Dataset Information

Cystatin C predicts cognitive decline in multiple system atrophy: A 1-year prospective cohort study.

ABSTRACT:

Background

Accumulating evidence has suggested that cystatin C is associated with cognitive impairment in patients with neurodegenerative diseases. However, the association between cystatin C and cognitive decline in patients with multiple system atrophy (MSA) remains largely unknown.

Objectives

The objective was to determine whether cystatin C was independently associated with cognitive decline in patients with early-stage MSA.

Methods

Patients with MSA underwent evaluation at baseline and the 1-year follow-up. Cognitive function was evaluated with Montreal cognitive assessment (MoCA). Changes in the MoCA score and the absolute MoCA score at the 1-year assessment were considered the main cognitive outcome. The cystatin C concentrations in patients with MSA and age, sex, and body mass index matched-healthy controls (HCs) were measured. A multiple linear regression model was used to test the association between cystatin C and cognitive decline.

Results

A total of 117 patients with MSA and 416 HCs were enrolled in the study. The cystatin C levels were significantly higher in patients with MSA than in HCs (p < 0.001). Cystatin C levels were negatively correlated with MoCA score at baseline and at 1-year follow-up. Multiple linear regression model adjusted for potential confounders showed that baseline cystatin C levels were significantly associated with the MoCA score (p = 0.004) or change in the MoCA score (p = 0.008) at 1-year follow-up.

Conclusion

Our results suggested that cystatin C may serve as a potential biomarker of cognitive decline in patients with early-stage MSA.

SUBMITTER: Zhang L

PROVIDER: S-EPMC9742413 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Cystatin C predicts cognitive decline in multiple system atrophy: A 1-year prospective cohort study.

Zhang Lingyu L Li Ruicen R Hou Yanbing Y Cao Bei B Wei Qianqian Q Ou Ruwei R Liu Kuncheng K Lin Junyu J Yang Tianmi T Xiao Yi Y Huang Wenxia W Shang Huifang H

Frontiers in aging neuroscience 20221128

<h4>Background</h4>Accumulating evidence has suggested that cystatin C is associated with cognitive impairment in patients with neurodegenerative diseases. However, the association between cystatin C and cognitive decline in patients with multiple system atrophy (MSA) remains largely unknown.<h4>Objectives</h4>The objective was to determine whether cystatin C was independently associated with cognitive decline in patients with early-stage MSA.<h4>Methods</h4>Patients with MSA underwent evaluatio ...[more]

PMID: 36518820

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Project description:BackgroundMultiple system atrophy (MSA) is a fatal and still poorly understood degenerative movement disorder that is characterised by autonomic failure, cerebellar ataxia, and parkinsonism in various combinations. Here we present the final analysis of a prospective multicentre study by the European MSA Study Group to investigate the natural history of MSA.MethodsPatients with a clinical diagnosis of MSA were recruited and followed up clinically for 2 years. Vital status was ascertained 2 years after study completion. Disease progression was assessed using the unified MSA rating scale (UMSARS), a disease-specific questionnaire that enables the semiquantitative rating of autonomic and motor impairment in patients with MSA. Additional rating methods were applied to grade global disease severity, autonomic symptoms, and quality of life. Survival was calculated using a Kaplan-Meier analysis and predictors were identified in a Cox regression model. Group differences were analysed by parametric tests and non-parametric tests as appropriate. Sample size estimates were calculated using a paired two-group t test.Findings141 patients with moderately severe disease fulfilled the consensus criteria for MSA. Mean age at symptom onset was 56·2 (SD 8·4) years. Median survival from symptom onset as determined by Kaplan-Meier analysis was 9·8 years (95% CI 8·1-11·4). The parkinsonian variant of MSA (hazard ratio [HR] 2·08, 95% CI 1·09-3·97; p=0·026) and incomplete bladder emptying (HR 2·10, 1·02-4·30; p=0·044) predicted shorter survival. 24-month progression rates of UMSARS activities of daily living, motor examination, and total scores were 49% (9·4 [SD 5·9]), 74% (12·9 [8·5]), and 57% (21·9 [11·9]), respectively, relative to baseline scores. Autonomic symptom scores progressed throughout the follow-up. Shorter symptom duration at baseline (OR 0·68, 0·5-0·9; p=0·006) and absent levodopa response (OR 3·4, 1·1-10·2; p=0·03) predicted rapid UMSARS progression. Sample size estimation showed that an interventional trial with 258 patients (129 per group) would be able to detect a 30% effect size in 1-year UMSARS motor examination decline rates at 80% power.InterpretationOur prospective dataset provides new insights into the evolution of MSA based on a follow-up period that exceeds that of previous studies. It also represents a useful resource for patient counselling and planning of multicentre trials.

Project description:BackgroundMultiple system atrophy is a rare, fatal neurodegenerative disorder with symptoms of autonomic failure plus parkinsonism, cerebellar ataxia, or both. We report results of the first prospective natural history study of multiple system atrophy in the USA, and the effects of phenotype and autonomic failure on prognosis.MethodsWe recruited participants with probable multiple system atrophy-of either the parkinsonism subtype (MSA-P) or the cerebellar ataxia subtype (MSA-C)-at 12 neurology centres in the USA specialising in movement or autonomic disorders. We followed up patients every 6 months for 5 years and assessed them with the Unified Multiple System Atrophy Rating Scale part I (UMSARS I; a functional score of symptoms and ability to undertake activities of daily living), UMSARS II (neurological motor evaluation), and the Composite Autonomic Symptoms Scale (COMPASS)-select (a measure of autonomic symptoms and autonomic functional status). We assessed potential predictors of outcome. We used Cox proportional hazards models to calculate univariate hazard ratios for shorter survival using age at disease onset as a continuous variable and sex, clinical phenotype, and early development of neurological and autonomic manifestations as categorical variables.FindingsWe recruited 175 participants. Mean age at study entry was 63·4 years (SD 8·6). Median survival from symptom onset was 9·8 years (95% CI 8·8-10·7) and median survival from enrolment was 1·8 years (0·9-2·7). Participants with severe symptomatic autonomic failure (symptomatic orthostatic hypotension, urinary incontinence, or both) at diagnosis (n=62) had a worse prognosis than those without severe disease (n=113; median survival 8·0 years, 95% CI 6·5-9·5 vs 10·3 years, 9·3-11·4; p=0·021). At baseline, patients with MSA-P (n=126) and MSA-C (n=49) had much the same symptoms and functional status: mean UMSARS I 25·2 (SD 8·08) versus 24·6 (8·34; p=0·835); mean UMSARS II 26·4 (8·8) versus 25·4 (10·5; p=0·764); COMPASS-select 43·5 (18·7) versus 42·8 (19·6; p=0·835). Progression over 5 years, assessed by change in UMSARS I, UMSARS II, and COMPASS-select, was modest.InterpretationProbable multiple system atrophy is a late-stage disease with short survival. The natural histories of MSA-P and MSA-C are similar and severe symptomatic autonomic failure at diagnosis is associated with worse prognosis.FundingUS National Institutes of Health, Mayo Clinic, and Kathy Shih Memorial Foundation.

Dataset Information

Cystatin C predicts cognitive decline in multiple system atrophy: A 1-year prospective cohort study.

Background

Objectives

Methods

Results

Conclusion

Publications

Cystatin C predicts cognitive decline in multiple system atrophy: A 1-year prospective cohort study.

Similar Datasets

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