Detecting Early Alzheimer's Using MR (DREAMER)

University of Aberdeen

Status: Enrolling

Conditions: Alzheimer Disease

Treatments: Other: Positron Emission Tomography (PET); Other: Blood Glucose Assessment; Other: Cognitive Assessment; Other: Magnetic Resonance Imaging (MRI)

Study type: Observational

Funder types: Other

Identifiers

NCT05614310

308185 (Other Identifier)

22\LO\0347 (Other Identifier)

2-001-22

TCS/21/03 (Other Grant/Funding Number)

Details and patient eligibility

About

Alzheimer's disease (AD) is the most common cause of dementia, affecting approximately 10% of individuals aged ≥ 65. Most available treatments aim at controlling symptoms at an early stage rather than providing a cure. Therefore, an accurate and early diagnosis of AD with appropriate management will slow the progression of the condition. Reduced cerebral glucose levels have been observed in patients with early AD. Glucose hypometabolism can be assessed by administering a radioactive glucose analogue, 2-deoxy-2-(18F) fluoro-D-glucose (18FDG), and imaging with PET (positron emission tomography). The high cost and limited availability of PET-CT (PET - computed tomography) still hamper its general clinical application. Moreover, the use of radioactive tracers in combination with the additional ionizing radiation of CT is not suitable for repeated measurements. Therefore, currently, the provisional diagnosis of AD is still based on the combination of clinical history, neurological examination, cognitive testing over a period of time, and structural neuroimaging. This has major time and resource implications.

A radically different and highly innovative means for imaging glucose with magnetic resonance imaging (MRI) has now been established, exploiting the interaction between hydroxyl protons in glucose and the protons in water; the method is termed glucose Chemical Exchange Saturation Transfer (glucoCEST). GlucoCEST MRI is a method that has no reliance on radiolabelled glucose analogues and could become widely implemented in clinic practice. We therefore aim to investigate the potential of glucoCEST MRI in Alzheimer's disease.

Full description

Alzheimer's disease (AD) is the most common cause of dementia, affecting approximately 10% of individuals aged ≥ 65. Most available treatments aim at controlling symptoms at an early stage rather than providing a cure. Therefore, an accurate and early diagnosis of AD with appropriate management will slow the progression of the condition. Reduced cerebral glucose levels have been observed in patients with early AD. Glucose hypometabolism can be assessed by administering a radioactive glucose analogue, 2-deoxy-2-(18F) fluoro-D-glucose (18FDG), and imaging with PET (positron emission tomography). The high cost and limited availability of PET-CT (PET - computed tomography) still hamper its general clinical application. Moreover, the use of radioactive tracers in combination with the additional ionizing radiation of CT is not suitable for repeated measurements. Therefore, currently, the provisional diagnosis of AD is still based on the combination of clinical history, neurological examination, cognitive testing over a period of time, and structural neuroimaging. This has major time and resource implications.

A radically different and highly innovative means for imaging glucose with magnetic resonance imaging (MRI) has now been established, exploiting the interaction between hydroxyl protons in glucose and the protons in water; the method is termed glucose Chemical Exchange Saturation Transfer (glucoCEST). GlucoCEST MRI is a method that has no reliance on radiolabelled glucose analogues and could become widely implemented in clinic practice. We believe that glucoCEST MRI has the potential to replace FDG-PET and improve patient healthcare as part of a routine clinical pathway in very early detection of AD.

The study will include 20 healthy volunteers for developing glucoCEST in the clinical 3T MRI scanner (development phase) and 20 volunteers without AD and 20 patients with clinically diagnosed AD (clinical phase). All participants will have a 3T brain MRI scan after they receive oral glucose. The participants in the clinical phase will have a 3T brain MRI scan, a brain PET scan and they will also undertake two cognitive tests.

The glucose uptake and clearance rate in the brain will be measured from PET and MRI scans and compared between groups and imaging modalities. Sensitivity and specificity of glucoCEST to detect AD will be also calculated.

Primary Objective: To estimate the sensitivity of glucose uptake as measured by glucoCEST MRI in patients with AD compared with age and sex matched controls.

Secondary objective: To investigate if the glucose uptake as measured by glucoCEST MRI is related to the glucose uptake as measured in FDG-PET.

The main aims of the study are:

1. To determine normal uptake and clearance rates of glucose in the brain as measured by dynamic glucoCEST MRI at 3T
2. To compare glucose uptake as measured by glucoCEST MRI and FDG-PET.
3. To compare glucose uptake as measured by glucoCEST MRI in patients with AD and age and sex matched controls.

Enrollment: 60 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

Development phase:

Controls (development group) must:

• be > 18 years
• consent to the study
• not report problems with memory.

Clinical phase

Patients must:

• be ≥ 65 years,
• able to provide informed consent to the study
• have been clinically diagnosed with AD by the mental health team.

Controls must:

• be ≥ 65 years
• able to provide consent to the study
• have a normal score in the ADAS-cog test and the Mini Mental State Examination test (MMSE)
• not report problems with memory.

Exclusion criteria

Subjects will not be considered if they:

• have a history of diabetes,
• have history of a major stroke (mini-stroke/Transient Ischaemic Attacks or lacunar stroke are acceptable),
• have contra-indications to MRI scanning such as implantable cardiac devices
• have family history in AD, to exclude possible gene mutations associated with AD
• have advanced AD who lack the capacity to consent.
• Are pregnant (for developmental phase)
• are unable to read or speak English

Trial design

60 participants in 4 patient groups

Development Group 1 (N = 10) (Development Phase)

Description:

Development group participants (N = 10) will undergo 1 magnetic resonance imaging (MRI) sessions. Before and after their MRI scan participants will be given a pinprick blood sugar test.

Treatment:

Other: Magnetic Resonance Imaging (MRI)

Other: Blood Glucose Assessment

Patients (N = 20) (Clinical Phase)

Description:

Patients (N = 20) will attend 2 visits up to 1 week apart. Patients will be asked to have a no-sugar diet and take no exercise for 24 hours before each visit and to avoid eating 6 hours before scan. Visit 1: Patients will undergo a positron emission tomography (PET) assessment. Before and after their PET assessment patients will be given a pinprick blood sugar test. PET assessment: Visit 2: Patients will undergo MRI assessment. Before and after their MRI scan patients will be given a pinprick blood sugar test. Healthy controls will complete cognitive assessments.

Treatment:

Other: Cognitive Assessment

Other: Magnetic Resonance Imaging (MRI)

Other: Blood Glucose Assessment

Other: Positron Emission Tomography (PET)

Healthy Controls (N = 20) (Clinical Phase)

Description:

Healthy controls (N = 20) will attend 2 visits up to 1 week apart. Healthy controls will be age matched (+/- 3 years) and sex matched to the patient group. Healthy controls will be asked to have a no-sugar diet and take no exercise for 24 hours before each visit and to avoid eating 6 hours before scan. Visit 1: Healthy Controls will undergo a positron emission tomography (PET) assessment. Before and after their PET assessment patients will be given a pinprick blood sugar test. PET assessment: Visit 2: Healthy Controls will undergo MRI assessment. Before and after their MRI scan patients will be given a pinprick blood sugar test. Healthy controls will complete cognitive assessments.

Treatment:

Other: Cognitive Assessment

Other: Magnetic Resonance Imaging (MRI)

Other: Blood Glucose Assessment

Other: Positron Emission Tomography (PET)

Development Group 2 (N = 10) (Development Phase)

Description:

To investigate the repeatability of MRI assessment, 10 development phase healthy volunteers will be recruited to undergo two repeated study assessments. The second visit will be between 7 and 14 days after their first visit. The second repeated study assessment will follow the same procedure as the first visit, consisting of blood glucose assessment and MRI assessment. Participants will be advised to fast from mid-night and avoid eating breakfast.

Treatment:

Other: Magnetic Resonance Imaging (MRI)

Other: Blood Glucose Assessment