MRI Assessment of Impaired Glucose Metabolism in Alzheimer's Disease

Diseases of dementia are chronic, untreatable, and cause a massive burden of morbidity. In this proposal, we seek to tackle the problem of better, earlier, and more efficient diagnosis using deuterium metabolic imaging (DMI). The study is divided in two sub-studies: 1) optimization and simplification of DMI protocols, and 2) a cross-sectional study of DMI in Alzheimer's patients and healthy controls.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Diagnostic test: Deuterium metabolic imaging

• Study Type: Observational
• Enrollment (Actual): 21

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Aarhus University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

In sub-study 1, the population is composed of healthy volunteers. In sub-study 2, patients with Alzheimer's disease and healthy age-matched controls are recruited.

Description

Inclusion criteria:

AD-patients:

• Aged 55-85 years.
• Male or female.
• AD diagnosis by the NIA-AA 2011 research criteria.8
• Able to give written informed consent.
• Mini-mental state examination (MMSE) equal to or above 18.9
• Brain FDG-PET performed at Aarhus University Hospital consistent with AD.

Healthy participants:

• Aged 18-85 years.
• Male or female.

Exclusion criteria:

All participants:

• Diabetes or any other metabolic disease.

• Other significant brain disease:

  • Strokes.
  • Tumors.
  • Chronic small vessel disease (clinically suspected, or Fazekas ≥ 2 if clinical MRI is available).
  • Epilepsy.
  • Other neurodegenerative or -inflammatory disease.

• Contraindications for MRI:

  • Pacemaker, neurostimulator or cochlear implant.
  • Metal foreign bodies such as fragments and irremovable piercings.
  • Unsafe medical implants (safety of heart valves, hips and the like must be confirmed).
  • Claustrophobia.
  • Largest circumference including arms > 160 cm.
• Pregnant - women must be post-menopausal or confirmed non-pregnant by an onsite test.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healhy volunteers; Repeated MRI and DMI for simplification of protocols. Repeated within 6 +/- 2 weeks.	Diagnostic test: Deuterium metabolic imaging; MRI after oral administration of 75g of [6,6'-2H2]glucose.
Alzheimer's disease patients; MRI and DMI to assess cerebral glucose metabolism. Single examination. Compared with PET.	Diagnostic test: Deuterium metabolic imaging; MRI after oral administration of 75g of [6,6'-2H2]glucose.
Healthy controls; MRI and DMI for comparison with AD patients.	Diagnostic test: Deuterium metabolic imaging; MRI after oral administration of 75g of [6,6'-2H2]glucose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Deuterium Metabolic Imaging	Glucose concentration in whole-brain referenced to baseline scan (sub-study 1).	Up to 150 mins after 2H-glucose ingestion
Deuterium Metabolic Imaging	Lactate concentrations in whole-brain referenced to baseline scan (sub-study 1).	Up to 150 mins after 2H-glucose ingestion
Deuterium Metabolic Imaging	Glx concentrations in whole-brain referenced to baseline scan (sub-study 1).	Up to 150 mins after 2H-glucose ingestion
Deuterium Metabolic Imaging	Lactate/glx ratio in the tempo-parietal cortex (sub-study 2).	Up to 150 mins after 2H-glucose ingestion
Deuterium Metabolic Imaging	Lactate/glx ratio in the hippocampus (sub-study 2).	Up to 150 mins after 2H-glucose ingestion
Deuterium Metabolic Imaging	Lactate/glx ratio in the posterior cingulum (sub-study 2).	Up to 150 mins after 2H-glucose ingestion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Deuterium Metabolic Imaging	Simpler DMI quantifications, including reference to external phantoms and internal reference, in the same regions defined in primary outcomes.	Up to 150 mins after 2H-glucose ingestion
Blood samples	Glucose	Up to 150 mins after 2H-glucose ingestion
Blood samples	2H-enrichment	Up to 150 mins after 2H-glucose ingestion
FDG-PET from the records (sub study 2)	Brain glucose uptake	At time of Deuterium Metabolic Imaging
Cognitive tests from the records (sub study 2)	The Mini-Mental State Exam (0-30, 30 is best)	At time of Deuterium Metabolic Imaging
Cognitive tests from the records (sub study 2)	Addenbrooke's Cognitive Examination (0-100, 100 is best)	At time of Deuterium Metabolic Imaging
Cerebrospinal fluid biochemistry from the records (sub study 2)	Total tau protein	At time of Deuterium Metabolic Imaging
Cerebrospinal fluid biochemistry from the records (sub study 2)	Phosphorylated tau	At time of Deuterium Metabolic Imaging
Cerebrospinal fluid biochemistry from the records (sub study 2)	Amyloid	At time of Deuterium Metabolic Imaging

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2022
• Primary Completion (Actual): October 27, 2023
• Study Completion (Actual): October 27, 2023

Study Registration Dates

• First Submitted: May 25, 2022
• First Submitted That Met QC Criteria: May 30, 2022
• First Posted (Actual): June 2, 2022

Study Record Updates

• Last Update Posted (Estimated): December 1, 2023
• Last Update Submitted That Met QC Criteria: November 30, 2023
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: DMI-AD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be shared after study completion and full anonymization.
• IPD Sharing Time Frame: After study is completed.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

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