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Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies

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Mathias Holsey Gramkow¹, Frederikke Kragh Clemmensen¹, Andreas Brink-Kjær^2,3

¹Danish Dementia Research Centre, Dept. of Neurology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association

|December 24, 2025

Summary

This summary is machine-generated.

Dynamic pupillary changes and reduced nighttime activity are promising digital biomarkers for Alzheimer's disease (AD) progression. These measures, from quantitative light reflex pupillometry (qLRP) and actigraphy, can aid in early AD prognostication and disease tracking.

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Area of Science:

Neuroscience
Biomarkers
Gerontology

Background:

Alzheimer's disease (AD) requires accessible prognostic biomarkers for disease-modifying therapies.
Quantitative light reflex pupillometry (qLRP) and actigraphy assess midbrain function and circadian activity, respectively, both altered in AD.
This study investigates the prognostic and disease-tracking capabilities of qLRP and actigraphy in early AD.

Purpose of the Study:

To determine the prognostic and disease-tracking capabilities of qLRP and actigraphy in early Alzheimer's disease.
To assess the association of pupillary and activity measures with clinical, cognitive, and neuroimaging progression.
To evaluate these digital biomarkers for AD prognostication and disease monitoring.

Main Methods:

A single-center longitudinal cohort study included 86 AD patients for qLRP and 58 for actigraphy, followed for 18-24 months.
qLRP and actigraphy were performed at baseline and follow-up; clinical progression, neuroimaging, and cognitive decline (MMSE) were assessed at 1-year follow-up.
Logistic regression and repeated measures correlation were used to analyze the association between biomarkers and disease progression.

Main Results:

Decreased resting pupillary diameter correlated with higher clinical progression risk and cognitive decline.
Baseline pupillary changes predicted neuroimaging progression.
Reduced nighttime activity and intra-daily step variability predicted clinical progression and cognitive decline.

Conclusions:

Dynamic pupillary changes and decreased nighttime activity serve as valuable digital biomarkers for AD.
These measures reflect changes in arousal states and disease progression.
qLRP and actigraphy demonstrate utility in easing AD prognostication and disease tracking.