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. 2024 Oct 1;7(10):e2441166.
doi: 10.1001/jamanetworkopen.2024.41166.

Pharmacologic Treatments for Dementia and the Risk of Developing Age-Related Macular Degeneration

Jingya Wang  1 , Christina Antza  1 , Wen Hwa Lee  2 , Jesse Coker  2 , Pearse A Keane  3 , Alastair K Denniston  1   3   4   5   6 , Krishnarajah Nirantharakumar  1   5   6 , Nicola J Adderley  1   6
Affiliations

Pharmacologic Treatments for Dementia and the Risk of Developing Age-Related Macular Degeneration

Jingya Wang et al. JAMA Netw Open. .

Abstract

Importance: Age-related macular degeneration (AMD) is the leading cause of blindness among people aged 50 years or older worldwide. There is a need for new strategies for the prevention and treatment of AMD. There is some limited evidence to suggest the possibility of a protective association of dementia medications with the development of some types of AMD, but the evidence is weak.

Objective: To investigate whether the dementia medications memantine and donepezil are associated with the risk of developing AMD.

Design, setting, and participants: Three population-based cohort studies were performed using data from the Clinical Practice Research Datalink GOLD and Aurum databases from May 15, 2002, to June 21, 2022. Participants included individuals with dementia (vascular dementia, nonvascular dementia, or Alzheimer disease) aged 40 years or older. Statistical analysis was carried out between February and November 2023.

Exposures: Exposures were dementia medications. Cohort 1 compared patients prescribed donepezil with those prescribed rivastigmine or galantamine using the new-user design. Cohort 2 compared memantine with donepezil, rivastigmine, or galantamine using the prevalent new-user design. In a sensitivity analysis, cohort 3 compared memantine with rivastigmine or galantamine only.

Main outcomes and measures: New diagnosis of AMD.

Results: There were 132 846 individuals (mean [SD] age, 80.4 [7.6] years; 61.8% women; mean [SD] body mass index [BMI], 25.5 [4.6]) with a diagnosis of dementia included in cohort 1, 159 419 individuals (mean [SD] age, 81.2 [7.6] years; 59.7% women; mean [SD] body mass index [BMI], 25.6 [4.7]) with a diagnosis of dementia included in cohort 2, and 92 328 individuals with a diagnosis of dementia included in cohort 3 (mean [SD] age, 80.9 [7.7] years; 58.5% women; mean [SD] body mass index [BMI], 25.5 [4.7]). The adjusted hazard ratio (HR) for donepezil compared with rivastigmine or galantamine (cohort 1) was 0.95 (95% CI, 0.67-1.35). The adjusted HR for memantine compared with donepezil, rivastigmine, or galantamine (cohort 2) was 1.03 (95% CI, 0.83-1.27). The adjusted HR for memantine vs rivastigmine or galantamine only (cohort 3) was 1.24 (95% CI, 0.83-1.86).

Conclusions and relevance: This cohort study of patients with dementia found no significant associations between memantine or donepezil compared with other dementia medications and the risk of development of AMD. Further research is recommended to examine any possible pathophysiological protective action of memantine and other dementia medications against the development of AMD.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Keane reported receiving personal fees from Boehringer Ingleheim, Roche, Novartis, Apellis, AbbVie, Bayer, and Topcon; being an equity owner of Big Picture Medical; and holding stock options from Bitfount outside the submitted work. Dr Denniston reported receiving grant support from Health Data Research UK outside the submitted work. Dr Nirantharakumar reported receiving grants from the National Institute for Health and Care Research, UK Research and Innovation/Medical Research Council, the Kennedy Trust for Rheumatology Research, Health Data Research UK, the Wellcome Trust, the European Regional Development Fund, the Institute for Global Innovation, Boehringer Ingelheim, Action Against Age-Related Macular Degeneration, Midlands Neuroscience Teaching and Development Funds, South Asian Health Foundation, Vifor Pharma, College of Police, and CSL Behring; and personal fees from Boehringer Ingleheim, MSD, Sanofi, and Cegedim outside the submitted work; and serving as a trustee of Network for Improving Critical Care Systems and Training (NICST), chief scientific officer of Dexter Ltd; and Medical Director of OpenClinical Social Enterprise. Dr Adderley reported receiving grants from the National Institute for Health Research outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Flowchart for the Participant Selection Procedure for Cohorts 1 and 2
AMD indicates age-related macular degeneration.
See this image and copyright information in PMC

Comment in

  • doi: 10.1001/jamanetworkopen.2024.41172

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