Feasibility and Diagnostic Potential of Multimodal Neuro-Ophthalmic Biomarkers in Young-Onset Dementia and Functional Cognitive Disorder.
4 affiliations
- 1Ulverscroft Eye Unit, School of Psychology and Vision Sciences, University of Leicester, Leicester, United Kingdom.
- 2School of Psychology and Vision Sciences, University of Leicester, Leicester, United Kingdom.
- 3The Evington Centre, Leicester General Hospital, Leicester, United Kingdom.
- 4Department of Ophthalmology, University Hospitals of Leicester NHS Trust, Infirmary Square, Leicester, United Kingdom.
Abstract
Purpose
To evaluate the feasibility and diagnostic utility of neuro-ophthalmic biomarkers as objective, culture-fair tools for distinguishing young-onset dementia (YOD) from functional cognitive disorder (FCD).Design
A cross-sectional observational study.Participants
Forty-five participants were recruited from a young-onset memory clinic, including cognitively normal controls (n = 18), individuals with FCD (n = 11), and patients with YOD (n = 16).Methods
Participants underwent point-of-care neuro-ophthalmic assessments, including virtual reality-based eye tracking (BulbiCAM) to measure saccadic and pupillary responses, and handheld electroretinography (ERG) (RETeval) to assess retinal ganglion cell function.Main outcome measures
Saccadic latency (horizontal and vertical), pupillometric parameters (constriction acceleration and velocity, relative afferent pupillary defect, and baseline diameter), and ERG photopic negative response (PhNR) amplitude and latency.Results
Saccadic latency was significantly prolonged in YOD compared with nondementia participants for horizontal (P = 0.0036) and vertical (P = 0.033) tasks, with 3-group analysis showing a stepwise increase from controls to FCD to YOD. Dynamic pupillometry also differentiated YOD, with reduced constriction acceleration (P = 0.0003) and velocity (P = 0.02), and similarly showed a stepwise decline from controls through FCD to YOD. Constriction acceleration showed the strongest single-marker performance (area under the curve [AUC] = 0.83), followed by horizontal saccadic latency (AUC = 0.77). Combining these 2 measures improved discrimination (AUC = 0.84), with high specificity (92.6%). Electroretinography PhNR measures showed nonsignificant trends toward reduced amplitude and delayed latency in cognitively impaired groups. Participant feedback supported feasibility, with over 93% reporting comfort and acceptability.Conclusions
Noninvasive neuro-ophthalmic assessments are feasible in memory clinic settings and show promise as rapid, objective, and culture-fair biomarkers for early detection of YOD. Dynamic pupillometry and saccadic latency, in particular, demonstrate potential for differentiating YOD from nondementia conditions, while their combined model showed high specificity, supporting possible value as a rule-in adjunct in clinical assessment. Larger, longitudinal studies are required to validate diagnostic thresholds and clinical implementation.Financial disclosures
The author has no/the authors have no proprietary or commercial interest in any materials discussed in this article.
Related
- Comprehensive Ophthalmic Evaluation of Clinically Normal Rhesus Monkeys (Macaca mulatta): Selected Ophthalmic Diagnostic Tests, Tear‐Film Biochemistry and Serum Correlations, Conjunctival Microbiota and Ophthalmic Artery Haemodynamics
- Beyond a diagnostic modality: the pivotal role of ultrasound biomicroscopy in ophthalmic care pathways.
- Artificial intelligence for ophthalmic vessel segmentation: from multimodal imaging to clinical translation
- HalluciGuard-eye: knowledge graph-enhanced retrieval-augmented generation for hallucination detection and mitigation in ophthalmic multimodal large language models
- Ophthalmic AI With Just Ten Examples: Comparing Multimodal Large Language Models, Vision Foundation Models, and Vision-Language Models
BibTeX
@article{karaer2026feasibility,
title = {{Feasibility and Diagnostic Potential of Multimodal Neuro-Ophthalmic Biomarkers in Young-Onset Dementia and Functional Cognitive Disorder.}},
author = {Irem Karaer and Callum Hunt and Seema Teli and Reenette Savant and Vanessa Rodwell and Ha-Jun Yoon and Gail D E Maconachie and Zhanhan Tu and Qadeer Arshad and Elizabeta B Mukaetova-Ladinska and Mervyn G Thomas},
journal = {Ophthalmology science},
year = {2026},
month = sep,
doi = {10.1016/j.xops.2026.101410},
url = {https://europepmc.org/article/MED/42921319},
note = {CC BY},
}
RIS
TY - JOUR
TI - Feasibility and Diagnostic Potential of Multimodal Neuro-Ophthalmic Biomarkers in Young-Onset Dementia and Functional Cognitive Disorder.
AU - Irem Karaer
AU - Callum Hunt
AU - Seema Teli
AU - Reenette Savant
AU - Vanessa Rodwell
AU - Ha-Jun Yoon
AU - Gail D E Maconachie
AU - Zhanhan Tu
AU - Qadeer Arshad
AU - Elizabeta B Mukaetova-Ladinska
AU - Mervyn G Thomas
PY - 2026
DA - 2026/09/17
JO - Ophthalmology science
DO - 10.1016/j.xops.2026.101410
UR - https://europepmc.org/article/MED/42921319
AB - Purpose To evaluate the feasibility and diagnostic utility of neuro-ophthalmic biomarkers as objective, culture-fair tools for distinguishing young-onset dementia (YOD) from functional cognitive disorder (FCD).Design A cross-sectional observational study.Participants Forty-five participants were recruited from a young-onset memory clinic, including cognitively normal controls (n = 18), individuals with FCD (n = 11), and patients with YOD (n = 16).Methods Participants underwent point-of-care neuro-ophthalmic assessments, including virtual reality-based eye tracking (BulbiCAM) to measure saccadic and pupillary responses, and handheld electroretinography (ERG) (RETeval) to assess retinal ganglion cell function.Main outcome measures Saccadic latency (horizontal and vertical), pupillometric parameters (constriction acceleration and velocity, relative afferent pupillary defect, and baseline diameter), and ERG photopic negative response (PhNR) amplitude and latency.Results Saccadic latency was significantly prolonged in YOD compared with nondementia participants for horizontal (P = 0.0036) and vertical (P = 0.033) tasks, with 3-group analysis showing a stepwise increase from controls to FCD to YOD. Dynamic pupillometry also differentiated YOD, with reduced constriction acceleration (P = 0.0003) and velocity (P = 0.02), and similarly showed a stepwise decline from controls through FCD to YOD. Constriction acceleration showed the strongest single-marker performance (area under the curve [AUC] = 0.83), followed by horizontal saccadic latency (AUC = 0.77). Combining these 2 measures improved discrimination (AUC = 0.84), with high specificity (92.6%). Electroretinography PhNR measures showed nonsignificant trends toward reduced amplitude and delayed latency in cognitively impaired groups. Participant feedback supported feasibility, with over 93% reporting comfort and acceptability.Conclusions Noninvasive neuro-ophthalmic assessments are feasible in memory clinic settings and show promise as rapid, objective, and culture-fair biomarkers for early detection of YOD. Dynamic pupillometry and saccadic latency, in particular, demonstrate potential for differentiating YOD from nondementia conditions, while their combined model showed high specificity, supporting possible value as a rule-in adjunct in clinical assessment. Larger, longitudinal studies are required to validate diagnostic thresholds and clinical implementation.Financial disclosures The author has no/the authors have no proprietary or commercial interest in any materials discussed in this article.
SN - 2666-9145
ER -