How Your Pupils Can Reveal Your Alzheimer’s Risk

Alzheimer’s disease is a progressive and incurable brain disorder that affects memory, thinking, and behavior. It is the most common cause of dementia, a general term for cognitive decline that interferes with daily life. Alzheimer’s disease usually affects people over 65 years old, but it can also occur in younger people who have a genetic predisposition.

One of the challenges of diagnosing and treating Alzheimer’s disease is that it often starts to damage the brain years or even decades before symptoms appear. Therefore, finding ways to detect the disease early and monitor its progression is crucial for developing effective interventions and improving the quality of life of patients and their caregivers.

In this article, we will introduce a new and simple method that may help to identify people who are at higher risk of developing Alzheimer’s disease before they experience cognitive decline. This method is based on measuring how quickly a person’s pupil dilates while they are taking cognitive tests.

What is pupillary response and how is it related to Alzheimer’s disease?

Pupillary response is the change in the diameter of the eye’s pupil in response to different stimuli, such as light, emotion, or cognitive effort. The pupil is the black hole in the center of the iris, the colored part of the eye. The pupil controls how much light enters the eye and reaches the retina, the light-sensitive layer at the back of the eye.

The size of the pupil is regulated by two sets of muscles in the iris: the sphincter muscle, which contracts to make the pupil smaller, and the dilator muscle, which relaxes to make the pupil larger. These muscles are controlled by two branches of the autonomic nervous system: the sympathetic branch, which activates the dilator muscle and causes pupil dilation in situations of stress, arousal, or alertness; and the parasympathetic branch, which activates the sphincter muscle and causes pupil constriction in situations of relaxation or rest.

Pupillary response can also reflect cognitive processes, such as attention, memory, and problem-solving. When a person performs a cognitive task that requires mental effort, such as remembering a list of words or solving a math problem, their pupil tends to dilate more than when they perform a simple or familiar task. This is because cognitive tasks activate a part of the brain called the locus coeruleus (LC), which is located in the brainstem and is involved in regulating arousal and attention. The LC stimulates the sympathetic branch of the autonomic nervous system and triggers pupil dilation.

The LC is also one of the first brain regions to be affected by Alzheimer’s disease. The LC contains neurons that produce a chemical called norepinephrine, which plays a role in modulating memory and cognition. In Alzheimer’s disease, these neurons degenerate and lose their ability to produce norepinephrine. Moreover, these neurons accumulate abnormal deposits of a protein called tau, which form tangles that impair their function and eventually kill them. Tau tangles are one of the hallmarks of Alzheimer’s disease, along with amyloid plaques, which are clumps of another protein that accumulate outside neurons and disrupt their communication.

Because of the link between pupillary response, LC, and tau tangles, researchers have proposed that measuring pupillary response during cognitive tasks could be a way to assess the health of the LC and detect early signs of Alzheimer’s disease.

What does the research say about pupillary response and Alzheimer’s risk?

A recent study published in Neurobiology of Aging by researchers at University of California San Diego School of Medicine suggested that measuring pupillary response during cognitive tasks could be a low-cost, non-invasive, and easy-to-administer method to screen individuals at increased genetic risk for Alzheimer’s disease before they show any symptoms.

The study involved 631 participants who were part of an ongoing longitudinal study on aging and cognition. The participants were between 56 and 66 years old and had no signs of cognitive impairment. They underwent genetic testing to determine their polygenic risk score (PRS) for Alzheimer’s disease, which is an aggregate measure of how many genetic variants associated with Alzheimer’s disease they carry. They also performed various cognitive tests that assessed their memory, attention, executive function, language, and visuospatial abilities.

While they were taking these tests, their pupillary response was measured using an eye tracker, which is a device that records the movement and size of the pupil. The researchers calculated the average pupil dilation for each test and compared it with the PRS and the cognitive performance of the participants.

The results showed that participants who had a higher PRS for Alzheimer’s disease also had greater pupil dilation during the most difficult cognitive tests, even if they performed equally well as those with a lower PRS. This suggests that they had to exert more mental effort to achieve the same level of performance, which could indicate a reduced cognitive reserve or a subtle impairment in the LC function.

The researchers also found that the association between PRS and pupillary response was stronger for tests that involved memory and executive function, which are the cognitive domains that are most affected by Alzheimer’s disease. Furthermore, they found that pupillary response was more strongly correlated with PRS than with age, education, or sex, which are other factors that can influence cognition and pupillary response.

The researchers concluded that pupillary response during cognitive tasks could be a useful biomarker to identify individuals who are at higher genetic risk for Alzheimer’s disease and who may benefit from early interventions to prevent or delay the onset of cognitive decline.

What are the implications and limitations of this method?

The study by Kremen and colleagues is not the first to suggest that pupillary response could be a potential indicator of Alzheimer’s disease. Previous studies have shown that people with mild cognitive impairment (MCI), which is often a precursor to Alzheimer’s disease, or with mild to moderate Alzheimer’s disease have greater pupil dilation and slower pupillary constriction than cognitively normal individuals. However, this study is the first to link pupillary response with genetic risk for Alzheimer’s disease in cognitively normal individuals.

This method has several advantages over other methods of detecting Alzheimer’s disease, such as brain imaging or cerebrospinal fluid analysis, which are expensive, invasive, and not widely available. Measuring pupillary response is relatively cheap, easy, and fast. It only requires an eye tracker and a computer, and it can be done in any setting. It is also non-invasive and does not expose the person to any radiation or needles. Moreover, it can be repeated over time to monitor changes in cognitive function and LC health.

However, this method also has some limitations and challenges. First, pupillary response is influenced by many factors other than cognition and LC function, such as light, emotion, medication, fatigue, or eye diseases. Therefore, these factors need to be controlled or accounted for when measuring and interpreting pupillary response. Second, pupillary response is not specific to Alzheimer’s disease. It may also reflect other conditions that affect the LC or cognition, such as Parkinson’s disease, depression, or anxiety. Therefore, pupillary response alone cannot diagnose Alzheimer’s disease, but it can be used as a screening tool to identify people who need further evaluation. Third, pupillary response is not a direct measure of LC function or tau pathology. It is an indirect and proxy measure that may not capture the full extent of the damage or dysfunction in the LC or other brain regions involved in Alzheimer’s disease.

Conclusion

In summary, pupillary response during cognitive tasks is a promising method to screen individuals who are at higher genetic risk for Alzheimer’s disease before they develop any symptoms. This method is based on the premise that people who have more genetic variants associated with Alzheimer’s disease also have more tau tangles in their LC, which impair their cognitive function and cause their pupils to dilate more when they perform difficult tasks. Measuring pupillary response is a simple, non-invasive, and affordable way to assess the health of the LC and detect early signs of cognitive decline. However, this method is not specific or definitive for Alzheimer’s disease, and it needs to be validated and refined with further research.