BACKGROUND: 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. OBJECTIVE: To assess the relevance of gray matter changes over time to changes in cognition in RRMS. DESIGN: 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. SETTING: Two university MS clinics. PATIENTS: 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). MAIN OUTCOME MEASURES: 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. RESULTS: 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). CONCLUSION: Progressive neocortical gray matter loss is relevant to MS-associated cognitive impairment and may represent a sensitive marker of deteriorating cognitive performance in RRMS.
BACKGROUND: 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. OBJECTIVE: To assess the relevance of gray matter changes over time to changes in cognition in RRMS. DESIGN: 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. SETTING: Two university MS clinics. PATIENTS: 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). MAIN OUTCOME MEASURES: 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. RESULTS: 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). CONCLUSION: Progressive neocortical gray matter loss is relevant to MS-associated cognitive impairment and may represent a sensitive marker of deteriorating cognitive performance in RRMS.
Authors: Tomas Uher; Jana Blahova-Dusankova; Dana Horakova; Niels Bergsland; Michaela Tyblova; Ralph H B Benedict; Tomas Kalincik; Deepa P Ramasamy; Zdenek Seidl; Jesper Hagermeier; Manuela Vaneckova; Jan Krasensky; Eva Havrdova; Robert Zivadinov Journal: J Neurol Date: 2014-06-22 Impact factor: 4.849
Authors: Sonia Batista; Robert Zivadinov; Marietta Hoogs; Niels Bergsland; Mari Heininen-Brown; Michael G Dwyer; Bianca Weinstock-Guttman; Ralph H B Benedict Journal: J Neurol Date: 2011-07-01 Impact factor: 4.849
Authors: Seyed-Parsa Hojjat; Charles Grady Cantrell; Rita Vitorino; Anthony Feinstein; Zahra Shirzadi; Bradley J MacIntosh; David E Crane; Lying Zhang; Sarah A Morrow; Liesly Lee; Paul O'Connor; Timothy J Carroll; Richard I Aviv Journal: Mult Scler Date: 2016-01-11 Impact factor: 6.312
Authors: Nicola De Stefano; Laura Airas; Nikolaos Grigoriadis; Heinrich P Mattle; Jonathan O'Riordan; Celia Oreja-Guevara; Finn Sellebjerg; Bruno Stankoff; Agata Walczak; Heinz Wiendl; Bernd C Kieseier Journal: CNS Drugs Date: 2014-02 Impact factor: 5.749