Cortical Thickness and Serum NfL Explain Cognitive Dysfunction in Newly Diagnosed Patients With Multiple Sclerosis

Abstract

Background and ObjectivesTo determine the relative importance of global or regional MRI and blood markers of neurodegeneration and neuroaxonal injury in predicting cognitive performance for recently diagnosed patients with multiple sclerosis (MS).MethodsThirty-five newly diagnosed patients with relapsing-remitting MS (RRMS) and 23 healthy controls (HCs) simultaneously completed a full clinical and neuropsychological assessment, structural brain MRI, and serum neurofilament light chain (sNfL) level test. Linear regression analyses were performed to determine which global or regional measures of gray matter (GM) atrophy and cortical thickness (CT), in combination with sNfL levels and clinical scores, are most strongly related to neuropsychological impairment.ResultsCompared with HCs, patients with MS showed bilateral thalamic GM atrophy (left, p = 0.033; right, p = 0.047) and diminished CT, particularly in the right superior and transverse temporal gyri (p = 0.045; p = 0.037). Regional atrophy failed to add predictive variance, whereas anxiety symptoms, sNfL, and global CT were the best predictors (R2 = 0.404; p < 0.001) of cognitive outcomes, with temporal thickness accounting for greater variance in cognitive deficits than global CT.DiscussionThalamic GM atrophy and thinning in temporal regions represent a distinctive MRI trait in the early stages of MS. Although sNfL levels alone do not clearly differentiate HCs and patients with RRMS, in combination with global and regional CT, sNfL levels can better explain the presence of underlying cognitive deficits. Hence, cortical thinning and sNfL increases can be considered 2 parallel neurodegenerative markers in the pathogenesis of progression in newly diagnosed patients with MS.

Serum neurofilament light and MRI predictors of cognitive decline in patients with secondary progressive multiple sclerosis: Analysis from the MS-STAT randomised controlled trial

“…31 These findings may relate to the location of the primary auditory cortex within the TTG, and its role in attention and learning from auditory cues. 30,32 The longitudinal changes in predictor variables, including change in sNfL, were not independently associated with cognitive performance, beyond the variance accounted for by baseline predictors. This may in part reflect the hypothesis that clinical progression, such as cognitive decline, is primed by earlier neuroinflammation.…”

Neurofilament light chain in blood as a diagnostic and predictive biomarker for multiple sclerosis: A systematic review and meta-analysis

“…For diagnosis value analysis, 4 studies detected plasma NfL (pNfL) concentrations [ 26 , 34 , 36 , 43 ] and the others measured serum NfL (sNfL) levels. Two studies applied ECL method [ 10 , 11 ], one used ELISA [ 40 ], and the others adopted the highly sensitive SIMOA mothed for NfL measurements in blood. Ten studies enrolled age-matched controls with MS patients [ 13 , 28 , 32 , 34 – 37 , 40 , 44 , 45 ] and 7 recruited sex-matched controls [ 28 , 32 , 34 – 36 , 40 , 43 ].…”

“…Two studies applied ECL method [ 10 , 11 ], one used ELISA [ 40 ], and the others adopted the highly sensitive SIMOA mothed for NfL measurements in blood. Ten studies enrolled age-matched controls with MS patients [ 13 , 28 , 32 , 34 – 37 , 40 , 44 , 45 ] and 7 recruited sex-matched controls [ 28 , 32 , 34 – 36 , 40 , 43 ]. The other 18 studies that did not declare whether controls were age-matched were then considered as not age-matched studies, even though there was no statistical difference of age at baseline comparison in some studies.…”

Emerging Biomarkers of Multiple Sclerosis in the Blood and the CSF: a Comprehensive Review of the Literature with a Focus on Neurofilaments and Therapeutic Considerations

“…Interestingly in a longitudinal assessment, baseline NfL levels correlated with the presence and volume of baseline Gd+ lesion; however, serum NfL levels at 52 weeks was not associated with Gd+ lesions at 52 weeks 320 . Similarly, another survey found no correlation between serum NfL levels and the number of Gd+ lesions 276,330 .…”

“…However, it has been suggested that a correlation between NfL levels and neuropsychological symptoms might exist. Accordingly, high serum NfL levels and cortical thickness have been reported to correlate with global neuropsychological performance measured by Brief Repeatable Battery of Neuropsychological Tests (BRB-N) and Paced Auditory Serial Addition Test (PASAT) 330 . In line with these results, a study on 39 patients showed an inverse association between CSF NfL levels and Brief International Cognitive Assessment for MS (BICAMS) test results in progressive but not RRMS 289 .…”