Association Between Pseudoexfoliation and Alzheimer’s Disease-Related Brain Atrophy

Won Cheol Jeong, Jin-Young Min, Tae Gu Kang, Heewon Bae


Pseudoexfoliation (PEX) syndrome is an age-related disorder characterized by the accumulation of extracellular material in the anterior eye segment. PEX pathogenesis is not fully understood, but amyloid which accumulates in the brain of patients with Alzheimer’s disease (AD) is a PEX component. PEX deposition shares features with amyloid aggregation in AD, and brain atrophy is a common AD feature, with β-amyloid accumulation among contributing factors. This study investigated whether PEX syndrome is associated with AD-related brain atrophy.


Pseudoexfoliation (PEX) syndrome is an age-related disorder characterized by the accumulation of extracellular material in the anterior segment of the eye [1]. PEX affects fibrillar deposition along the periphery of the lens and iris in the eye. The deposition of this material in the trabecular meshwork could be the cause of PEX glaucoma, resulting in aqueous outflow obstruction and increased intraocular pressure (IOP) [2]. PEX material has been found in various structures of visceral organs like the lung, liver, kidney, and gall bladder, as well as the cerebral meninges [3].

Materials and Methods

This study enrolled participants who underwent ophthalmic examination and brain MRI between January 2015 and August 2021 at the Ophthalmologic Department of Veterans Health Service (VHS) medical center (n = 529). In total, 128 participants were diagnosed with PEX. Participants with a history of ophthalmologic surgery or disease that could affect PEX observation, and those with neurological disorders that could be a problem in the evaluation of AD, were excluded. After excluding participants with a history of ophthalmic surgery, ocular trauma, optic nerve atrophy, uveitis, diabetic retinopathy, age-related macular degeneration, or neurological disorders, such as stroke, dementia, or Parkinson’s disease, 48 participants were included in the study group.


Among the 96 participants, 16 and 5 patients in the PEX and control groups, respectively, were diagnosed with dementia. There was a statistically significant difference in the rate of AD (P<0.01). In total, 16 patients in the PEX group and 5 patients in the control group were newly diagnosed with AD according to the National Institute on Aging-Alzheimer’s Association guidelines. Patients were classified into three groups based on Mini-Mental State Examination (MMSE) scores (20–25, mild; 10–19, moderate; and 0–9, severe) according to severity.


In another study, Cumurcu et al. compared 67 PEX patients with 67 age-, sex-, and educational-background-matched control subjects. The results revealed that the frequency of AD was 67.2% in the PEX group and 26.9% in the control group, and this difference was significantly different [14]. The method was similar to that of our study, but unlike our study, which diagnosed AD through follow-up observation, it was a cross-sectional study. There was a difference in that the two previously mentioned studies diagnosed AD based on clinical symptoms, and our study evaluated AD based on brain MRI of the participants. Although the above studies do not provide a mechanism for the association between PEX and AD with consistent results, they suggest commonalities in the material deposit pathway. Amyloid and related substances were detected in PEX material, similar to their deposition in patients with AD [18]


This study found a significantly higher incidence of brain atrophy and AD in patients with PEX compared to control participants. We suggest that PEX material in the anterior segments reflects amyloid accumulation in the brain. It can be considered that PXG, which is a severe form of PEX, is associated with advanced AD. Further investigations are required to determine the relationship between PEX and AD with a view to establishing PEX as a predictor of AD.

Citation: Jeong WC, Min J-Y, Kang TG, Bae H (2023) Association between pseudoexfoliation and Alzheimer’s disease-related brain atrophy. PLoS ONE 18(6): e0286727.

Editor: Sanjoy Bhattacharya, Bascom Palmer Eye Institute, UNITED STATES

Received: February 20, 2023; Accepted: May 22, 2023; Published: June 8, 2023

Copyright: © 2023 Jeong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: The authors received no specific funding for this work.

Competing interests: The authors have declared that no competing interests exist.

National Healthcare CMO Summit USANational Healthcare CNO Summit USA