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Initial Technical and Clinical Validation of Mobile Pupillometry with Virtual Reality: A Digital Biomarker for Screening Cognitive Function and Impairment
Brendler A, Fietz J, Bauer A, Pfahl D, Higgins S, Vidovic E, Brückl T, BeCOME Working Group et al.. medRxiv, 2026-07-17
Topic: Brain imaging, connectivity and assessment
Cognitive impairment is a prevalent symptom extending from physiological ageing to disease. It commonly manifests itself in initial memory problems, progressing and co-occurring in more severe conditions such as Mild Cognitive Impairment, Alzheimer’s Disease and Major Depressive Disorder. However, current non-invasive screening assessments either lack biological information or are invasive and restricted to specialized centers with complex and cost-intensive set-ups. Here, we conducted an initial validation of mobile pupillometry with Virtual Reality (VR) under experimental conditions as a digital biomarker for cognitive impairment by testing required biomarker-specific properties. For this purpose, we first assessed its construct validity by testing healthy participants (n=43) on an n-back task in VR while pupil size was measured. Mixed effects models revealed that similar to lab-based eye-tracking systems, pupil size increased in a sensible and distinguishable fashion as a function of working memory load. Second, to test the signal’s reliability, the same participants were tested on the identical set-up two to three months after their first visit. We observed that the pupil response profile was highly stable over this period. Third, for its clinical validity, we examined patients (n=89) from three different cohorts with varying degrees of cognitive impairment and compared them to healthy control participants (n=81). Mixed-effects models indicated that pupil size was reduced as a function of cognitive impairment levels at higher cognitive load and that this effect was stronger pronounced with increasing age. In conclusion, we provide initial evidence for mobile pupillometry being a sensitive, reliable and clinically valid digital biomarker for cognitive functioning and impairment, which offers desirable properties due to its quick, automatized and location-independent set-up.
Key findings
- Mixed effects models revealed that similar to lab-based eye-tracking systems, pupil size increased in a sensible and distinguishable fashion as a function of working memory load.
- We observed that the pupil response profile was highly stable over this period.
- Mixed-effects models indicated that pupil size was reduced as a function of cognitive impairment levels at higher cognitive load and that this effect was stronger pronounced with increasing age.
- In conclusion, we provide initial evidence for mobile pupillometry being a sensitive, reliable and clinically valid digital biomarker for cognitive functioning and impairment, which offers desirable properties due to its quick, automatized and location-independent set-up.
Study details
- Participants43
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 27 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 17 of the 62 points we could judge it on, which is 27 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 1 / 4 | 43 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 17 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 17 of the 62 points we could judge it on is 27 out of 100. |
| Total | 27 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Brendler, A., Fietz, J., Bauer, A., Pfahl, D., Higgins, S., Vidovic, E., et al. (2026). Initial Technical and Clinical Validation of Mobile Pupillometry with Virtual Reality: A Digital Biomarker for Screening Cognitive Function and Impairment. medRxiv. https://doi.org/10.64898/2026.07.15.26358187
Vancouver
Brendler A, Fietz J, Bauer A, Pfahl D, Higgins S, Vidovic E, et al. Initial Technical and Clinical Validation of Mobile Pupillometry with Virtual Reality: A Digital Biomarker for Screening Cognitive Function and Impairment. medRxiv. 2026. doi:10.64898/2026.07.15.26358187.
BibTeX
@article{brendler2026-bd891c91,
author = {Brendler, A. and Fietz, J. and Bauer, A. and Pfahl, D. and Higgins, S. and Vidovic, E. and Brückl, T. and {BeCOME Working Group} and others},
title = {{Initial Technical and Clinical Validation of Mobile Pupillometry with Virtual Reality: A Digital Biomarker for Screening Cognitive Function and Impairment}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.07.15.26358187},
url = {https://doi.org/10.64898/2026.07.15.26358187}
}
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