Examining the structural correlates of amyloid‐beta in people with DLB

Abstract

AbstractBackgroundDementia with Lewy bodies (DLB) is a neurodegenerative disorder characterized pathologically by the deposition of alpha synuclein. Many patients with DLB also have brain compatible with Alzheimer’s disease (namely Amyloid‐β and tau), which can lead to challenges with clinical diagnosis and management. In this study we aim to understand the influence of Aβ on brain atrophy in DLB patients.Method19 participants with probable DLB underwent 3T MRI T1‐weighted (voxel size=0.8x0.8x0.8mm3, TR=2400ms, TE=2.31ms) and β‐amyloid (Aβ) PET (radiotracer 18F‐NAV4694) imaging. Participants were grouped into Aβ negative (n=10; age=71.6±5.8 years) and Aβ positive (n=9; age=75.1±4.3 years) with a threshold of 50 centiloid units to identify neuropathological change (Amadoru et al. 2020). Brain volume measures (regional subcortical grey matter and global white and grey matter) were segmented from T1‐weighted images with FreeSurfer (Fischl et al. 2002, Fischl 2012). Given previous literature suggesting prominence of thalamic structural changes in DLB, we also specifically analysed changes in the thalamus by segmenting the thalamus into 25 nuclei, which were then grouped into six regions (anterior, lateral, ventral, intralaminar, medial and posterior) (Watson et al. 2017, Iglesias et al. 2018). All brain volumes were expressed as fractions of intracranial volume to account for differences in head size. Group comparison analyses were not controlled for age and sex as both these covariates did not statistically differ between groups.ResultBrain volume differed significantly between Aβ‐ and Aβ+ DLB patients in the left thalamus (Aβ‐:4.39±0.37x103, Aβ+:4.07±0.19x103, p=0.03) and right thalamus (Aβ‐:4.17±0.34x103, Aβ+:3.84±0.22 x103, p=0.03). Specifically, the ventral (LEFT; Aβ‐:1.78±0.15, Aβ+:1.63±0.14, p=0.03. RIGHT; Aβ‐:1.83±0.15, Aβ+:1.65±0.12, p=0.01) and posterior (LEFT; Aβ‐:1.30±0.12, Aβ+:1.17±0.10, p=0.04. RIGHT; Aβ‐:1.42±0.14, Aβ+:1.21±0.12, p=0.003) regions were significantly reduced in Aβ+ compared to Aβ‐ DLB patients.ConclusionWe demonstrated significant thalamic atrophy in Aβ+ patients compared to Aβ‐ DLB patients. We did not observe significant differences in grey matter and hippocampal volume between patient groups. This study showed that AD‐related processes in DLB patients are associated with thalamic atrophy, specifically in the ventral and posterior regions. Future studies would benefit a larger DLB cohort to further understand the association between AD‐related pathology and the regional thalamic correlates of clinical function.