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Comorbidity of dementia and age-related macular degeneration calls for clinical awareness: a meta-analysis
  1. Shi Song Rong1,2,
  2. Bo Yee Lee1,
  3. Andrew K Kuk3,
  4. Xin Ting Yu4,
  5. Suki S Li1,
  6. Jian Li1,5,
  7. Yanjun Guo6,
  8. Yilin Yin2,
  9. David L Osterbur7,
  10. Jason C S Yam1,
  11. Carol Y Cheung1,
  12. Li Jia Chen1,
  13. Tien Y Wong8,9,
  14. Danny Siu-Chun Ng1
  1. 1 Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China
  2. 2 Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA
  3. 3 Department of Ophthalmology, Tung Wah Eastern Hospital, Hong Kong, Hong Kong
  4. 4 Department of Nutrition, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA
  5. 5 Department of Ophthalmology, School of Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University, Hangzhou, China
  6. 6 Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
  7. 7 Countway Library of Medicine, Harvard Medical School, Boston, Massachusetts, USA
  8. 8 Ophthalmology and Visual Science Program, Singapore National Eye Centre, Singapore, Singapore
  9. 9 Duke-NUS Medical School, National University of Singapore, Singapore, Singapore
  1. Correspondence to Dr Danny Siu-Chun Ng, Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China; dannyng{at}; Dr Shi Song Rong, Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear, Boston, Massachusetts, USA; Shisong_Rong{at}


Aim To determine the association between dementia and age-related macular degeneration (AMD) using meta-analysis.

Methods We searched in the MEDLINE, EMBASE, Web of Knowledge, PsycInfo and Cochrane database of systematic reviews for studies published from March 1959 to March 2018. We included cross-sectional, case–control and cohort studies that evaluated the association of dementia/Alzheimer's disease (AD) with AMD (as outcome) and the association of AMD with dementia/AD (as outcome). Studies that compared cognitive functions between AMD and controls were also included. The summary outcomes, namely odds ratio (OR), relative risk, mean differences and corresponding 95% CIs, were estimated using random effects models. We performed sensitivity analysis based on study quality and individual study effect to control for potential biases.

Results Among 2159 citation records, we identified 21 studies consisting of 7 876 499 study subjects for meta-analysis. Patients with dementia (padjusted≤0.017, OR≥1.24, I2≤9%) or AD (p=0.001, ORunadjusted=2.22, I2=50%) were at risk for AMD, particularly for late AMD (padjusted<0.001, OR=1.37, I2=0). AMD was also significantly associated with increased risk of AD/cognitive impairment (padjusted=0.037, OR=2.42, I2=38%). Moreover, patients with AMD had poorer cognitive functions when compared with controls, including Mini-Mental State Examination (p<0.001, I2≤79%) and Trail Making Test A (p<0.001, I2=0). Sensitivity analysis and Egger’s test indicated our results were less likely biased.

Conclusions A significant association between dementia/AD and AMD calls for greater clinical awareness. The cost-effectiveness of routine screening for the other condition in patients with primary diagnosis of dementia/AD or AMD requires further study.

  • macula
  • degeneration
  • retina
  • epidemiology

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  • SSR and BYL are joint first authors.

  • Contributors Study design: SSR and DSCN. Acquisition of data: BYL, SSL, AKK, YY, DLO and SSR. Assessment of quality of studies: XTY, BYL, JL and SSR. Data analysis and interpretation of results: SSR. Drafting of the manuscript: SSR and BYL. Critical revision of the manuscript for important intellectual content: SSR, DSCN, CYC, TYW, LJC, JCSY and YG. Study supervision: SSR and DSCN.

  • 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 for publication Not required.

  • Ethics approval The meta-analysis study is exempt from ethics approval.

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

  • Data sharing statement All the data in the systematic review and meta-analysis are published data and are available in the articles we summarised. Moreover, the data sets used and/or analysed during the current study are available from the corresponding author on reasonable request.

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