Brain Iron Toxicity and Neurodegeneration - A 7T MRI Study

Recruiting

• Conditions: Prodromal Alzheimer's Disease; Mild Cognitive Impairment
• Interventions: Other: MRI at 7T

• Registration Number: NCT04992975
• Lead Sponsor: Nottingham University Hospitals NHS Trust

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2021-07-21
• Study First Submitted QC: 2021-07-28
• Study First Posted: 2021-08-06
• Study Start: 2021-09-10
• Status Verified: 2024-02
• Last Update Submitted: 2024-03-20
• Last Update Posted: 2024-03-21
• Primary Completion: 2025-03
• Study Completion: 2025-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Alzheimer's disease	MRI at 7T	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.
Control group	MRI at 7T	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.

Primary Outcome Measures

Name	Time	Method
Quantitative Susceptibility Mapping, QSM (from 7T MRI data) to hippocampal subfield volume loss at 1 year	one 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)

Secondary Outcome Measures

Name	Time	Method
neuropsychological measures in relation to QSM and volume loss in hippocampal subfields	one year	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.
cross-sectional and longitudinal changes in QSM in the hippocampal subfields	one year	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

Trial Locations

Locations (1)

Nottingham University Hospitals NHS Trust; 🇬🇧 Nottingham, East Midland, United Kingdom