Splenial white matter integrity is associated with memory impairments in posterior cortical atrophy.

Margot Juliëtte Overman,Samrah Ahmed,Christopher Butler,Giovanna Zamboni

doi:10.1093/braincomms/fcab060

Abstract

Posterior cortical atrophy is an atypical form of Alzheimer’s disease characterized by visuospatial impairments and predominant tissue loss in the posterior parieto-occipital and temporo-occipital cortex. Whilst episodic memory is traditionally thought to be relatively preserved in posterior cortical atrophy, recent work indicates that memory impairments form a common clinical symptom in the early stages of the disease. Neuroimaging studies suggest that memory dysfunction in posterior cortical atrophy may originate from atrophy and functional hypoconnectivity of parietal cortex. The structural connectivity patterns underpinning these memory impairments, however, have not been investigated. This line of inquiry is of particular interest, as changes in white matter tracts of posterior cortical atrophy patients have been shown to be more extensive than expected based on posterior atrophy of grey matter. In this cross-sectional diffusion tensor imaging MRI study, we examine the relationship between white matter microstructure and verbal episodic memory in posterior cortical atrophy. We assessed episodic memory performance in a group of posterior cortical atrophy patients (n = 14) and a group of matched healthy control participants (n = 19) using the Free and Cued Selective Reminding Test with Immediate Recall. Diffusion tensor imaging measures were obtained for 13 of the posterior cortical atrophy patients and a second control group of 18 healthy adults. Patients and healthy controls demonstrated similar memory encoding performance, indicating that learning of verbal information was preserved in posterior cortical atrophy. However, retrieval of verbal items was significantly impaired in the patient group compared with control participants. As expected, tract-based spatial statistics analyses showed widespread reductions of white matter integrity in posterior cortical regions of patients compared with healthy adults. Correlation analyses indicated that poor verbal retrieval in the patient group was specifically associated with microstructural damage of the splenium of the corpus callosum. Post-hoc tractography analyses in healthy controls demonstrated that this splenial region was connected to thalamic radiations and the retrolenticular part of the internal capsule. These results provide insight into the brain circuits that underlie memory impairments in posterior cortical atrophy. From a cognitive perspective, we propose that the association between splenial integrity and memory dysfunction could arise indirectly via disruption of attentional processes. We discuss implications for the clinical phenotype and development of therapeutic aids for cognitive impairment in posterior cortical atrophy.

Highlights

Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by prominent impairments of visuospatial abilities, independent from ocular disease
There was no significant difference in Immediate Cued Recall scores between PCA patients and HC1 (U 1⁄4 184, P 1⁄4 0.131), suggesting that encoding of verbal items was spared in PCA
There were no increases in FA or decreases in MD in PCA patients relative to the HC2 group

Summary

Introduction

Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by prominent impairments of visuospatial abilities, independent from ocular disease. PCA is most commonly associated with Alzheimer’s disease neuropathology, some patients present with features more closely resembling Lewy body dementia, corticobasal degeneration or prion disease.[1,2] Tissue loss and hypometabolism resulting from these processes are predominantly observed in posterior parieto-occipital and temporo-occipital cortex.[3,4,5,6] In contrast to the amnestic presentation of Alzheimer’s disease, episodic memory is traditionally thought to be relatively preserved in PCA until later stages of the disease.[7,8] recent work has shown that memory processes are compromised in the majority of PCA patients, and form an oft-reported early clinical symptom.[9,10,11] The emerging profile of Splenium in posterior cortical atrophy memory impairment is one of decreased encoding and retrieval of verbal information.[10,12] Recognition and sensitivity to cues in memory retrieval appear to be less affected, with PCA patients achieving scores within the normal range when cues to recall are utilised.[13,14]

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