The association between California Verbal Learning Test performance and fibre impairment in multiple sclerosis: evidence from diffusion tensor imaging

Abstract

The California Verbal Learning Test (CVLT) is recognized as a standard clinical tool for assessing episodic memory difficulties in multiple sclerosis (MS), but its neural correlates have not yet been examined in detail in this patient population. We combined neuropsychological examination and diffusion tensor imaging (DTI) analysis in a group of MS patients (N = 50) and demographically matched healthy participants (N = 20). We investigated the degree of impairment of the uncinate fascicle (UF), the superior longitudinal fascicle (SLF), the fornix (FX) and the cingulum (CG). The patients were impaired on all CVLT parameters and the DTI parameters correlated moderately with disease-related variables. Regression analyses in the complete study sample showed that CVLT learning scores correlated with impairment of the right UF. This association reached marginal significance in the patient sample. In contrast to other studies claiming retrieval deficits, our results suggest that encoding and consolidation deficits may play a major role in verbal memory impairments in MS. The findings also provide evidence for an association between degree of myelination of prefrontal fibre pathways and encoding efficiency. Finally, DTI-derived measurements appear to reflect disease progression in MS. The results are discussed in light of functional MRI studies investigating compensatory brain activity during cognitive processing in MS.

Abnormal Long-Term Episodic Memory Profiles in Multiple Sclerosis?

“…To our knowledge, retrieval abilities, operationalized as the difference between free and cued recalls, have only rarely been reported in association with the CVLT in MS [27]. In the past, most authors compared delayed recall and recognition.…”

“…In previous group studies, executive memory difficulties in MS have been widely reported [8,[26][27][28] and have generally been described as encoding impairments [8,23]. Some authors are operationalized this deficit as a pathological score for both cued recalls and delayed recognition [28,26], although a storage deficit could also explain this long-term profile.…”

“…Some authors are operationalized this deficit as a pathological score for both cued recalls and delayed recognition [28,26], although a storage deficit could also explain this long-term profile. For others, encoding refers either to the first recallT1 [21,[38][39][40][41] which corresponds to the change of information from sensory input into a form that the memory system can store, or to the evolution throughout the first five trials (learning or acquisition), which corresponds to the change resulting from practice [9,16,27,[42][43][44][45][46]. Our individual results point to the existence of both these latter deficits, with encoding deficits being three times more common than learning deficits (58% and 19% of MS patients respectively).…”

“…Despite the existence of these numerous indices, approximately half of all the published experimental studies that used the CVLT to examine MS memory have only considered a few scores, the most popular being the total recall of the first five trials [9,27,29,30]. Among the most comprehensive studies [7,8,21,[23][24][25][26]28], only Diamond and colleagues [21] and Stegen and colleagues [8] exhaustively reported on raw scores.…”

Neuroimaging in Multiple Sclerosis: Neurotherapeutic Implications

“…Spectroscopy can be used to detect metabolites that reflect axonal/neuronal integrity and has been used as a measure of neuroprotective effects [103] and excitotoxicity [104]. Diffusion tensor imaging can be used to monitor tract-specific changes that may be more closely linked to clinical measures [105,106] and may be particularly powerful when combined with functional measures, such as functional MRI [107]. T1/T2 relaxation is another quantitative approach that may provide a better metric for diffuse brain changes occurring beyond traditional white matter regions [108] and to quantify myelin content [109].…”