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Published online before print October 25, 2006, doi:10.1212/01.wnl.0000244749.20056.d4)
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Volume 68, Number 7, February 13, 2007
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Received March 6, 2006
Accepted August 7, 2006

Amyloid, hypometabolism, and cognition in Alzheimer disease. An [11C]PIB and [18F]FDG PET study

P. Edison MRCP, H. A. Archer MRCP, R. Hinz PhD, A. Hammers PhD, N. Pavese MD, Y. F. Tai MRCP, G. Hotton MRCP, D. Cutler BSc, N. Fox PhD, A. Kennedy MD, M. Rossor MD, DSc, and D. J. Brooks MD, DSc*

From MRC Clinical Sciences Centre and Division of Neuroscience (P.E., A.H., N.P., Y.F.T., G.H., A.K., M.R., D.J.B.), Hammersmith Hospital, Imperial College London; Dementia Research Centre (H.A.A., D.C., N.F., M.R.), UCL, Institute of Neurology; and Hammersmith Imanet (R.H., D.J.B.), GE Healthcare, UK.


* To whom correspondence should be addressed. E-mail: david.brooks{at}csc.mrc.ac.uk.

Abstract-- Objective: To investigate the association between brain amyloid load in Alzheimer disease (AD) measured by [11C]PIB-PET, regional cerebral glucose metabolism (rCMRGlc) measured by [18F]FDG-PET, and cognition. Methods: Nineteen subjects with AD and 14 controls had [11C]PIB-PET and underwent a battery of psychometric tests. Twelve of those subjects with AD and eight controls had [18F]FDG-PET. Parametric images of [11C]PIB binding and rCMRGlc were interrogated with a region-of-interest atlas and statistical parametric mapping. [11C]PIB binding and rCMRGlc were correlated with scores on psychometric tests. Results: AD subjects showed twofold increases in mean [11C]PIB binding in cingulate, frontal, temporal, parietal, and occipital cortical areas. Higher cortical amyloid load correlated with lower scores on facial and word recognition tests. Two patients fulfilling the clinical criteria for AD had normal [11C]PIB at baseline. Over 20 months this remained normal in one but increased in the cingulate of the other. Mean levels of temporal and parietal rCMRGlc were reduced by 20% in AD and these correlated with mini mental scores, immediate recall, and recognition memory test for words. Higher [11C]PIB uptake correlated with lower rCMRGlc in temporal and parietal cortices. Conclusion: [11C]PIB-PET detected an increased amyloid plaque load in 89% of patients with clinically probable Alzheimer disease (AD). The high frontal amyloid load detected by [11C]PIB-PET in AD in the face of spared glucose metabolism is of interest and suggests that amyloid plaque formation may not be directly responsible for neuronal dysfunction in this disorder.




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