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Amyloid Load, Hippocampal Volume Loss, and Diffusion Tensor Imaging Changes in Early Phases of Brain Aging
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. CIRD, Geneva, Switzerland; Univ Geneva, Fac Med, Geneva, Switzerland.ORCID iD: 0000-0001-7433-0203
Univ Geneva, Univ Hosp Geneva, Dept Rehabil & Geriatr, Geneva, Switzerland;Univ Geneva, Dept Psychiat, Geneva, Switzerland.
Univ Geneva, Dept Psychiat, Geneva, Switzerland;Geneva Univ Hosp, Div Inst Measures, Med Direct, Geneva, Switzerland.
Geneva Univ Hosp, Dept Diagnost, Div Nucl Med & Mol Imaging, Geneva, Switzerland.
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2019 (English)In: Frontiers in Neuroscience, ISSN 1662-4548, E-ISSN 1662-453X, Vol. 13, article id 1228Article in journal (Refereed) Published
Abstract [en]

Background and Purpose Amyloid imaging, gray matter (GM) morphometry and diffusion tensor imaging (DTI) have all been used as predictive biomarkers in dementia. Our objective was to define the imaging profile of healthy elderly controls as a function of their cognitive trajectories and explore whether amyloid burden and white matter (WM) microstructure changes are associated with subtle decrement of neuropsychological performances in old age. Materials and Methods We performed a 4.5-year longitudinal study in 133 elderly individuals who underwent cognitive testing at inclusion and follow-up, amyloid PET, MRI including DTI sequences at inclusion, and APOE epsilon 4 genotyping. All cases were assessed using a continuous cognitive score (CCS) taking into account the global evolution of neuropsychological performances. Data processing included region of interest analysis of amyloid PET analysis, GM densities and tract-based spatial statistics (TBSS)-DTI. Regression models were built to explore the association between the CCS and imaging parameters controlling for significant demographic and clinical covariates. Results Amyloid uptake was not related to the cognitive outcome. In contrast, GM densities in bilateral hippocampus were associated with worst CCS at follow-up. In addition, radial and axial diffusivities in left hippocampus were negatively associated with CCS. Amyloid load was associated with decreased VBM and increased radial and axial diffusivity in the same area. These associations persisted when adjusting for gender and APOE4 genotype. Importantly, they were absent in amygdala and neocortical areas studied. Conclusion The progressive decrement of neuropsychological performances in normal aging is associated with volume loss and WM microstructure changes in hippocampus long before the emergence of clinically overt symptoms. Higher amyloid load in hippocampus is compatible with cognitive preservation in cases with better preservation of GM densities and WM microstructure in this area.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA , 2019. Vol. 13, article id 1228
Keywords [en]
amyloid deposition, APOE genotyping, magnetic resonance imaging, normal aging, positron emission tomography
National Category
Neurosciences Neurology
Identifiers
URN: urn:nbn:se:uu:diva-400019DOI: 10.3389/fnins.2019.01228ISI: 000499822900001PubMedID: 31803008OAI: oai:DiVA.org:uu-400019DiVA, id: diva2:1380981
Available from: 2019-12-19 Created: 2019-12-19 Last updated: 2019-12-19Bibliographically approved

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