cohort studies were included in the meta-analysis. Ten prospective studies investigated the association between vision impairment and incident dementia only,18Naël V. Pérès K. Dartigues J.F. et al.Vision loss and 12-year risk of dementia in older adults: the 3C cohort study.Eur J Epidemiol. 2019; 34: 141-152Crossref PubMed Scopus (34) Google Scholar, 19Davies-Kershaw H.R. Hackett R.A. 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