Aβ Amyloid & Glucose Metabolism in Three Variants of Primary Progressive Aphasia

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 variants of PPA using [11C]PIB and [18F]FDG-PET. METHODS—Patients meeting PPA criteria (N=15) were classified as logopenic aphasia (LPA), progressive non-fluent 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 all PIB-positive cases, 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 patterns in PIBpositive PNFA and SD were similar to PIB-negative cases. Language regions showed asymmetric left hypometabolism in PPA (p<0.005) but not in AD. INTERPRETATION—LPA is associated with Aβ amyloidosis, suggesting that sub-classification of PPA based on language features can help predict the likelihood of underlying 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. Corresponding Author: Gil D. Rabinovici, MD, UCSF Memory & Aging Center, 350 Parnassus Ave., Suite 706, San Francisco, CA 94143, Tel.: (415) 514-9320, Fax: (415) 476-4800, Email: [email protected]. Disclosures: Dr. Jagust has received consulting fees from GE Healthcare, which holds a license agreement with the University of Pittsburgh based on the PIB compound described in this manuscript. The other authors do not report potential conflicts of interest. NIH Public Access Author Manuscript Ann Neurol. Author manuscript; available in PMC 2009 February 26. Published in final edited form as: Ann Neurol. 2008 October ; 64(4): 388–401. doi:10.1002/ana.21451. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript