title: Two-year follow-up of amyloid deposition in patients with Alzheimer's disease.
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.
authors.affiliation: Uppsala Imanet AB, Imanet, GE Healthcare Uppsala University, Uppsala.
authors.forename: Henry
authors.initials: H
authors.lastname: Engler
authors.forename: Anton
authors.initials: A
authors.lastname: Forsberg
authors.forename: Ove
authors.initials: O
authors.lastname: Almkvist
authors.forename: Gunnar
authors.initials: G
authors.lastname: Blomquist
authors.forename: Emma
authors.initials: E
authors.lastname: Larsson
authors.forename: Irina
authors.initials: I
authors.lastname: Savitcheva
authors.forename: Anders
authors.initials: A
authors.lastname: Wall
authors.forename: Anna
authors.initials: A
authors.lastname: Ringheim
authors.forename: Bengt
authors.initials: B
authors.lastname: Långström
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D003072:Cognition Disorders / Q000209:etiology; D018450:Disease Progression; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography / Q000379:methods; D011569:Psychiatric Status Rating Scales; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013844:Thiazoles / Q000493:pharmacokinetics
chemical_list: C507573:(N-methyl-C-11)-2-(4-methylamino-phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D019275:Radiopharmaceuticals; D013844:Thiazoles; D019788:Fluorodeoxyglucose F18