Alzheimer’s patients receiving acetylcholinesterase inhibitor therapy had a 6% lower hazard of AMD.
Alzheimer’s patients receiving acetylcholinesterase inhibitor therapy had a 6% lower hazard of AMD. Photo: NEI. Click image to enlarge. 

While no cure exists for Alzheimer’s disease, the use of acetylcholinesterase inhibitors have been shown to help improve these patients’ quality of life. Subsequently, this workhorse therapy has revealed secondary benefits, including lower mortality, myocardial infarction, stroke risk and even slowed progression of chronic kidney disease. Now, a recent observational study suggests acetylcholinesterase inhibitors (AChEIs) may reduce the incidence of age-related macular degeneration in those with Alzheimer’s.

The retrospective cohort analysis, published in JAMA Ophthalmology, included health care facilities within the US Department of Veterans Affairs between 2000 and 2023. Participants were patients diagnosed with Alzheimer’s between ages 55 and 80 with no preexisting AMD diagnosis, totaling 21,823 veterans. Those in the treatment group receiving AChEIs every additional year resulted in a 6% lower hazard of AMD, compared to untreated patients.

Some research has correlated Alzheimer’s and AMD development based on drusen-producing peptides in these patients, theoretically triggering subsequent AMD. The study authors stated that their hypothesis was “based on the idea that AMD may be linked to neuroinflammatory processes in the macula. Preclinical studies have suggested that AChEIs may have the ability to mitigate neuroinflammation.” AChEIs have also been found to promote vasoprotection and maintain the integrity of the microvasculature in the eye, which may provide a potential protective effect against AMD, according to other research.

Randomized clinical trials would be necessary to truly evaluate any cause-and-effect relationship, according to the authors. They point out their treatment allocation wasn’t randomized, therefore making selection bias and confounding factors possible. “Our study used as many variables in the propensity model as possible, including all diagnoses within a year prior to study index to minimize any systematic differences,” they wrote. The use of data from the VA also potentially limits the generalizability of the findings to the broader population, according to the authors. “Lastly, this study does not account for genetic risk factors which could confound the results,” they concluded.

Ultimately, this study bolsters the body of literature demonstrating the secondary benefits of AChEIs which may play a significant role in treatment decisions for Alzheimer’s patients.

Sutton SS, Magagnoli J, Cummings TH, Hardin JW, Ambati J. Alzheimer Disease treatment with acetylcholinesterase inhibitors and incident Age-Related Macular Degeneration. JAMA Ophthalmol. January 4, 2024. [Epub ahead of print].