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. INTERPRETATION: 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.
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 ADpatients (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 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.
Authors: D Neary; J S Snowden; L Gustafson; U Passant; D Stuss; S Black; M Freedman; A Kertesz; P H Robert; M Albert; K Boone; B L Miller; J Cummings; D F Benson Journal: Neurology Date: 1998-12 Impact factor: 9.910
Authors: G J Klein; X Teng; W J Jagust; J L Eberling; A Acharya; B W Reutter; R H Huesman Journal: IEEE Trans Med Imaging Date: 1997-08 Impact factor: 10.048
Authors: Randy L Buckner; Abraham Z Snyder; Benjamin J Shannon; Gina LaRossa; Rimmon Sachs; Anthony F Fotenos; Yvette I Sheline; William E Klunk; Chester A Mathis; John C Morris; Mark A Mintun Journal: J Neurosci Date: 2005-08-24 Impact factor: 6.167
Authors: Michelle T Fodero-Tavoletti; David P Smith; Catriona A McLean; Paul A Adlard; Kevin J Barnham; Lisa E Foster; Laura Leone; Keyla Perez; Mikhalina Cortés; Janetta G Culvenor; Qiao-Xin Li; Katrina M Laughton; Christopher C Rowe; Colin L Masters; Roberto Cappai; Victor L Villemagne Journal: J Neurosci Date: 2007-09-26 Impact factor: 6.167
Authors: Guy M McKhann; David S Knopman; Howard Chertkow; Bradley T Hyman; Clifford R Jack; Claudia H Kawas; William E Klunk; Walter J Koroshetz; Jennifer J Manly; Richard Mayeux; Richard C Mohs; John C Morris; Martin N Rossor; Philip Scheltens; Maria C Carrillo; Bill Thies; Sandra Weintraub; Creighton H Phelps Journal: Alzheimers Dement Date: 2011-04-21 Impact factor: 21.566
Authors: Clifford R Jack; Marilyn S Albert; David S Knopman; Guy M McKhann; Reisa A Sperling; Maria C Carrillo; Bill Thies; Creighton H Phelps Journal: Alzheimers Dement Date: 2011-04-21 Impact factor: 21.566
Authors: David A Wolk; Julie C Price; Charles Madeira; Judy A Saxton; Beth E Snitz; Oscar L Lopez; Chester A Mathis; William E Klunk; Steven T DeKosky Journal: Alzheimers Dement Date: 2012-01-30 Impact factor: 21.566