Window to the mind: Pupils may help identify Alzheimer’s decades before symptoms appear

SAN DIEGO — There’s an old saying that the eyes are the window to the soul. While that very well may be the case, a new study finds that they may also be a window to the mind and an accurate predictor of the onset of Alzheimer’s disease long before actual symptoms begin to appear.

Researchers from the University of California, San Diego, say that measuring how quickly and drastically a person’s pupil dilates while solving a problem or thinking critically may serve as an accurate, low-cost, and low-invasive way to screen for Alzheimer’s decades before any symptoms appear.

Alzheimer’s disease, a devastating condition that results in cognitive deterioration and memory loss, only reveals itself late in life. However, the condition actually begins taking root and damaging the brain many years before symptoms appear. With this in mind, early detection is key to slowing the disease’s progression. If the research team’s findings about pupil behavior are accurate and reliable, it would represent a major breakthrough in the early detection and treatment of Alzheimer’s among genetically at risk patients all over the world.

Up until now, the majority of researchers studying the early onset and progression of Alzheimer’s have focused on two areas: the build up of a certain type of protein plaques, amyloid-beta, in the brain, and the entanglement of another protein, called tau, in the brain. Both of these proteins have been shown to slowly damage and kill neurons, resulting in a slowly-but-surely progression into cognitive dysfunction, and ultimately Alzheimer’s.

For this study, the research team focused on pupil responses in the eye. Pupillary responses are controlled by a cluster of neurons in the brain stem called the locus coeruleus (LC). Besides just controlling pupil adjustments, the LC also helps regulate arousal and modulate cognitive function. Tau, one of the aforementioned proteins directly linked to cognitive decline, and Alzheimer’s earliest known biomarker, first develops within the LC.

Besides just changing pupil sizes in response to light and other stimulants, the LC also drives pupillary responses (changes in diameter) during cognitive tasks or critical thinking. Generally speaking, pupils get bigger the more difficult the task or question. So, researchers theorized that a buildup of tau in the LC may also influence pupil behavior during a cognitive task.

Furthermore, prior research has already suggested that adults with mild cognitive impairment, often an accurate indicator of Alzheimer’s development later on in life, exhibited greater pupil dilation and cognitive effort while performing a task compared to cognitively normal individuals. This was true even when both groups produced generally the same results in reference to the task.

For their experiment, the research team theorized that middle aged, cognitively normal individuals with a genetic predisposition for Alzheimer’s would also display greater, and faster, pupil dilation during a cognitive task. After performing an experiment with 1,119 men between the ages of 56-66, the researchers’ theory was confirmed: cognitively normal participants who showed no sign of Alzheimer’s besides a genetic susceptibility to the disease, were associated with greater pupil dilation and greater cognitive effort over all.

“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,” explains Dr. William S. Kremen, the study’s first author, in a release.

The study is published in the Neurobiology of Aging.