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Title: Independent contribution of temporal beta-amyloid deposition to memory decline in the pre-dementia phase of Alzheimer's disease.
Austin Authors: Chételat, Gaël;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 
Institutional Author: Australian Imaging Biomarkers and Lifestyle Study of ageing (AIBL) Research Group
Affiliation: Department of Nuclear Medicine and Centre for PET, Austin Health, 145 Studley Road, Heidelberg, VIC 3084, Australia
Issue Date: 9-Feb-2011
Publication information: Brain : A Journal of Neurology 2011; 134(Pt 3): 798-807
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 [(11)C]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.
DOI: 10.1093/brain/awq383
Journal: Brain
Type: Journal Article
Subjects: Aged
Aged, 80 and over
Alzheimer Disease.complications.pathology.radionuclide imaging
Amyloid beta-Peptides.metabolism
Aniline Compounds.diagnostic use
Brain.pathology.radionuclide imaging
Brain Mapping
Carbon Radioisotopes.diagnostic use
Cognition Disorders.complications.pathology.radionuclide imaging
Imaging, Three-Dimensional.methods
Magnetic Resonance Imaging.methods
Memory Disorders.etiology.pathology.radionuclide imaging
Middle Aged
Positron-Emission Tomography.methods
Regression Analysis
Thiazoles.diagnostic use
Appears in Collections:Journal articles

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