Hippocampal shape alterations are associated with regional Aβ load in cognitively normal elderly individuals

Abstract

Aβ deposition is a driving force of Alzheimer's disease pathology and can be detected early by amyloid positron emission tomography. Identifying presymptomatic structural brain changes associated with Aβ deposition might lead to a better understanding of its consequences and provide early diagnostic information. In this respect we analyzed measures of cortical thickness and subcortical volumes along with hippocampal, thalamic and striatal shape and surface area by applying novel analysis strategies for structural magnetic resonance imaging. We included 69 cognitively normal elderly subjects after careful clinical and neuropsychological workup. Standardized uptake value ratios (cerebellar reference) for uptake of 11-C-Pittsburgh Compound B (PiB) were calculated from positron emission tomographic data for a cortical measurement and for bilateral hippocampus, thalamus and striatum. Associations to shape, surface area, volume and cortical thickness were tested using regression models that included significant predictors as covariates. Left anterior hippocampal shape was associated with regional PiB uptake (P < 0.05, FDR corrected), whereas volumes of the hippocampi and their subregions were not associated with cortical or regional PiB uptake (all P > 0.05, FDR corrected). Within the entorhinal cortical region of both hemispheres, thickness was negatively associated with cortical PiB uptake (P < 0.05, FDR corrected). Hence, localized shape measures and cortical thickness may be potential biomarkers of presymptomatic Alzheimer's disease.

Hippocampal alterations and functional correlates in adolescents and young adults with congenital heart disease

“…However, evaluation of the hippocampus performed to date has been restricted to whole volume measurement only. M. Chakravarty et al, 2015;McDermott et al, 2019;Schroeder et al, 2017). M. Chakravarty et al, 2015;McDermott et al, 2019;Schroeder et al, 2017).…”

Subcortical amyloid load is associated with shape and volume in cognitively normal individuals

“…This concurs with the occurrence of significant amounts of Aβ in the thalamus of AD (Braak & Braak, ). Shape abnormalities in the thalamus associated with Aβ have also been reported in cognitively normal individuals (Schroeder et al, ) as well as in MCI patients who showed cognitive worsening over a 2‐year period (Kalin et al, ). Interestingly, we also found that some of the surface change in the thalamus were also due to changes in shape only (i.e., surface remains abnormal even when analyses were corrected for size and global scalings), particularly in regions which did not show surface changes when investigating the effect of local volume change.…”

“…A vertex‐based surface approach was used to investigate Aβ‐associated local surface changes in subcortical structures and whether these changes related more to local volume or shape. Surface‐based approaches have proven efficient in the detection of subtle surface abnormalities in subcortical structures in AD, MCI, and cognitively normal individuals (Csernansky et al, ; de Flores et al, ; Kalin et al, ; Leh et al, ; Schroeder et al, ). Unlike our previous analyses using subcortical overall volumes, we found that subcortical regional PiB retention values were associated with the surface of the bilateral hippocampus and thalamus and the right pallidum.…”

“…Such approaches have mainly revealed inward surface displacement in regions corresponding to the CA1 subfield and subiculum in AD and MCI patients (de Flores et al, ; Kalin et al, ) but also surface changes in the amygdala and the lateral ventricles (Tang et al, ). In cognitively normal individuals, surface deformation has also been found in association to Aβ burden in the hippocampal head and body and in the thalamus (Achterberg et al, ; Carmichael et al, ; Csernansky et al, ; Schroeder et al, ). In comparison to using overall volume values, surface changes were also shown to improve the detection of future cognitive changes (Achterberg et al, ; Carmichael et al, ; Csernansky et al, ).…”

“…Moreover, a recent PET staging of amyloidosis showed that high Aβ in the striatum predicted hippocampal atrophy and cognitive impairment better than cortical Aβ (Hanseeuw, Betensky, et al, ). In addition, in contrast to cortical PiB retention, only retention in the hippocampus revealed inward and outward surface changes in the CA1 subfield and subiculum regions in cognitively normal individuals (Schroeder et al, ). However, the effect of subcortical regional Aβ on subcortical morphology in cognitively normal individuals remains to be understood.…”