Gender-related effect of clinical and genetic variables on the cognitive impairment in multiple sclerosis

Savettieri, Giovanni; Messina, Demetrio; Andreoli, Virginia; Bonavita, Simona; Caltagirone, Carlo; Cittadella, Rita; Farina, D.; Fazio, Maria; Girlanda, Paolo; Pira, Francesco Le; Liguori, Maria; Lugaresi, Alessandra; Nocentini, Ugo; Reggio, A.; Salemi, Giuseppe; Tedeschi, Gioacchino; Trojano, María; Valentino, Paola; Quattrone, Aldo

doi:10.1007/s00415-004-0508-y

Cited by 155 publications

(137 citation statements)

References 32 publications

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“…16 -18 Apart from an effect on information processing speed, 19 the effect of deep gray matter (DGM) atrophy on other cognitive domains remains unclear. In addition, while cognitive dysfunction differs between sexes, 13,20 whether potential sex differences in MS-inflicted DGM atrophy affect cognition has not been studied before.…”

Section: Discussionmentioning

confidence: 99%

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Subcortical atrophy and cognition

Schoonheim

Popescu²,

Lopes³

et al. 2012

Neurology

190

172

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Objectives: Gray matter (GM) atrophy is common in multiple sclerosis (MS), as is cognitive dysfunction. Understanding the exact relationship between atrophy and cognition requires further investigation. The aim of this study was to investigate the relationship between subcortical GM atrophy and cognition in early relapsing onset MS.Methods: Structural MRI and neuropsychological evaluations were performed in 120 patients (80 women) and 50 controls (30 women), part of an early inception cohort, 6 years postdiagnosis. Deep GM volumes were segmented automatically. Cognition was assessed in 7 domains.Stepwise linear regression was used to predict average cognition in the patient group.Results: Most deep GM volumes were reduced in patients, with larger effects on average in men (Ϫ11%) than in women (Ϫ6.3%). Only the bilateral hippocampus, amygdala, and right nucleus accumbens in men, and right hippocampus and nucleus accumbens, bilateral amygdala, and putamen in women, showed no atrophy compared to controls. All cognitive domains except visuospatial memory were affected in men; none were significantly affected in women. In the MS group, average cognition was best predicted by thalamic volume, sex, and education (adjusted R 2 ϭ 0.31), while lesion volume was not a significant predictor in the model. Conclusions:Six years postdiagnosis, almost all subcortical structures were affected by MS, especially in men. Cognition was most severely affected in male patients. Thalamic volume, sex, and education best predicted average cognition. These results underline the relevance of specific subcortical structures to cognition, as well as the relevance of (sex-specific) atrophy in MS. Neurology ® 2012;79:1754-1761 GLOSSARY BRB-N ϭ Brief Repeatable Battery for Neurological disease; DGM ϭ deep gray matter; DMT ϭ disease-modifying therapy; EDSS ϭ Expanded Disability Status Scale; GLM ϭ general linear model; GM ϭ gray matter; MS ϭ multiple sclerosis; NBV ϭ normalized whole brain volume; NCGMV ϭ normalized cortical gray matter volume; NDGMV ϭ normalized deep gray matter volume; NGMV ϭ normalized total gray matter volume; NWMV ϭ normalized total white matter volume; RRMS ϭ relapsingremitting multiple sclerosis; WM ϭ white matter.Atrophy of the gray matter (GM) and white matter (WM) is frequently found in multiple sclerosis (MS), 1,2 and can be reliably measured with MRI.3 Although already present in early stages, GM atrophy becomes much more dominant in the progressive phase of the disease. 4 As the clinical relevance and the specific histopathologic substrate of GM atrophy in MS is not well known, it is the subject of many recent studies. 5,6 While the relationship between brain atrophy and clinical measures has been investigated extensively in the past, 7 how atrophy relates to cognition is only recently becoming clearer. -11As cognitive dysfunction is common and present in all stages of the disease, 12-15 exploring the relationship between atrophy and cognition could provide valuable new information.As most studies that focus...

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Section: Discussionmentioning

confidence: 99%

“…13,20 DGM atrophy was most pronounced in the caudate, pallidum, and thalamus, although all DGM structures were found to be atrophic, except bilateral amygdala and the right hippocampus and nucleus accumbens. Volume reductions were generally larger in male patients (table e-1).…”

Section: Figure 2 Cognitive Correlations Of Thalamic Volumementioning

confidence: 94%

Subcortical atrophy and cognition

Schoonheim

Popescu²,

Lopes³

et al. 2012

Neurology

190

172

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“…4 Males have increased rates of brain atrophy, disability accrual, and cognitive impairment, irrespective of disease type. 5,6 In addition to chromosomal and epigenetic factors, gonadal hormones may contribute to sex-related differences in inflammation and neurodegeneration in MS. 7,8 Age-related declines in male testosterone levels 9 have been hypothesized to partially explain the later onset of MS relative to women.…”

Section: Introductionmentioning

confidence: 99%

The role of testosterone in MS risk and course

Chitnis

2018

Mult Scler

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Abstract:There is significant animal model data demonstrating a benefit of testosterone on both inflammatory and neuroprotective mechanisms relevant to multiple sclerosis (MS). Several studies have demonstrated lowered testosterone levels in up to 40% of men with MS. Lower testosterone levels were correlated with worsened scores of physical and cognitive disability. There is increasing data suggesting a role of testosterone in MS risk. A pilot study has demonstrated significant benefits of testosterone replacement therapy on cognitive, radiological, and immunological outcome measures in men with MS. Larger studies in other conditions have demonstrated concerns in terms of cardiovascular risk, which indicate the need for careful monitoring upon administration to MS patients. Further studies are needed to develop safer testosterone preparations, which preserve its multiple beneficial effects, as well as multicenter clinical trials to evaluate safety, dosing, and efficacy in larger populations of men with MS. Additionally, studies are needed to further explore the role of androgens as a risk factor for MS, particularly at key life transitions.

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“…S druge strane, i žene i muškarci osećaju zamor i fizičku slabost sa sličnom učestalošću (50,51). Osećaj kognitivne iscrpljenosti je takođe slično zastupljen kod žena i muškaraca (52).…”

Section: Polne Razlike U Epidemiološkim I Kliničkim Karakteristkama Msunclassified

Sex differences in the clinical presentation and therapy of multiple sclerosis

Nacka-Aleksić¹

2016

Arh farmaciju

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Kratak sadržajMultipla skleroza (MS) se češće javlja kod žena nego kod muškaraca i disproporcija između obolevanja žena i muškaraca od ove bolesti pokazuje tendenciju stalnog rasta. Pol ima kritičnu ulogu u razvoju, progresiji, kliničkim manifestacijama MS i odgovoru na terapiju. Ove razlike su, najverovatnije, posledica delovanja genetskih, epigenetskih i hormonskih faktora, razlika u izloženosti pojedinim sredinskim faktorima, kao i bioloških razlika između imunskog i nervnog sistema žena i muškaraca. Polne razlike u svim ovim aspektima se moraju uzeti u obzir prilikom dizajniranja i tumačenja rezultata istraživanja vezanih za patogenezu MS, a posebno prilikom razvoja novih terapijskih strategija i kliničkih istraživanja lekova namenjenih lečenju ove bolesti. Razumevanje mehanizama koji stoje u osnovi polnih razlika u patogenezi i/ili odgovoru na terapiju u MS bi moglo biti relevantno i za širi spektar autoimunskih bolesti u kojima je izražen polni dimorfizam u incidenci i prevalenci i/ili kliničkim manifestacijama bolesti.Ključne reči: polne razlike, multipla skleroza, DMT

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Gender-related effect of clinical and genetic variables on the cognitive impairment in multiple sclerosis

Abstract: The findings demonstrate that clinical and genetic factors play a role in men affected by MS developing cognitive impairment.

Cited by 155 publications

References 32 publications

Subcortical atrophy and cognition

Subcortical atrophy and cognition

The role of testosterone in MS risk and course

Sex differences in the clinical presentation and therapy of multiple sclerosis

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