Detecting Early Alzheimer's Using MR

Summary

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.

Conditions

• Alzheimer Disease

Interventions

OTHER

Magnetic Resonance Imaging (MRI)

Participants will be asked to lie in the MRI scanner while we collect 3D T1- and T2-weighted images and a 3D FLAIR image to exclude pathology (e.g. stroke). Participants will ingest a glucose solution (75 g Dextrose) so dynamic glucoCEST images can be acquired to measure glucose uptake and clearance.

OTHER

Blood Glucose Assessment

A blood testing meter will be used to measure the blood sugar levels before and after the scans. Normal reading for a nondiabetic person after fasting is 70-99 mg/dl (3.9-6 mmol/L). If abnormal blood sugar levels are detected (sugar levels outside the above normal range), the participant will no longer be eligible for the study and they will be withdrawn.

OTHER

Positron Emission Tomography (PET)

Participants will be administered a radioactive glucose analogue, 2-deoxy-2-(18F) fluoro-D-glucose (18FDG) through a canula inserted into a vein in the arm or hand and asked to sit quietly for 1 h. After 1 h they will be asked to lie quietly and without talking in the PET scanner and a PET brain scan will be performed.

OTHER

Cognitive Assessment

Participants will be asked to undertake two cognitive tests (the Alzheimer's Disease Assessment Scale ADAS-cog test and the Mini Mental State Examination test - MMSE). These are standard clinical tests used to determine cognitive dysfunction in Alzheimer's disease.

Sponsors & Collaborators

• NHS Grampian

  collaborator OTHER_GOV

• University of Aberdeen

  lead OTHER

Principal Investigators

• Gordon Waiter, PhD · University of Aberdeen

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-11-15

Primary Completion

2025-12-31

Completion

2025-12-31

Countries

• United Kingdom

Study Locations