Aβ amyloid and glucose metabolism in three variants of primary progressive aphasia

Gil D. Rabinovici, William J. Jagust, Ansgar J. Furst, Jennifer M. Ogar, Caroline A. Racine, Elizabeth C. Mormino, James P. O'Neil, Rayhan A. Lal, Nina Dronkers, Bruce L. Miller, Maria Luisa Gorno-Tempini

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352 Scopus citations

Abstract

Objective: Alzheimer's disease (AD) is found at autopsy in up to one third of patients with primary progressive aphasia (PPA), but clinical features that predict AD pathology in PPA are not well defined. We studied the relationships between language presentation, Aβ amyloidosis, and glucose metabolism in three PPA variants using [11C]-Pittsburgh compound B ([ 11C]PIB) and [18F]-labeled fluorodeoxyglucose positron emission tomography ([18F]FDG-PET). Methods: Patients meeting PPA criteria (N = 15) were classified as logopenic aphasia (LPA), progressive nonfluent aphasia (PNFA), or semantic dementia (SD) based on language testing. [11C]PIB distribution volume ratios were calculated using Logan graphical analysis (cerebellar reference). [18F]FDG images were normalized to pons. Partial volume correction was applied. Results: Elevated cortical PIB (by visual inspection) was more common in LPA (4/4 patients) than in PNFA (1/6) and SD (1/5) ( p < 0.02). In PIB-positive PPA, PIB uptake was diffuse and indistinguishable from the pattern in matched AD patients (n = 10). FDG patterns were focal and varied by PPA subtype, with left temporoparietal hypometabolism in LPA, left frontal hypometabolism in PNFA, and left anterior temporal hypometabolism in SD. FDG uptake was significant asymmetric (favoring left hypometabolism) in PPA ( p < 0.005) but not in AD. Interpretation: LPA is associated with Aβ amyloidosis, suggesting that subclassification of PPA based on language features can help predict the likelihood of AD pathology. Language phenotype in PPA is closely related to metabolic changes that are focal and anatomically distinct between subtypes, but not to amyloid deposition patterns that are diffuse and similar to AD.

Original languageEnglish (US)
Pages (from-to)388-401
Number of pages14
JournalAnnals of Neurology
Volume64
Issue number4
DOIs
StatePublished - Oct 2008

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Rabinovici, G. D., Jagust, W. J., Furst, A. J., Ogar, J. M., Racine, C. A., Mormino, E. C., O'Neil, J. P., Lal, R. A., Dronkers, N., Miller, B. L., & Gorno-Tempini, M. L. (2008). Aβ amyloid and glucose metabolism in three variants of primary progressive aphasia. Annals of Neurology, 64(4), 388-401. https://doi.org/10.1002/ana.21451