Beta amyloid deposition maps onto hippocampal and subiculum atrophy in dementia with Lewy bodies

Abstract

Although dementia with Lewy bodies (DLB) is a synucleinopathy, it is frequently accompanied by β-amyloid accumulation (Aβ). Elucidating the relationships of Aβ with grey matter atrophy in DLB may yield insights regarding the contributions of comorbid Alzheimer's disease to its disease progression. Twenty healthy controls and twenty-five DLB subjects underwent clinical assessment, [18F]-Florbetapir and 3T MRI. Freesurfer was used to estimate cortical thickness and subcortical volumes and PetSurfer was used to quantify [18F]-Florbetapir standardised uptake value ratio. Principal component analysis was used to identify the dominant Aβ component for correlations with regional cortical thickness, hippocampal subfields and subcortical structures. Relative to healthy controls, the DLB group demonstrated increased Aβ in widespread regions encompassing the frontal and temporo-parietal cortices, whereas cortical thinning was restricted to the temporal lobe. Amongst DLB subjects, the Aβ component was significantly associated with more severe hippocampal and subiculum atrophy. These findings may reflect an early process of superimposed AD-like atrophy in DLB, thereby conferring support for the therapeutic potential of anti-Aβ interventions in people with DLB.

The combined effect of amyloid-β and tau biomarkers on brain atrophy in dementia with Lewy bodies

“…Our results are consistent with previous findings on the association between amyloid β-related pathology and atrophy in the medial temporal lobe in DLB ( Sarro et al, 2016 , van der Zande et al, 2018 , Shimada et al, 2013 , Mak et al, 2019b , Kantarci et al, 2012a , Kantarci et al, 2012b ). Although MTA is less frequent in DLB when compared with AD ( Shimada et al, 2013 , Barber et al, 2000 Mar , Ballmaier et al, 2004 ), previous studies suggest that when MTA is present, it could reflect concomitant AD-related pathology ( Sarro et al, 2016 , van der Zande et al, 2018 ).…”

“…This finding suggests that AD pathology may contribute to medial temporal lobe atrophy (MTA) in DLB ( Elder et al, 2017 ; Sarro et al, 2016 ). Similarly, when amyloid is present the patterns of deposition and atrophy resembles that observed in AD ( Shimada et al, 2013 , Donaghy et al, 2015 , Irwin and Hurtig, 2018 , Mak et al, 2019a ) Understanding the underlying mechanisms of regional brain atrophy that could reflect distinct pathologies could have treatment implications. For example, a typical AD pattern of brain atrophy involving the medial temporal lobes and posterior cortices was associated with poorer response to acetylcholinesterase inhibitors in DLB patients ( Graff-Radford et al, 2012 ).…”

Genetic Architecture and Molecular, Imaging and Prodromic Markers in Dementia with Lewy Bodies: State of the Art, Opportunities and Challenges

“…A faster atrophy, in particular in the medial temporal lobe, has been reported by several reports in DLB patients when compared to those without concomitant pathology [205][206][207][208][209]. Overall, this evidence demonstrates that when amyloid is present, it mainly contributes to temporal lobar atrophy, with a pattern of brain deposition and atrophy resembling that observed in AD [210][211][212].…”

“…[11C]-PK11195 positron PET-imaging is a tool able to correctly estimate the microglial activation in the brain. Preliminary data demonstrate the colocalization between [18F]-AV1451 and [11C]-PK11195 tracers, thus suggesting that tau-pathology may have synergistic interactions with neuroinflammation and other processes occurring in DLB [212].…”

FreeSurfer based segmentation of hippocampal subfields: a review of methods and applications, with a novel quality control procedure for ENIGMA studies and other collaborative efforts

“…Parkinson's disease (PD, including dementia) (Pereira et al, 2013;Stav et al, 2016;Foo et al, 2017;Lenka et al, 2018;Uribe et al, 2018;Low et al, 2019;Park et al, 2019) Frontotemporal dementia (Bocchetta et al, 2018), LBD and beta amyloid (Mak et al, 2019) Multisystem atrophy and PD (Wang et al, 2019) Amyotrophic lateral sclerosis (Christidi et al, 2019), primary lateral sclerosis (Finegan et al, 2019)…”