Contrasting longitudinal changes in amygdala integrity in early Alzheimer’s disease and frontotemporal dementia subtypes

Abstract

AbstractBackgroundThe amygdala is a complex and heavily connected subcortical brain structure. It plays a central role in regulating social, emotional and cognitive processes. Amygdala atrophy has been previously reported in Alzheimer’s disease (AD) and in frontotemporal dementia (FTD), although the findings are inconsistent. In addition, the trajectories of atrophy progression over time are unclear. The aim of this study was to determine the structural changes of the amygdala in early AD and FTD and map their changes over time.MethodPatients clinically diagnosed with amnestic AD (n = 20) or with FTD (behavioural variant FTD (bvFTD) = 20; semantic dementia (SD) = 20, primary nonfluent aphasia (PNFA) = 20), and 20 matched healthy controls (HC) completed whole brain structural MRI annually across multiple time points. Automated regional parcellation of the amygdala into three subregions was performed with FreeSurfer 7.1.1 using the T1‐weighted images. Linear mixed effects models were applied to identify changes in amygdala volumes over time.ResultAt baseline, bvFTD, SD and AD, but not PNFA, displayed significant overall amygdala volume loss compared with HC. Atrophy was most severe and asymmetrical (Left > Right) in SD. No subregional differences emerged across the clinical groups. Longitudinal analyses revealed a significantly greater amygdalar atrophy rate overall in all patient groups compared with HC. The greatest volume reduction was found in the right amygdala, which was significantly most pronounced in SD, across all subregions. In contrast, only the AD and PNFA groups showed a significant change over time in the left amygdala.ConclusionThese findings identified global amygdala changes in AD and FTD. Importantly, these changes have a different time and location signature depending on the disease. In FTD, they occur early and more severely in SD and bvFTD, but later in PNFA. In AD, atrophy seems to take a more protracted course. In all groups, the right amygdala was affected later than the left. These findings have implications for the diagnosis and monitoring of these dementias. Future analyses will examine the relations of these alterations in amygdala integrity with social cognition and emotion regulation, functions known to be variably compromised in AD and FTD.