Novel Diagnostic and Disease Stage Biomarkers in AD (TRACK-AD)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Alzheimer Disease; Mild Cognitive Impairment; Vascular Dementia; Dementia With Lewy Bodies; Healthy Controls; Neuro-Degenerative Diseases
• Intervention / Treatment: Other: Long-term study; Other: Cross-sectional study; Other: Short-term study

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 350

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Danish Dementia Research Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 110 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

In the longitudinal study (1) the investigators will include 100 patients diagnosed with mild cognitive impairment due to Alzheimer's disease or diagnosed with mild to moderate Alzheimer's disease. In the short-term study (2) the investigators will include 40 patients who are under investigation of a neurodegenerative disease. In the cross-sectional study (3) the investigatorswill include 50 patients with Alzheimer's disease, 50 healthy controls without brain disease, and 100 patients with other forms of dementia (dementia with Lewy body, vascular dementia, normal pressure hydrocephalus, frontotemporal dementia).

Description

1. 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

2. 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
3. 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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

8

Cohorts and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Danish Dementia Research Centre
• Investigators: Principal Investigator: Frederikke Kragh Clemmensen, MD, Danish Dementia Research Centre, Rigshospitalet, Copenhagen, Denmark; Principal Investigator: Mathias Holsey Gramkow, MD, Danish Dementia Research Centre, Rigshospitalet, Copenhagen, Denmark; Principal Investigator: Kristian Steen Frederiksen, MD, PhD, Danish Dementia Research Centre, Rigshospitalet, Copenhagen, Denmark; Principal Investigator: Steen Gregers Hasselbalch, DMSc, Danish Dementia Research Centre, Rigshospitalet, Copenhagen, Denmark; Principal Investigator: Anja Hviid Simonsen, MSc Pharm PhD, Danish Dementia Research Centre, Rigshospitalet, Copenhagen, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: December 1, 2021
• First Submitted That Met QC Criteria: January 3, 2022
• First Posted (Actual): January 4, 2022

Study Record Updates

• Last Update Posted (Actual): October 16, 2023
• Last Update Submitted That Met QC Criteria: October 13, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Biomarkers; Actigraphy; Pupillometry; Blood-based biomarkers
• Additional Relevant MeSH Terms: Mental Disorders; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Neurocognitive Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Tauopathies; Cognition Disorders; Intracranial Arterial Diseases; Intracranial Arteriosclerosis; Leukoencephalopathies; Dementia; Alzheimer Disease; Cognitive Dysfunction; Neurodegenerative Diseases; Lewy Body Disease; Dementia, Vascular
• Other Study ID Numbers: H-21040317

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No