Franziska E Hildesheim1, Ralph H B Benedict2, Robert Zivadinov1,3, Michael G Dwyer1,3, Tom Fuchs1, Dejan Jakimovski1, Bianca Weinstock-Guttman2, Niels Bergsland4,5. 1. Department of Neurology, Buffalo Neuroimaging Analysis Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, 100 High St., Buffalo, NY, 14203, USA. 2. Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, Jacobs Comprehensive MS Treatment and Research Center, University at Buffalo, Buffalo, NY, USA. 3. Center for Biomedical Imaging at Clinical Translational Science Institute, University at Buffalo, State University of New York, Buffalo, NY, USA. 4. Department of Neurology, Buffalo Neuroimaging Analysis Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, 100 High St., Buffalo, NY, 14203, USA. npbergsland@bnac.net. 5. IRCCS, Fondazione Don Carlo Gnocchi ONLUS, Milan, Italy. npbergsland@bnac.net.
Abstract
BACKGROUND: The nucleus basalis of Meynert (NBM), representing the major source of cerebral cholinergic innervations, is vulnerable to neurodegeneration in Alzheimer's and Parkinson's disease. OBJECTIVE: To determine associations between NBM properties and cognitive outcomes in patients with multiple sclerosis (PwMS). METHODS: 84 PwMS and 19 controls underwent 3T MRI, the Paced Auditory Serial Addition Test (PASAT) and subtests of the Brief International Cognitive Assessment for MS (BICAMS). NBM volume, fractional anisotropy, mean diffusivity (MD), axial diffusivity and radial diffusivity (D⊥) were calculated. Analyses assessed relationships between cognition and NBM measures. Linear regressions evaluated the prognostic value of baseline measures in predicting cognitive change over 3 years of follow-up (n = 67). RESULTS: Cognitive tests correlated with NBM diffusivity in PwMS (range r = - 0.29 to r = - 0.40, p < 0.05). After accounting for NBM volume, NBM MD and D⊥ explained additional variance (adjusted R2 range 0.08-0.20, p < 0.05). Correlations between NBM imaging metrics and cognitive tests remained significant when including imaging parameters of other cognitive key brain regions in the models. After controlling for age, education, and baseline cognitive test score, NBM measures predicted change in cognition over follow-up in 5 of 10 and 2 of 10 assessments in the relapsing-remitting sample (n = 43) (adjusted R2 range from 0.23 to 0.38, p < 0.05) and secondary progressive sample (adjusted R2 of 0.280 and 0.183), respectively. CONCLUSIONS: NBM damage is linked to cognitive impairment in PwMS.
BACKGROUND: The nucleus basalis of Meynert (NBM), representing the major source of cerebral cholinergic innervations, is vulnerable to neurodegeneration in Alzheimer's and Parkinson's disease. OBJECTIVE: To determine associations between NBM properties and cognitive outcomes in patients with multiple sclerosis (PwMS). METHODS: 84 PwMS and 19 controls underwent 3T MRI, the Paced Auditory Serial Addition Test (PASAT) and subtests of the Brief International Cognitive Assessment for MS (BICAMS). NBM volume, fractional anisotropy, mean diffusivity (MD), axial diffusivity and radial diffusivity (D⊥) were calculated. Analyses assessed relationships between cognition and NBM measures. Linear regressions evaluated the prognostic value of baseline measures in predicting cognitive change over 3 years of follow-up (n = 67). RESULTS: Cognitive tests correlated with NBM diffusivity in PwMS (range r = - 0.29 to r = - 0.40, p < 0.05). After accounting for NBM volume, NBM MD and D⊥ explained additional variance (adjusted R2 range 0.08-0.20, p < 0.05). Correlations between NBM imaging metrics and cognitive tests remained significant when including imaging parameters of other cognitive key brain regions in the models. After controlling for age, education, and baseline cognitive test score, NBM measures predicted change in cognition over follow-up in 5 of 10 and 2 of 10 assessments in the relapsing-remitting sample (n = 43) (adjusted R2 range from 0.23 to 0.38, p < 0.05) and secondary progressive sample (adjusted R2 of 0.280 and 0.183), respectively. CONCLUSIONS: NBM damage is linked to cognitive impairment in PwMS.
Authors: Stijn Denissen; Oliver Y Chén; Johan De Mey; Maarten De Vos; Jeroen Van Schependom; Diana Maria Sima; Guy Nagels Journal: J Pers Med Date: 2021-12-11