Screening for Early Alzheimer’s Using Pupillary Response

Alzheimer’s disease (AD) begins to alter and damage the brain years—even decades—before symptoms appear, making early identification of AD risk paramount to slowing its progression. In a study published today in Neurobiology of Aging, UCSD scientists say that, with further developments, measuring 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.

In recent years, researchers investigating the pathology of AD have primarily directed their attention at two causative or contributory factors: the accumulation of amyloid-beta plaques and tau tangles. Both have been linked to damaging and killing neurons, resulting in progressive cognitive dysfunction.

The new study focuses on pupillary responses that are driven by the locus coeruleus (LC), a cluster of neurons in the brainstem involved in regulating arousal and also modulating cognitive function. Tau is more strongly associated with cognition than amyloid-beta; it first appears in the LC and is the earliest occurring known biomarker for AD.

The LC drives pupillary response during cognitive tasks: The more difficult the brain task, the bigger the pupils get. In previously published work, the researchers reported that adults with mild cognitive impairment, often a precursor to AD, displayed greater pupil dilation and cognitive effort than cognitively normal individuals, even if both groups produced equivalent results. In their latest paper, the scientists link 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,” says first author William Kremen.