Brain Blood Flow and Sugar Transport in Alzheimer's Disease With and Without Diabetes - A Pilot Imaging Study
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In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: [18F]FDG PET, [11C]PIB.
- Who it may be relevant to
- Registry conditions: Alzheimer Dementia (AD), Diabete Type 2. Basic parameters: 60 years — 90 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Denmark
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Imaging Biomarkers in Alzheimer's Disease - an Exploratory PET Study
Overview
Alzheimer's disease is the most common cause of dementia and affects a growing number of older adults. Although harmful proteins build up in the brain, we still do not fully understand why some brain regions are affected earlier or more severely than others. Many people with Alzheimer's disease also have problems with blood flow and sugar handling in the brain, and these changes may play an important role in disease development. People with type 2 diabetes are at especially high risk of developing Alzheimer's disease and often experience a more severe disease course. This pilot study aims to improve our understanding of how brain blood flow and sugar use are altered in Alzheimer's disease, and whether these changes differ in people with and without type 2 diabetes. We will study three groups: people with Alzheimer's disease without diabetes, people with Alzheimer's disease and type 2 diabetes, and healthy older individuals. By comparing these groups, we aim to identify early brain changes that may contribute to cognitive decline. Participants will undergo advanced brain imaging using positron emission tomography (PET) scans. One scan uses a radioactive sugar tracer to measure how the brain takes up and uses glucose. Importantly, a new non-invasive method will also allow us to estimate how efficiently glucose is transported from the blood into the brain. This is a key process that may be impaired in Alzheimer's disease, but has previously required invasive procedures. The new approach avoids arterial cannulation, making the study safer and more comfortable for participants. A second PET scan will assess brain blood flow and blood vessel function, including how well the vessels can respond to increased demand. Participants will also complete cognitive tests to assess memory and thinking abilities. Ultimately, this research may contribute to earlier diagnosis, better monitoring of disease progression, and development of new treatment strategies for Alzheimer's disease.
Detailed description
1. Synopsis / Summary
Design: Comparative imaging study.
Population: 60 participants:
Group A: 20 patients with suspected Alzheimer's disease (AD) without type 2 diabetes (T2D)
Group B: 20 patients with suspected AD + T2D
Group C: 20 healthy age-matched controls
Procedures:
Dynamic \[11C\]PiB positron emission tomography (PET) after acetazolamide: early phase as perfusion/vascular function marker; late phase as β-amyloid load.
Dynamic \[18F\]FDG PET with heart scans and prebolus method: glucose transport and cerebral metabolic rate of glucose (CMRglc).
Magnetic resonance imaging (MRI) (if not available within 5 years and clinically acceptable): assessment of white matter lesions (Fazekas score) and vascular markers.
Neuropsychological testing (if not already available clinically).
Primary endpoint: Volume and overlap of abnormal regions across imaging biomarkers (with diabetes status considered).
Secondary endpoints: Correlation between cognitive index score and biomarker volumes.
Timeline: First subject first visit Sep 2025; last subject last visit Dec 2026; end of trial Sep 2027. 2. Background and Rationale
Dementia prevalence is rising; Alzheimer's disease and vascular dementia account for the majority of cases, often co-existing ("mixed dementia"). AD is characterized by early β-amyloid deposition and later neurodegeneration, with hypometabolism and perfusion abnormalities in characteristic parietotemporal regions. T2D is associated with cognitive impairment and increased dementia risk, potentially via impaired insulin signaling and altered brain glucose handling.
A key methodological barrier has been robust, clinically feasible quantification of glucose transport across the blood-brain barrier (BBB). Prior work suggests blood-brain glucose transport is sensitive to AD-related changes and may respond to metabolic interventions. Conventional glucose transport estimation requires arterial cannulation and high temporal resolution. We have developed a non-invasive approach using an image-derived input function with heart scanning and a prebolus strategy (method manuscript in preparation), enabling estimation of CMRglc and glucose transport in the same FDG session.
For vascular reserve, acetazolamide challenge probes endothelial-mediated vasodilation. We will use early-phase \[11C\]PiB as a perfusion proxy (validated against FDG/perfusion measures in prior studies).
Overall aim: Map and compare regional extent and overlap of quantitative imaging biomarkers in suspected AD with and without T2D versus healthy controls. 3. Hypotheses
Patients with suspected AD are amyloid-positive on \[11C\]PiB PET.
Aside from amyloid load, biomarkers show broadly similar regional patterns within subjects, but differ in affected volume.
Glucose transport impairment affects a larger cortical volume than glucose metabolism impairment (CMRglc).
Perfusion during vasodilation shows larger affected volume than glucose metabolism.
White matter lesion burden co-localizes with affected regions and differs by diabetes status. 4. Objectives and Endpoints 4.1 Primary objective
Map neurodegenerative PET biomarkers and vascular MRI markers in suspected AD and compare the volume and overlap of regional involvement across biomarkers (accounting for T2D).
4.2 Secondary objectives
Relate imaging biomarker volumes to cognitive performance.
4.3 Primary endpoint
Volume and overlap of:
Reduced glucose transport from FDG PET
Reduced CMRglc from FDG PET
Increased amyloid load from late \[11C\]PiB PET (standard uptake value ratio, (SUVR) \> 1.5, cortex vs cerebellum)
Reduced perfusion during vasodilation from early \[11C\]PiB PET
White matter lesions (none / some / confluent; incl. Fazekas scoring)
4.4 Secondary endpoints
Association between cognitive index score and volumes of the above abnormalities.
4.5 Exploratory endpoints
Associations between imaging volumes and metabolic/clinical measures (body mass index (BMI), waist, fasting glucose/insulin measures, etc.). 5. Methods 5.1 Design
Comparative cross-sectional imaging study with prespecified group comparisons (A vs B vs C).
5.2 Schedule
Procedures are conducted over 2-3 study visits. 6. Trial Population 6.1 Recruitment
Interventions
- Diagnostic test [18F]FDG PET
Regional glucose metabolism as well as glucose transport will be assessed. - Diagnostic test [11C]PIB
Early perfusion PET after acetazolamide infusion as well as late amyloid load will be assessed.
Primary outcome measures
- Glucose transport [Time frame: at inclusion]
Secondary outcome measures (3)
- Glucose metabolism [Time frame: at inclusion]
- Amyloid load [Time frame: at inclusion]
- Stress perfusion [Time frame: at inclusion]
Eligibility criteria
Inclusion criteria
- suspected Alzheimer's disease
- type 2 diabetes (group A)
- able and willing to comply with study protocoil´´l
Exclusion criteria
- type 2 diabetes (group B and C)
- significant brain disease apart from dementia (group A and B)
- significant vascular or neurological disease (group C)
- active cancer treatment
- history of alcohol or drug abuse
- severe claustrophobia
- pregnancy or breastfeeding
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Observational model
- Case-control
Study locations
Denmark · 1 center
- Copenhagen University Hospital Herlev — Herlev
Publications
- Gejl M, Brock B, Egefjord L, Vang K, Rungby J, Gjedde A. Blood-Brain Glucose Transfer in Alzheimer's disease: Effect of GLP-1 Analog Treatment. Sci Rep. 2017 Dec 13;7(1):17490. doi: 10.1038/s41598-017-17718-y. PMID 29235507
- Bach MJ, Larsen ME, Kellberg AO, Henriksen AC, Fuglsang S, Rasmussen IL, Lonsdale MN, Lubberink M, Marner L. Non-invasive [15O]H2O PET measurements of cerebral perfusion and cerebrovascular reactivity using an additional heart scan. J Cereb Blood Flow Metab. 2025 Jun;45(6):1144-1152. doi: 10.1177/0271678X251313743. Epub 2025 Jan 20. PMID 39829334
Identifiers
NCT: NCT07482072 · H-25047865