The association of cognitive impairment with gray matter atrophy and cortical lesion load in clinically isolated syndrome

https://doi.org/10.1016/j.msard.2016.08.008Get rights and content

Highlights

  • Visual memory was the most significantly affected cognitive domain in our patients with CIS.

  • Cognitive impairment was related to cerebral atrophy at this stage of disease.

  • The volume of deep GM structures correlated with SPART scores.

  • Cerebellar cortical volume was one of the predictors of visual memory impairment.

  • Cortical lesions, which was detected in 76% of patients, had no impact on cognition.

Abstract

Background

Multiple sclerosis can impair cognition from the early stages and has been shown to be associated with gray matter damage in addition to white matter pathology.

Objectives

To investigate the profile of cognitive impairment in clinically isolated syndrome (CIS), and the contribution of cortical inflammation, cortical and deep gray matter atrophy, and white matter lesions to cognitive decline.

Methods

Thirty patients with clinically isolated syndrome and twenty demographically- matched healthy controls underwent neuropsychologic assessment through the Rao Brief Repeatable Battery, and brain magnetic resonance imaging with double inversion recovery using a 3T scanner.

Results

Patients with clinically isolated syndrome performed significantly worse than healthy controls on tests that evaluated verbal memory, visuospatial learning and memory, and verbal fluency. Significant deep gray matter atrophy was found in the patients but cortical volume was not lower than the controls. Visual memory tests correlated with the volume of the hippocampus, cerebral white matter and deep gray matter structures and with cerebellar cortical atrophy. Cortical or white matter lesion load did not affect cognitive test results.

Conclusion

In our patients with CIS, it was shown that cognitive impairment was mainly related to cerebral white matter, cerebellar cortical and deep gray matter atrophy, but not with cortical inflammation, at least in the early stage of disease.

Introduction

Cognitive impairment may be present during the early stages of multiple sclerosis (MS) (Achiron and Barak, 2003) with a prevalence ranging from 40% to 70% (Amato et al., 2006). It has a dramatic impact on personal, social and occupational function (Amato et al., 2006). MS-related cognitive deterioration is characterized by involvement of recent memory, sustained attention, information processing speed, and executive function (Rao et al., 1991). The Brief Repatable Battery of Neuropsychological Tests (BRBN) assesses cognitive domains that are most frequently impaired in MS and incorporates tests of verbal memory, visual memory, attention, concentration, speed of information processing, and verbal fluency (Rao et al., 1991). Although cognitive profile has interpatient heterogenicity, information processing speed is generally accepted as the mostly affected cognitive domain in MS (DeLuca et al., 2004, Tekok-Kilic et al., 2007).

Recent studies showed that brain atrophy assesment was a better predictor of cognitive impairment in MS than lesion burden (Benedict et al., 2004, Bermel and Bakshi, 2006). Although the relationship between cognitive deterioration and subcortical white matter (WM) pathology remains controversial (Benedict et al., 2004, Rovaris et al., 2000, Rao et al., 1989), there is increasing evidence of a primary role of cortical pathology in determining cognitive disability (Tekok-Kilic et al., 2007, Portaccio et al., 2006, Benedict et al., 2006a,b). Gray matter (GM) atrophy appears to have unique, (Sanfilipo et al., 2006) if not greater (Dalton et al., 2004, Bakshi et al., 2005) clinical significance than WM lesions and/or volume. GM atrophy is more strongly related to cognitive decline, especially when the cerebral cortex is assessed (Amato et al., 2004, Benedict et al., 2006a, Benedict et al., 2006b). Besides cortical atrophy, cortical lesion load was recently shown to be associated with progression of cognitive disability in MS (Calabrese et al. (2012). Increased ability of detection of cortical lesions in MS by double inversion recovery (DIR) sequences has been shown previously (Wattjes et al., 2007).

In this study, we assessed the extent and the most affected domains of cognitive impairment and its probable correlations with GM pathology in a clinical cohort of patients with clinically isolated syndrome (CIS) who presented with a first episode suggestive of MS.

Section snippets

Participants

Thirty patients with CIS were studied [20 women and 10 men, mean age±standard deviation (SD) 31.4±8.5 years]. The recruited patients had been followed up at the neuroimmunology clinic of Hacettepe University Hospital between 2012 and 2014. McDonald's criteria were used for the diagnosis of CIS. Patients with visual or upper limb involvement that would interfere with neuropsychologic testing, other neurologic disease, major systemic disease, major psychiatric illness, drug or alcohol addiction,

Results

Main characteristics of patients with CIS and controls are detailed in Table 1.

Discussion

The prevalence of cognitive impairment in our CIS group (6.6%) was actually low when compared with rates in the literature, which range from 18% to 57%, (Feuillet et al., 2007, Khalil et al., 2011) and 40% to 70% (Rao et al., 1991, Benedict et al., 2006a, Benedict et al., 2006b) according to different reference criteria for CIS and MS, respectively. This might be due to the stringent criteria we used while analyzing the tests and the relatively short disease duration of our patients. In

Conflicts of interest

The authors report no conflicts of interest.

Acknowledgements

The authors thank the National Magnetic Resonance Research Centre (UMRAM) for providing the MRI facility, and Anıl Dolgun and Özgür Tosun for their help in the statistical work.

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