Novel Diagnostic and Disease Stage Biomarkers in AD

Study Overview
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Brief Summary
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This study will investigate the efficacy of novel biomarkers, namely blood-based biomarkers, pupillometry and actigraphy to track and predict progression of Alzheimer's disease (AD). Furthermore, the study will investigate the diagnostic value of pupillometry and actigraphy for AD.

Detailed Description
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This study consist of three sub-studies. In study 1, participants diagnosed with mild cognitive impairment due to AD or mild to moderate AD will be followed for up to 24 months with repeated blood samples, pupillometry, actigraphy, cognitive tests and a control brain scan. In study 2, patients under investigation of a neurodegenerative disease who have a planned lumbar puncture in the Memory clinic will be invited to this study. Participants will undergo pupillometry and blood samples two times approximately one and four weeks after the lumbar puncture. In study 3, participants with a dementia diagnosis will undergo pupillometry and actigraphy at a single visit.

Official Title
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TRacking Alzheimer´s Disease: a Study of Disease trajeCtory and Development of Diagnostic and Disease Stage biomarKers in AD (TRACK-AD)

Conditions
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Alzheimer Disease, Mild Cognitive Impairment, Neuro-Degenerative Diseases, Vascular Dementia, Dementia With Lewy Bodies, Healthy Controls

Intervention / Treatment
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* Other: Long-term study
* Other: Short-term study
* Other: Cross-sectional study


Participation Criteria
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Eligibility Criteria
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Longitudinal study: Inclusion criteria: MCI due to AD, or mild or moderate AD dementia according to the National Institute on Aging and Alzheimer's Association (NIA-AA) diagnostic criteria Caregiver willing to participate as an informant MMSE >19 at inclusion Brain FDG-PET/MRI or FDG/PET-CT Able to cooperate to the investigations and give informed consent Exclusion criteria: Other neurological or psychiatric illness that may affect neurofilament light (NfL) levels (severe neuropathy, multiple sclerosis (MS), stroke within the last 3 months, Wernicke encephalopathy) Diagnosis of previous or current major psychiatric disorder (schizophrenia, bipolar disorder, psychosis) within last 2 years Excessive alcohol intake or substance abuse within the last 2 years Ophthalmological disorders that may affect pupillometry Participating in drug trials or other intervention trials Short-term study: Inclusion criteria: Patients under investigation of a neurodegenerative disease MMSE >19 Scheduled lumbar puncture/lumbar puncture performed within the last week prior to inclusion Written consent form to the Danish Dementia Biobank Able to cooperate to the investigations Exclusion criteria: Other neurological or psychiatric illness that may affect NfL levels (severe neuropathy, MS, stroke within the last 3 months, Wernicke encephalopathy) Excessive alcohol intake or substance abuse within the last 2 years Ophthalmological disorders that may affect pupillometry Participating in drug trials or other intervention trials Cross-sectional study: Inclusion criteria - Patients: A diagnosis of a dementia disorder Caregiver willing to participate as an informant MMSE >15 at inclusion Able to cooperate to the investigations Able to give informed consent Exclusion criteria - Patients: Diagnosis of previous or current major psychiatric disorder (schizophrenia, bipolar disorder, psychosis) within last 2 years Excessive alcohol intake or substance abuse within the last 2 years Other known brain disorder Ophthalmological disorders that may affect pupillometry Participating in drug trials or other intervention trials Inclusion criteria - Healthy Controls: Able to cooperate to the investigations Normal cognition Age 50-90 year Exclusion criteria - Healthy Controls: Diagnosis of previous or current major psychiatric disorder (schizophrenia, bipolar disorder, psychosis) within last 2 years Excessive alcohol intake or substance abuse within the last 2 years Other known brain disorder Ophthalmological disorders that may affect pupillometry

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 110 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MCI<br>Patients suffering from mild cognitive impairment (MCI) due to Alzheimer's disease. | Other: Long-term study<br>* No intervention. Investigations: cognitive tests, blood samples, pupillometry, actigraphy, and FDG-PET/MR brain scan.<br>|
| AD<br>Patients diagnosed with mild to moderate Alzheimer's disease (AD) | Other: Long-term study<br>* No intervention. Investigations: cognitive tests, blood samples, pupillometry, actigraphy, and FDG-PET/MR brain scan.<br>Other: Cross-sectional study<br>* No intervention. Investigations: cognitive tests, pupillometry and actigraphy.<br>|
| NDD<br>Patients under investigation of a neurodegenerative disease (NDD) | Other: Short-term study<br>* No intervention. Investigations: blood samples and pupillometry.<br>|
| DLB<br>Patients diagnosed with Dementia with Lewy Bodies (DLB) | Other: Cross-sectional study<br>* No intervention. Investigations: cognitive tests, pupillometry and actigraphy.<br>|
| VaD<br>Patients with vascular dementia (VaD) | Other: Cross-sectional study<br>* No intervention. Investigations: cognitive tests, pupillometry and actigraphy.<br>|
| FTD<br>Frontotemporal dementia (FTD) | Other: Cross-sectional study<br>* No intervention. Investigations: cognitive tests, pupillometry and actigraphy.<br>|
| NPH<br>Normal pressure hydrocephalus (NPH) | Other: Cross-sectional study<br>* No intervention. Investigations: cognitive tests, pupillometry and actigraphy.<br>|
| Healthy Controls<br>Healthy Controls without brain disease | Other: Cross-sectional study<br>* No intervention. Investigations: cognitive tests, pupillometry and actigraphy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in CDR | Clinical Dementia Rating (CDR), a clinical tool for grading the relative severity of dementia with scores ranging from 0 (no impairment) to 3 (severe impairment). | Two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in MMSE | Mini Mental Status Examination (MMSE), used to test global cognitive function | Two years | 
| Changes in MR brain scan | Magnetic Resonance Imaging (MR), used to asses changes in volumetric measurements | 12 months | 
| FDG-PET brain scan | Fluorodeoxyglucose (FDG)-Positron Emission Tomography (PET) of the brain, used to asses changes in brain metabolism | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Biomarkers, Pupillometry, Actigraphy, Blood-based biomarkers