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A multi‐study analysis of the spatial‐temporal progression of amyloid deposition and its utility for longitudinal studies
Author(s) -
Alves Isadora Lopes,
Collij Lyduine,
Fantoni Enrico R,
Heeman Fiona,
Salvadó Gemma,
Buckley Christopher,
Farrar Gill,
Gispert Juan Domingo,
Barkhof Frederik
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.044707
Subject(s) - neuropathology , amyloid (mycology) , pathology , positron emission tomography , dementia , pathological , medicine , neuroscience , psychology , disease
Background Although a dichotomous and visual interpretation of amyloid PET is sufficient in clinical routine, regional image assessment may yield additional opportunities in the research setting. Understanding the regional‐temporal evolution of amyloid pathology may enable earlier pathological identification, as well as a more fine‐grained assessment of the extent and associated risk of amyloid pathology beyond traditional dichotomous measures. This multi‐study analysis of neuropathology and PET studies assessed the potential for the detection of regional amyloid deposition patterns and its utility for staging amyloid pathology in vivo . Method A total of 15 studies (neuropathology and PET imaging based) have been included for review. First, an overall assessment of the similarities and discrepancies in the described ordering of amyloid pathology was performed in view of the methodological differences and limitations. Secondly, a multi‐tracer amyloid PET staging system was performed with a variety of cohorts to demonstrate the utility of such a methodology in comparison with traditional global dichotomous measures of pathology. The chosen system has been developed based on cross‐sectional PET data from 400 subjects (100 per tracer, including [ 11 C]PiB, [ 18 F]florbetapir, [ 18 F]florbetaben, and [ 18 F]flutemetamol), applied to >3000 scans and related to clinical and biological markers of Alzheimer’s disease. Result Although methodological discrepancies between studies need to be considered, it can be observed that 1) cortical generally precedes striatal accumulation, 2) medial neocortical regions are seen to accumulate amyloid earlier than lateral regions in PET studies (influenced by signal distortion), and 3) the placement of temporal regions in the pathological ordering is remarkably variable across studies (Figure 1). Multiple PET‐based staging systems have been successfully applied to various cohorts, but a multi‐tracer approach demonstrated that between‐tracer discrepancies influence the observed regional ordering and should be taken into account (Figure 2). Finally, PET‐based amyloid stage strongly relates to demographic and clinical measures, detects pre‐global amyloid burden, characterizes distinct levels of pathology beyond a CSF plateau phase, and predicts future cognitive decline (Figure 3). Conclusion With modest agreement to neuropathology, models for staging amyloid pathology using PET imaging could improve subject selection into secondary prevention trials and potentially guide visual assessment in clinical routine.