Nonfluent/agrammatic PPA with in-vivo cortical amyloidosis and Pick's disease pathology

Issue title: Primary Progressive Aphasia and Post-Stroke Aphasia: Some Complementary Insights into Brain-Behavior Relationships/Hemispatial Neglect and Related Disorders

Article type: Research Article

Authors: Caso, Francesca^; | Gesierich, Benno | Henry, Maya | Sidhu, Manu | LaMarre, Amanda | Babiak, Miranda | Miller, Bruce L. | Rabinovici, Gil D. | Huang, Eric J. | Magnani, Giuseppe | Filippi, Massimo | Comi, Giancarlo | Seeley, William W. | Gorno-Tempini, Maria Luisa

Affiliations: Memory and Aging Center, University of California, San Francisco, CA, USA | Department of Neurology, Scientific Institute and University Hospital San Raffaele, Milan, Italy

Note: [] Correspondence to: Francesca Caso, Memory and Aging Center, Department of Neurology, University of California, San Francisco, 350 Parnassus Avenue, Suite 905, San Francisco, CA 94143-1207, USA. E-mail: FCaso@memory.ucsf.edu

Abstract: The role of biomarkers in predicting pathological findings in the frontotemporal dementia (FTD) clinical spectrum disorders is still being explored. We present comprehensive, prospective longitudinal data for a 66 year old, right-handed female who met current criteria for the nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA). She first presented with a 3-year history of progressive speech and language impairment mainly characterized by severe apraxia of speech. Neuropsychological and general motor functions remained relatively spared throughout the clinical course. Voxel-based morphometry (VBM) showed selective cortical atrophy of the left posterior inferior frontal gyrus (IFG) and underlying insula that worsened over time, extending along the left premotor strip. Five years after her first evaluation, she developed mild memory impairment and underwent PET-FDG and PiB scans that showed left frontal hypometabolism and cortical amyloidosis. Three years later (11 years from first symptom), post-mortem histopathological evaluation revealed Pick's disease, with severe degeneration of left IFG, mid-insula, and precentral gyrus. Alzheimer's disease (AD) (CERAD frequent/Braak Stage V) was also detected. This patient demonstrates that biomarkers indicating brain amyloidosis should not be considered conclusive evidence that AD pathology accounts for a typical FTD clinical/anatomical syndrome.

Keywords: Nonfluent primary progressive aphasia, PPA, apraxia of speech, Voxel-based morphometry, PiB-PET, Pick's disease, Alzheimer disease, Frontotemporal dementia

DOI: 10.3233/BEN-2012-120255

Journal: Behavioural Neurology, vol. 26, no. 1-2, pp. 95-106, 2013