Amyloid Load, Hippocampal Volume Loss, and Diffusion Tensor Imaging Changes in Early Phases of Brain Aging.

Sven Haller,Marie-Louise Montandon,Johan Lilja,Valentina Garibotto,François R Herrmann,Cristelle Rodriguez,Panteleimon Giannakopoulos

doi:10.3389/fnins.2019.01228

Abstract

Background and PurposeAmyloid 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 MethodsWe 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.ResultsAmyloid 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.ConclusionThe 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.

Highlights

The current use of Alzheimer disease (AD) related amyloid/tau/neurodegeneration profile is made with the a priori idea that the first cognitive changes follows the elevation of brain amyloid and accumulation of neurofibrillary tangles (Soldan et al, 2019)
Among the different imaging technics that could be used to predict the cognitive trajectories in normal aging, amyloid positron emission tomography (PET) imaging, magnetic resonance imaging (MRI), and diffusion tensor imaging (DTI) assessing white matter (WM) and gray matter (GM) microstructure are likely to address at least partly temporally distinct processes (Bosch et al, 2012)
These data indicated that Aß accumulation arises later in life on a background of preexisting structural deficits that are associated with normal aging and not with amyloid pathology per se (Jack et al, 2015)

Summary

Introduction

The current use of Alzheimer disease (AD) related amyloid/tau/neurodegeneration profile is made with the a priori idea that the first cognitive changes follows the elevation of brain amyloid and accumulation of neurofibrillary tangles (Soldan et al, 2019). Unlike hippocampal volume decrease that usually becomes significant after 60 years of age and is APOE4-independent, amyloid PET positivity is more frequent after 70 years of age with an increase of amyloid burden in the presence of APOE4 allele These data indicated that Aß accumulation arises later in life on a background of preexisting structural deficits that are associated with normal aging and not with amyloid pathology per se (Jack et al, 2015). 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

Objectives

Methods

Results

Discussion

Conclusion