PhD-student
Forough Sodaei
University of Southern Denmark, The Faculty of Health Sciences, Department of Clinical Research, KI, OUH, Research unit of Psychiatry
| Project management | ||
| Project status | Open | |
| Data collection dates | ||
| Start | 01.06.2025 | |
| End | 01.06.2028 | |
Cerebral blood flow, glucose metabolism, amyloid plaque and neurofibrillary tangles formation in mild cognitive impairment and Alzheimer's patients
Short summary
We aim to assess cerebral blood flow, glucose metabolism, and amyloid plaques in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI), compared to age-matched healthy controls. Using hybrid PET/MRI and blood sampling, we will test the hypothesis that AD and MCI exhibit reduced perfusion and metabolism, with higher amyloid levels-more pronounced in AD-to better understand aging pathology and identify sensitive biomarkers.
Rationale
Aging is a gradual process marked by physiological and behavioral changes, especially in the brain. These include reduced neurogenesis, mitochondrial dysfunction, oxidative stress, and declining cognitive function. Key contributors to brain aging and age-related disorders like mild cognitive impairment (MCI) and Alzheimer's disease (AD) are decreased neurotransmitter levels and increased beta-amyloid (Aβ) deposition. The brain, though only 2% of body mass, consumes 20-25% of body glucose. Glucose metabolism, particularly aerobic glycolysis, declines with age and is associated with mitochondrial dysfunction and oxidative stress. While cerebral blood flow (CBF) may remain stable in normal aging, cerebral metabolic rates of oxygen (CMRO₂) and glucose (CMRglc) both decline. Imaging of Aβ and Tau protein using PET tracers like [¹¹C]PiB and ¹⁸F-MK-6240 shows promise for early AD diagnosis, though challenges remain, including amyloid buildup in cognitively normal individuals. PET and PET/MRI imaging have become essential in diagnosing neurodegenerative disorders, offering insight into brain metabolism, blood flow, and pathology. This project aims to use PET, MRI, fMRI, and MRS-alongside blood sampling-to measure and correlate cerebral glucose metabolism, blood flow, and amyloid plaque formation in MCI and AD patients. These findings will be compared to data from age-matched healthy subjects collected in a previous study phase. Additionally, the project will apply deep learning techniques to help develop early predictors of neurodegenerative diseases.
Description of the cohort
We will perform a cross sectional study.30 mild AD and 30 MCI patients will be recruited from the dementia clinic of OUH/Svendborg hospitals. AD patients will be naïve to AD treatments. All subjects (or Guardian/Legal Representative) will be issued an information sheet and required to provide written informed consent before participating in this study. The mild AD and MCI subjects will be psychologically evaluated by a clinician/geriatrician. They will be able to personally give consent once they are declared fit to do so by the clinician. We will explain the procedure to them and their next of kin, if requested, and mention the purpose of our research and why it is important to do this kind of research. We will then obtain the consent from the next of kin.
Data and biological material
For each participant: -Biochemical category: 50 ml blood sample -Imaging category: FDG PET datasets, Amyloid PET datasets, MRI datasets including DTI, fMRI, structural MRI, MRS, etc. -Assessment category: clinical datasets including neuropsychological assessments