Three Eye Conditions Linked to Higher Alzheimer's Risk

Damian McNamara

August 14, 2018

Three eye diseases have been linked to an increased risk for Alzheimer's disease (AD), results of a large, longitudinal, population-based study suggest.

Glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR) were associated with a 40% to 50% increased risk for AD.

Participants recently diagnosed with glaucoma had a 46% increased likelihood of developing AD. Similarly, the risk among those recently diagnosed with AMD or diabetic retinopathy had a 50% increased AD risk compared with their counterparts without these conditions.

"I am hoping our results will help increase awareness among ophthalmologists and primary care physicians. If they have a patient with one of these eye conditions, they should consider asking about cognitive status," Cecilia S. Lee, assistant professor of ophthalmology at the University of Washington School of Medicine in Seattle, told Medscape Medical News.

In addition, if there is concern about cognitive dysfunction, refer patients to a neurologist for further workup, she said. "That is what we would recommend at this point."

Although the study evaluated individuals with degenerative eye conditions for subsequent risk for AD or all-cause dementia, there is a potential for the association to be bidirectional. When neurologists evaluate patients for possible dementia, they may also want to ask about eye health, she said.  

The study was published online August 8 in Alzheimer's & Dementia.

"Window to the Brain"

Often referred to as "the window to the brain," the eyes provide substantial information on brain health, the investigators note. Previous research suggests glaucoma, DR, and AMD may be linked to dementia because of shared characteristics, including progressive neurodegeneration, amyloid β deposition, and chronic microvascular insults.

The investigators point out that most of the earlier research examining a potential association between dementia and eye disorders have lacked large, prospective cohorts with precise dementia definitions.

They also note that no previous research has examined a potential association between AMD, DR, glaucoma, and cataracts.

To examine this potential association, investigators used data from the Adult Changes in Thought (ACT), an ongoing prospective cohort study of more than 5400 adults aged 65 years or older who were dementia-free at enrollment and followed until development of dementia, dropout, or death.

Participants underwent cognitive screening with the Cognitive Abilities Screening Instrument, as well as medical history and risk factor evaluations, at recruitment and every 2 years.

Those scoring 85 or higher on the cognitive screen received a standardized diagnostic evaluation, including a physical exam, neurologic exam, and neuropsychological test battery.

AD was diagnosed by using the National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria.  

Eye disorders were diagnosed using the International Classification of Diseases, 9th revision.

Adjusted analyses revealed a significant association between three of the eye disorders and AD risk. 

Table. Adjusted Risk for AD by Eye Disorder

Eye Disorder Hazard Ratio (95% Confidence Interval) P Value
Glaucoma 0.95 (0.80 - 1.14) .61
AMD 1.20 (1.02 - 1.40) .03
DR 1.44 (1.08 - 1.94) .02
Based on adjusted Cox models compared with participants without each condition.


Differences by Disease Duration

Complete data were available for 3877 participants who accumulated 31,142 person-years of follow-up (mean > 8 years per person).

Ten percent of the cohort had a glaucoma diagnosis at study enrollment. Another 7% developed glaucoma during the study. In addition, 9% of participants had an AMD diagnosis at enrollment and 18% developed AMD during the study. Four percent had a DR diagnosis at enrollment and 3% developed DR during the study.

A total of 331 participants had two of the degenerative eye conditions and 27 participants had all three disorders.

During the study there were 792 incident cases of AD. The investigators found recent glaucoma had a hazard ratio (HR) of 1.46 (P = .01) but the risk was not elevated for established glaucoma (HR, 0.87; P = .19).

They found no association between recent AMD and AD risk (HR, 1.20; P =.12). However, investigators found a 50% increased risk for AD associated with established AMD (HR, 1.50; P < .001).

Participants with recent (HR, 1.50; P = .045) and established (HR, 1.50; P =.03) DR  had an increased AD risk.

Interestingly, the investigators found no association between cataracts and elevated AD risk, suggesting the findings associated with the glaucoma, AMD, and DR are not solely attributable to aging.

"The first thing that came to mind was that these diseases are so prevalent in the aging population, we thought maybe we were just picking up a signal from age. The lack of a link with cataracts reassured us that the risk for developing Alzheimer's disease associated with those other three eye conditions was real.

"We're not saying that people with those conditions will develop Alzheimer's. These are relatively preliminary data but important findings that will hopefully open new areas where we can focus our research," Lee said.

All-Cause Dementia

The researchers also examined a potential association with the eye conditions and risk for all-cause dementia, which was diagnosed by consensus using Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria and found a similar relationship.

The risk among individuals with glaucoma was observed but somewhat attenuated among those with a recent diagnosis. Recent and established AMD and DR were associated with all-cause dementia, particularly DR.

"Subsequent studies of ophthalmic diseases in relation to Alzheimer's disease and dementia may provide important insights into shared pathological pathways, thus enabling better techniques to prevent and treat," the authors write.

Study strengths include its longitudinal nature and the fact that participants were dementia-free at baseline. In addition, a panel of experts made the AD and dementia diagnoses. 

A potential limitation is that 90% of study participants self-identified as white, which may limit the generalizability of the findings to other populations.

"We are planning further studies to identify the exact connection between these eye conditions and Alzheimer's disease," Lee said. One avenue of research is to study the potential role of vascular changes.

An "Exciting Time"

Commenting on the findings for Medscape Medical News, Andrew Iwach, MD, an ophthalmologist at Sutter Health in San Francisco, California, and a spokesperson for the American Academy of Ophthalmology, said the study "points out something we've known for a long time — the eye is the only place in the body where one can see an artery, nerve, or vein without incision or some kind of surgery. This gives us a unique glimpse into some potential systemic diseases."

Physicians have known for years that the eyes can reveal signs of systemic high blood pressure, diabetes, and other conditions. The difference now, Iwach said, is that advances in technology allow doctors to see the finer structures of the eye in greater detail and in a more reproducible way.

Regarding the current finding of an association between glaucoma, AMD, or DR and risk for AD, he believes the findings have important implications.

"The impact for the population, for society, is huge because having a noninvasive way to gather this information [is important]."

More work is needed because "there is a difference between seeing something and data you can actually act on."

"The bottom line is having the noninvasive ability to look at these critical structures — and we've already shown this in other diseases — makes a huge difference. This is an exciting time."

Lee and Iwach have disclosed no relevant financial relationships.

Alzheimers Dement. Published online August 8, 2018. Full text

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