Previous studies have shown that the nucleus basalis of Meynert (NBM), a group of neurons in the basal forebrain representing the major source of cholinergic innervations for the cerebral and subcortical cortex, is particularly vulnerable to neurodegeneration in Alzheimer’s disease (AD) and Parkinson’s disease (PD). Microstructural NBM damage, as reflected by increased diffusion tensor imaging (DTI)-derived measures of diffusivity, has been shown to be related to cognitive impairment in these diseases. As of now, the NBM has been scarcely investigated in multiple sclerosis (MS).
To determine associations between microstructural properties of the NBM and cognitive outcomes in patients with MS (PwMS).
84 PwMS (54 relapsing-remitting MS, 30 secondary progressive MS) underwent 3T MRI with a protocol that included a diffusion-weighted imaging acquisition. All PwMS underwent cognitive assessment with the Brief International Cognitive Assessment for MS (BICAMS), which includes the Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test-Revised (BVMT-R) and California Verbal Learning Test-2nd edition (CVLT-2). Standard DTI measures, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were calculated. A probabilistic map of the NBM was utilized to calculate DTI-derived measures. Partial correlations were used to assess the relationship between BICAMS cognitive outcomes and DTI assessments of the NBM, controlling for age and education.
Neuropsychological outcomes correlated with altered diffusivity within the NBM in PwMS. SDMT scores were associated with NBM measures of MD (r=-0.38, p<0.001), AD (r=-0.26, p=0.017), and RD (r=-0.40, p<0.001). BVMT-R was associated with MD (r=-0.33, p=0.002) and RD (r=-0.37, p=0.001), while CVLT-2 was associated with MD (r=-0.27, p=0.015), AD (r=-0.22, p=0.050) and RD (r=-0.27, p=0.016). After accounting for normalized NBM volume, NBM RD explained additional variance for SDMT (R2=0.24, p<0.001) and BVMT-R (R2=0.18, p=0.001), while NBM MD was retained for CVLT-2 (R2=0.17, p=0.015).
Our results show an association between cognitive impairment and microstructural NBM damage in PwMS, highlighting the potential role of NBM damage in determining the cognitive state in PwMS.