Verbal fluency among older adults with multiple sclerosis: Word generation slope and fronto-striatal white matter integrity
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Abstract
•Objective: Verbal fluency (VF) is sensitive to cognitive decline in Multiple Sclerosis (MS). The decreasing rate of within-person word generation in VF, here referred to as slope, provides information beyond that of traditional total scores. Executively driven verbal functioning (represented, in part, by VF) is associated with fronto-subcortical systems, including fronto-striatal white matter. White matter degradation is a key feature of MS and is common in normal aging. We examined total VF and VF slope and their potential relationship with fronto-striatal white matter integrity and lesion load in older adults with and without MS. •Participants and Methods: 82 community-dwelling, dementia-free individuals with (Mage=64.6 ±4.2) and 84 without MS (Mage=69.8 ±6.6) completed standard 60-sec letter (LVF) and category (CVF) VF tasks and a 3T MRI scan. Mean fractional anisotropy (FA) and white matter lesion load of two white matter tracts (anterior caudate nucleus to the superior frontal cortex [CA-SFC] and nucleus accumbens to the rostral middle frontal cortex [NAcc-RMFC]) were examined in relation to total VF and VF slope in each group. •Results: Linear mixed effects models (LMEMs) showed negative VF slopes in both groups. Linear regressions and LMEMs showed that total scores and slopes, respectively, did not differ significantly between groups. Linear regressions indicated that greater whole-brain and right NAcc-RMFC lesion loads were associated with lower toal CVF in MS only. Left NAcc-RMFC lesion load was only related with lower total CVF in MS when adjusted for demographic variables. Three-way LMEMs revealed that CVF slope is attenuated with age and MS exacerbates this attenuation. •Conclusion: Similar total VF and VF slopes between groups suggest that the semantic and executive processes involved are similar in aging with and without MS. However, whole-brain and specified NAcc-RMFC lesion loads, but not FA, were associated with lower total CVF in MS. Thus, the disease-related pathology of white matter captured by lesion load may uniquely affect CVF performance in older adults with MS. The interaction effect of age and MS in CVF slope indicates a compound deleterious effect of aging and MS on the more semantically driven version of VF.