Brain Iron Toxicity and Neurodegeneration - A 7T MRI Study

Study Overview
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Brief Summary
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A longitudinal observational neuroimaging study of individuals with Early Onset Alzheimer's disease during the prodromal phase, and matched control group - Ultrahigh Field MRI study at 7T

Detailed Description
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This study aims to determine whether high resolution MRI at 7T and Quantitative Susceptibility Mapping (QSM) can demonstrate a specific pattern of iron overload in strategically important areas of brain as a sensitive marker of pathological Alzheimer's disease i.e. patients with subjective or mild cognitive impairment associated with Amyloid or tau pathological state in the cerebrospinal fluid.

Official Title
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Brain Iron Toxicity and Neurodegeneration - An Ultrahigh Field (7T) MRI Study

Conditions
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Prodromal Alzheimer's Disease, Mild Cognitive Impairment

Intervention / Treatment
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* Other: MRI at 7T


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to provide informed consent Patients with pathological diagnosis of Alzheimer's disease according to the National Institute on Aging and Alzheimer's Association, NIA-AA, criteria (Alzheimer's group) or cognitively normal individuals within 1.5 standard deviation of normal in all tests (control group) Exclusion Criteria: Lack of mental capacity to consent to study involvement Not speaking English before age 5 years Learning disability Schizophrenia Substance misuse Implanted devices not certified as compatible with ultra-high field MRI (e.g. cardiac pacemaker) Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 |
| --- | --- |
| Alzheimer's disease<br>Patients with Early Onset Alzheimer's disease (with known cerebrospinal fluid Amyloid/tau status) during prodromal or mild phase will have MRI of the brain at 7T, neurocognitive assessments, and blood test to check APOe status. Repeat neuroimaging and neurocognitive tests after one year. | Other: MRI at 7T<br>* MRI at 7T<br>|
| Control group<br>Age and gender matched individuals with normal cognition will have MRI of the brain at 7T, neurocognitive assessments and blood test to check APOe status. Repeat neuroimaging, neurocognitive tests after one year. | Other: MRI at 7T<br>* MRI at 7T<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantitative Susceptibility Mapping, QSM (from 7T MRI data) to hippocampal subfield volume loss at 1 year | Relationship between QSM at recruitment and to hippocampal subfield volume (QSM and hippocampal subfield volume are obtained from 7T MRI Susceptibility Weighted and T1 Weighted images) | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cross-sectional and longitudinal changes in QSM in the hippocampal subfields | cross-sectional and longitudinal changes in QSM in the local hippocampal subfield QSM and volume loss after 1 year. QSM and hippocampal subfields volume will be obtained from 7T MRI data | one year | 
| neuropsychological measures in relation to QSM and volume loss in hippocampal subfields | neuropsychological measures at 0 and 12 months in relation to QSM and volume loss in hippocampal subfields (adjusted for APOe). QSM and hippocampal subfield volume loss are obtained from 7T MRI Susceptibility Weighted and T1 Weighted images. | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ultrahigh Field MRI, 7T MRI, QSM