TY - JOUR
T1 - Multiple white matter tract abnormalities underlie cognitive impairment in RRMS
AU - Yu, Hui Jing
AU - Christodoulou, Christopher
AU - Bhise, Vikram
AU - Greenblatt, Daniel
AU - Patel, Yashma
AU - Serafin, Dana
AU - Maletic-Savatic, Mirjana
AU - Krupp, Lauren B.
AU - Wagshul, Mark E.
N1 - Funding Information:
The study was supported by the Lourie Foundation Incorporated , the National Multiple Sclerosis Society (Pediatric MS Center of Excellence) , the National Center for Research Resources (grant # 5-MO1-RR-10710 ), an independent medical grant from EMD Serono and Pfizer Inc, and an independent medical grant from Biogen Idec.
PY - 2012/2/15
Y1 - 2012/2/15
N2 - Diffusion tensor imaging (DTI) is a sensitive tool for detecting microstructural tissue damage . in vivo. In this study, we investigated DTI abnormalities in individuals with relapsing remitting multiple sclerosis (RRMS) and examined the relations between imaging-based measures of white matter injury and cognitive impairment. DTI-derived metrics using tract-based spatial statistics (TBSS) were compared between 37 individuals with RRMS and 20 healthy controls. Cognitive impairment was assessed with three standard tests: the Symbol Digit Modalities Test (SDMT), which measures cognitive processing speed and visual working memory, the Rey Auditory Verbal Learning Test (RAVLT), which examines verbal memory, and the Paced Auditory Serial Addition Test (PASAT), which assesses sustained attention and working memory. Correlations between DTI-metrics and cognition were explored in regions demonstrating significant differences between the RRMS patients and the control group. Lower fractional anisotropy (FA) was found in RRMS participants compared to controls across the tract skeleton (0.40. ±. 0.03 . vs. 0.43. ±. 0.01, p. <. 0.01). In areas of reduced FA, mean diffusivity was increased and was dominated by increased radial diffusivity with no significant change in axial diffusivity, an indication of the role of damage to CNS myelin in MS pathology. In the RRMS group, voxelwise correlations were found between FA reduction and cognitive impairment in cognitively-relevant tracts, predominantly in the posterior thalamic radiation, the sagittal stratum, and the corpus callosum; the strongest correlations were with SDMT measures, with contributions to these associations from both lesion and normal-appearing white matter. Moreover, results using threshold-free cluster enhancement (TFCE) showed more widespread white matter involvement compared to cluster-based thresholding. These findings indicate the important role for DTI in delineating mechanisms underlying MS-associated cognitive impairment and suggest that DTI could play a critical role in monitoring the clinical and cognitive effects of the disease.
AB - Diffusion tensor imaging (DTI) is a sensitive tool for detecting microstructural tissue damage . in vivo. In this study, we investigated DTI abnormalities in individuals with relapsing remitting multiple sclerosis (RRMS) and examined the relations between imaging-based measures of white matter injury and cognitive impairment. DTI-derived metrics using tract-based spatial statistics (TBSS) were compared between 37 individuals with RRMS and 20 healthy controls. Cognitive impairment was assessed with three standard tests: the Symbol Digit Modalities Test (SDMT), which measures cognitive processing speed and visual working memory, the Rey Auditory Verbal Learning Test (RAVLT), which examines verbal memory, and the Paced Auditory Serial Addition Test (PASAT), which assesses sustained attention and working memory. Correlations between DTI-metrics and cognition were explored in regions demonstrating significant differences between the RRMS patients and the control group. Lower fractional anisotropy (FA) was found in RRMS participants compared to controls across the tract skeleton (0.40. ±. 0.03 . vs. 0.43. ±. 0.01, p. <. 0.01). In areas of reduced FA, mean diffusivity was increased and was dominated by increased radial diffusivity with no significant change in axial diffusivity, an indication of the role of damage to CNS myelin in MS pathology. In the RRMS group, voxelwise correlations were found between FA reduction and cognitive impairment in cognitively-relevant tracts, predominantly in the posterior thalamic radiation, the sagittal stratum, and the corpus callosum; the strongest correlations were with SDMT measures, with contributions to these associations from both lesion and normal-appearing white matter. Moreover, results using threshold-free cluster enhancement (TFCE) showed more widespread white matter involvement compared to cluster-based thresholding. These findings indicate the important role for DTI in delineating mechanisms underlying MS-associated cognitive impairment and suggest that DTI could play a critical role in monitoring the clinical and cognitive effects of the disease.
KW - Cognitive impairment
KW - Diffusion tensor imaging
KW - Relapsing remitting multiple sclerosis
KW - Threshold-free cluster enhancement
KW - Tract-based spatial statistics
UR - http://www.scopus.com/inward/record.url?scp=84855175563&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84855175563&partnerID=8YFLogxK
U2 - 10.1016/j.neuroimage.2011.10.053
DO - 10.1016/j.neuroimage.2011.10.053
M3 - Article
C2 - 22062194
AN - SCOPUS:84855175563
SN - 1053-8119
VL - 59
SP - 3713
EP - 3722
JO - NeuroImage
JF - NeuroImage
IS - 4
ER -