Regional dynamics of amyloid-beta deposition in healthy elderly, mild cognitive impairment and Alzheimer's disease: a voxelwise PiB-PET longitudinal study

Villain, Nicolas, Chetelat, Gael, Grassiot, Blandine, Bourgeat, Pierrick, Jones, Gareth, Ellis, Kathryn A., Ames, David, Martins, Ralph N., Eustache, Francis, Salvado, Olivier, Masters, Colin L., Rowe, Christopher C. and Villemagne, Victor L. (2012) Regional dynamics of amyloid-beta deposition in healthy elderly, mild cognitive impairment and Alzheimer's disease: a voxelwise PiB-PET longitudinal study. Brain, 135 7: 2126-2139. doi:10.1093/brain/aws125


Author Villain, Nicolas
Chetelat, Gael
Grassiot, Blandine
Bourgeat, Pierrick
Jones, Gareth
Ellis, Kathryn A.
Ames, David
Martins, Ralph N.
Eustache, Francis
Salvado, Olivier
Masters, Colin L.
Rowe, Christopher C.
Villemagne, Victor L.
Title Regional dynamics of amyloid-beta deposition in healthy elderly, mild cognitive impairment and Alzheimer's disease: a voxelwise PiB-PET longitudinal study
Formatted title
Regional dynamics of amyloid-β deposition in healthy elderly, mild cognitive impairment and Alzheimer's disease: a voxelwise PiB-PET longitudinal study
Journal name Brain   Check publisher's open access policy
ISSN 0006-8950
1460-2156
Publication date 2012-07-01
Sub-type Article (original research)
DOI 10.1093/brain/aws125
Volume 135
Issue 7
Start page 2126
End page 2139
Total pages 14
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Formatted abstract
Amyloid-β deposition in Alzheimer’s disease is thought to start while individuals are still cognitively unimpaired and it is hypothesized that after an early phase of fast accumulation, a plateau is reached by the time of cognitive decline. However, few longitudinal Pittsburgh compound B-positron emission tomography studies have tested this hypothesis, and with conflicting results. The purpose of this work is to further our understanding of the dynamics of amyloid-β deposition in a large longitudinal cohort. A total of 32 patients with Alzheimer’s disease, 49 subjects with mild cognitive impairment and 103 healthy controls underwent two Pittsburgh compound B-positron emission tomography scans 18 months apart. For each participant, a parametric map of Pittsburgh compound B-positron emission tomography rate of change was created [(follow-up scan − baseline scan)/follow-up duration] and entered in a voxelwise three-way analysis of covariance, with clinical status (healthy controls, mild cognitive impairment or Alzheimer’s disease), disease progression (clinical conversion from healthy controls to mild cognitive impairment or Alzheimer’s disease, or from mild cognitive impairment to Alzheimer’s disease) and Pittsburgh compound B status (positive versus negative) as independent factors. Only a significant effect of the Pittsburgh compound B status was found: both Pittsburgh compound B-positive and -negative subjects showed a significant increase in amyloid-β deposition, with this increase being significantly higher in Pittsburgh compound B-positive individuals. This finding suggests either that Pittsburgh compound B-negative individuals have slower rates of amyloid-β accumulation than positive, or that the proportion of individuals showing significant increase in amyloid-β deposition, termed ‘Pittsburgh compound B accumulators’, is higher within the Pittsburgh compound B-positive group than within the Pittsburgh compound B-negative group. The bimodal distribution of the individual rates of neocortical amyloid-β accumulation observed support the existence of ‘Pittsburgh compound B non-accumulators’ and ‘Pittsburgh compound B accumulators’ and different clustering analyses led to a consistent threshold to separate these two subgroups (0.014–0.022 standardized uptake value ratiopons/year). The voxelwise three-way analysis of covariance was thus recomputed with the ‘Pittsburgh compound B accumulators’ only and the results were almost unchanged, with the Pittsburgh compound B-positive group showing higher accumulation than the Pittsburgh compound B-negative group. Finally, a significant negative correlation was found between Pittsburgh compound B rate of change and Pittsburgh compound B baseline burden, but only in the Pittsburgh compound B-positive group (r = −0.24; P = 0.025). Higher rates of amyloid-β deposition are associated with higher amyloid-β burden suggesting that amyloid-β deposition does not reach a plateau when cognitive impairments manifest but is instead an ongoing process present even at the Alzheimer’s disease stage. amyloid-β accumulation also seems to slow down at the latest stages of the process, i.e. in participants with the highest amyloid burden. Furthermore, this study identified the existence of Pittsburgh compound ‘accumulators’ and ‘non-accumulators’, notably within the Pittsburgh compound B-negative group, which may be a relevant concept for future studies.
Keyword Alzheimer's disease
Mild cognitive impairment
Normal ageing
Amyloid-beta imaging
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
School of Information Technology and Electrical Engineering Publications
Centre for Advanced Imaging Publications
 
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