Independent contribution of temporal β-amyloid deposition to memory decline in the pre-dementia phase of Alzheimer's disease

Chetelat, Gael, Villemagne, Victor L., Pike, Kerryn E., Ellis, Kathryn A., Bourgeat, Pierrick, Jones, Gareth, O'Keefe, Graeme J., Salvado, Olivier, Szoeke, Cassandra, Martins, Ralph N., Ames, David, Masters, Colin L., Rowe, Christopher C. and Australian Imaging Biomarkers Life (2011) Independent contribution of temporal β-amyloid deposition to memory decline in the pre-dementia phase of Alzheimer's disease. Brain, 134 3: 798-807. doi:10.1093/brain/awq383


Author Chetelat, Gael
Villemagne, Victor L.
Pike, Kerryn E.
Ellis, Kathryn A.
Bourgeat, Pierrick
Jones, Gareth
O'Keefe, Graeme J.
Salvado, Olivier
Szoeke, Cassandra
Martins, Ralph N.
Ames, David
Masters, Colin L.
Rowe, Christopher C.
Australian Imaging Biomarkers Life
Title Independent contribution of temporal β-amyloid deposition to memory decline in the pre-dementia phase of Alzheimer's disease
Journal name Brain   Check publisher's open access policy
ISSN 0006-8950
1460-2156
Publication date 2011-03
Sub-type Article (original research)
DOI 10.1093/brain/awq383
Volume 134
Issue 3
Start page 798
End page 807
Total pages 10
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2012
Language eng
Formatted abstract
The relationship between β-amyloid deposition and memory deficits in early Alzheimer's disease is unresolved, as past studies show conflicting findings. The present study aims to determine the relative contribution of regional β-amyloid deposition, hippocampal atrophy and white matter integrity to episodic memory deficits in non-demented older individuals harbouring one of the characteristic hallmarks of Alzheimer's disease, i.e. with β-amyloid pathology. Understanding these relationships is critical for effective therapeutic development. Brain magnetic resonance imaging and [ 11C]Pittsburgh Compound B-positron emission tomography scans were obtained in 136 non-demented individuals aged over 60 years, including 93 healthy elderly and 43 patients with mild cognitive impairment. Voxel-based correlations were computed between a memory composite score and grey matter volume, white matter volume and β-amyloid deposition imaging datasets. Hierarchical linear regression analyses were then performed using values extracted in regions of most significant correlations to determine the relative contribution of each modality to memory deficits. All analyses were conducted pooling all groups together as well as within separate subgroups of cognitively normal elderly, patients with mild cognitive impairment and individuals with high versus low neocortical β-amyloid. Brain areas of highest correlation with episodic memory deficits were the hippocampi for grey matter volume, the perforant path for white matter volume and the temporal neocortex for β-amyloid deposition. When considering these three variables together, only hippocampal volume and temporal β-amyloid deposition provided independent contributions to memory deficits. In contrast to global β-amyloid deposition, temporal β-amyloid deposition was still related to memory independently from hippocampal atrophy within subgroups of cognitively normal elderly, patients with mild cognitive impairment or cases with high neocortical β-amyloid. In the pre-dementia stage of Alzheimer's disease, subtle episodic memory impairment is related to β-amyloid deposition, especially in the temporal neocortex, and independently from hippocampal atrophy, suggesting that both factors should be independently targeted in therapeutic trials aimed at reducing cognitive decline.
Keyword β-amyloid
Alzheimer's disease
Episodic memory
Hippocampus atrophy
Pittsburgh Compound-B-PET
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ
Additional Notes First published online: 9 February 2011.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Centre for Advanced Imaging Publications
 
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