Multiple Sclerosis (MS) is an autoimmune disease that affects the central nervous system (CNS). MS is considered a leading cause of neurological disability. Its pathophysiology includes both an inflammatory and demyelinating component which lead to axonal loss and neuronal degeneration (Oh et al., 2018). Its course varies among patients ranging from mild to severe. The diagnosis is based on the clinical presentation caused by demyelinating lesions on MRI with dissemination in time and space (Sand, 2015).

Once MS suspected, MRI imaging is considered a sensitive way to detect the brain and spinal cord lesions (Brownlee et al., 2017). Advanced MRI modalities such as diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI) yield more detailed data about structural lesions and better understanding more than the conventional MRI scans (Zivadinov and Leist, 2005).

There is little data regarding the relationship between cognitive impairment and MS course. Some studies have examined the effect of disease duration on cognitive deficits, indicating that they tend to increase with time. However, the age act as a confounder (Lynch et al., 2005; Rogers and Panegyres, 2007). Among patients with radiologically isolated syndrome, cognitive deficits have been observed, and their profile is similar to that of RRMS and clinically isolated syndromes (CIS), while cognitive impairment is more prominent in RRMS than CIS (Achiron et al., 2013; Brochet and Ruet, 2019; Chiaravalloti and DeLuca, 2008).

DTI metrics are superior to the conventional MRI modalities. in evaluating the white matter architecture (Lin et al., 2008). Additionally, FA and MD can quantitively evaluate the integrity of white matter tracts distorted by CNS disease (Lope-Piedrafita, 2018). FA provides data on water anisotropy diffusion according to the orientation of fibers in comparison while MD which evaluates the average diffusivity in all directions (Basser and Pierpaoli, 2011).

Symbol Digit Modality Test (SDMT) is one of the most used tests in the evaluation of cognitive status among MS patients. It measures attention, concentration, and information processing speed (Smith, 1982). Paced auditory serial addition test (PASAT) test is another measure of cognitive function. SDMT has more validity and reliability than PASAT- 3 s test (Sonder et al., 2014). Additionally, SDMT is simpler and has a relatively higher sensitivity than PASAT-3 in the assessment of cognition in MS (López-Góngora et al., 2015).

Previous studies reported a correlation between cognitive impairment and several gray matter structures, such as caudate, putamen, thalamus, cerebellum and cortical surface thickness (Bross et al., 2021; Matias-Guiu et al., 2018). Limited data are available on the contribution of white matter to the cognitive status of MS population (Lorefice et al., 2020; Nocentini et al., 2014). The aim of this study is to shed more light on the correlations between certain WM regions and cognition using 3T MRI and clinical tests, such as the SDMT and PASAT-3. This can guide us further to early detection of cognitive impairment among MS patients, especially patients with mild disability.

A significant correlation between CI and lesions WML consistent with the classic concept of a disconnection syndrome was observed in one of the earliest MRI research on CI in MS (Rao et al., 1989a). More recent MRI research found links between CI and deep and cortical gray matter (GM) atrophy (Meijer et al., 2018a; Pravatà et al., 2017a; Matías-Guiu et al., 2018a; Riccitelli et al., 2011a; Gouveia et al., 2017a; Schoonheim and Geurts, 2019a; Eijlers et al., 2017a). We found mixed results regarding the role of WML load and GM atrophy to CI in MS when we analyzed the several structural brain MRI studies on CI in MS, to the best of our knowledge, with the biggest numbers of CI patients included (Rao et al., 1989b; Eijlers et al., 2017b; Schoonheim and Geurts, 2019b; Gouveia et al., 2017b; Riccitelli et al., 2011b; Matías-Guiu et al., 2018b; Pravatà et al., 2017b; Meijer et al., 2018b).

The aim of this study is to shed more light on the correlations between certain WM regions and cognition using 3T MRI and clinical tests, such as the SDMT and PASAT-3. This can guide us further to early detection of cognitive impairment among MS patients, especially patients with mild disability.