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Background <p>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.</p> Methods <p>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<sup>®</sup>). We assessed clinically evaluated progression, Mini Mental-State Examination (MMSE), visual progression on [<sup>18</sup>F]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).</p> Results <p>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, <i>p</i> = 0.004) and a decrease in this variable from baseline–3 months could predict visual progression of [<sup>18</sup>F]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.</p> Discussion <p>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.</p>

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

  • 期刊论文

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  • 发表日期：

    2025年7月11日

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  • Mathias Holsey Gramkow,
  • Frederikke Kragh Clemmensen,
  • Ulrich Lindberg,
  • Ian Law,
  • Otto Mølby Henriksen,
  • Gunhild Waldemar,
  • Steen Gregers Hasselbalch,
  • Kristian Steen Frederiksen

摘要

Background

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.

Methods

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).

Results

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.

Discussion

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.