Imaging beta-amyloid burden in aging and dementia.
OBJECTIVE
To compare brain beta-amyloid (Abeta) burden measured with [(11)C]Pittsburgh Compound B (PIB) PET in normal aging, Alzheimer disease (AD), and other dementias.


METHODS
Thirty-three subjects with dementia (17 AD, 10 dementia with Lewy bodies [DLB], 6 frontotemporal dementia [FTD]), 9 subjects with mild cognitive impairment (MCI), and 27 age-matched healthy control subjects (HCs) were studied. Abeta burden was quantified using PIB distribution volume ratio.


RESULTS
Cortical PIB binding was markedly elevated in every AD subject regardless of disease severity, generally lower and more variable in DLB, and absent in FTD, whereas subjects with MCI presented either an "AD-like" (60%) or normal pattern. Binding was greatest in the precuneus/posterior cingulate, frontal cortex, and caudate nuclei, followed by lateral temporal and parietal cortex. Six HCs (22%) showed cortical uptake despite normal neuropsychological scores. PIB binding did not correlate with dementia severity in AD or DLB but was higher in subjects with an APOE-epsilon4 allele. In DLB, binding correlated inversely with the interval from onset of cognitive impairment to diagnosis.


CONCLUSIONS
Pittsburgh Compound B PET findings match histopathologic reports of beta-amyloid (Abeta) distribution in aging and dementia. Noninvasive longitudinal studies to better understand the role of amyloid deposition in the course of neurodegeneration and to determine if Abeta deposition in nondemented subjects is preclinical AD are now feasible. Our findings also suggest that Abeta may influence the development of dementia with Lewy bodies, and therefore strategies to reduce Abeta may benefit this condition.
Rowe
C C
CC
Department of Nuclear Medicine, Centre for PET, Austin Health, Heidelberg, Victoria, Australia. christopher.rowe@austin.org.au
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S
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Ackermann
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Gong
S J
SJ
Pike
K
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Savage
G
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Cowie
T F
TF
Dickinson
K L
KL
Maruff
P
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Darby
D
D
Smith
C
C
Woodward
M
M
Merory
J
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Tochon-Danguy
H
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O'Keefe
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Klunk
W E
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Mathis
C A
CA
Price
J C
JC
Masters
C L
CL
Villemagne
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D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis*; D000814:Aniline Compounds; D001057:Apolipoproteins E / Q000235:genetics; D001923:Brain Chemistry; D002250:Carbon Radioisotopes; D003072:Cognition Disorders / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D003704:Dementia / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006179:Gyrus Cinguli / Q000737:chemistry / Q000000981:diagnostic imaging; D006801:Humans; D020961:Lewy Body Disease / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000737:chemistry / Q000000981:diagnostic imaging; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D013844:Thiazoles
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D001057:Apolipoproteins E; D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D013844:Thiazoles