# Prognostic value of light reflex pupillometry in Alzheimer’s disease – a longitudinal cohort study

## TL;DR

This study shows that measuring the pupil's reaction to light can help predict the progression of Alzheimer's disease.

## Contribution

The study demonstrates the potential of quantitative light reflex pupillometry as a new, non-invasive biomarker for Alzheimer's progression.

## Key findings

- Smaller resting pupil size was linked to a higher risk of clinical progression in Alzheimer's patients.
- Reduced pupillary response to light predicted cognitive decline and visual signs of disease progression.
- qLRP showed promising but not definitive associations with dementia severity measures.

## Abstract

The pupillary light reflex (PLR) has been indicated as a biomarker in Alzheimer’s disease and may be suitable for easy prognostication. We sought to evaluate the prognostic potential of quantitative light reflex pupillometry (qLRP) in early AD.

At baseline, 3-months, 12-months and at 18/24-months follow-up (FU), we carried out qLRP with a hand-held pupillometer (PLR-3000, NeurOptics®). We assessed clinically evaluated progression, Mini Mental-State Examination (MMSE), visual progression on [18F]FDG-PET and Clinical Dementia Rating Sum-of-Boxes (CDR-SoB) at 1-year FU. Logistic and linear regression models were fitted with baseline qLRP and the short-term dynamic qLRP change from baseline visit to 3 months as predictors with adjustment for age and sex. We evaluated logistic regression models by the cross-validated area under the receiver operating curve (AUC).

A decrease in resting pupillary diameter was associated with a higher risk of clinically evaluated progression (odds ratio 4.3, 95% confidence interval (CI): 1.2–16.9) and predicted this outcome with an associated AUC of 0.65. Less relative pupillary change after light stimulus measured at baseline was associated with cognitive decline on MMSE (β = -5.1, 95% CI: -1.6 – -8.6, p = 0.004) and a decrease in this variable from baseline–3 months could predict visual progression of [18F]FDG-PET (AUC 0.63). There were no significant associations between qLRP and changes in the CDR-SoB, although estimates were in the same direction.

qLRP holds promise as a prognostic, bedside, digital biomarker in Alzheimer’s disease, possibly reflecting changes in the arousal state as a disease progression marker. Our results await confirmation in larger cohorts.

The online version contains supplementary material available at 10.1186/s13195-025-01794-8.