Pupil dilation provides clues to future Alzheimer’s risk

How quickly a person's pupil dilates while they are taking cognitive tests may be a low-cost, low-invasive method to aid in screening individuals at increased genetic risk for AD before cognitive decline begins

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that affects the quality of life of those affected by the disease. The most common form of dementia, Alzheimer’s disease negatively impacts thinking, memory, behavior. Currently, there is no cure for Alzheimer’s disease but treatments can slow its progression.

Detecting the disease early is crucial for treatments to be initiated and to prevent the progression of the disease. Alzheimer’s disease starts to damage the brain years or decades before symptoms appear. Hence, early detection and identification of AD risk are crucial to slowing its progression.

In a new study published in the journal Neurobiology of Aging, a team of researchers at the University of California San Diego School of Medicine suggest that measuring how rapidly the pupil of the eyes dilate while taking cognitive tests may be an alternative, non-invasive, and affordable screening test to detect those who are at higher risk of Alzheimer’s disease before they experience cognitive decline.

The researchers investigated the pathology of Alzheimer’s disease and focused on two major contributors to the disease - accumulation of protein plaque, called amyloid-beta, in the brain and tau tangles. Both of these factors have been tied to cognitive dysfunction.

Pupillary responses may hint AD risk

The study shows how pupillary responses to specific neurons in the brain called locus coeruleus (LC), which are involved in cognitive function and arousal. One of the earliest biomarkers of AD, the tau proteins, first appear in the locus coeruleus. The tau tangles are associated with cognitive abilities more than the amyloid-beta.

The LC stimulates a pupillary response, for instance, the changing diameter of the eye’s pupils, during cognitive tasks. A person’s pupils get bigger when a brain task is harder or more complicated. It follows a previous study wherein the researchers reported that people with mild cognitive impairment, one precursor to Alzheimer’s disease, showed greater pupil dilation than those without any cognitive problems.

In the study, however, the researchers wanted to find the connection between pupillary dilation responses with identified AD risk genes.

"Given the evidence linking pupillary responses, LC and tau and the association between pupillary response and AD polygenic risk scores (an aggregate accounting of factors to determine an individual's inherited AD risk), these results are proof-of-concept that measuring pupillary response during cognitive tasks could be another screening tool to detect Alzheimer's before symptom appear," Dr. William Kremen, study lead author, said.

Still no predictive test for Alzheimer’s disease

Alzheimer’s disease is a global health problem. In the United States, it is the 6th leading cause of death and about 5.5 million Americans are living with the condition.

At present, there is still no cure for Alzheimer’s disease and there is no available predictive test. A diagnosis of the disease is commonly made through clinical consultation, which may stem from the history, medical interview, signs and symptoms, and assessment.

Tests including scans, blood and urine samples, and psychiatric assessment help rule out other health conditions with similar symptoms. The only way a confirmation is made is when the patient dies, and the brain tissue is examined.

The noble test is less invasive, more targeted, and easy to do.

“Identifying the specific genes associated with the pupillary response factors may improve understanding of the functioning of the LC-NE system and of genetically-mediated factors affecting risk for MCI (mild cognitive impairment) and AD (Alzheimer’s disease),” the researchers conclude in the study.

The new method of detecting AD is a promising diagnostic test to help people with Alzheimer’s disease and their families.

Journal reference:

Kremen, W., Panizzon, M., Elman, J., Granholm, E., Andreassen, O., Dale, A., Gillespie. N., Gustavson, D., Logue, M., Lyons, M., Neale, M., Reynolds, C., Whitsel, N., and Franz, C. (2019). Pupillary dilation responses as a midlife indicator of risk for Alzheimer’s Disease: Association with Alzheimer’s disease polygenic risk. Neurobiology of Aging. https://www.sciencedirect.com/science/article/pii/S0197458019303215?via%3Dihub