MRI derived brain atrophy in PSP and MSA-P. Determining sample size to detect treatment effects

Area of Science:

• Neuroimaging
• Neurology
• Clinical Trials

Background:

• Progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) are characterized by progressive brain atrophy.
• Serial MRI is a valuable tool for quantifying brain volume changes and atrophy rates.

Purpose of the Study:

• To evaluate MRI-derived whole brain and regional atrophy rates as progression markers in PSP and the Parkinsonian variant of MSA (MSA-P).
• To estimate sample sizes for clinical trials investigating disease-modifying treatments for PSP and MSA-P.

Main Methods:

• 17 PSP patients, 9 MSA-P patients, and 18 healthy controls underwent two MRI brain scans.
• Brain and regional atrophy rates (midbrain, pons, cerebellum, ventricles) were measured using registered MRI scans.
• The impact of scan interval on atrophy rate variance and sample size was analyzed.

Main Results:

• Regional atrophy rates, specifically in the midbrain for PSP and pons/cerebellum for MSA-P, require fewer subjects for detecting treatment effects compared to whole brain atrophy rates.
• A longer scan interval reduced the variance of measured atrophy rates, enhancing statistical power.
• Regional atrophy metrics offer a more practical and powerful approach for monitoring disease progression in clinical trials.

Conclusions:

• Volumetric serial MRI, particularly using regional atrophy rates, is a more efficient method for monitoring disease progression in PSP and MSA-P.
• This approach can optimize the design and reduce the sample size requirements for clinical trials targeting these neurodegenerative diseases.