Abstract Details

Title NODDI Microstructural Abnormalities in Normal-Appearing Gray Matter and White Matter Contribute to Cognitive Impairment in Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) P14 - Poster Session 14 (11:45 AM-12:45 PM)

Poster/Presentation
Number 12-002

Objective

Using neurite orientation dispersion and density imaging (NODDI), a multi-compartment diffusion model to better evaluate the complexity of brain neuroanatomical microarchitecture, we aimed to explore the associations between microarchitecture abnormalities of focal lesions and normal-appearing (NA) tissues and cognitive impairment in multiple sclerosis (MS) patients.

Background

Heterogeneous pathological processes contribute to cognitive impairment impairment in MS. The application of advanced magnetic resonance imaging (MRI) techniques more specific to the different pathological substrates of MS is likely to improve our understanding of the relationship between structural damage and cognitive impairment in MS patients.

Design/Methods

One hundred and fifty-two MS patients and 48 healthy controls (HC) underwent a brain 3T acquisition. MS patients with ≥1 abnormal test in ≥2 domains of Rao’s battery were defined as cognitively impaired (CI). A cognitive impairment index (CII) was also derived. NODDI-derived intracellular (ICV_f) and orientation dispersion index (ODI) were assessed in cortical and white matter (WM) lesions, thalamus, NA cortex and NAWM.

Results

Fifty-two (34.2%) MS patients were CI. CI and cognitively preserved (CP) MS patients vs HC showed significantly decreased NA cortex, thalamic and NAWM ICV_f (p<0.001) and NA cortex ODI (p≤0.001). CI MS patients showed also a significantly increased NAWM ODI (p=0.003). CI vs CP MS patients had significantly decreased NA cortex and NAWM ICV_f (p≤0.022), and increased NAWM ODI (p=0.001). No lesional microstructural differences were found in CI vs CP MS patients, except for decreased WM lesion ODI in CI vs CP MS patients (p=0.023). NA cortex ICV_f and NAWM ICV_f and ODI were significantly correlated with CII (r from -0.32 to 0.32 p from <0.001 to 0.03).

Conclusions

NA cortex, thalamic and NAWM neuro-axonal loss, together with NAWM inflammation, gliosis and loss of tissue coherence, are associated with cognitive impairment in MS. NODDI could disentangle in vivo the complex processes determining cognitive dysfunctions.

Authors/Disclosures
Paolo Preziosa (Ospedale San Raffaele) PRESENTER	Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb . Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck.
	No disclosure on file
Elisabetta Pagani	Elisabetta Pagani has nothing to disclose.
	No disclosure on file
Damiano Mistri, MSC (Università Vita-Salute San Raffaele)	Mr. Mistri has nothing to disclose.
Andrea Falini	No disclosure on file
Maria A. Rocca (Neuroimaging Research Unit)	Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, Roche. Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AstraZaneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono SpA, Novartis, Roche, Sanofi and Teva. The institution of Maria Assunta Rocca has received research support from MS Society of Canada, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.
Massimo Filippi, MD, FAAN (Ospedale San Raffaele, Neuroimaging Research Unit)	Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA. Dr. Filippi has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.

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