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

Abstract

PurposeAmyloid 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.MethodsIn this study 238 [11C]Pittsburgh compound-B (PIB) datasets from five different European centres were pooled. Of these 238 datasets, 18 were excluded, leaving [11C]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.Results[11C]PIB retention in the neocortical and subcortical brain regions was significantly higher in AD patients than in age-matched controls. Intermediate [11C]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 [11C]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.ConclusionThis study demonstrated the robustness of [11C]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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-012-2237-2) contains supplementary material, which is available to authorized users.

Perspective on future role of biological markers in clinical therapy trials of Alzheimer's disease: A long-range point of view beyond 2020

“…Furthermore, amyloidimaging alone may not be helpful with regard to distinguishing between amyloid-positive subtypes of AD (typical AD, logopenic variant of progressive aphasia, and posterior cortical atrophy) [261]. With regard to early diagnosis, a number of studies demonstrated a high predictive value of a positive amyloid-scan in the stage of MCI with regard to conversion to AD [275,276]. Even in subjects with subjective memory impairment, increased levels of amyloid deposition have been described [277] and Reiman et al (2009) were able to demonstrate elevated amyloid-levels in asymptomatic carriers of the APOE e4 allele [278].…”

Dual-phase amyloid PET: hitting two birds with one stone

“…Indeed, we know that while amyloid negativity has an excellent negative predictive value for conversion [21,22], among amyloid-positive MCI subjects, the interval to progression can be variable, and functional measures can predict more accurately the time to conversion [23,24]. Although the value of FDG PET in this setting is well established, perfusion measures should be validated for this specific and highly interesting indication [25][26][27][28].…”

Appropriate use criteria for amyloid PET imaging cannot replace guidelines: On behalf of the European Association of Nuclear Medicine

“…Subsequently many studies have replicated this finding [3][4][5][6][7]. Also, a substantial number of papers on [ 11 C]PiB PET have been published in the European Journal of Nuclear Medicine and Molecular Imaging, which underscores the recognition of the importance of this topic by the Editorial Board of our Journal [8][9][10][11]. Importantly, several studies confirmed that the in vivo observations with [ 11 C]PiB PET are highly correlated with post-mortem assessment of amyloid pathology [12][13][14] [21,22].…”