Does focal inflammation have an impact on cognition in multiple sclerosis? An MRI study

Fenu, Giuseppe; Arru, M.; Lorefice, Lorena; Frau, Jessica; Coghe, Giancarlo; Fronza, Marzia; Loi, L.; Barracciu, Maria Antonietta; Marrosu, Maria Giovanna; Cocco, Eleonora

doi:10.1016/j.msard.2018.05.012

Cited by 10 publications

(11 citation statements)

References 19 publications

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“…Moreover, these indices of CNS inflammation were down-regulated in GA-treated mice. These findings support a role for focal inflammation in the cognitive impairments detected using the T-maze task, in accord with a recent study that used MRI parameters and showed a connection between focal inflammation and cognitive loss in MS patients 46 . One of the ways by which focal inflammation contributes to cognitive impairment has been attributed to the lack of fine-tuning between the blood supply and the neuronal needs, elucidated in our recent studies 27 .…”

Section: Discussionsupporting

confidence: 92%

Cognitive impairment in an animal model of multiple sclerosis and its amelioration by glatiramer acetate

Aharoni

Schottlender

Bar-Lev

et al. 2019

Sci Rep

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The severe motor impairment in the MS animal model experimental autoimmune encephalomyelitis (EAE) obstructs the assessment of cognitive functions. We developed an experimental system that evaluates memory faculties in EAE-affected mice, irrespective of their motor performance, enabling the assessment of cognitive impairments along the disease duration, the associated brain damage, and the consequences of glatiramer acetate (GA) treatment on these manifestations. The delayed-non-matching to sample (DNMS) T-maze task, testing working and long term memory was adapted and utilized. Following the appearance of clinical manifestations task performances of the EAE-untreated mice drastically declined. Cognitive impairments were associated with disease severity, as indicated by a significant correlation between the T-maze performance and the clinical symptoms in EAE-untreated mice. GA-treatment conserved cognitive functions, so that despite their exhibited mild motor impairments, the treated mice performed similarly to naïve controls. The cognitive deficit of EAE-mice coincided with inflammatory and neurodegenerative damage to the frontal cortex and the hippocampus; these damages were alleviated by GA-treatment. These combined findings indicate that in addition to motor impairment, EAE leads to substantial impairment of cognitive functions, starting at the early stages and increasing with disease aggravation. GA-treatment, conserves cognitive capacities and prevents its disease related deterioration.

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Section: Discussionsupporting

confidence: 92%

Cognitive impairment in an animal model of multiple sclerosis and its amelioration by glatiramer acetate

Aharoni

Schottlender

Bar-Lev

et al. 2019

Sci Rep

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“…Mechanisms underlying slowed IPS in MS are still uncertain and are probably linked to a cortical–subcortical disconnection as a result of focal gray- and white-matter demyelination, as well as neuronal and brain volume loss [ 5 , 6 , 7 , 9 , 11 ]. An impairment in IPS was described simultaneously with Gd+ lesions, suggesting that cognition may also be influenced by focal inflammation [ 8 , 46 ]. CI was reported to range from 20% to 65–70% as a function of different disease subtypes, disease duration, and NPS test battery [ 2 , 3 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

“…Lastly, Gd+ lesions and WMLL were previously associated with impaired cognition [ 7 , 8 , 46 ]. We confirmed that patients with high WMLL at diagnosis achieved worse cognitive performances, but no differences were observed when comparing patients in terms of focal activity.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, IPS is probably not the consequence of a specific brain lesion but is more likely the result of a network disconnection syndrome [ 5 , 6 ]. Imaging studies have provided evidence of the role of white-matter demyelination, as well as focal inflammation, in cognition [ 7 , 8 , 9 , 10 ]. However, the extent of white-matter abnormalities did not fully explain CI in MS patients [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Serum Vitamin D as a Marker of Impaired Information Processing Speed and Early Disability in Multiple Sclerosis Patients

et al. 2021

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Slowed information processing speed (IPS) is the hallmark and first cognitive domain to be altered in multiple sclerosis (MS) patients. Insufficient serum vitamin D was previously associated with disease development, relapses, and progression, but little is reported on cognition. However, vitamin D and cognitive impairment (CI) in other neurodegenerative diseases have already been linked. We explored the possible correlation between vitamin D and IPS at diagnosis and early disability at last follow-up in 81 MS patients. At diagnosis, we collected vitamin D levels and performed a Symbol Digit Modalities Test (SDMT). Raw scores were adjusted for age, gender, and educational level. Early disability was evaluated with MS severity score (MSSS) and age-related MSSS (ARMSS). A total of 71 patients (86.58%) showed hypovitaminosis D (19.71 ± 8.76 ng/mL) and 18 patients (21.95%) had CI. Patients with CI showed severe hypovitaminosis D (p = 0.004). No patients with sufficient vitamin D levels had CI. We found a positive correlation between vitamin D levels at diagnosis and (1) SDMT raw and z-score that persisted after correction for sunlight exposure and MRI baseline characteristics, and (2) EDSS, MSSS, and ARMSS after a mean 2 year follow-up. Low vitamin D levels may affect both cognition and early disability in newly diagnosed MS patients.

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“…More in detail, in 2015, Damasceno and colleagues showed in clinically stable MS patients that the presence of Gd+ lesions was associated with cognitive performance independently from other MRI metrics such as cortical lesions or corpus callosum damage, 5 while later Fenu and colleagues showed that the presence of otherwise asymptomatic Gd+ lesions was associated with a loss of practice effect during serial cognitive evaluations. 6…”

mentioning

confidence: 99%

Do isolated cognitive relapses exist? Yes

Pardini

2021

Mult Scler

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Does focal inflammation have an impact on cognition in multiple sclerosis? An MRI study

Cited by 10 publications

References 19 publications

Cognitive impairment in an animal model of multiple sclerosis and its amelioration by glatiramer acetate

Cognitive impairment in an animal model of multiple sclerosis and its amelioration by glatiramer acetate

Serum Vitamin D as a Marker of Impaired Information Processing Speed and Early Disability in Multiple Sclerosis Patients

Do isolated cognitive relapses exist? Yes

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