Brain Advance Access published online on July 19, 2006
Brain, doi:10.1093/brain/awl178
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1 Uppsala Imanet AB, Imanet, GE Healthcare, Uppsala University, Uppsala, Sweden
* To whom correspondence should be addressed. 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.
Received March 18, 2006
Revised May 26, 2006
Accepted June 7, 2006
Article
Two-year follow-up of amyloid deposition in patients with Alzheimer's disease
Henry Engler 1, Anton Forsberg 2, Ove Almkvist 3, Gunnar Blomquist 4, Emma Larsson 2, Irina Savitcheva 5, Anders Wall 1, Anna Ringheim 1, Bengt Långström 6, and Agneta Nordberg 7 *
2 Division of Molecular Neuropharmacology, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
3 Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Psychology, Stockholm University, Stockholm, Sweden
4 Uppsala Imanet AB, Imanet, GE Healthcare, Uppsala University, Uppsala, Sweden; Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden
5 Uppsala University Hospital, Uppsala University, Uppsala, Sweden
6 Uppsala Imanet AB, Imanet, GE Healthcare, Uppsala University, Uppsala, Sweden; Department of Biochemistry and Organic Chemistry, Uppsala University, Uppsala, Sweden
7 Division of Molecular Neuropharmacology, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm
Agneta Nordberg, E-mail: Agneta.K.Nordberg{at}ki.se
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