University of California, San Francisco, UCSF Medical Center
Is there a higher frequency of glaucoma in patients with Alzheimer’s disease? Are glaucoma patients at greater risk for Alzheimer’s? This article looks at the latest research exploring possible connections between these diseases of mind and sight.
Glaucoma is a group of neurodegenerative eye diseases that leads to damage of the optic nerve (the bundle of nerve fibers that carries information from the eye to the brain), which can then lead to vision loss and possibly blindness. Glaucoma is a leading cause of irreversible blindness in the United States and the world. In 2020, about 80 million people have glaucoma worldwide, and this number is expected to increase to over 111 million by 2040.
Alzheimer’s disease (AD) is the most common cause of dementia. Like glaucoma, it is a neurodegenerative disease and is characterized by specific changes in the brain. A definitive diagnosis requires the presence of clinical dementia to the extent that impairs daily activities, as well as two hallmarks of the disease: neurofibrillary tangles that occur inside of the brain cells, and amyloid beta plaques, which are found outside of the brain cells. Worldwide, 50 million people are believed to be living with Alzheimer's disease or other dementias. By 2050, the numbers could exceed 152 million. Every 3 seconds, a new case of dementia occurs somewhere in the world.
Both diseases affect older populations and involve selective loss of certain types of neurons. They are both neurodegenerative, chronic, and progressive diseases that are age-related and cause irreversible neuronal cell loss. They are both also major public health concerns as the population of the United States ages. Glaucoma and AD are thought to share, at least in part, some common features as both are age-related neurodegenerative diseases.
The link between the two diseases was first observed several decades ago when researchers discovered that there was a higher frequency of glaucoma in patients with AD through an analysis of death certificates. Subsequently, there were several populations of AD patients that were examined for the prevalence of glaucoma and it was found that there was almost a two- to three-fold increase in glaucoma diagnosis in these patients.
Several large retrospective studies have not demonstrated that glaucoma patients have an increased risk of Alzheimer’s disease or other dementia diagnoses. Indeed, one of these studies actually showed that there was a decreased risk of Alzheimer disease or other dementia diagnosis in patients with open-angle glaucoma.
More recently, however, researchers conducted a prospective study in France that showed that glaucoma patients were four times more likely to develop dementia. Interestingly, this finding was not associated with high eye pressures or glaucoma medication usage, suggesting that perhaps the patients who are most vulnerable may be those with normal eye pressures, or low-tension glaucoma.
From a scientific perspective, it has been shown that Alzheimer’s patients may have retinal nerve fiber layer thinning and loss of the retinal ganglion cells that compose the optic nerve, both hallmarks of glaucoma. One of the pathologic hallmarks of Alzheimer’s disease, an abnormal tau protein, has been found in the vitreous jelly (the clear jelly-like substance that fills the space from the lens to the back of the eye.) of the eyes of glaucoma patients. There have also been studies using animal models of glaucoma demonstrating that there is amyloid beta protein (also a hallmark of Alzheimer’s disease) in the retina. Exposure to amyloid beta resulted in increased retinal ganglion cell loss, while treatment of these animals with drugs that are commonly used in the treatment of AD resulted in decreased death of the retinal ganglion cells that are lost in glaucoma.
At this juncture, there are conflicting reports as to whether open-angle glaucoma patients truly have an increased risk of developing dementia such as Alzheimer’s disease. This is an area of active research. As scientists uncover shared underlying mechanisms connecting the two diseases, they can potentially identify novel treatment targets and share what they learn between the fields of neurology and ophthalmology in order to better treat patients suffering from these diseases.
Yvonne Ou, MD, is a board certified ophthalmologist who specializes in glaucoma, including medical, laser and surgical therapies; cataract evaluation and treatment including combined cataract and glaucoma surgery; glaucoma filtering and implant surgery; and newer procedures.
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