A European multicentre PET study of fibrillar amyloid in Alzheimer’s disease

• DOI: 10.1007/s00259-012-2237-2
• Publication Date: 2012-09-07T05:14:23Z
• Authors: Agneta Nordberg; Stephen F. Carter; Juha Rinne; Alexander Drzezga; David J. Brooks; Rik Vandenberghe; Daniela Perani; Anton Forsberg; Bengt Långström; Noora Scheinin; Mira Karrasch; Kjell Någren; Timo Grimmer; Isabelle Miederer; Paul Edison; Aren Okello; Koen Van Laere; Natalie Nelissen; Mathieu Vandenbulcke; Valentina Garibotto; Ove Almkvist; Elke Kalbe; Rainer Hinz; Karl Herholz
• Keywords: Male; Amyloid; Amyloid/analysis; Alzheimer Disease/diagnostic imaging; ddc:616.0757; ta3112; info:eu-repo/classification/ddc/616.0757; 03 medical and health sciences; Cognition; Apolipoproteins E; 0302 clinical medicine; Alzheimer Disease; Humans; Aged; Apolipoproteins E/analysis; Brain Chemistry; Aniline Compounds; PIB; Mild cognitive impairment; Brain; Alzheimer's disease; Multicentre PET; Middle Aged; Brain/diagnostic imaging; MCI; 3. Good health; Europe; Thiazoles; Radiology Nuclear Medicine and imaging; Case-Control Studies; Positron-Emission Tomography; Original Article; Female; Radiopharmaceuticals

Amyloid PET tracers have been developed for in vivo detection of brain fibrillar amyloid deposition in Alzheimer's disease (AD). To serve as an early biomarker in AD the amyloid PET tracers need to be analysed in multicentre clinical studies.In this study 238 [(11)C]Pittsburgh compound-B (PIB) datasets from five different European centres were pooled. Of these 238 datasets, 18 were excluded, leaving [(11)C]PIB datasets from 97 patients with clinically diagnosed AD (mean age 69 ± 8 years), 72 patients with mild cognitive impairment (MCI; mean age 67.5 ± 8 years) and 51 healthy controls (mean age 67.4 ± 6 years) available for analysis. Of the MCI patients, 64 were longitudinally followed for 28 ± 15 months. Most participants (175 out of 220) were also tested for apolipoprotein E (ApoE) genotype.[(11)C]PIB retention in the neocortical and subcortical brain regions was significantly higher in AD patients than in age-matched controls. Intermediate [(11)C]PIB retention was observed in MCI patients, with a bimodal distribution (64 % MCI PIB-positive and 36 % MCI PIB-negative), which was significantly different the pattern in both the AD patients and controls. Higher [(11)C]PIB retention was observed in MCI ApoE ε4 carriers compared to non-ApoE ε4 carriers (p < 0.005). Of the MCI PIB-positive patients, 67 % had converted to AD at follow-up while none of the MCI PIB-negative patients converted.This study demonstrated the robustness of [(11)C]PIB PET as a marker of neocortical fibrillar amyloid deposition in brain when assessed in a multicentre setting. MCI PIB-positive patients showed more severe memory impairment than MCI PIB-negative patients and progressed to AD at an estimated rate of 25 % per year. None of the MCI PIB-negative patients converted to AD, and thus PIB negativity had a 100 % negative predictive value for progression to AD. This supports the notion that PIB-positive scans in MCI patients are an indicator of prodromal AD.