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

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.

Effect Modifiers of TDP-43-Associated Hippocampal Atrophy Rates in Patients with Alzheimer’s Disease Neuropathological Changes

“…However, our finding of cross-sectionally larger hippocampal volumes with increasing neuritic plaque stage in cognitively unimpaired group is counterintu-itive. Several neuroimaging studies that use amyloid positron emission tomography as a measure of A␤ burden report no association between A␤ and hippocampal volumes in asymptomatic patients and/or patients with MCI [50] or weak association with HA [51][52][53][54][55][56] with stronger evidence in cases of subcortical versus cortical A␤ deposition [57]. CERAD neuritic plaque staging used in this study assesses only cortical deposition of A␤ with subcortical regions not included for screening [37] in contrast to Thal phases [58] and therefore might not represent a direct association between A␤ and atrophy in subcortical regions, e.g., hippocampus.…”

Long Longitudinal Tract Lesion Contributes to the Progression of Alzheimer's Disease

“…MTL substructures are the earliest regions affected by AD pathology, mainly amyloid deposition, and neurofibrillary tangle tau pathology. Anatomically, WM degeneration in AD follows the topographic progression of cortical AD pathology (49,50). As mentioned above, AD pathological invasion was initially localized in MTL, and then gradually spread to the temporal, parietal, and frontal lobes.…”

“…SVM provides great potential for future artificial intelligence aided diagnosis, and has been increasingly implemented in various classification problems ( 49 ). For instance, SVM successfully classified multiple sclerosis patients from healthy controls with accuracies as high as 89% by combined DTI and functional data ( 50 ).…”

Differential regulation of insulin signalling by monomeric and oligomeric amyloid beta-peptide

“… 70 The latter two effects are tightly linked to memory formation and learning, processes that take place in the hippocampus, the brain centre most severely damaged in Alzheimer’s disease due to the high Aβ load. 71 , 72 …”