Amyloid, hypometabolism, and cognition in Alzheimer disease: an [11C]PIB and [18F]FDG PET study
Edison P, Archer HA, Hinz R, Hammers A, Pavese N, Tai YF, et al.;
Commented by , 30 Mar 2007
Aim of the study
Investigate the association between brain amyloid load in AD measured by [11C]PIB-PET, regional cerebral glucose metabolism (rCMRGlc) measured by [18F]FDG-PET, and cognition.
Method
Nineteen subjects age 55 to 79 with clinically probable AD and 14 controls had [11C]PIB-PET, 12 of the subjects with AD and 8 controls also had [18F]FDG-PET, all had a battery of psychometric tests. Parametric images of [11C]PIB binding and rCMRGlc were interrogated with a region-of-interest atlas and statistical parametric mapping, then [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 in comparison to the control group (p < 0.001). Higher cortical amyloid load correlated with lower scores on facial and word recognition tests. 2/19 subjects with clinically probable AD had normal [11C]PIB at baseline, then at 20 months one remained normal and one had increased amyloid binding in the cingulate only.
Mean levels of temporal and parietal rCMRGlc were reduced by 20% in subjects with AD compared to control subjects (p < 0.0005 and 0.0002 respectively), and these correlated with Mini Mental State Examination scores, immediate recall, recognition memory tests for words. 2/12 subjects with AD had normal rCMRGlc. Higher [11C]PIB uptake correlated with lower rCMRGlc in temporal (p = 0.047, r = -0.583) and parietal (p = 0.041, r = -0.595) but not in the frontal cortical regions.
Professor Gauthier's comments
The authors conclude that the increased [11C]PIB uptake in 17/19 subjects with AD may constitute a sensitive diagnostic marker for AD. The high frontal uptake has been noted in previous study and although not correlating with the reduction in cMRGlc, it is in keeping with the know pathological distribution of beta amyloid in AD.
The relatively low uptake of [11C]PIB in areas know to be involved early in AD such as the hippocampus and amygdala raises the question as to whether amyloid deposition is necessarily associated with neuronal dysfunction, as reflected by the reduced glucose metabolism in these areas and impaired performance on tests of recall.
The broader issue of whether amyloid deposition plays a pivotal role on the pathophysiology of AD relative to neurofibrillary tangles formation and cerebrovascular pathology is still an open question.
The PET tracer [11C]PIB (also known as "Pittsburgh compound B") has been used as an amyloid imaging agent for AD since the first publication by Klunk et al. (ref. 1). PET using FDDNP, another amyloid marker of interest, has been reported by Small et al. (ref. 2).
Editorials for the current article Bateman & Eidelberg (ref. 3) and for the article by Small et al. (ref. 4) and van Berckel & Scheltens (ref. 5) caution against premature use of amyloid PET for preclinical or very early clinical diagnosis, but highlight the potential benefit in longitudinal natural history study of AD and potential response to amyloid-lowering treatments.
References
1. Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, et al. Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Annals of Neurology 2004; 55 (3); 306-319
2. Small GW, Kepe V, Ercoli LM, Siddarth P, Bookheimer SY, Miller KJ, et al. PET of brain amyloid and tau in mild cognitive impairment. New England Journal of Medicine 2006; 355 (25); 2652-2663
3. Bateman RJ, Eidelberg D. Testing a test for Alzheimer disease. Neurology 2007; 68 (7); 482-483
4. Small GW, Kepe V, Ercoli LM, Siddarth P, Bookheimer SY, et al. PET of brain amyloid and tau in mild cognitive impairment. New England Journal of Medicine 2006; 355 (25); 2652-2663
5. van Berckel BN, Scheltens P. Getting a grip on Alzheimer's disease: imaging amyloid in the brain. Lancet Neurology 2007; 6 (3); 204-206