2023 American Academy of Neurology Abstract Website

Matteo Azzimonti¹, Paolo Preziosa³, Paola Valsasina², Elisabetta Pagani², Olga Marchesi², Nicolò Tedone², Carmen Vizzino², Massimo Filippi³, Maria Rocca³
¹Neuroimaging Research Unit, Division of Neuroscience, and Neurology Unit, ²Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, ³Neuroimaging Research Unit, Division of Neuroscience, and Neurology Unit, IRCCS San Raffaele Scientific Institute; Vita-Salute San Raffaele University

Objective:

To apply a multiparametric MRI approach to identify mechanisms associated with cognitive worsening in multiple sclerosis (MS).

Background:

Heterogeneous processes may contribute to cognitive impairment in MS; however, its association with brain structural and functional MRI changes still need to be fully explored.

Design/Methods:

Brain dual-echo, 3D T1-weighted, diffusion-weighted imaging, and resting state (RS) functional MRI scans were acquired at baseline and after median follow up of 3.4 years in 35 MS patients and 22 healthy controls (HC). Associations between cognitive worsening at Rao’s battery and longitudinal changes in T2-hyperintense lesion location, WM microstructural damage, gray matter (GM) atrophy and RS functional connectivity (FC) were explored using tract-based spatial statistic, tensor-based morphometry and independent component analysis.

Results:

Fifteen (43%) MS patients were cognitively impaired at baseline and 10 (29%) showed cognitive deterioration at follow-up. At baseline, compared to HC, MS patients showed widespread WM damage and GM atrophy, and decreased RS FC in some clusters of executive control (ECN) and working memory networks (WMN). At follow-up, annualized volume loss of caudate nucleus was significantly higher in MS patients with vs without cognitive deterioration (-1.2% vs -0.2%, p<0.05). No significant between-group differences in lesion location, WM microstructural changes or GM atrophy were found. Compared to stable MS patients, worsened patients showed decreased RS FC in right hippocampus of right WMN and in right insula of default mode network. In the opposite comparison, increased RS FC in left insula of ECN was found.

Conclusions:

While cognitively-stable MS patients showed increased RS FC in left insula, possibly reflecting a compensatory mechanism, cognitive deterioration in MS patients was associated with decreased RS FC in several functional brain networks, with limited GM atrophy progression. Our study suggests that, in MS patients already characterized by substantial structural damage, cognitive deterioration might be secondary to functional network collapse.