Article

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: 7.01). 08/2007; 64(8):1157-61. DOI: 10.1001/archneur.64.8.1157
Source: PubMed

ABSTRACT 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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    • "In one study, a positive correlation between cortical volume values and performance in verbal memory, verbal fluency, and attention/concentration testing in cognitively impaired MS patients were reported (Amato et al., 2004). In a later study, patients with cognitive impairment displayed less cortical volume compared with cognitively preserved MS patients (Amato et al., 2007). Thus, progressive neocortical grey matter loss is likely to be relevant for MS-associated cognitive impairment. "
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    • "Decreased cerebral volume at 1 year of progression is correlated with the existence of cognitive impairment at 5 years (Summers et al., 2008). In addition, there is a distinct correlation between overall cortical thickness and cognitive impairment (Amato et al., 2007; Calabrese et al., 2010). "
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    • "Neuropsychological performance of patients with cognitive decline has been documented to correlate with cortical brain volume (Amato et al., 2004; Benedict et al., 2006a; Morgen et al., 2006), as well as cortical thickness (Calabrese et al., 2010). GM volume assessed longitudinally decreased more progressively in MS patients with deteriorating cognitive performance compared to patients with stable or improving cognitive state (Amato et al., 2007). The relevance of cortical damage in cognitive dysfunction of MS patients has been highlighted by studies of regional cortical atrophy (Calabrese et al., 2010; Morgen et al., 2006; Tekok-Kilic et al., 2007). "
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