Author Of 2 Presentations
YI02.03 - Identifying distinct cognitive phenotypes in multiple sclerosis
Cognitive impairment is one of the most disabling symptoms of multiple sclerosis (MS), affecting about 50% of patients.
We sought to define homogeneous cognitive phenotypes in a large cohort of MS patients by using a data-driven approach, and to assess their distinctive clinical and MRI features.
A cohort of 1212 MS patients and 196 healthy controls (HC) from 8 Italian MS centers underwent cognitive evaluation with Rao’s Brief Repeatable Battery and Stroop Color Word Test. A subgroup (172 MS patients and 50 HC) also underwent a 3T MRI examination, including 3D T1-weighted and dual-echo sequences. Latent-profile analysis was used on cognitive tests’ z-scores for identifying cognitive phenotypes. Linear regression and mixed effects models were used to define the clinical and MRI features of each phenotype.
Five cognitive phenotypes were identified, characterized by “preserved-cognition” (19%), “mild verbal memory/semantic fluency” impairment (30%), “mild-multi-domain” impairment (19%), “severe-attention/executive” impairment with mild impairment of other domains (14%), and “severe-multi-domain” impairment (18%). “Preserved-cognition” patients had shorter disease duration and lower Expanded Disability Status Scale (EDSS) score than all other groups, and mildly impaired phenotypes included patients with shorter disease duration and less likely progressive disease compared to severely impaired groups. However, the “preserved-cognition” group also included patients with progressive disease and high EDSS scores, and severely impaired phenotypes were also represented in early MS stages. Comparing each phenotype to “preserved-cognition” group, distinctive MRI features emerged: “mild verbal memory/semantic fluency” patients had reduced hippocampal volume (p=0.02), “mild-multi-domain” reduced cortical gray matter volume (p=0.04), “severe-attention/executive” higher lesion volume (p=0.04) and severe-multi-domain” extensive brain damage (p<0.01 for lesion, brain, gray matter and thalamic volumes).
We identified five cognitive phenotypes of MS patients, with distinctive MRI substrates. By defining homogenous and clinically meaningful groups, this characterization may be useful for future research on cognitive impairment in MS, and for defining personalized management approaches and rehabilitative strategies in clinical practice.
YI02.05 - Cognition and socio-professional attainment in paediatric onset multiple sclerosis: a reappraisal after 10 years
- A. Bellinvia
- R. Fratangelo
- E. Portaccio
- M. Fonderico
- L. Tudisco
- L. Razzolini
- L. Pastò
- B. Goretti
- C. Niccolai
- A. Ghezzi
- M. Zaffaroni
- L. Pippolo
- L. Moiola
- M. Falautano
- C. Celico
- R. Viterbo
- F. Patti
- C. Chisari
- P. Gallo
- A. Riccardi
- M. Borghi
- M. Simone
- A. Bertolotto
- C. Pozzilli
- V. Bianchi
- M. Roscio
- V. Martinelli
- G. Comi
- M. Filippi
- M. Trojano
- M. Amato
Cognitive impairment (CI) affects nearly 30% of paediatric patients with Multiple Sclerosis (MS) and has a negative impact on school performance and participation in social activities. This study is a re-appraisal of cognitive functioning and socio-professional attainment in adulthood in an Italian cohort of paediatric MS patients after 10 years from baseline neuropsychological assessment.
To re-assess cognitive performance and its impact on socio-professional attainment in our cohort of paediatric MS patients after 10 years from baseline evaluation and to determine predictors of the individual outcomes.
Sixty-three paediatric patients were assessed at baseline and 48 followed-up after five years. To date, 31 out of these 48 patients (17 females, mean age 27.9±2.5 years, mean EDSS 1.7±1.6) were reassessed on an extensive neuropsychological battery and compared with a matched group of 31 healthy controls. CI was defined as the failure of > 2 tests. Socio-professional attainment was evaluated on the Work and Social Assessment Scale (WSAS). Predictors of CI and WSAS score were assessed through multivariable logistic and linear models.
After a mean follow-up of 12.5±2.3 years, 15 (54%) subjects were classified as cognitively impaired. Patients with CI compared with those cognitively preserved at follow-up had higher Expanded Disability Status Scale (EDSS) score (1.9±1.4 vs 1.0±0.7; p = 0.046), lower baseline intelligence quotient (IQ) (86.2±23.8 vs 103.6±14.7; p = 0.025) and were less frequently treated with disease modifying therapy (DMT) at baseline [6 (35.3%) vs 11 (78.6%); p = 0.016]. In the regression model, CI after 10 years was related to lower IQ (OR 0.93, 95% CI 0.87-0.99, p = 0. 027) and absence of DMT at baseline assessment (OR 17.78 95%; 1.72-183.65, p = 0.017).
Baseline predictors of worse socio-professional attainment on the WSAS in adulthood were CI (B=6.3, p=0.016), higher EDSS (B=2.2, p=0.023) and higher age at onset (B=0.6, p=0.041). As for 10-year correlates, only CI was associated to poor functional outcome (B=5.2, p=0.006).
Complete data collection is ongoing; available findings to date show that in paediatric onset subjects CI remains significant in adulthood, is related to lower cognitive reserve, higher levels of neurological impairment and delay in DMT initiation. Moreover, CI plays a key role in predicting the subject social performance and professional outcome. Early treatment and promotion of strategies aimed at enhancing cognitive reserve are recommended in paediatric patients with MS.
Author Of 1 Presentation
P0516 - BDNF Val66Met polymorphism effect on hippocampal subfields in multiple sclerosis patients (ID 1688)
Brain-derived neurotrophic factor (BDNF) can promote neuronal growth and repair, playing a key role in synaptic plasticity, especially in the hippocampus. The BDNF Val66Met polymorphism was shown to strongly affect BDNF function, but its role in modulating gray matter damage in multiple sclerosis (MS) patients is still not clear.
Considering BDNF relevance on hippocampal function, we aimed to explore the effect of BDNF Val66Met polymorphism on the atrophy of hippocampal subfields and its role in cognitive functioning in MS patients.
Using a 3T scanner, we obtained dual-echo and 3DT1-weighted sequences from 50 MS patients and 15 healthy controls (HC). MS patients also underwent genotype analysis of BDNF and an extensive neuropsychological evaluation. Hippocampal subfields were segmented by using Freesurfer 7.0.1 software. Multiple linear regression models adjusted for age, sex and disease duration were used for between-group comparisons and analysis of associations.
The BDNF Val66Met polymorphism was found in 22 MS patients (44%). Compared to HC, MS patients had reduced volumes of: bilateral hippocampus-amygdala transition area (HATA); left cornus ammonis (CA)1, CA3 and granule cell layer of dentate gyrus (GCL-DG); and right fimbria and presubiculum. BDNF Val66Met polymorphism carriers compared to wild-type (Val66Val) MS patients had higher volume of left hippocampal CA1, CA3, CA4, GCL-DG, molecular layer of subiculum and HATA; and of right hippocampal tail, fissure and presubiculum. In MS patients, higher volume in left CA3 and in right presubiculum correlated with better performance in semantic fluency, while higher volume in left GCL-DG correlated with better visuo-spatial memory performance.
The BNDF Val66Met polymorphism has a protective role in MS patients against both hippocampal atrophy and cognitive deterioration. BDNF genotype may be a potential biomarker for predicting cognitive prognosis, and an interesting target to study for neuroprotective strategies.