Measuring pupil dilation offers promising early-stage Alzheimer’s diagnostic test
Scientists from the University of California San Diego School of Medicine are suggesting Alzheimer’s disease may be detected years before symptoms appear by examining pupil dilation. The new study reveals measuring the speed of pupil dilation while a person undertakes a cognitive test could help identify early, pre-symptomatic stages of Alzheimer’s.
The eye is turning out to be a profound window into a person’s brain health with a number of different recent studies homing in on biomarkers in the eye correlating with cognitive decline and neurodegeneration. A fascinating 2018 study revealed a distinct correlation between several degenerative eye diseases and the onset of Alzheimer's disease, implying eye health can act as an effective proxy for the health of many brain areas.
Other research has intriguingly uncovered links between thinning of a layer in the retina, a decrease in small retinal blood vessels at the back of the eye, and the very earliest stages of Alzheimer’s disease. It has also been suggested that amyloid beta proteins, the toxic compounds associated with damaged brain cells, can be detected at the back of the eye in numbers that correlate with amounts building up in the brain.
None of these potential tests have reached clinical deployment yet, but they all would ultimately require complicated, and possibly expensive, imaging technologies to effectively screen patients. In a new study, published in the Neurobiology of Aging, an innovative method is described that is cheap, non-invasive and could hypothetically be implemented relatively quickly in clinics around the globe.
The research is founded on the observation that tau proteins, another protein associated with Alzheimer’s cognitive decline, tend to initially build up and damage a region of the brain known as the locus coeruleus (LC). Prior research has found the LC largely drives pupillary dilation responses, so the new research set out to determine whether early tau accumulations in the LC could alter pupil dilation in a way that allows for the identification of pre-symptomatic Alzheimer’s.
A previously published study from the current research team demonstrated adults with mild cognitive impairment showed greater pupil dilation when taking a cognitive test, compared to a cognitively healthy adult. Importantly, these pupil dilation differences occurred even when both groups performed equally on the cognitive tests.
In the latest study from the research team a large number of cognitively healthy middle-aged adults were administered the test. Their pupillary responses were then measured against genetic risk scores for Alzheimer’s to see whether this particular test could identify genetically at-risk individuals years before any symptoms appear. The results indeed confirmed an association between pupillary responses during cognitive tasks and genetic risk scores for Alzheimer’s, despite all the subjects still presenting as cognitively normal.
“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,” says Willam Kremen, first author on the new study.
As Kremen notes, the test in still in a proof-of-concept stage. More work is needed to verify these results in larger, more diverse cohorts, and it will be interesting to ascertain at how young an age these pupillary responses are detectable.
The new study was published in the journal Neurobiology of Aging.
Source: UC San Diego Health