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O4‐07‐03: PATHOLOGIC VALIDATION OF THE EADC‐ADNI HARMONIZED HIPPOCAMPAL PROTOCOL
Author(s) -
Apostolova Liana,
Zarow Chris,
Biado Kristina,
Hurtz Sona,
Boccardi Marina,
Somme Johanne,
Honarpisheh Hedieh,
Blanken Anna,
Brook Jenny,
Tung Spencer,
Ng Denise,
Alger Jeffrey,
Vinters Harry,
Bocchetta Martina,
Duvernoy Henri,
Jack Clifford,
Frisoni Giovanni
Publication year - 2014
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 - 10.1016/j.jalz.2014.04.423
Subject(s) - hippocampal formation , subiculum , neuroimaging , atrophy , pathology , medicine , neuroscience , temporal lobe , alzheimer's disease , dementia , nuclear medicine , psychology , disease , epilepsy , dentate gyrus
monoclonal antibody, in patients with prodromal or mild Alzheimer’s disease (AD). Retrospective analyses of both bapineuzumab and solanezumab data have shown substantially higher percentages of negative amyloid PET findings in APOE ε4 non-carriers than in APOE ε4 carriers in the mild and moderate AD sub-study populations. We report our amyloid PET screening results by APOE ε4 status in the prodromal and mild AD study populations. Methods: During screening, patients fulfilling clinical criteria for either prodromal or mild AD underwent florbetapir PET scanning and APOE genotyping. Florbetapir PET scans were visually evaluated for amyloid plaque burden. Results: Data from the first 250 patients were included in this analysis. Similar to the bapineuzumab and solanezumab results, we have observed a substantially higher percentage of negative amyloid PET findings in APOE ε4 non-carriers than in APOE ε4 carriers (highlighted in bold in Table 1). However, the overall incidence of negative amyloid scans observed in 221AD103 is substantially higher than that reported in the two Phase III studies, likely attributable to the earlier stage of AD patients being recruited in this study (prodromal/mild, mean MMSE w 25 vs. mild/moderate AD, mean MMSE w21 in the Phase III studies). This finding is also consistent with the solanezumab results in that the percentage of negative amyloid PET findings was higher in mild (27%) than in moderate (13%) AD groups. Conclusions: These results suggest that: (1) selecting subjects having AD pathology based on clinical criteria remains a challenge; (2) enrichment by using amyloid PET imaging is effective and feasible; (3) enrichment by assessing amyloid plaque burden is critically important to clinical studies in early stages of AD because of a higher incidence of negative amyloid findings; and (4) APOE genotyping may potentially improve the economy of enrichment by amyloid PET, via lowering the likelihood of negative amyloid findings.