Effect of comorbidity on mortality in multiple sclerosis

Marrie, Ruth Ann; Elliott, Lawrence; Marriott, James; Cossoy, Michael; Blanchard, James; Leung, Stella; Yu, Nancy

doi:10.1212/wnl.0000000000001718

Cited by 185 publications

(151 citation statements)

References 37 publications

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“…Psychiatric comorbidity is associated with increased hospitalizations, increased mortality, and lower health‐related quality of life in MS (Marrie et al. 2015b,c). Psychiatric comorbidity is also associated with poor adherence to therapy (Mohr et al.…”

Section: Introductionmentioning

confidence: 99%

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Physical comorbidities increase the risk of psychiatric comorbidity in multiple sclerosis

et al. 2016

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BackgroundRisk factors for psychiatric comorbidity in multiple sclerosis (MS) are poorly understood.ObjectiveWe evaluated the association between physical comorbidity and incident depression, anxiety disorder, and bipolar disorder in a MS population relative to a matched general population cohort.MethodsUsing population‐based administrative data from Alberta, Canada we identified 9624 persons with MS, and 41,194 matches. Using validated case definitions, we estimated the incidence of depression, anxiety disorder, and bipolar disorder, and their association with physical comorbidities using Cox regression, adjusting for age, sex, socioeconomic status, and index year.ResultsIn both populations, men had a lower risk of depression and anxiety disorders than women, as did individuals who were ≥45 years versus <45 years at the index date. The risk of bipolar disorder declined with increasing age. The risks of incident depression (HR 1.92; 1.82–2.04), anxiety disorders (HR 1.52; 1.42–1.63), and bipolar disorder (HR 2.67; 2.29–3.11) were higher in the MS population than the matched population. These associations persisted essentially unchanged after adjustment for covariates including physical comorbidities. Multiple physical comorbidities were associated with psychiatric disorders in both populations.ConclusionPersons with MS are at increased risk of psychiatric comorbidity generally, and some physical comorbidities are associated with additional risk.

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Section: Introductionmentioning

confidence: 99%

“…It also did not evaluate the association of physical comorbidity with psychiatric comorbidities other than depression, even though other psychiatric conditions often co‐occur with depression and contribute to poor outcomes (Marrie et al. 2015b,c). …”

Section: Introductionmentioning

confidence: 99%

Physical comorbidities increase the risk of psychiatric comorbidity in multiple sclerosis

et al. 2016

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“… The relapse rate was 50% lower when patients switched from injectable diseasemodifying treatment to natalizumab than when they switched to fingolimod, but no difference was observed in disability progression 6 .  Although MS patients live longer than before, their life expectancy remains ~7 years shorter than that of a matched healthy population; treatment of comorbidities might improve survival 8 …”

Section: Competing Interestsmentioning

confidence: 99%

“…The impact of comorbidities on clinical symptoms and disability progression in MS is becoming clear, and knowledge of how physical and mental comorbidities affect MS will improve management of the complexity of the disease. In 2015, Marrie et al 8 addressed the question of whether comorbidities are responsible for the reduced survival associated with MS. They used population-based administrative data to study 5,797 people with MS and 28,807 healthy controls who were matched for sex, year of birth and geographical region.…”

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confidence: 99%

Managing the complexity of multiple sclerosis

Ciccarelli

Thompson

2016

Nat Rev Neurol

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The application of imaging biomarkers has provided new insights into the mechanisms of damage in multiple sclerosis (MS) and the risk of MS development and progression. The goal of eliminating all disease activity requires a timely escalation of treatment. This increasing complexity is compounded by the need to treat comorbidities.Multiple sclerosis (MS) is an increasingly complex disease in terms of its pathogenesis, comorbidities, prognosis and treatment, and successful patient management requires knowledge of this complexity. In 2015, there have been advances in our understanding of the mechanisms of the disease, ways in which to formulate patient prognoses, how best to escalate treatment escalation, and the role of comorbidities. All of these aspects need to be incorporated into an effective management plan (Fig. 1).The mechanisms that underlie the pathogenesis of MS are yet to be fully elucidated, but they are known to include a cascade of events that induce physical and cognitive deficits. A reduction in neuronal integrity and function that affects the grey matter compartment is thought to be the key pathological process that leads to cognitive impairment in MS. However, findings of a study published by Freeman et al. 1 in 2015 suggest that synaptic and/or dendritic damage occurs prior to quantifiable grey matter volume loss, and might reflect neuronal and axonal loss that contributes to clinical deficits.In this study, Freeman et al. 1 used [ 11 C]flumazenil ([ 11 C]FMZ) PET, which quantifies GABAA receptor density in vivo, to identify grey matter damage beyond cortical lesions 2 . FMZ is an antagonist of the central benzodiazepine receptor, a component of the GABAA receptor complex that is present on axosomatic and axodendritic synapses throughout the cortical and subcortical grey matter. The number of [ 11 C]FMZ binding sites per grey matter region was lower in several cortical areas (the parietal, cingulate, and insular cortices and the left frontal cortex) and subcortical regions (the thalamus, hippocampus and amygdala) in patients with MS than in healthy controls. Greater amounts of neuronal damage were seen in patients with secondary-progressive MS than in patients with relapsing-remitting MS (RRMS), but the most striking result was that [ 11 C]FMZ binding was lower in patients with RRMS than in healthy controls, even in the absence of significant grey matter atrophy. A significant relationship was found between the level of cortical [ 11 C]FMZ binding and performance on several cognitive tests. A goal of future research is to provide neuroprotective and reparative therapies that could be applied at such early stages of MS to stop or at least slow down neurodegeneration and reduce cognitive impairment in progressive MS 3 .Clinically isolated syndromes (CIS) represent a patient's first neurological episode that is suggestive of MS. Most patients with CIS develop RRMS within 5 years of onset, and most patients with MS develop progressive MS 10-15 years after onset of MS. Although challenging, formulat...

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“…3 When MS occurs in the presence of comorbidities, the combined effect of and interactions between conditions often result in a more rapid progression of disability, a reduction in quality of life, and an increase in mortality. 4 Comorbidity, which refers broadly to physical or mental conditions that exist at the time of diagnosis of MS or later but that are not a consequence of MS, occurs in up to 50% of individuals with this disease. 5 added database-specific terms for randomized controlled trials (RCTs) to limit the results to intervention research.…”

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confidence: 99%