Neuroimaging of autobiographical memory in dementia with Lewy bodies: a story of insula

Abstract

Although deficits in learning and retrieving new information are well characterized in dementia with Lewy bodies, autobiographical memory has never been explored in this disease. Yet, autobiographical memory impairments are a pervasive feature of dementia, well characterized in other neurodegenerative diseases. Moreover, autobiographical memory corresponds to an extension over time of the self, which we hypothesize is altered in dementia with Lewy bodies and impairment of which could be linked to the insular atrophy occurring from an early stage of the disease. In this study, we sought to characterize autobiographical memory impairments and explore their neural correlates in dementia with Lewy bodies, on the assumption that insular damage could impact the self, including its most elaborate components, such as autobiographical memory. Twenty patients with prodromal to mild dementia with Lewy bodies were selected to participate in this exploratory study along with 20 healthy control subjects. The Autobiographical Interview was used to assess autobiographical memory. Performances were compared between patients and control subjects, and an analysis across life periods and recall conditions was performed. 3D magnetic resonance images were acquired for all participants, and correlational analyses were performed in the patient group using voxel-based morphometry. The behavioural results of the Autobiographical Interview showed that autobiographical memory performances were significantly impaired in dementia with Lewy body patients compared to control subjects in a temporally ungraded manner, for both the free recall and the specific probe conditions (P < 0.0001), though with greater improvement after probing in the patient group. Furthermore, autobiographical memory impairments were correlated with grey matter volume within right insular cortex, temporoparietal junction, precuneus, putamen, left temporal cortex, bilateral parahippocampus and cerebellum, using a threshold of P = 0.005 uncorrected. The behavioural results confirm the existence of temporally ungraded autobiographical memory impairments in dementia with Lewy bodies, from the early stage of the disease. As we expected, neuroimaging analysis revealed a role for the insula and the precuneus in autobiographical memory retrieval, two regions associated with elementary aspects of the self, among other brain regions classically associated with autobiographical memory, such as medial temporal lobe and temporoparietal junction. Our findings provide important insights regarding the involvement of the insula in the self and suggest that insular damage could lead to a global collapse of the self, including its more elaborated components, such as autobiographical memory.

Keywords: Autobiographical Interview self; autobiographical memory; dementia with Lewy bodies; insula.

Graphical Abstract

Figure 1

Total scores of episodic richness for the free recall and probed recall on the Autobiographical Interview, for all participants. Mann–Whitney U-tests were used to compare the free recall score and probed recall score for both dementia with Lewy body patients (n = 20) and control subjects (n = 20). *P < 0.0001 (error bars represent standard deviation). DLB, dementia with Lewy bodies.

Figure 2

Profile of free recall (A) and probed recall (B) across life periods on the Autobiographical Interview for all participants. Two-way repeated measures ANOVAs, including age as nuisance covariate, were conducted to examine the effect of life period across the different recall conditions, for both dementia with Lewy body patients (n = 20) and control subjects (n = 20). Bonferroni correction was applied for multiple comparisons (error bars represent standard deviation). DLB, dementia with Lewy bodies.

Figure 3

VBM analyses for the Autobiographical Interview free recall condition in the dementia with Lewy bodies group. Multiple linear regression was used to obtain correlation for Autobiographical Interview free recall score and GM volume in patients with dementia with Lewy bodies (n = 20). GM volumes within right posterior insula (A and B), left parahippocampal gyrus and right temporoparietal junction (B) and right precuneus (C) are positively correlated with the free recall score on the Autobiographical Interview, using a threshold of P = 0.005 uncorrected, including age, gender, TIV and MMSE score as nuisance covariates (k = 50).

Figure 4

VBM analyses for the Autobiographical Interview probed recall condition in the dementia with Lewy bodies group. Multiple linear regression was used to obtain correlation for Autobiographical Interview probed recall score and GM volume in patients with dementia with Lewy bodies (n = 20). GM volumes within right posterior insula (A and B), left inferior temporal and parahippocampal gyri (B) and right precuneus and parahippocampal gyrus (C) are positively correlated with the probed recall score on the Autobiographical Interview, using a threshold of P = 0.005 uncorrected, including age, gender, TIV and MMSE score as nuisance covariates (k = 50).