In June 2023, the National Institute on Aging (NIA) [of the National Institutes of Health
(NIH)] released a report on changes in the retina (the layer of cells lining the back wall
of the inside the eye that perceives light and signals the brain so one can see) and their
relationship to stages of Alzheimer’s disease (AD).
As noted in the study, this research and others are related to NIH’s AD+ADRD
Research Implementation Milestone 9.F, Initiate studies to develop minimally invasive
biomarkers for detection of cerebral amyloidosis, A, and AD-related dementias
pathophysiology.
The NIA set out to develop and test at least three minimally invasive biomarkers that
could be utilized in studies related to AD and other types of dementia. The latest study by Koronyo et al. (2023) at Cedars-Sinai Medical Center in Los Angeles examined how the retina reflects changes in the brain during AD. The
researchers analyzed retina and brain tissue from 86 deceased donors.
Research Findings
- Amyloid deposits (a protein that our bodies produce naturally) in the retina were five times higher in people with mild cognitive impairment (MCI) and nine times higher in those with AD compared to people who are not cognitively impaired.
- The deposits were unevenly distributed across the retina, with most in the inner layers and regions of the retina related to peripheral vision.
- Changes in the retina were correlated with brain changes as they progressed. This finding suggests that amyloid deposits in the retina increase as Alzheimer’s worsens and could potentially be used for early AD discovery.
- The finding also indicates that these retinal microglia (resident immune cells of the brain and retina) may not be working properly, allowing the accumulation of amyloid deposits over time.
- Researchers compared the proteins in the retinas and brain tissue of donors with AD with those with normal cognition. They discovered that in the brains and retinas of people with AD, proteins associated with inflammation and the breakdown of neurons were activated. Conversely, proteins that help produce cellular energy and light perception were constrained, suggesting that AD-related changes in the brain may be mirrored in the retina. Thus, retinal changes may be a possible predictor of later cognitive decline.
Other Studies
In another study at Mt. Sinai, researchers discovered that abnormalities in blood vessels
in the eye are a major factor in the progression of Alzheimer’s disease. The only way to detect
these changes is through post-mortem brain tissue samples. However, this may change as
more research is conducted into advanced retinal imaging.
In addition, several studies are being conducted about the association of cognitive
decline with vision loss. Dr. Niranjani Nagarajan et al. (2022) conducted a literature
review indicating that “a majority of studies examining the vision–cognition relationship
report that VI (visual impairment) is associated with more cognitive decline, cognitive
impairment, or dementia among older adults.” More research is needed to understand
this association and to test interventions that can lessen the cognitive consequences of
VI.
Summary
The research into using retina changes as a biomarker for AD is very promising, as are
the studies on abnormalities in blood vessels in the eye. Hopefully, as the Koronyo et al.
(2023) NIA article concludes, “These discoveries may contribute to the development of
diagnostics for the early detection and monitoring of the disease.”
References
Koronyo Y, et al. Retinal pathological features and proteome signatures of Alzheimer’s
disease. Acta Neuropathologica. 2023. Epub Feb. 11. doi:10.1007/s00401-023-02548-2
Nagarajan, N., Assi, L., Varadaraj, V., Motaghi, M., Sun, Y., Couser, E., Ehrlich, J. R.,
Whitson, H., & Swenor, B. K. (2022). Vision impairment and cognitive decline
among older adults: a systematic review. BMJ open, 12(1), e047929.
https://doi.org/10.1136/bmjopen-2020-047929