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Engler, H. et al. Two-year follow-up of amyloid deposition in patients with Alzheimer's disease. Brain 129, 2856-2866

Department of Psychology, Stockholm University, Tukholma, Stockholm, Sweden
Brain (Impact Factor: 10.23). 11/2006; 129(Pt 11):2856-66. DOI: 10.1093/brain/awl178
Source: PubMed

ABSTRACT Beta amyloid is one of the major histopathological hallmarks of Alzheimer's disease. We recently reported in vivo imaging of amyloid in 16 Alzheimer patients, using the PET ligand N-methyl[11C]2-(4'-methylaminophenyl)-6-hydroxy-benzothiazole (PIB). In the present study we rescanned these 16 Alzheimer patients after 2.0 +/- 0.5 years and have described the interval change in amyloid deposition and regional cerebral metabolic rate for glucose (rCMRGlc) at follow-up. Sixteen patients with Alzheimer's disease were re-examined by means of PET, using PIB and 2-[18F]fluoro-2-deoxy-d-glucose (FDG) after 2.0 +/- 0.5 years. The patients were all on cholinesterase inhibitor treatment and five also on treatment with the N-methyl-d-aspartate (NMDA) antagonist memantine. In order to estimate the accuracy of the PET PIB measurements, four additional Alzheimer patients underwent repeated examinations with PIB within 20 days (test-retest). Relative PIB retention in cortical regions differed by 3-7% in the test-retest study. No significant difference in PIB retention was observed between baseline and follow-up while a significant (P < 0.01) 20% decrease in rCMRGlc was observed in cortical brain regions. A significant negative correlation between rCMRGlc and PIB retention was observed in the parietal cortex in the Alzheimer patients at follow-up (r = 0.67, P = 0.009). A non-significant decline in Mini-Mental State Examination (MMSE) score from 24.3 +/- 3.7 (mean +/- standard deviation) to 22.7 +/- 6.1 was measured at follow-up. Five of the Alzheimer patients showed a significant decline in MMSE score of >3 (21.4 +/- 3.5 to 15.6 +/- 3.9, P < 0.01) (AD-progressive) while the rest of the patients were cognitively more stable (MMSE score = 25.6 +/- 3.1 to 25.9 +/- 3.7) (AD-stable) compared with baseline. A positive correlation (P = 0.001) was observed in the parietal cortex between Rey Auditory Verbal Learning (RAVL) test score and rCMRGlc at follow-up while a negative correlation (P = 0.018) was observed between RAVL test and PIB retention in the parietal at follow-up. Relatively stable PIB retention after 2 years of follow-up in patients with mild Alzheimer's disease suggests that amyloid deposition in the brain reaches a plateau by the early clinical stages of Alzheimer's disease and therefore may precede a decline in rCMRGlc and cognition. It appears that anti-amyloid therapies will need to induce a significant decrease in amyloid load in order for PIB PET images to detect a drug effect in Alzheimer patients. FDG imaging may be able to detect a stabilization of cerebral metabolism caused by therapy administered to patients with a clinical diagnosis of Alzheimer's disease.

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    • "-FDG to become a superior measure of disease severity [5] [14] [15]. Thus the combined use of both amyloid and [ 18 F]-FDG PET can aid early diagnosis, disease staging and possibly therapeutic evaluation. "
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    Current Alzheimer research 07/2015; 12(7). DOI:10.2174/1567205012666150710104713 · 3.80 Impact Factor
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    • "In the context of current models of the AD pathophysiologic cascade ( Jack et al., 2013 ), these findings suggest that A β may exert both local and remote effects on brain metabolism, the latter potentially due to deafferentation of remote areas ( Bourgeat et al., 2010 ). Traditional univariate approaches have similarly demonstrated both local and remote correlations between PiB and FDG ( Cohen et al., 2009 ; Edison et al., 2007 ; Engler et al., 2006 ). Our results are further congruent with a recent report in mild cognitive impairment, which showed via pICA that increased amyloid-β burden in the left precuneus / cuneus and medial-temporal regions was associated with increased brain atrophy rates in the left medial-temporal and parietal regions, while increased amyloid-β burden in bilateral precuneus / cuneus and parietal regions was associated with increased brain atrophy rates in the right medial temporal regions ( Tosun et al., 2011 ). "
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    Clinical neuroimaging 03/2014; 4. DOI:10.1016/j.nicl.2014.03.005 · 2.53 Impact Factor
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    • "Patients with subtle cognitive deficits, who will later develop AD, can be identified with [ 11 C]PIB-PET [5]. However, in longitudinal studies, clinically deteriorating AD patients demonstrated a largely unchanged [ 11 C]PIB-PET-signal [7] [8]. Thus the ability to monitor disease progression or assess therapeutic efficacy with [ 11 C]PIB-PET-imaging seems rather limited. "
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