Longitudinal anatomic, functional, and molecular characterization of Pick disease phenotypes
Jennifer L. Whitwell, Nirubol Tosakulwong, Christopher C. Schwarz, Matthew L. Senjem, Anthony J. Spychalla, Joseph R. Duffy, Jon Graff-Radford, Mary M. Machulda, Bradley F. Boeve, David S. Knopman, Ronald C. Petersen, Val J. Lowe, Clifford R. Jack, Dennis W. Dickson, Joseph E. Parisi, Keith A. Josephs
Abstract
<h3>Objective</h3> To characterize longitudinal MRI and PET abnormalities in autopsy-confirmed Pick disease (PiD) and determine how patterns of neurodegeneration differ with respect to clinical syndrome. <h3>Methods</h3> Seventeen patients with PiD were identified who had antemortem MRI (8 with behavioral variant frontotemporal dementia [bvFTD-PiD], 6 with nonfluent/agrammatic primary progressive aphasia [naPPA-PiD], 1 with semantic primary progressive aphasia, 1 with unclassified primary progressive aphasia, and 1 with corticobasal syndrome). Thirteen patients had serial MRI for a total of 56 MRIs, 7 had [<sup>18</sup>F]fluorodeoxyglucose PET, 4 had Pittsburgh compound B (PiB) PET, and 1 patient had [<sup>18</sup>F]flortaucipir PET. Cross-sectional and longitudinal comparisons of gray matter volume and metabolism were performed between bvFTD-PiD, naPPA-PiD, and controls. Cortical PiB summaries were calculated to determine β-amyloid positivity. <h3>Results</h3> The bvFTD-PiD and naPPA-PiD groups showed different foci of volume loss and hypometabolism early in the disease, with bvFTD-PiD involving bilateral prefrontal and anterior temporal cortices and naPPA-PiD involving left inferior frontal gyrus, insula, and orbitofrontal cortex. However, patterns merged over time, with progressive spread into prefrontal and anterior temporal lobe in naPPA-PiD, and eventual involvement of posterior temporal lobe, motor cortex, and parietal lobe in both groups. Rates of frontotemporal atrophy were faster in bvFTD-PiD than naPPA-PiD. One patient was β-amyloid–positive on PET with low Alzheimer neuropathologic changes at autopsy. Flortaucipir PET showed elevated uptake in frontotemporal white matter. <h3>Conclusion</h3> Patterns of atrophy and hypometabolism differ in PiD according to presenting syndrome, although patterns of neurodegeneration appear to converge over time.