VR pupillometry to detect cognitive impairment

Task-evoked Pupillometry in AD, MCI, and Depression-Related Cognitive Impairment

This project will try VR-based eye-tracking pupillometry to see if pupil responses can detect and track cognitive problems in adults with Alzheimer's, mild cognitive impairment, depression-related cognitive impairment, or no cognitive issues.

Quick facts

• Study type: Observational
• Enrollment: 140 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Max-Planck-Institute of Psychiatry (Academic / other)
• Locations: 1 site (München, Bavaria)
• Trial ID: NCT07402356 on ClinicalTrials.gov

What this trial studies

This prospective, single-center, repeated-measures study uses VR headsets with eye-tracking to record pupil responses alongside behavioral tests at baseline and at 3- and 6-month follow-ups. Adults (18–80 years) are assigned to one of four cohorts (n=35 each): biomarker-supported Alzheimer's disease, MCI without Alzheimer pathology, depressive disorder with cognitive impairment, or healthy controls. The protocol links pupil dynamics to locus coeruleus–noradrenergic arousal systems that are implicated early in Alzheimer pathology and may change with cognitive decline. Data will be used to compare pupil metrics across cohorts and over time to determine whether VR-based pupillometry offers a practical, noninvasive longitudinal biomarker.

Who should consider this trial

Good fit: Adults aged 18–80 who can read German, can give informed consent, and fall into one of the cohorts (CSF-supported Alzheimer's, MCI without AD, depressive disorder with cognitive impairment, or healthy control) are ideal candidates.

Not a fit: People with recent stroke, Parkinson's syndrome, multiple sclerosis, lifetime psychotic or bipolar disorder, acute substance abuse, recent psychotropic medication changes, inability to consent, or who cannot read German may not be suitable or likely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could provide a noninvasive, practical tool for earlier detection and monitoring of cognitive decline, potentially enabling timelier interventions.

How similar studies have performed: Pupillometry and LC-related pupil metrics have shown promising signals in prior Alzheimer's and cognitive research, but VR-based eye-tracking approaches are newer and have limited longitudinal validation.

Eligibility criteria

Inclusion Criteria:

1. Written informed consent.
2. Age 18-80 years.
3. Ability to read and understand German.
4. For patient cohorts: suspected or confirmed diagnosis of AD/MCI/depressive disorder with cognitive impairment according to clinical assessment and routine documentation.

Exclusion Criteria:

1. Acute suicidality (e.g. BDI suicidality item \> 1).
2. Change of psychotropic medication within the last 4 weeks.
3. Lifetime psychotic disorder (ICD-10 F20-29).
4. Lack of capacity to consent.
5. Lifetime bipolar disorder (ICD-10 F31).
6. Acute substance abuse or harmful use of alcohol or other psychoactive substances.
7. Parkinson's syndrome (ICD-10 G20).
8. Multiple sclerosis (ICD-10 G35).
9. Stroke within the last 12 months.

Where this trial is running

München, Bavaria

• Max Planck Institute of Psychiatry — München, Bavaria, Germany (Recruiting)

Study contacts

• Principal investigator: Victor I. Spoormaker, PhD — Max-Planck-Institute of Psychiatry
• Study coordinator: Eva Vidovic, MD

Conditions Alzheimer s Disease; Major Depressive Disorder; Mild Cognitive Impairment; Dementia; Alzheimer's Disease; Pupillometry; Biomarkers; Amyloid beta-Peptides