MRI Assessment of Impaired Glucose Metabolism in Alzheimer's Disease

Study Overview
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Brief Summary
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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.

Official Title
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MRI Assessment of Impaired Glucose Metabolism in Alzheimer's Disease

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Diagnostic Test: Deuterium metabolic imaging


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

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

What is the study measuring?
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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 |