Multi-tracer model for staging cortical amyloid deposition using PET imaging

Lyduine E Collij, Fiona Heeman, Gemma Salvadó, Silvia Ingala, Daniele Altomare, Arno Wilde, Elles Konijnenberg, Marieke van Buchem, Maqsood Yaqub, Pawel Markiewicz, Sandeep S V Golla, Viktor Wottschel, Alle Meije Wink, Pieter Jelle Visser, Charlotte E Teunissen, Adriaan A Lammertsma, Philip Scheltens, Wiesje M van der Flier, Ronald Boellaard, Bart N M van BerckelJosé Luis Molinuevo, Juan Domingo Gispert, Mark E Schmidt, Frederik Bsarkhof, Isadora Lopes Alves, ALFA Study; for the Alzheimer’s Disease Neuroimaging Initiative;on behalf of the AMYPAD Consortium

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OBJECTIVE: To develop and evaluate a model for staging cortical amyloid deposition using PET with high generalizability. METHODS: Three thousand twenty-seven individuals (1,763 cognitively unimpaired [CU], 658 impaired, 467 with Alzheimer disease [AD] dementia, 111 with non-AD dementia, and 28 with missing diagnosis) from 6 cohorts (European Medical Information Framework for AD, Alzheimer's and Family, Alzheimer's Biomarkers in Daily Practice, Amsterdam Dementia Cohort, Open Access Series of Imaging Studies [OASIS]-3, Alzheimer's Disease Neuroimaging Initiative [ADNI]) who underwent amyloid PET were retrospectively included; 1,049 individuals had follow-up scans. With application of dataset-specific cutoffs to global standard uptake value ratio (SUVr) values from 27 regions, single-tracer and pooled multitracer regional rankings were constructed from the frequency of abnormality across 400 CU individuals (100 per tracer). The pooled multitracer ranking was used to create a staging model consisting of 4 clusters of regions because it displayed a high and consistent correlation with each single-tracer ranking. Relationships between amyloid stage, clinical variables, and longitudinal cognitive decline were investigated. RESULTS: SUVr abnormality was most frequently observed in cingulate, followed by orbitofrontal, precuneal, and insular cortices and then the associative, temporal, and occipital regions. Abnormal amyloid levels based on binary global SUVr classification were observed in 1.0%, 5.5%, 17.9%, 90.0%, and 100.0% of individuals in stage 0 to 4, respectively. Baseline stage predicted decline in Mini-Mental State Examination (MMSE) score (ADNI: n = 867, F = 67.37, p < 0.001; OASIS: n = 475, F = 9.12, p < 0.001) and faster progression toward an MMSE score ≤25 (ADNI: n = 787, hazard ratio [HR]stage1 2.00, HRstage2 3.53, HRstage3 4.55, HRstage4 9.91, p < 0.001; OASIS: n = 469, HRstage4 4.80, p < 0.001). CONCLUSION: The pooled multitracer staging model successfully classified the level of amyloid burden in >3,000 individuals across cohorts and radiotracers and detects preglobal amyloid burden and distinct risk profiles of cognitive decline within globally amyloid-positive individuals.

Original languageEnglish
Pages (from-to)e1538-e1553
Issue number11
Early online date16 Jul 2020
Publication statusPublished - 15 Sep 2020

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