Association of Neocortical Volume Changes With Cognitive Deterioration in Relapsing-Remitting Multiple Sclerosis

Department of Neurology, University of Florence, Viale Morgagni, 85-50134 Florence, Italy.
JAMA Neurology (Impact Factor: 7.42). 08/2007; 64(8):1157-61. DOI: 10.1001/archneur.64.8.1157
Source: PubMed


We previously reported selective decreases of neocortical volumes in patients with early relapsing-remitting (RR) multiple sclerosis (MS) with mild cognitive impairment, with a good correlation between cortical volumes and cognitive measures.
To assess the relevance of gray matter changes over time to changes in cognition in RRMS.
A longitudinal survey after 2.5 years. Each patient underwent a magnetic resonance imaging (MRI) protocol identical to that performed at baseline; cognitive performance was reassessed with the Rao Brief Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis.
Two university MS clinics.
Of 41 patients with RRMS who participated in the original cross-sectional study, 28 were available for the follow-up evaluation (18 women; mean +/- SD age, 37.1 +/- 8.9 years; mean +/- SD MS duration, 7.3 +/- 2.9 years; mean +/- SD Expanded Disability Status Scale score, 1.8 +/- 1.5).
We measured the percentage of brain volume changes, normalized cortical volume (NCV) changes, and normalized deep gray matter volume changes on conventional T1-weighted MRIs and changes in lesion load on T2-weighted MRIs. The number of tests failed on the Rao Brief Repeatable Battery were used to classify the patients as cognitively deteriorating or stable or improving.
We identified 12 of 28 cognitively deteriorating and 16 of 28 stable or improving patients. These subgroups did not differ in the mean +/- SD percentage of brain volume changes (-2.1% +/- 1.2% vs -1.3% +/- 1.3%; P = .11), normalized deep gray matter volume changes (-2.1 +/- 2.8 mL vs -0.6 +/- 3.1 mL; P = .60), and changes in lesion load on T2-weighted MRIs (1.9 +/- 2.6 mL vs 1.6 +/- 2.3 mL; P = .73). However, NCV changes were significantly higher in deteriorating than in stable or improving patients (-43.0 +/- 18.9 mL vs -17.8 +/- 26.6 mL; P = .007). In deteriorating patients, NCV changes were correlated with performance in a verbal fluency test (r = 0.73; P < .001). In a regression model, only NCV changes were significantly associated with deteriorating cognitive performance (odds ratio, 0.8; 95% confidence interval, 0.7-0.9).
Progressive neocortical gray matter loss is relevant to MS-associated cognitive impairment and may represent a sensitive marker of deteriorating cognitive performance in RRMS.

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    • "Neuroimaging findings have also provided evidence on the association between cognitive impairment and the extent of brain damage at the cortical and subcortical gray matter levels (Geurts, Calabrese, Fisher, & Rudick, 2012; Rovaris et al., 2000). Specifically, some studies highlight the relationship between thalamic and neocortical volume and cognitive impairment in MS patients (Amato et al., 2007) as well as the reduction in cortical activity in the prefrontal and parietal areas of brain and attentional problems (Pepping & Ehde, 2005). "
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    ABSTRACT: This study examines the long-term effectiveness of a combined cognitive-behavioral and neuropsychological intervention in a woman of 19 years old with multiple sclerosis, by evaluating functional neuroimaging, neuropsychological and psychometric testing. The results showed a partial improvement in some brain areas and brain inflammatory activity. There was an increase in attention, verbal memory, and nonverbal executive functioning as well as in the emotional state at posttest and one-year follow-up. This study indicates the need for including components of both cognitive-behavioral therapy and neuropsychological rehabilitation based on an individualized and tailored plan in standard treatments for multiple sclerosis. Future studies should further develop these contributions.
    No preview · Article · Oct 2014 · Neurocase
    • "Therefore, the normal appearing WM (NAWM) pathology did not strictly parallel the level of disconnection within networks in our study. As neither regional macroscopic lesions nor regional NAWM damage fully explained resting state connectivity changes, the functional disconnection in associative networks could be related to GM pathology, which has already been proposed to act on cognitive dysfunction (Amato et al., 2007; Calabrese et al., 2011; Morgen et al., 2006). "
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    ABSTRACT: Severe cognitive impairment involving multiple cognitive domains can occur early during the course of multiple sclerosis (MS). We investigated resting state functional connectivity changes in large-scale brain networks and related structural damage underlying cognitive dysfunction in patients with early MS. Patients with relapsing MS (3-5 years disease duration) were prospectively assigned to two groups based on a standardized neuropsychological evaluation: (1) cognitively impaired group (CI group, n = 15), with abnormal performances in at least 3 tests; (2) cognitively preserved group (CP group, n = 20) with normal performances in all tests. Patients and age-matched healthy controls underwent a multimodal 3T magnetic resonance imaging (MRI) including anatomical T1 and T2 images, diffusion imaging and resting state functional MRI. Structural MRI analysis revealed that CI patients had a higher white matter lesion load compared to CP and a more severe atrophy in gray matter regions highly connected to networks involved in cognition. Functional connectivity measured by integration was increased in CP patients versus controls in attentional networks (ATT), while integration was decreased in CI patients compared to CP both in the default mode network (DMN) and ATT. An anatomofunctional study within the DMN revealed that functional connectivity was mostly altered between the medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC) in CI patients compared to CP and controls. In a multilinear regression model, functional correlation between MPFC and PCC was best predicted by PCC atrophy. Disconnection in the DMN and ATT networks may deprive the brain of compensatory mechanisms required to face widespread structural damage. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
    No preview · Article · Sep 2014 · Human Brain Mapping
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    • "Several authors investigated the role of GM and its association with CI. In a group of RRMS patients, Amato et al. [69] found that cortical atrophy was correlated with a poor performance on NPS testing. In particular neocortical atrophy was associated with impairment in verbal memory, verbal fluency, and attention. "
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    ABSTRACT: Multiple sclerosis (MS) is an immune-mediated disease affecting central nervous system (CNS). Although MS is classically considered a white matter (WM) disease, the involvement of gray matter (GM) in the pathogenic process has been confirmed by pathology studies and MRI studies. Impairment of cognitive domains such as memory, mental processing speed, attention, and executive function can occur from the early stage of the disease and tends to worsen over time, despite stable physical symptoms. WM demyelination is moderately correlated with CI, suggesting that probably WM abnormalities alone cannot fully explain the extent of clinical symptoms in MS, including CI. Several MRI techniques have shown the involvement of GM in MS and the association between GM damage, physical disability, and CI. The aim of this review is to provide an overview of CI and GM damage assessed by structural brain MRI.
    Full-text · Article · Jan 2014
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