VR Pupillometry in Cognitive Impairment
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18-80
SponsorMax-Planck-Institute of Psychiatry
About this trial
With disease-modifying therapies emerging for dementia and related conditions, identifying cognitive decline as early as possible is increasingly important. This prospective, single-center, repeated-measures study evaluates whether VR-based eye-tracking pupillometry can provide a practical, non-invasive biomarker of cognitive impairment and its progression over time. Pupil responses are linked to brain arousal systems relevant to cognitive dysfunction, including the locus coeruleus, which is affected early in Alzheimer's disease. Adults aged 18-80 years will be assigned to one of four cohorts (n=35 per cohort): i) Alzheimer's disease (supported by CSF biomarkers), ii) mild cognitive impairment (MCI) without Alzheimer's Disease, iii) depressive disorder with cognitive impairment, iv) healthy controls. Participants will undergo initial assessments at baseline and follow-up visits after 3 and 6 months. At each visit, pupil responses and behavioral metrics are recorded during a pupillary light reflex paradigm, a resting-state fixation block, a working-memory task (N-back), and a reward task. Pupillometric and behavioral metrics will be compared across cohorts and related to routine neuropsychological measures (MoCA, CERAD) and available clinical biomarkers (CSF markers; blood biomarkers). The primary objective is to determine whether task-evoked pupil response profiles sensitively quantify cognitive impairment, differ between cohorts, and track change over time. The long-term goal is to validate an easy-to-use, outpatient-compatible assessment to support objective characterization and monitoring of cognitive disorders.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Written informed consent.
Age 18-80 years.
Ability to read and understand German.
For patient cohorts: suspected or confirmed diagnosis of AD/MCI/depressive disorder with cognitive impairment according to clinical assessment and routine documentation.
Disqualifiers
Acute suicidality (e.g. BDI suicidality item > 1).
Change of psychotropic medication within the last 4 weeks.
Lifetime psychotic disorder (ICD-10 F20-29).
Lack of capacity to consent.
Trial population
Adults aged 18-80 years will be recruited at the Max Planck Institute of Psychiatry (Munich, Germany) from inpatient wards and outpatient clinics. Patients have a suspected or confirmed clinical diagnosis of Alzheimer's disease, mild cognitive impairment, or depressive disorder with cognitive impairment. Routine clinical measures (neuropsychological testing and, CSF biomarkers, blood biomarkers, imaging) will be linked to study pupillometry outcomes.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Not listed
Trial groups
140 Participants
are grouped into 4 trial groupsGroup A: Alzheimer's Disease
Group B: Mild Cognitive Impairment without Alzheimer's Disease
Group C: Depressive Disorder With Cognitive Impairment
Group D: Healthy Controls
Trial outcomes
Primary outcomes
1
Task-evoked pupil dilation during N-Back
Pupil response metrics (mean relative pupil diameter in each condition) recorded with VR eye tracking during the N-back task for each condition (fixation, 0-back, 1-back, 2-back).
Time frame
BaselineSecondary outcomes
1
Resting-state pupil dynamics
Mean and variability of pupil diameter during resting fixation.
Time frame
Baseline, 3 months, 6 months.2
Reward-task pupil response
Pupil response metrics (mean relative pupil diameter in each condition) recorded with VR eye tracking during each condition (reward, control).
Time frame
Baseline, 3 months, 6 months.3
N-back behavioral performance
Behavioral performance during the VR N-back task, quantified as accuracy and reaction time for each load condition ( 0-, 1-, 2-back).
Time frame
Baseline, 3 months, 6 months.4
Montreal Cognitive Assessment (MoCA)
Global cognitive screening tool used to quantify overall cognitive impairment. Range: 0-30; higher scores indicate better cognitive performance.
Time frame
Baseline, 3 months, 6 months.Other outcomes
1
Between-group differences in N-back pupil metrics
Comparison of the primary N-back pupil load metric across the four cohorts (Alzheimer's disease, mild cognitive impairment, depressive disorder with cognitive impairment, healthy controls).
Time frame
Baseline, 3 months, 6 months.2
Association between task-evoked pupil responses and cognitive test performance
Association between the N-back pupil metrics and cognitive performance measures (MoCA total score; CERAD-Plus subtest z-scores).
Time frame
Baseline, 6 months.3
Association between task-evoked pupil responses and AD pathology markers
Association between the N-back pupil metrics and available biomarkers of AD pathology (CSF and blood-based biomarkers).
Time frame
Baseline through 6 months, using biomarker time points available4
Change from baseline in N-back pupil metrics
Within-participant change from baseline in the prespecified N-back pupil load metric
Time frame
Baseline, 3 months, 6 months.Sponsors and contacts
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Source ClinicalTrials.gov