skip to main content


Title: Sex‐Specific Differences in Life Span Brain Volumes in Multiple Sclerosis
ABSTRACT BACKGROUND AND PURPOSE

Numerous sex‐specific differences in multiple sclerosis (MS) susceptibility, disease manifestation, disability progression, inflammation, and neurodegeneration have been previously reported. Previous magnetic resonance imaging (MRI) studies have shown structural differences between female and male MS brain volumes. To determine sex‐specific global and tissue‐specific brain volume throughout the MS life span in a real‐world large MRI database.

METHODS

A total of 2,199 MS patients (female/male ratio of 1,651/548) underwent structural MRI imaging on either a 1.5‐T or 3‐T scanner. Global and tissue‐specific volumes of whole brain (WBV), white matter, and gray matter (GMV) were determined by utilizing Structural Image Evaluation using Normalisation of Atrophy Cross‐sectional (SIENAX). Lateral ventricular volume (LVV) was determined with the Neurological Software Tool for REliable Atrophy Measurement (NeuroSTREAM). General linear models investigated sex and age interactions, and post hoc comparative sex analyses were performed.

RESULTS

Despite being age‐matched with female MS patents, a greater proportion of male MS patients were diagnosed with progressive MS and had lower normalized WBV (P < .001), GMV (P< .001), and greater LVV (P< .001). In addition to significant stand‐alone main effects, an interaction between sex and age had an additional effect on the LVV (F‐statistics = 4.53,P= .033) and GMV (F‐statistics = 4.59,P= .032). The sex and age interaction was retained in both models of LVV (F‐statistics = 3.31,P= .069) and GMV (F‐statistics = 6.1,P= .003) when disease subtype and disease‐modifying treatment (DMT) were also included. Although male MS patients presented with significantly greater LVV and lower GMV during the early and midlife period when compared to their female counterparts (P< .001 for LVV andP< .019 for GMV), these differences were nullified in 60+ years old patients. Similar findings were seen within a subanalysis of MS patients that were not on any DMT at the time of enrollment.

CONCLUSION

There are sex‐specific differences in the LVV and GMV over the MS life span.

 
more » « less
NSF-PAR ID:
10376673
Author(s) / Creator(s):
 ;  ;  ;  ;  ;  ;  ;  ;  
Publisher / Repository:
Wiley-Blackwell
Date Published:
Journal Name:
Journal of Neuroimaging
Volume:
30
Issue:
3
ISSN:
1051-2284
Page Range / eLocation ID:
p. 342-350
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract Objective

    Neurodegenerative conditions often manifest radiologically with the appearance of premature aging. Multiple sclerosis (MS) biomarkers related to lesion burden are well developed, but measures of neurodegeneration are less well‐developed. The appearance of premature aging quantified by machine learning applied to structural MRI assesses neurodegenerative pathology. We assess the explanatory and predictive power of “brain age” analysis on disability in MS using a large, real‐world dataset.

    Methods

    Brain age analysis is predicated on the over‐estimation of predicted brain age in patients with more advanced pathology. We compared the performance of three brain age algorithms in a large, longitudinal dataset (>13,000 imaging sessions from >6,000 individual MS patients). Effects of MS, MS disease course, disability, lesion burden, and DMT efficacy were assessed using linear mixed effects models.

    Results

    MS was associated with advanced predicted brain age cross‐sectionally and accelerated brain aging longitudinally in all techniques. While MS disease course (relapsing vs. progressive) did contribute to advanced brain age, disability was the primary correlate of advanced brain age. We found that advanced brain age at study enrollment predicted more disability accumulation longitudinally. Lastly, a more youthful appearing brain (predicted brain age less than actual age) was associated with decreased disability.

    Interpretation

    Brain age is a technically tractable and clinically relevant biomarker of disease pathology that correlates with and predicts increasing disability in MS. Advanced brain age predicts future disability accumulation.

     
    more » « less
  2. Abstract Study Objectives

    To use relatively noisy routinely collected clinical data (brain magnetic resonance imaging (MRI) data, clinical polysomnography (PSG) recordings, and neuropsychological testing), to investigate hypothesis-driven and data-driven relationships between brain physiology, structure, and cognition.

    Methods

    We analyzed data from patients with clinical PSG, brain MRI, and neuropsychological evaluations. SynthSeg, a neural network-based tool, provided high-quality segmentations despite noise. A priori hypotheses explored associations between brain function (measured by PSG) and brain structure (measured by MRI). Associations with cognitive scores and dementia status were studied. An exploratory data-driven approach investigated age-structure-physiology-cognition links.

    Results

    Six hundred and twenty-three patients with sleep PSG and brain MRI data were included in this study; 160 with cognitive evaluations. Three hundred and forty-two participants (55%) were female, and age interquartile range was 52 to 69 years. Thirty-six individuals were diagnosed with dementia, 71 with mild cognitive impairment, and 326 with major depression. One hundred and fifteen individuals were evaluated for insomnia and 138 participants had an apnea–hypopnea index equal to or greater than 15. Total PSG delta power correlated positively with frontal lobe/thalamic volumes, and sleep spindle density with thalamic volume. rapid eye movement (REM) duration and amygdala volume were positively associated with cognition. Patients with dementia showed significant differences in five brain structure volumes. REM duration, spindle, and slow-oscillation features had strong associations with cognition and brain structure volumes. PSG and MRI features in combination predicted chronological age (R2 = 0.67) and cognition (R2 = 0.40).

    Conclusions

    Routine clinical data holds extended value in understanding and even clinically using brain-sleep-cognition relationships.

     
    more » « less
  3. Abstract Objective

    Common obesity‐associated genetic variants at the fat mass and obesity‐associated (FTO) locus have been associated with appetitive behaviors and altered structure and function of frontostriatal brain regions. The authors aimed to investigate the influence ofFTOvariation on frontostriatal appetite circuits in early life.

    Methods

    Data were drawn from RESONANCE, a longitudinal study of early brain development. Growth trajectories of nucleus accumbens and frontal lobe volumes, as well as total gray matter and white matter volume, by risk allele (AA) carrier status onFTOsingle‐nucleotide polymorphism rs9939609 were examined in 228 children (102 female, 126 male) using magnetic resonance imaging assessments obtained from infancy through middle childhood. The authors fit functional concurrent regression models with brain volume outcomes over age as functional responses, andFTOgenotype, sex, BMIzscore, and maternal education were included as predictors.

    Results

    Bootstrap pointwise 95% CI for regression coefficient functions in the functional concurrent regression models showed that the AA group versus the group with no risk allele (TT) had greater nucleus accumbens volume (adjusted for total brain volume) in the interval of 750 to 2250 days (2–6 years).

    Conclusions

    These findings suggest that common genetic risk for obesity is associated with differences in early development of brain reward circuitry and argue for investigating dynamic relationships among genotype, brain, behavior, and weight throughout development.

     
    more » « less
  4. null (Ed.)
    Abstract Anxiety has been associated with greater risk of Alzheimer’s disease (AD) and existing research has identified structural differences in regional brain tissue in anxious compared to healthy samples, but results have been variable and somewhat inconsistent. We sought to determine the effect of anxiety on regional brain volumes by cognitive and apolipoprotein e (APOE) e4 status using data from a large, national dataset. A secondary analysis of the National Alzheimer’s Coordinating Center Uniform (NACC) Data Set was conducted using complete MRI data from 1,371 participants (mean age: 70.5; SD: 11.7). Multiple linear regression was used to estimate the adjusted effect of anxiety (via the Neuropsychiatric Inventory Questionnaire) on regional brain volumes through measurement of 30 structural MRI biomarkers. Anxiety was associated with lower total brain and total cortical gray matter volumes and increased lateral ventricular volume (p<.05). Lower mean volumes were also observed in all hippocampal, frontal lobe, parietal lobe, temporal lobe, and right occipital lobe volumes among participants who reported anxiety. Conversely, greater ventricular volumes were also correlated with anxiety. Findings suggest that anxiety is associated with significant atrophy in multiple brain regions and ventricular enlargement, even after controlling for intracranial volume and demographic covariates. Anxiety-related changes to brain morphology may contribute to greater AD risk. 
    more » « less
  5. Abstract Background

    Atrial fibrillation (AF) significantly reduces health‐related quality of life (HRQoL), previously measured in clinical trials using patient‐reported outcomes (PROs). We examined AF PROs in clinical practice and their association with subsequent clinical management.

    Methods

    The Utah My Evaluation (mEVAL) program collects the Toronto AF Symptom Severity Scale (AFSS) in AF outpatients at the University of Utah. Baseline factors associated with worse AF symptom score (range 0–35, higher is worse) were identified in univariate and multivariable analyses. Secondary outcomes included AF burden and AF healthcare utilization. We also compared subsequent clinical management at 6 months between patients with better versus worse AF HRQoL.

    Results

    Overall, 1338 patients completed the AFSS symptom score, which varied by sex (mean 7.26 for males vs. 10.27 for females;p < .001), age (<65, 9.73; 65–74, 7.66; ≥75, 7.58;p < .001), heart failure (9.39 with HF vs. 7.67 without;p < .001), and prior ablation (7.28 with prior ablation vs. 8.84;p < .001). In multivariable analysis, younger age (mean difference 2.92 for <65 vs. ≥75;p < .001), female sex (mean difference 2.57;p < .001), pulmonary disease (mean difference 1.88; p < .001), and depression (mean difference 2.46;p < .001) were associated with higher scores. At 6‐months, worse baseline symptom score was associated with the use of rhythm control (37.1% vs. 24.5%;p < .001). Similar cofactors and results were associated with increased AF burden and health care utilization scores.

    Conclusions

    AF PROs in clinical practice identify highly‐symptomatic patients, corroborating findings in more controlled, clinical trials. Increased AFSS score correlates with more aggressive clinical management, supporting the utility of disease‐specific PROs guiding clinical practice.

     
    more » « less