eprintid: 1474199 rev_number: 28 eprint_status: archive userid: 608 dir: disk0/01/47/41/99 datestamp: 2016-01-26 14:33:15 lastmod: 2021-09-19 23:36:21 status_changed: 2016-01-26 14:33:15 type: article metadata_visibility: show creators_name: Andrews, KA creators_name: Frost, C creators_name: Modat, M creators_name: Cardoso, MJ creators_name: Rowe, CC creators_name: Villemagne, V creators_name: Fox, NC creators_name: Ourselin, S creators_name: Schott, JM title: Acceleration of hippocampal atrophy rates in asymptomatic amyloidosis ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F86 divisions: B04 divisions: C05 divisions: F42 keywords: Asymptomatic amyloidosis; Hippocampus; Atrophy; Acceleration; MRI; PET note: © 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). abstract: Increased rates of brain atrophy measured from serial magnetic resonance imaging precede symptom onset in Alzheimer's disease and may be useful outcome measures for prodromal clinical trials. Appropriate trial design requires a detailed understanding of the relationships between β-amyloid load and accumulation, and rate of brain change at this stage of the disease. Fifty-two healthy individuals (72.3 ± 6.9 years) from Australian Imaging, Biomarkers and Lifestyle Study of Aging had serial (0, 18 m, 36 m) magnetic resonance imaging, (0, 18 m) Pittsburgh compound B positron emission tomography, and clinical assessments. We calculated rates of whole brain and hippocampal atrophy, ventricular enlargement, amyloid accumulation, and cognitive decline. Over 3 years, rates of whole brain atrophy (p < 0.001), left and right hippocampal atrophy (p = 0.001, p = 0.023), and ventricular expansion (p < 0.001) were associated with baseline β-amyloid load. Whole brain atrophy rates were also independently associated with β-amyloid accumulation over the first 18 months (p = 0.003). Acceleration of left hippocampal atrophy rate was associated with baseline β-amyloid load across the cohort (p < 0.02). We provide evidence that rates of atrophy are associated with both baseline β-amyloid load and accumulation, and that there is presymptomatic, amyloid-mediated acceleration of hippocampal atrophy. Clinical trials using rate of hippocampal atrophy as an outcome measure should not assume linear decline in the presymptomatic phase. date: 2015-03-01 date_type: published official_url: http://dx.doi.org/10.1016/j.neurobiolaging.2015.10.013 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1105883 doi: 10.1016/j.neurobiolaging.2015.10.013 lyricists_name: Andrews, Abigail lyricists_name: Cardoso, Manuel lyricists_name: Fox, Nicholas lyricists_name: Modat, Marc lyricists_name: Ourselin, Sebastien lyricists_name: Schott, Jonathan lyricists_id: AANDR19 lyricists_id: MJMCA47 lyricists_id: NCIFO25 lyricists_id: MMODA28 lyricists_id: SOURS59 lyricists_id: JMSCH12 actors_name: Schott, Jonathan actors_name: Barczynska, Patrycja actors_id: JMSCH12 actors_id: PBARC91 actors_role: owner actors_role: impersonator full_text_status: public publication: Neurobiology of Aging volume: 39 pagerange: 99-107 issn: 0197-4580 citation: Andrews, KA; Frost, C; Modat, M; Cardoso, MJ; Rowe, CC; Villemagne, V; Fox, NC; ... Schott, JM; + view all <#> Andrews, KA; Frost, C; Modat, M; Cardoso, MJ; Rowe, CC; Villemagne, V; Fox, NC; Ourselin, S; Schott, JM; - view fewer <#> (2015) Acceleration of hippocampal atrophy rates in asymptomatic amyloidosis. Neurobiology of Aging , 39 pp. 99-107. 10.1016/j.neurobiolaging.2015.10.013 <https://doi.org/10.1016/j.neurobiolaging.2015.10.013>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1474199/1/1-s2.0-S0197458015005175-main.pdf