Abeta amyloid and 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, Abeta 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.


CONCLUSIONS
LPA is associated with Abeta 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.
Rabinovici
Gil D
GD
Memory and Aging Center, University of California San Francisco, San Francisco, CA 94143, USA. grabinovici@memory.ucsf.edu
Jagust
William J
WJ
Furst
Ansgar J
AJ
Ogar
Jennifer M
JM
Racine
Caroline A
CA
Mormino
Elizabeth C
EC
O'Neil
James P
JP
Lal
Rayhan A
RA
Dronkers
Nina F
NF
Miller
Bruce L
BL
Gorno-Tempini
Maria Luisa
ML
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000704:Analysis of Variance; D000814:Aniline Compounds / Q000378:metabolism; D018888:Aphasia, Primary Progressive / Q000145:classification* / Q000000981:diagnostic imaging / Q000378:metabolism*; D002247:Carbon Isotopes / Q000378:metabolism; D003704:Dementia / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007802:Language; D007807:Language Tests; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods; D013844:Thiazoles / Q000378:metabolism
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D002247:Carbon Isotopes; D013844:Thiazoles; D019788:Fluorodeoxyglucose F18; D005947:Glucose