Alzheimer's Imaging Consortium

Area of Science:

• Neuroimaging
• Alzheimer's Disease Research
• Biomarker Discovery

Background:

• Diffusion MRI (dMRI) measures of cortical microstructure correlate with amyloid pathology, neuroinflammation, and predict future brain atrophy.
• Previous work demonstrated the practicality of dMRI in a clinical setting using 1.5T MRI.
• Anti-amyloid treatments like Lecanemab reduce clinical decline but accelerate brain volume loss, a phenomenon not fully understood.

Purpose of the Study:

• To explore the utility of dMRI measures for early diagnosis in Alzheimer's Disease (AD).
• To track treatment response in patients undergoing anti-amyloid therapy.
• To investigate the microstructural basis of volumetric changes, including pseudo-atrophy, during treatment.

Main Methods:

• Recruited patients meeting Lecanemab criteria, confirming amyloid positivity via PET or CSF.
• Acquired T1-weighted anatomical MRI and dMRI (32 directions, b=1000 s/mm²) on a 1.5T scanner.
• Processed MRI data using FreeSurfer, FSL, and proprietary software to derive microstructural measures (AngleR, ParlPD, PerpPD+).

Main Results:

• Enrolled 17 AD patients, analyzing 59 scans across baseline and 2, 3, and 6-month follow-ups.
• Found baseline associations between cognitive scores (MMSE), cortical disarray (AngleR), and p-tau levels.
• Observed regional associations between changes in microstructural measures (PerpPD+) and overall clinical improvement scores.

Conclusions:

• Initiated a real-world observational study to investigate microstructural changes during anti-amyloid treatment.
• Established microstructural imaging measures as sensitive treatment biomarkers that correlate with clinical changes.
• Future research with larger datasets will explore predicting clinical change using baseline cortical disarray.