Regional hippocampal atrophy reflects memory impairment in patients with early relapsing remitting multiple sclerosis

Abstract

Background: Research work has shown that hippocampal subfields are atrophic to varying extents in multiple sclerosis (MS) patients. However, studies examining the functional implications of subfield-specific hippocampal damage in early MS are limited. We aim to gain insights into the relationship between hippocampal atrophy and memory function by investigating the correlation between global and regional hippocampal atrophy and memory performance in early MS patients.

Methods: From the Italian Neuroimaging Network Initiative (INNI) dataset, we selected 3D-T1-weighted brain MRIs of 219 early relapsing remitting (RR)MS and 246 healthy controls (HC) to identify hippocampal atrophic areas. At the time of MRI, patients underwent Selective-Reminding-Test (SRT) and Spatial-Recall-Test (SPART) and were classified as mildly (MMI-MS: n.110) or severely (SMI-MS: n:109) memory impaired, according to recently proposed cognitive phenotypes.

Results: Early RRMS showed lower hippocampal volumes compared to HC (p < 0.001), while these did not differ between MMI-MS and SMI-MS. In MMI-MS, lower hippocampal volumes correlated with worse memory tests (r = 0.23-0.37, p ≤ 0.01). Atrophic voxels were diffuse in the hippocampus but more prevalent in cornu ammonis (CA, 79%) than in tail (21%). In MMI-MS, decreased subfield volumes correlated with decreases in memory, particularly in the right CA1 (SRT-recall: r = 0.38; SPART: r = 0.34, p < 0.01). No correlations were found in the SMI-MS group.

Conclusion: Hippocampal atrophy spreads from CA to tail from early disease stages. Subfield hippocampal atrophy is associated with memory impairment in MMI-MS, while this correlation is lost in SMI-MS. This plays in favor of a limited capacity for an adaptive functional reorganization of the hippocampi in MS patients.

Keywords: Hippocampal atrophy; MRI; Memory impairment; Multiple sclerosis.

Fig. 1

Segmentation of the seven hippocampal subfields. The seven hippocampal subfields automatically segmented using Freesurfer are shown on the anterior (a, b, c) and posterior view (d, e, f), in the coronal (a, d), sagittal (b, e), and axial (c, f) planes

Fig. 2

Differences in hippocampal volumes between early relapsing–remitting multiple sclerosis (RRMS) and healthy controls (HC). The figure shows the hippocampal regions with higher atrophy in early RRMS compared to HC in axial (a), coronal (b) and sagittal (c) view. Atrophied voxels are shown in a colour scale from yellow to red, from the most to the less significant, respectively

Fig. 3

Correlations between hippocampal subfields and memory tests in the whole group of early relapsing–remitting multiple sclerosis (RRMS) and in the mildly memory impaired (MMI)-MS subgroup. The figure shows highlighted in different colors the voxels significantly correlating with memory tests in early RRMS (a) and in the MMI-MS subgroup (b). In Early MS, reduced subfield volumes correlated with decrease in memory performances, with the closest correlations with right CA1 volume, which was the highest in the MMI-MS subgroup