OBJECTIVE: Alzheimer's disease (AD) pathology of amyloid β (Aβ) accumulation and neurodegeneration may be relevant to preclinical cognitive decline. The objective of this study was to relate AD-sensitive biomarkers of Aβ and neurodegeneration and their interaction to longitudinal cognitive change in cognitively normal elderly. METHODS: Thirty-eight older people completed at least three consecutive neuropsychological examinations. Using positron emission tomography (PET), Aβ plaque burden was measured with [(11)C]Pittsburgh compound B (PiB). PiB retention was dichotomized into a positive (n = 13) and negative (n = 25) PiB status. Neurodegenerative biomarkers were extracted within AD-vulnerable regions of interest (ROIs)-namely, the hippocampus and temporoparietal cortical areas. Within each ROI, metabolism was quantified with [(18)F] fluorodeoxyglucose (FDG) PET, and the gray matter structure was evaluated using volume (hippocampus) or thickness (cortical regions). ROI-specific functional and structural biomarkers were combined further into cross-modality neurodegenerative composite measures. Using hierarchical regression models, PiB and the neurodegenerative biomarkers were related to cognitive trajectories. RESULTS: PiB positivity was associated with memory and nonmemory worsening. The neurodegenerative biomarkers modified these relationships. Longitudinal cognitive decline was accelerated in those individuals who exhibited both PiB positivity and lower neurodegenerative biomarker scores, although the two measures appeared to be independent. PiB retention interacted predominantly with the cortical neurodegenerative composite for nonmemory change. Memory decline was best explained by the interaction between PiB and the hippocampal neurodegenerative composite, suggesting regional specificity of the neurodegenerative modulations. CONCLUSIONS: Our findings indicate that cognitive trajectories deteriorate at a faster rate in cognitively normal individuals expressing Aβ burden and neurodegeneration within specific AD-sensitive regions.
OBJECTIVE:Alzheimer's disease (AD) pathology of amyloid β (Aβ) accumulation and neurodegeneration may be relevant to preclinical cognitive decline. The objective of this study was to relate AD-sensitive biomarkers of Aβ and neurodegeneration and their interaction to longitudinal cognitive change in cognitively normal elderly. METHODS: Thirty-eight older people completed at least three consecutive neuropsychological examinations. Using positron emission tomography (PET), Aβ plaque burden was measured with [(11)C]Pittsburgh compound B (PiB). PiB retention was dichotomized into a positive (n = 13) and negative (n = 25) PiB status. Neurodegenerative biomarkers were extracted within AD-vulnerable regions of interest (ROIs)-namely, the hippocampus and temporoparietal cortical areas. Within each ROI, metabolism was quantified with [(18)F] fluorodeoxyglucose (FDG) PET, and the gray matter structure was evaluated using volume (hippocampus) or thickness (cortical regions). ROI-specific functional and structural biomarkers were combined further into cross-modality neurodegenerative composite measures. Using hierarchical regression models, PiB and the neurodegenerative biomarkers were related to cognitive trajectories. RESULTS:PiB positivity was associated with memory and nonmemory worsening. The neurodegenerative biomarkers modified these relationships. Longitudinal cognitive decline was accelerated in those individuals who exhibited both PiB positivity and lower neurodegenerative biomarker scores, although the two measures appeared to be independent. PiB retention interacted predominantly with the cortical neurodegenerative composite for nonmemory change. Memory decline was best explained by the interaction between PiB and the hippocampal neurodegenerative composite, suggesting regional specificity of the neurodegenerative modulations. CONCLUSIONS: Our findings indicate that cognitive trajectories deteriorate at a faster rate in cognitively normal individuals expressing Aβ burden and neurodegeneration within specific AD-sensitive regions.
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