Longitudinal anatomic, functional, and molecular characterization of Pick disease phenotypes

Area of Science:

• Neurodegenerative diseases
• Neuroimaging
• Neuropathology

Background:

• Pick disease (PiD) is a form of frontotemporal dementia characterized by tau pathology.
• Understanding the in vivo neurodegenerative patterns associated with different clinical syndromes in PiD is crucial for diagnosis and management.

Purpose of the Study:

• To characterize longitudinal MRI and PET abnormalities in autopsy-confirmed Pick disease.
• To determine how neurodegeneration patterns in PiD differ based on clinical presentation.

Main Methods:

• Seventeen patients with autopsy-confirmed PiD underwent antemortem MRI and PET scans.
• Serial MRI, [18F]fluorodeoxyglucose PET, Pittsburgh compound B (PiB) PET, and [18F]flortaucipir PET were utilized.
• Cross-sectional and longitudinal analyses compared gray matter volume and metabolism between behavioral variant FTD-PiD, naPPA-PiD, and controls.

Main Results:

• Early disease stages showed distinct atrophy and hypometabolism foci: bvFTD-PiD involved prefrontal and anterior temporal cortices, while naPPA-PiD affected the left inferior frontal gyrus, insula, and orbitofrontal cortex.
• Over time, neurodegeneration patterns converged, with widespread involvement of prefrontal, temporal, motor, and parietal lobes in both groups.
• Frontotemporal atrophy progressed faster in bvFTD-PiD than naPPA-PiD. One patient was amyloid-positive but had minimal Alzheimer pathology at autopsy.

Conclusions:

• Neuroimaging reveals distinct patterns of atrophy and hypometabolism in PiD that vary with the initial clinical syndrome.
• These neurodegenerative patterns tend to converge over the course of the disease.