Characterization of annual disease progression of multiple sclerosis patients: A population-based study

Freilich, Jonatan; Manouchehrinia, Ali; Trusheim, Mark R.; Baird, Lynn G.; Desbiens, Sophie; Berndt, Ernst R.; Hillert, Jan

doi:10.1177/1352458517706252

Cited by 10 publications

(7 citation statements)

References 23 publications

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“…[38][39][40] The association of LTL with all outcome measures was attenuated after adjustment for chronological age. [1][2][3]5,6 Age-adjusted models could be considered overly conservative, because the effect of LTL demonstrated in these models does not include the contribution of biological aging that occurs under the umbrella of effects associated with chronological age. [1][2][3]5,6 Age-adjusted models could be considered overly conservative, because the effect of LTL demonstrated in these models does not include the contribution of biological aging that occurs under the umbrella of effects associated with chronological age.…”

Section: Discussionmentioning

confidence: 99%

“…This confounding by chronological age was expected given that telomere length shortens with age 10,25 and age is associated with disability progression. [1][2][3]5,6 Age-adjusted models could be considered overly conservative, because the effect of LTL demonstrated in these models does not include the contribution of biological aging that occurs under the umbrella of effects associated with chronological age. However, the strength of our approach was to include this conservative model adjusting for birthdate and disease duration.…”

Section: Discussionmentioning

confidence: 99%

“…The association of LTL with all outcome measures was attenuated after adjustment for chronological age. This confounding by chronological age was expected given that telomere length shortens with age and age is associated with disability progression . Age‐adjusted models could be considered overly conservative, because the effect of LTL demonstrated in these models does not include the contribution of biological aging that occurs under the umbrella of effects associated with chronological age.…”

Section: Discussionmentioning

confidence: 99%

“…In pediatric MS, there are very few cases with a primary progressive (PP) phenotype (0.9% vs 8.5% in adults) and children with relapsing onset MS take longer to reach the secondary progressive (SP) phase of disease (32 vs 18 years) . In adults, chronological age has been associated with time to disability milestones independent of disease duration, with older patients experiencing shorter time intervals to ambulatory dysfunction . The average age at diagnosis of progressive MS in adults is 10 years older than that of relapsing–remitting (RR) MS, and age at onset of progression is highly similar between PP and SP disease (about 45 years) .…”

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confidence: 99%

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Telomere Length Is Associated with Disability Progression in Multiple Sclerosis

Krysko

Henry

Cree

et al. 2019

Annals of Neurology

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Objective: To assess whether biological aging as measured by leukocyte telomere length (LTL) is associated with clinical disability and brain volume loss in multiple sclerosis (MS). Methods: Adults with MS/clinically isolated syndrome in the University of California, San Francisco EPIC cohort study were included. LTL was measured on DNA samples by quantitative polymerase chain reaction and expressed as telomere to somatic DNA (T/S) ratio. Expanded Disability Status Scale (EDSS) and 3-dimensional T1-weighted brain magnetic resonance imaging were performed at baseline and follow-up. Associations of baseline LTL with cross-sectional and longitudinal outcomes were assessed using simple and mixed effects linear regression models. A subset (n = 46) had LTL measured over time, and we assessed the association of LTL change with EDSS change with mixed effects models. Results: Included were 356 women and 160 men (mean age = 43 years, median disease duration = 6 years, median EDSS = 1.5 [range = 0-7], mean T/S ratio = 0.97 [standard deviation = 0.18]). In baseline analyses adjusted for age, disease duration, and sex, for every 0.2 lower LTL, EDSS was 0.27 higher (95% confidence interval [CI] = 0.13-0.42, p < 0.001) and brain volume was 7.4mm 3 lower (95% CI = 0.10-14.7, p = 0.047). In longitudinal adjusted analyses, those with lower baseline LTL had higher EDSS and lower brain volumes over time. In adjusted analysis of the subset, LTL change was associated with EDSS change over 10 years; for every 0.2 LTL decrease, EDSS was 0.34 higher (95% CI = 0.08-0.61, p = 0.012). Interpretation: Shorter telomere length was associated with disability independent of chronological age, suggesting that biological aging may contribute to neurological injury in MS. Targeting aging-related mechanisms is a potential therapeutic strategy against MS progression.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Telomere Length Is Associated with Disability Progression in Multiple Sclerosis

Krysko

Henry

Cree

et al. 2019

Annals of Neurology

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“…They reach disability milestones within several years rather than several decades. These observations of the association of age with MS progression are independent of disease duration (4,5,10,15).…”

Section: Introductionmentioning

confidence: 67%

What telomeres teach us about MS

Miner

Graves

2021

Multiple Sclerosis and Related Disorders

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Changes in the Risk of Reaching Multiple Sclerosis Disability Milestones In Recent Decades

et al. 2019

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IMPORTANCE Clinicians' experience and findings from recent natural history studies suggest that multiple sclerosis (MS) may now be running a more slowly progressing course than before. OBJECTIVE To investigate whether the risk of reaching MS disability milestones has changed over the last decade in Sweden. DESIGN, SETTING, AND PARTICIPANTS A nationwide population-based retrospective cohort study. By April 2017, 12 512 patients with available information on demographics, MS phenotype, and date of MS onset and diagnosis were registered in the Swedish MS Registry of which 7331 patients with at least 2 recorded Expanded Disability Status Scale scores (EDSS) and diagnosed between January 1995 and December 2010 were included. No further exclusion criteria were applied. Patients were followed up until December 2016 with a median duration follow-up of 8.5 (interquartile range, 4.7-13.8) years. Statistical analysis began in April 2017. MAIN OUTCOMES AND MEASURES Patients were followed up from MS onset date to the date of sustained EDSS 3.0, 4.0, and 6.0. To handle interval-censored observations, a Weibull model was fit, and the change in the risk of EDSS 3.0, 4.0, and 6.0 over calendar years was estimated and hazard ratios (HRs) with corresponding CIs were calculated. RESULTS Of 7331 patients, 5196 (70.9%) were women, and the mean (SD) age at diagnosis was 38.3 (11.7) years. Adjusting for sex, number of clinic visits, diagnostic delay, and onset age, a 3% decrease per calendar year of diagnosis for the risk of sustained EDSS 3.0 (HR, 0.97; 95% CI, 0.96-0.97), a 6% decrease for the risk of EDSS 4.0 (HR, 0.94; 95% CI, 0.93-0.95), and a 7% decrease for the risk of EDSS 6.0 (HR, 0.93; 95% CI, 0.91-0.94) among patients with relapsing-onset MS was found. The trends were not significant for patients with progressive-onset MS (EDSS 3.

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Characterization of annual disease progression of multiple sclerosis patients: A population-based study

Abstract: Our study confirms that established factors associated with MS disease worsening in time to disease milestones also have impacts on annual progression. This approach adds granularity to what EDSS these factors have an influence.

Cited by 10 publications

References 23 publications

Telomere Length Is Associated with Disability Progression in Multiple Sclerosis

Telomere Length Is Associated with Disability Progression in Multiple Sclerosis

What telomeres teach us about MS

Changes in the Risk of Reaching Multiple Sclerosis Disability Milestones In Recent Decades

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