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13 pages, 568 KB  
Article
Digit Span Tests Are More Sensitive than SDMT for Detecting Working Memory Impairment and Correlate with Metabolic Alterations in White Matter and Deep Gray Matter Nuclei in Multiple Sclerosis: A GABA-Edited Magnetic Resonance Spectroscopy Study
by Ján Grossmann, Marián Grendár, Petra Hnilicová, Nina Kováčiková, Lucia Kotul’ová, Wolfgang Bogner, Egon Kurča and Ema Kantorová
Int. J. Mol. Sci. 2025, 26(18), 8842; https://doi.org/10.3390/ijms26188842 - 11 Sep 2025
Viewed by 337
Abstract
In this paper, we aimed to evaluate the efficacy and usefulness of three brief, easy-to-administer, and repeatable tests, namely SDMT, Digit Span Forward (DSF), and Digit Span Backward (DSB) in MS patients (MSp), and compared the results with those of healthy volunteers (CONs). [...] Read more.
In this paper, we aimed to evaluate the efficacy and usefulness of three brief, easy-to-administer, and repeatable tests, namely SDMT, Digit Span Forward (DSF), and Digit Span Backward (DSB) in MS patients (MSp), and compared the results with those of healthy volunteers (CONs). We were hoping to identify the most sensitive test that could be used regularly in clinical practice. In addition, we tried to identify the metabolic background of the cognitive setting using the advanced radiological method, Mescher–Garwood (MEGA)-edited 1H Magnetic Resonance Spectroscopy (1H-MRS). A total of 22 relapsing MSp and 22 CONs were enrolled. The SDMT, DSF, and DSB tests were used on all participants. The patients also underwent a 1H-MRS brain examination. In addition to N-Acetyl-Aspartate (tNAA), Myoinositol (mIns), Choline (tCho), and Creatine (tCr) were also evaluated GABA and Glutamate–Glutamine (Glx) ratios. CONs were superior to MSp in the results of all neurocognitive tests. The DSB was found to be the most sensitive test for identifying MSp. The SDMT in MSp correlated with inflammatory and degenerative metabolites in the thalamus, hippocampus, and corpus callosum. A correlation between increased Glx- and GABA-ratios and SDMT was found. Unlike the SDMT, the DSF and DSB showed correlations with inflammatory metabolites in the caudate nucleus and hypothalamus. DSF correlated with GABA ratios in the hippocampus. Our study confirms the efficacy of DSF and DSB tests in evaluating working memory cognitive impairment in MSp, showing an association of the tests with specific brain metabolites. Full article
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13 pages, 524 KB  
Article
Plasma Neurofilament Light Chain Is Associated with Cognitive Functions but Not Patient-Reported Outcomes in Multiple Sclerosis
by Valerio Nicolella, Federica Novarella, Fabrizia Falco, Carmela Polito, Rosa Sirica, Evelina La Civita, Vincenzo Criscuolo, Giuseppe Corsini, Antonio Luca Spiezia, Alessia Castiello, Antonio Carotenuto, Maria Petracca, Roberta Lanzillo, Giuseppe Castaldo, Vincenzo Brescia Morra, Daniela Terracciano and Marcello Moccia
Neurol. Int. 2025, 17(9), 144; https://doi.org/10.3390/neurolint17090144 - 9 Sep 2025
Viewed by 745
Abstract
Objective: We aimed to explore associations between plasma neurofilament light chain (pNfL) and cognition through patient-reported outcomes (PROs) in multiple sclerosis (MS). Methods: In this cross-sectional study, we included 211 people with MS (PwMS) and collected data from pNfL (fully automated chemiluminescent enzyme [...] Read more.
Objective: We aimed to explore associations between plasma neurofilament light chain (pNfL) and cognition through patient-reported outcomes (PROs) in multiple sclerosis (MS). Methods: In this cross-sectional study, we included 211 people with MS (PwMS) and collected data from pNfL (fully automated chemiluminescent enzyme immunoassay), EDSS, education, cognition (the Symbol Digit Modalities Test (SDMT), California Verbal Learning Test-II (CVLT II), and Brief Visuospatial Memory Test–Revised (BVMT-R)), the Modified Fatigue Impact Scale (MFIS), Beck Depression Inventory (BDI-II), Beck Anxiety Inventory (BAI), and Pittsburgh Sleep Quality Index (PSQI). Results: On multivariate linear regression models, higher educational attainment was significantly associated with lower pNfL (high school: Coeff = −0.22, 95% CI = −0.41 to −0.04, p = 0.019; university: Coeff = −0.22, 95% CI = −0.42 to −0.02, p = 0.030). In logistic regression models, the likelihood of having pNfL levels above normal thresholds increased by 56% for each one-point increment in the EDSS score (OR = 1.56, 95% CI = 1.23 to 1.98, p < 0.001) and was 2.5 times greater in individuals with impaired SDMT (OR = 2.50, 95% CI = 2.20 to 5.21, p = 0.014). No statistically significant associations were observed between pNfL and CVLT-II, BVMT-R, BDI-II, MFIS, BAI, or PSQI. Conclusions: Neuro-axonal damage in people with MS manifests clinically as increased disability and reduced attention and processing speed. However, these effects may be mitigated by greater brain resilience, as suggested by the protective role of higher educational attainment. The PROs assessed in this study showed no significant associations with pNfL levels, possibly due to measurement errors and heterogeneity, with limited sensitivity to neuro-axonal damage. Full article
(This article belongs to the Section Aging Neuroscience)
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24 pages, 843 KB  
Article
Brain Atrophy and Cognitive Impairment in Primary and Secondary Progressive Multiple Sclerosis Cohort—Similar Progressive MS Phenotype
by Bartosz Gajewski, Małgorzata Siger, Iwona Karlińska, Igor A. Bednarski, Mariola Świderek-Matysiak and Mariusz Stasiołek
Int. J. Mol. Sci. 2025, 26(17), 8523; https://doi.org/10.3390/ijms26178523 - 2 Sep 2025
Viewed by 529
Abstract
The diagnosis and monitoring of progressive multiple sclerosis (PMS) require further development of fast and effective clinical tools. Relations between MRI-based brain atrophy measures and cognitive impairment in people with primary progressive and secondary progressive MS (PwPPMS, n = 20 and PwSPMS, n [...] Read more.
The diagnosis and monitoring of progressive multiple sclerosis (PMS) require further development of fast and effective clinical tools. Relations between MRI-based brain atrophy measures and cognitive impairment in people with primary progressive and secondary progressive MS (PwPPMS, n = 20 and PwSPMS, n = 19, respectively) were investigated in a prospective study with follow-up after a mean 14.97 ± 4.67 months. MRI analysis showed that at baseline and follow-up in PwSPMS, the left thalamic fraction and corpus callosum fraction were significantly lower than in PwPPMS (baseline: 0.39 ± 0.04 vs. 0.44 ± 0.06, p = 0.0203 and 0.26 ± 0.05 vs. 0.30 ± 0.05, p = 0.0097; respectively and follow-up: 0.40 ± 0.04 vs. 0.44 ± 0.07, p = 0.0443 and 0.25 ± 0.06 vs. 0.30 ± 0.05, p = 0.0103, respectively). In contrast, only at baseline, PwPPMS had a significantly lower cerebellar white matter fraction (CWMF) than PwSPMS (1.83 ± 0.20 vs. 2.01 ± 0.24, p = 0.0132). No other significant differences were observed in the MRI fractions at either study time point or in the changes of the MRI fractions between the PwPPMS and PwSPMS. However, a significant decline in the right putaminal fraction was found during observation in PwSPMS (0.332% ± 0.05% vs. 0.328% ± 0.05%, p = 0.0479). Cognitive test scores and their changes did not differ significantly between the subgroups. Declines in the Brief Visuospatial Memory Test Revised in the whole PMS group (18.74 ± 7.43 vs. 17.03 ± 7.61, p = 0.0209) and in PwPPMS (19.50 ± 8.29 vs. 17.20 ± 7.72, p = 0.0338), as well as in the Brief International Cognitive Assessment for Multiple Sclerosis in PwPPMS (1.05 ± 0.89 vs. 1.25 ± 1.02, p = 0.0421), were observed. In both PwPMS and PwPPMS, a worsening on the Symbol Digit Modalities Test (SDMT) was associated with the reduction of fractions of white matter, cerebellum and right thalamus. SDMT performance also correlated with both gray matter fraction (GMF) and CWMF in the whole group, and with cerebellar gray matter fraction (CGMF) in PwPPMS. In PwSPMS, only Stroop Color and Word Test scores correlated with GMF and CGMF. In conclusion, subtle differences between PwPPMS and PwSPMS were detected both in MRI and neuropsychological parameters. Thus, our results indicate the need for a multicomponent attempt in characterizing progression in different clinical courses of MS. Full article
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14 pages, 1391 KB  
Article
Correlation of Neurodegenerative Biomarkers and Functional Outcome in Patients with Relapsing–Remitting Multiple Sclerosis
by Elina Polunosika, Monta Feldmane, Daina Pastare, Joel Simren, Kaj Blennow, Nauris Zdanovskis, Henrik Zetterberg, Renars Erts and Guntis Karelis
Neurol. Int. 2025, 17(8), 123; https://doi.org/10.3390/neurolint17080123 - 7 Aug 2025
Viewed by 448
Abstract
Background and Objectives: Multiple sclerosis (MS) is a chronic autoimmune, inflammatory, and neurodegenerative central nervous system disease. Neurodegeneration plays a central role in long-term disease progression. Materials and Methods: This cross-sectional study examined the relationship between neurodegenerative biomarkers, namely plasma neurofilament [...] Read more.
Background and Objectives: Multiple sclerosis (MS) is a chronic autoimmune, inflammatory, and neurodegenerative central nervous system disease. Neurodegeneration plays a central role in long-term disease progression. Materials and Methods: This cross-sectional study examined the relationship between neurodegenerative biomarkers, namely plasma neurofilament light chain (pNfL) levels and MRI-derived brain volume measurements, and clinical outcomes in 49 patients with relapsing–remitting multiple sclerosis (RRMS). Plasma NfL levels were quantified using Simoa technology, while MRI data was analyzed via FreeSurfer to measure volumes of grey and white matter, specific brain structures, and ventricular sizes. Cognitive performance was assessed using the Symbol Digit Modalities Test (SDMT) and Brief Visuospatial Memory Test-Revised (BVMT-R). Disability was evaluated using the Expanded Disability Status Scale (EDSS). Results: The results indicated significant positive correlations between SDMT scores and volumes of grey matter, white matter, and various subcortical structures, suggesting that preserved brain volume is linked to better cognitive performance. Negative correlations were observed between SDMT scores and ventricular volumes, as well as between SDMT scores and EDSS scores, implying that cognitive decline corresponds with structural brain deterioration and increased disability. No significant associations were found between BVMT-R scores and imaging data or disability measures. Plasma NfL levels showed significant correlations with early disease relapses and enlargement of the third and fourth ventricles, but not with brain volume, cognitive tests, or EDSS scores. Conclusions: These findings indicate that MRI-based brain volumetrics, particularly grey and white matter measures, are stronger indicators of cognitive function and disability in RRMS than plasma NfL. Full article
(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)
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14 pages, 497 KB  
Article
Sensitivity and Specificity of a Revised Version of the TRACK-MS Screening Battery for Early Detection of Cognitive Impairment in Patients with Multiple Sclerosis
by Luisa T. Balz, Ingo Uttner, Daniela Taranu, Deborah K. Erhart, Tanja Fangerau, Stefanie Jung, Herbert Schreiber, Makbule Senel, Ioannis Vardakas, Dorothée E. Lulé and Hayrettin Tumani
Biomedicines 2025, 13(8), 1902; https://doi.org/10.3390/biomedicines13081902 - 4 Aug 2025
Viewed by 731
Abstract
Background/Objectives: Cognitive impairment is one of the most common and debilitating clinical features of Multiple Sclerosis (MS). Neuropsychological assessment, however, is time-consuming and requires personal resources, so, due to limited resources in daily clinical practice, information on cognitive profiles is often lacking, [...] Read more.
Background/Objectives: Cognitive impairment is one of the most common and debilitating clinical features of Multiple Sclerosis (MS). Neuropsychological assessment, however, is time-consuming and requires personal resources, so, due to limited resources in daily clinical practice, information on cognitive profiles is often lacking, despite its high prognostic relevance. Time-saving and effective tools are required to bridge this gap. This study evaluates the sensitivity and specificity of a revised version of TRACK-MS (TRACK-MS-R), a recently published screening tool to identify cognitive impairment in MS in a fast and reliable way, offering a balance between efficiency and diagnostic yield for the individual patient. Methods: In this prospective cross-sectional study, 102 MS patients and 94 age-, sex-, and education-matched healthy controls (HC) completed an extensive neuropsychological assessment, including TRACK-MS-R, to test for cognitive processing speed (Symbol Digit Modalities Test, SDMT) and verbal fluency (Regensburger Word Fluency Test, RWT). Sensitivity of TRACK-MS-R was assessed by using the BICAMS-M battery as a reference, and specificity was determined by comparing MS patients to HC. Results: TRACK-MS-R demonstrated high sensitivity (97.44%) when compared to the gold standard as represented by BICAMS-M for early and accurately detecting cognitive impairment in MS patients. Additionally, as a potential cognitive marker, TRACK-MS-R showed a specificity of 82.98% in distinguishing MS patients from healthy controls. Conclusions: TRACK-MS-R proves to be a highly sensitive and time-efficient screening tool for detecting cognitive impairment in patients with MS, while demonstrating good specificity compared to HC. Whereas high sensitivity is a prerequisite for a valid screening tool, its relatively modest specificity compared to BICAMS-M (62.9%) calls for caution in interpreting standalone results but instead indicates more extensive neuropsychological testing. Its briefness and diagnostic accuracy support its implementation in routine clinical practice, particularly in time-constrained settings. Full article
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13 pages, 4113 KB  
Article
VS Profile Inversion in Heterogeneous Granular Soil Deposits: Implications for Structural Design in a Study Site (Italy)
by Ferdinando Totani
Appl. Sci. 2025, 15(9), 5032; https://doi.org/10.3390/app15095032 - 1 May 2025
Viewed by 325
Abstract
Many urbanised areas of the Apennines, in Italy, have complex soil stratifications. A typical example is the outskirts of the city of L’Aquila, which is founded on highly heterogeneous soil layers and was severely affected by a strong earthquake in 2009. In such [...] Read more.
Many urbanised areas of the Apennines, in Italy, have complex soil stratifications. A typical example is the outskirts of the city of L’Aquila, which is founded on highly heterogeneous soil layers and was severely affected by a strong earthquake in 2009. In such conditions, shear wave velocity profiles (VS) obtained from in situ tests such as the Seismic Dilatometer Marchetti Test (SDMT) provide reliable analyses of the local seismic response. This article presents the mono-dimensional (1D) and two-dimensional (2D) seismic response analyses conducted to characterise the soil foundation of the hospital complex and adjacent university buildings in L’Aquila before their seismic retrofitting. This study emphasises the importance of accurate soil characterisation prior to repair interventions, especially in deposits where there are VS inversions and in the presence of geometrically irregular and large structures. Under these conditions, estimating the motion amplitudes of the deposit’s higher modes beyond the fundamental level is essential in accurately characterising the seismic response, especially for buildings where higher structural modes play a significant role. The results show that approximating the VS profile with simplified procedures, as proposed by the Italian Building Code of 2018 (equivalent VS, similar to average), leads to incorrect estimates of seismic action. Full article
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16 pages, 2545 KB  
Systematic Review
Cognitive Impairment in Newly Diagnosed Patients with Multiple Sclerosis: A Systematic Review of Related Molecular Biomarkers and a Meta-Analysis of Associated Demographic and Disease-Related Characteristics
by Konstantina Stavrogianni, Vasileios Giannopapas, Dimitrios K. Kitsos, Niki Christouli, Vassiliki Smyrni, Athanasios K. Chasiotis, Alexandra Akrivaki, Evangelia-Makrina Dimitriadou, John S. Tzartos, Georgios Tsivgoulis, George P. Paraskevas, Dimitrios Peschos, Konstantinos I. Tsamis and Sotirios Giannopoulos
J. Clin. Med. 2025, 14(8), 2630; https://doi.org/10.3390/jcm14082630 - 11 Apr 2025
Cited by 1 | Viewed by 970
Abstract
Background/Objectives: Neuropsychological impairment (NI) is common in newly diagnosed patients with multiple sclerosis (pwMS). This study has two main objectives; the systematic review aims to describe the relationship between NI and molecular biomarkers in newly diagnosed pwMS, and the meta-analysis aims to [...] Read more.
Background/Objectives: Neuropsychological impairment (NI) is common in newly diagnosed patients with multiple sclerosis (pwMS). This study has two main objectives; the systematic review aims to describe the relationship between NI and molecular biomarkers in newly diagnosed pwMS, and the meta-analysis aims to explore the relationship between NI, age, disability status, and disease duration in this patient group. Methods: We conducted a systematic review, with 20 studies meeting the inclusion criteria. Out of these, 12 studies were included in the meta-analysis. We analyzed three key cognitive measures—the Symbol Digit Modalities Test (SDMT), the Paced Auditory Serial Addition Test (PASAT), and the Selective Reminding Test–long-term storage (SRT-LTS)—in relation to demographic and MS-related characteristics. Results: Neurofilament light chain (NfL) levels were consistently associated with NI, especially a slower information processing speed (IPS). Other biomarkers, including chitinase 3-like 1 (CHI3L1), brain-derived neurotrophic factor (BDNF), apolipoprotein E4 allele (APOE4), and vitamin D, also showed promising correlations with NI. A meta-regression analysis of 2380 pwMS indicated a negative association between SDMT score and disability status (p = 0.01). No significant associations were found for the PASAT with age, disability status, or disease duration (p > 0.05). Conclusions: These findings highlight the role of NfL as a biomarker related to NI in newly diagnosed pwMS and the association between IPS and disability status. Further research is needed with more homogeneous samples in terms of the disease duration, along with standardized cognitive assessments and a broader range of biomarkers, to improve our understanding and management of cognitive difficulties in the early stages of MS. Full article
(This article belongs to the Special Issue Biomarkers and Diagnostics in Neurological Diseases)
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11 pages, 915 KB  
Article
Backward Walking as a Marker of Mobility and Disability in Multiple Sclerosis: A Cross-Sectional Analysis
by Meral Seferoğlu, Abdulkadir Tunç, Ali Özhan Sıvacı, Samed Öncel, Tuğba Düztaban, Hamide Dikilitaş, Abdul Samed Görgül and Muhammed Furkan Öztürkci
Diagnostics 2025, 15(7), 936; https://doi.org/10.3390/diagnostics15070936 - 6 Apr 2025
Viewed by 874
Abstract
Background: Mobility impairments in multiple sclerosis (MS) significantly affect quality of life. This study evaluated the clinical utility and sensitivity of the Backward Timed 25-Foot Walk Test (B-T25FW) and its associations with key clinical measures in MS. Methods: A cross-sectional study was [...] Read more.
Background: Mobility impairments in multiple sclerosis (MS) significantly affect quality of life. This study evaluated the clinical utility and sensitivity of the Backward Timed 25-Foot Walk Test (B-T25FW) and its associations with key clinical measures in MS. Methods: A cross-sectional study was conducted with 129 ambulatory patients with MS from two centers. Disability (Expanded Disability Status Scale, EDSS), cognition (Symbol Digit Modalities Test, SDMT), manual dexterity (Nine-Hole Peg Test, 9HPT), fatigue, and forward and backward walking were assessed. Correlation and receiver operating characteristic (ROC) analyses were performed. Results: The participants included in the study were 76% female, with a mean age of 38 years, and the majority were diagnosed with relapsing–remitting MS (86.8%). Backward and forward walking times significantly correlated with key clinical measures, including the EDSS, SDMT, and 9HPT. Backward walking times showed moderate correlations with EDSS (r = 0.469) and weaker but significant correlations with 9HPT (r = 0.452) and disease duration (r = 0.245). Both walking tests were negatively correlated with SDMT scores. For prognostic purposes, forward walking exhibited slightly higher predictive power compared to backward walking. Conclusions: The B-T25FW is a clinically relevant, practical, and sensitive tool for assessing mobility impairments in individuals with MS. Its integration into clinical practice could complement forward walking assessments, enhancing disease monitoring and guiding interventions. Future research should validate its longitudinal utility. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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11 pages, 231 KB  
Article
Cognitive–Motor Coupling in Multiple Sclerosis: Do Chronological Age and Physical Activity Matter?
by Brenda Jeng, Peixuan Zheng and Robert W. Motl
Brain Sci. 2025, 15(3), 274; https://doi.org/10.3390/brainsci15030274 - 5 Mar 2025
Viewed by 996
Abstract
Background: People with multiple sclerosis (MS) often demonstrate both cognitive and physical dysfunctions, particularly with greater age and lower physical activity levels, and there is evidence of a relationship between these outcomes (i.e., cognitive–motor coupling) in MS. To date, little is known [...] Read more.
Background: People with multiple sclerosis (MS) often demonstrate both cognitive and physical dysfunctions, particularly with greater age and lower physical activity levels, and there is evidence of a relationship between these outcomes (i.e., cognitive–motor coupling) in MS. To date, little is known about cognitive–motor coupling when controlling for chronological age and levels of physical activity. Objectives: We examined cognitive–motor coupling in people with MS while accounting for chronological age and physical activity. Methods: The sample included 290 people with MS between the ages of 22 and 77 years. Participants underwent the Symbol Digit Modalities Test (SDMT) for cognitive processing speed and the California Verbal Learning and Memory Test–Second Edition (CVLT-II) for verbal learning and memory. Participants completed the 6-Minute Walk and the Timed 25-Foot Walk tests for walking endurance and speed, respectively. Participants wore an accelerometer for a 7-day period to measure moderate-to-vigorous physical activity (MVPA). Results: The bivariate correlation analyses indicated that cognitive function had moderate-to-strong associations with motor function (range of rs between 0.433 and 0.459). The linear regression analyses indicated cognitive–motor coupling between SDMT and motor function (with a range of β between 0.139 and 0.145) when controlling for demographic and clinical characteristics. The regression analyses further indicated that the CVLT-II was associated with motor function (with a range of β between 0.125 and 0.135) when controlling for demographic and clinical characteristics. When age and MVPA were entered into the regression analyses, SDMT was still associated with the motor function of individuals (β = 0.119), and CVLT-II was still associated with the motor function of individuals (with a range of β between 0.115 and 0.124). Conclusions: Cognitive–motor coupling is present in people with MS independent of chronological age and levels of physical activity. This warrants further investigation of the underlying mechanism and potential approaches for the management of co-occurring MS-related dysfunction. Full article
(This article belongs to the Special Issue From Bench to Bedside: Motor–Cognitive Interactions—2nd Edition)
35 pages, 19469 KB  
Article
Integrated Geotechnical Analysis of Allophanic Volcanic Ash Soils: SDMT and Laboratory Perspectives
by Eddy Fernando Sanchez, Jorge Albuja-Sánchez and Maritza Córdova
Appl. Sci. 2025, 15(3), 1386; https://doi.org/10.3390/app15031386 - 29 Jan 2025
Cited by 2 | Viewed by 1064
Abstract
The geological study area is volcano-tectonic in nature. Microscopic observations and mineralogical analyses revealed the presence of allophane and diatom clusters whose mineral compositions coincided with weathered andesites and dacites. Edometric consolidation tests showed a high porosity and a reduction in the void [...] Read more.
The geological study area is volcano-tectonic in nature. Microscopic observations and mineralogical analyses revealed the presence of allophane and diatom clusters whose mineral compositions coincided with weathered andesites and dacites. Edometric consolidation tests showed a high porosity and a reduction in the void ratio by up to five times. These are highly compressible soils with a Cc/Cs ratio of 12 to 15 and a specific gravity (Gs) of 2.4. Low initial bulk density (1.10 Mg/m3), high plasticity, and SUCS (OH) classification are typical of soft soils, with an effective friction angle (ɸ’CD) of 25.5° to 30° and effective cohesion (c’CD) of 11.90 to 47.27 KPa. The shear wave velocity for the first 10 m (Vs10) on average ranged from 78 m/s to 120 m/s, whereas that for the first 30 m (Vs30) was 169 m/s. The permeability, which was calculated indirectly, was between 2 × 10−7 and 3 × 10−8 m/s. With an organic matter content between 5% and 25%, the Caupicho soil is an organic mineral sediment that is not considered peat (non-peat). The results of this study serve as a basis for future analyses of soil dynamics, bearing capacity, and consolidation settlements in the medium and long term in an area of high urban growth in southern Quito, Ecuador. Full article
(This article belongs to the Special Issue Geotechnical Engineering: Principles and Applications)
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14 pages, 1277 KB  
Article
Functional and Cognitive Impairment in Patients with Relapsing–Remitting Multiple Sclerosis: Cognitive Tests and Plasma Neurofilament Light Chain Levels
by Elina Polunosika, Joel Simren, Arta Akmene, Nikita Klimovskis, Kaj Blennow, Daina Pastare, Henrik Zetterberg, Renars Erts and Guntis Karelis
Medicina 2025, 61(1), 70; https://doi.org/10.3390/medicina61010070 - 3 Jan 2025
Cited by 1 | Viewed by 1580
Abstract
Background and Objectives: Multiple sclerosis (MS) is a chronic inflammatory, autoimmune, and neurodegenerative disease of the central nervous system. The disease can manifest and progress with both physical and cognitive symptoms, affecting the patient’s daily activities. The aim of our study was to [...] Read more.
Background and Objectives: Multiple sclerosis (MS) is a chronic inflammatory, autoimmune, and neurodegenerative disease of the central nervous system. The disease can manifest and progress with both physical and cognitive symptoms, affecting the patient’s daily activities. The aim of our study was to investigate the correlation between functional status, cognitive functions, and neurofilament light chain levels in plasma in MS patients. Materials and Methods: In a cross-sectional study, MS patients with a relapsing–remitting course (according to McDonald’s criteria, 2017) (n = 42) from Riga East University Hospital and a control group (n = 42) were included. In the MS group, the functional status was determined using the Expanded Disability Status Scale (EDSS), and neurofilament light chain levels in plasma (pNfL) were detected using single molecule array (Simoa) technology. The symbol digit modalities test (SDMT), brief visuospatial memory test—revised (BVMT-R), and the nine-hole peg test (9-HPT) were performed on the MS and control groups, dividing the groups by education level. Results: On the SDMT spreading speed, the MS group performed worse than the control group. The median score for the control group was 94.0, and for the MS group, it was 81.3. Slower performance on the SDMT also correlated with a higher EDSS in the MS group. Cognitive processing speed and memory were better in the control group and among individuals with higher education in both groups. For the BVMT-R, we found no difference between the two groups; both groups were able to learn the task equally well, but we found a weak correlation between age and learning in both groups, which could be related to the normal aging process. Execution reaction speed on the 9-HPT with the dominant hand was slower in the MS group (24.1 s) than in the control group (19.4 s). In the MS group, we observed a trend between SDMT performance and pNfL levels: higher pNfL levels were found in individuals who performed more slowly on the SDMT. Conclusions: Cognitive and fine motor dysfunction correlates with neurological impairment and plasma neurofilament light chain levels in MS patients. Full article
(This article belongs to the Section Neurology)
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17 pages, 2137 KB  
Article
Validation of a Set of Clinical Criteria for the Diagnosis of Secondary Progressive Multiple Sclerosis
by Alin Ciubotaru, Daniel Alexa, Cristina Grosu, Lilia Böckels, Ioana Păvăleanu, Alexandra Maștaleru, Maria Magdalena Leon, Roxana Covali, Emanuel Matei Roman, Cătălina Elena Bistriceanu, Cristina Mihaela Ghiciuc, Doina Azoicăi and Emilian Bogdan Ignat
Brain Sci. 2024, 14(11), 1141; https://doi.org/10.3390/brainsci14111141 - 14 Nov 2024
Cited by 1 | Viewed by 1509
Abstract
Background/Objectives: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by progressive impairment of neuronal transmission due to focal demyelination. The most common form is RRMS (relapsing-remitting multiple sclerosis), which, under the influence of certain factors, can [...] Read more.
Background/Objectives: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by progressive impairment of neuronal transmission due to focal demyelination. The most common form is RRMS (relapsing-remitting multiple sclerosis), which, under the influence of certain factors, can progress to SPMS (secondary progressive multiple sclerosis). Our study aimed to validate the criteria proposed by a working group of the Romanian Society of Neurology versus the criteria proposed by a group of experts from Spain, Karolinska, and Croatia concerning the progression from RRMS to SPMS. Methods: This was done by gathering epidemiological data (age, gender) and by applying clinical tests such as the 9HPT (9-hole peg test), 25FWT (25-foot walk test), and EDSS (expanded disability status scale) tests and the SDMT test (symbol digit modalities test). The present research is a cohort study that included a number of 120 patients diagnosed with MS according to the McDonald Diagnostic Criteria 2017. The study was carried out between January 2023 and April 2024, including patients hospitalized in the Neurology Clinic of the Clinical Rehabilitation Hospital from Iasi, Romania. The data were collected at baseline (T0) and at a 12-month interval (T1). Results: The statistical analysis was conducted using Kaiser–Meyer–Olkin analysis, which indicated a value of 0.683, thus validating the clinical tests used. The correlation matrix and the linear regression for all the tests showed highly significant statistical results. Furthermore, the ROC curve analysis of the criteria suggested by the working group of the Romanian Society of Neurology demonstrated that the EDSS, 9HPT, and 25FWT are highly sensitive in diagnosing SPMS, an opinion that is shared with the Spanish experts, but not with the Karolinska expert panel. Using the criteria given by the Croatian expert group in the ROC curve analysis showed that only the EDSS was strongly significant for the progression to the SPMS phase. Conclusions: In conclusion, all clinical methods used demonstrated that they are valid and can contribute to identifying patients with an increased risk of progression. The model proposed by the Romanian Society of Neurology working group is similar to other countries’ expert opinions and can be used to detect the risk of disease progression and establish a more tailored therapeutic management of SPMS. Full article
(This article belongs to the Section Neuropharmacology and Neuropathology)
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11 pages, 242 KB  
Article
Severe Cognitive Impairment in Trauma-Affected Refugees—Exploring the Impact of Traumatic Brain Injury
by Linda Nordin, Søren Kit Bothe, Sean Perrin and Ia Rorsman
J. Clin. Med. 2024, 13(17), 5096; https://doi.org/10.3390/jcm13175096 - 28 Aug 2024
Cited by 1 | Viewed by 1731
Abstract
Background/Objectives: This study explores the relationship between cognitive performance measured by the Symbol Digit Modality Test (SDMT) and the severity of self-reported head injury, traumatic brain injury (TBI), post-traumatic stress disorder (PTSD), depression, pain, and psychosocial dysfunction in a population of trauma-affected [...] Read more.
Background/Objectives: This study explores the relationship between cognitive performance measured by the Symbol Digit Modality Test (SDMT) and the severity of self-reported head injury, traumatic brain injury (TBI), post-traumatic stress disorder (PTSD), depression, pain, and psychosocial dysfunction in a population of trauma-affected refugees. Refugees, especially those who have been subjected to torture, often face various difficulties, such as PTSD, depression and somatic disturbances (e.g., pain), which can significantly impact their day-to-day functioning. Methods: Participants included 141 adult refugees (38% women) with a mean age of 45.4 years (SD = 9.4) and 9.7 years (SD = 4.9) of education who were referred for treatment of post-traumatic distress to DIGNITY, Danish Institute Against Torture. Participants completed standardized self-report measures of PTSD, anxiety, depression, pain, and health-related disability and measures of trauma history, physical injuries including head injury and loss of consciousness, and the SDMT, a quick standardized performance-based measure of cognitive impairment. Results: Eighty-eight percent of participants evidenced signs of substantial cognitive impairment as indexed by lower SDMT scores. Those with a self-reported history of TBI, marked by loss of consciousness, exhibited lower SDMT scores and higher health-related disabilities. Severity of PTSD, depression, anxiety, and pain were highly correlated with lower SDMT scores. TBI history was not significantly associated with the severity of PTSD, depression, anxiety, or pain, suggesting a complex interplay among these factors. Conclusions: Cognitive impairments are prevalent in trauma-affected refugees, interacting with symptoms of post-traumatic stress and pain, likely explaining the high disability levels in this population. Further research should employ a broader range of cognitive measures and detailed investigations of head injury/TBI experiences to investigate their impact on overall functioning, treatment response, and longer-term outcomes. This study adds to a small but growing body of studies documenting cognitive impairments in trauma-affected refugees, highlighting the importance of addressing cognitive impairments in treatment for trauma-affected refugees, particularly those with histories of torture and TBI. Clinicians working with trauma-affected refugees should consider the assessment of cognitive difficulties as part of comprehensive care planning. Full article
(This article belongs to the Section Clinical Neurology)
17 pages, 729 KB  
Article
The Faces of “Too Late”—A Surprisingly Progressive Cohort of “Stable” Relapsing Remitting Multiple Sclerosis Patients
by Alin Ciubotaru, Cristina Grosu, Daniel Alexa, Roxana Covali, Alexandra Maștaleru, Maria Magdalena Leon, Thomas Gabriel Schreiner, Cristina Mihaela Ghiciuc, Emanuel Matei Roman, Doina Azoicăi and Emilian Bogdan Ignat
Medicina 2024, 60(9), 1401; https://doi.org/10.3390/medicina60091401 - 26 Aug 2024
Cited by 4 | Viewed by 1705
Abstract
Background and Objectives: Although available therapies have changed the natural evolution of multiple sclerosis (MS), in time some patients assume a progressive course and no longer respond to treatment. There is no definitive clinical or laboratory parameter to certify MS progression from [...] Read more.
Background and Objectives: Although available therapies have changed the natural evolution of multiple sclerosis (MS), in time some patients assume a progressive course and no longer respond to treatment. There is no definitive clinical or laboratory parameter to certify MS progression from relapsing remitting MS (RRMS) to secondary progressive MS (SPMS) in early phases of transition. Our study aims to evaluate the value of clinical parameters and serum neurofilament light chain levels (sNfLs) as early warning signs of conversion to SPMS. Materials and Methods: The Expanded Disability Status Scale (EDSS), Nine-Hole Peg Test (9HPT), 25-foot walk test (25FWT) and Symbol Digit Modalities Test (SDMT) were evaluated at 12 months apart in a cohort of 83 RRMS treated patients. sNfLs were evaluated at the second time point. Results: sNfLs correlate with EDSS and SDMT, with EDSS change and disease duration. Clinical parameters correlate among themselves and perform well in supporting the diagnosis of SPMS in logistic regression and ROC curves analysis. Eighty percent of the RRMS patients in our study (of which 65% are treated with high-efficacy disease-modifying drugs) showed some type of progression independent of relapses (PIRA) after 12 months, with one in five patients experiencing isolated cognitive worsening and almost two-thirds some type of motor worsening. We found no differences in terms of progression between patients treated with platform drugs versus high-efficacy drugs. Conclusions: An elevated level of progression independent of relapses (PIRA) was found in our cohort, with high-efficacy drugs providing no supplementary protection. As sNfL levels were correlated with the progression of EDSS (the main clinical progression marker), they may be considered potential prognostic markers, but further studies are necessary to precisely define their role in this direction. The lack of early sensitive markers for risk of progression may contribute to therapeutic delay and failure. Full article
(This article belongs to the Section Neurology)
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19 pages, 768 KB  
Article
Unlocking Cognitive Potential: Association of Sarcopenia and Mediterranean Diet on Cognitive Function in Community-Dwelling Elderly of the Dalmatian Region
by Julija Jelaska, Marijana Vučković, Ivana Gugić Ordulj, Ela Kolak, Lucija Šolić Šegvić, Zdravka Đapić Kolak, Irena Keser and Josipa Radić
Nutrients 2024, 16(7), 991; https://doi.org/10.3390/nu16070991 - 28 Mar 2024
Viewed by 2200
Abstract
The aim of this study was to determine the association between muscle strength, adherence to the Mediterranean diet (MeDi) and cognitive function in community-dwelling elderly. General data, data of body composition and anthropometric parameters, clinical and laboratory findings, cognitive test questionnaires (Mini-Mental State [...] Read more.
The aim of this study was to determine the association between muscle strength, adherence to the Mediterranean diet (MeDi) and cognitive function in community-dwelling elderly. General data, data of body composition and anthropometric parameters, clinical and laboratory findings, cognitive test questionnaires (Mini-Mental State Examination—MMSE, Trail Making Test—TMT, Symbol Digit Modalities Test—SDMT), and nutritional assessments (Mini Nutritional Assessment—MNA, Mediterranean Diet Serving Score—MDSS) were obtained for each study participant. Handgrip strength (HS) was used as one of the key parameters for defining probable sarcopenia, among the Short Physical Performance Battery test (SPPB) (for defining physical activity) and the strength, assistance with walking, rising from a chair, climbing stairs, and falls questionnaire (SARC-F). Our cross-sectional study involved 114 participants aged ≥ 60 years, and two-thirds of the participants were female (76.3% vs. 23.7%). Probable sarcopenia was found in 34.7% of them. Using bivariate regression analysis, cognitive deficit among the sarcopenic population was associated with the following groups of collected data: (a) sociodemographic-associated factors—advanced age (OR: 1.07; p = 0.004), single marital status (OR: 3.25; p = 0.03), and low level of education (OR: 0.22; p < 0.003); (b) behavioral-associated factors—duration of institutionalization (OR: 1.05; p = 0.007), performance of heavy physical work (OR: 6.26; p = 0.001), low physical activity (OR: 0.08; p = 0.002), and risk of malnutrition (OR: 3.87; p = 0.005); (c) disease-related factors—loss of appetite (OR: 2.24; p = 0.04), information processing speed (OR: 0.88; p < 0.001), blood pressure systolic/diastolic variables (OR: 0.96/0.96; p = 0.002/0.02), medications (OR: 1.19; p = 0.005), predictive sarcopenia score ≥ 4 (OR: 3.1; p = 0.003), and low muscle strength (OR: 0.92; p = 0.002). Cognitive preservation among the sarcopenic population was associated with married status (OR: 0.23; p = 0.20), a high level of education (OR: 0.18; p = 0.002), smoking (OR: 0.33; p = 0.02), high physical activity (OR: 0.07; p < 0.001), and dietary habits using poultry (OR: 0.12; p = 0.004). The results suggest a significant association between sarcopenia and cognitive function in community-dwelling elderly, highlighting the need for regular nutritional interventions in this special population. Full article
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