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