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Sex Differences in Gray Matter Atrophy in Early Multiple Sclerosis: A Comprehensive Analysis of Brain Atrophy Progression
Sex Differences in Gray Matter Atrophy in Early Multiple Sclerosis: A Comprehensive Analys...
Sex Differences in Gray Matter Atrophy in Early Multiple Sclerosis: A Comprehensive Analysis of Brain Atrophy Progression

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20260202103627
ISBN  
9798315777960
DDC  
610
저자명  
McQueen, Breona Symone.
서명/저자  
Sex Differences in Gray Matter Atrophy in Early Multiple Sclerosis: A Comprehensive Analysis of Brain Atrophy Progression
발행사항  
[Sl] : University of California, Los Angeles, 2025
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2025
형태사항  
117 p
주기사항  
Source: Dissertations Abstracts International, Volume: 86-11, Section: B.
주기사항  
Advisor: Mackenzie-Graham, Allan.
학위논문주기  
Thesis (Ph.D.)--University of California, Los Angeles, 2025.
초록/해제  
요약Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system characterized by inflammation, neuroaxonal loss, and progressive neurological disability. Females are more susceptible to MS than males, with a ratio of approximately 3:1. Increased susceptibility of females occurs in many autoimmune diseases, suggestive of a fundamental sex-dependent immune mechanism as its etiology. Gray matter (GM) atrophy, a strong predictor of disability progression in MS, is not uniformly distributed across the brain and differs by sex. Brain atrophy, specifically gray matter (GM) atrophy, serves as a putative surrogate for neurodegeneration in MS. Regional gray matter atrophy has been observed in MS with clinical disabilities correlating strongly with atrophy in disability-specific neuroanatomical regions. Sensitive neuroimaging tools capable of detecting early, region-specific GM changes are needed to identify predictive biomarkers of clinical progression in MS.The primary aim of this dissertation was to investigate sex differences in the progression of gray matter (GM) atrophy during early multiple sclerosis (MS) and to identify region-specific predictors of clinical impairment. Sex differences in regional GM atrophy in MS were evaluated using a cohort of female and male MS subjects with age- and disease- matched healthy controls to reveal insights relevant to sex differences in neurodegeneration. In the third chapter, we employed voxel-based morphometry (VBM) and FreeSurfer-based cortical thickness analysis of cross-sectional data between MS patients and healthy controls. We found that while whole-brain GM volume did not differ significantly between patients and controls, region-specific GM loss was evident in both sexes. Females exhibited focal atrophy in the cerebellum, while males showed a broader pattern of neurodegeneration involving the cerebellum, thalamus, and medial frontal cortex-regions associated with motor control and executive function. Notably, males also demonstrated significantly worse performance on the 9-Hole Peg Test (9HPT), and cortical volume was positively correlated with PASAT3 cognitive scores in males but not females. In the fourth chapter, we conducted a longitudinal analysis of the same MS cohort to evaluate sex-specific trajectories of GM atrophy over time. Using voxel-wise analyses and regression analyses, we generated disability-specific GM atrophy maps and identified deep GM structures-particularly the cortex, thalamus and cerebellum-as vulnerable regions in both sexes. However, males displayed more statistically significant declines in GM volume and more pronounced associations between regional atrophy and measures of cognitive and motor disability.Together, these findings suggest that GM atrophy manifests differently between sexes early in the disease, with men exhibiting statistically significant widespread neurodegeneration and stronger structure-function correlations. Understanding these sex-based patterns of atrophy may provide critical insight into MS pathophysiology and help guide the development of more personalized and neuroprotective treatment strategies.
일반주제명  
Medicine
일반주제명  
Neurosciences
일반주제명  
Pathology
일반주제명  
Medical imaging
키워드  
Multiple sclerosis
키워드  
Gray matter atrophy
키워드  
Voxel-based morphometry
키워드  
Brain atrophy
키워드  
Sex differences
기타저자  
University of California, Los Angeles Physics and Biology in Medicine 009Y
기본자료저록  
Dissertations Abstracts International. 86-11B.
전자적 위치 및 접속  
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MARC

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■020    ▼a9798315777960
■035    ▼a(MiAaPQ)AAI32046550
■040    ▼aMiAaPQ▼cMiAaPQ
■0820  ▼a610
■1001  ▼aMcQueen,  Breona  Symone.
■24510▼aSex  Differences  in  Gray  Matter  Atrophy  in  Early  Multiple  Sclerosis:  A  Comprehensive  Analysis  of  Brain  Atrophy  Progression
■260    ▼a[Sl]▼bUniversity  of  California,  Los  Angeles▼c2025
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2025
■300    ▼a117  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  86-11,  Section:  B.
■500    ▼aAdvisor:  Mackenzie-Graham,  Allan.
■5021  ▼aThesis  (Ph.D.)--University  of  California,  Los  Angeles,  2025.
■520    ▼aMultiple  sclerosis  (MS)  is  a  chronic  demyelinating  disease  of  the  central  nervous  system  characterized  by  inflammation,  neuroaxonal  loss,  and  progressive  neurological  disability.  Females  are  more  susceptible  to  MS  than  males,  with  a  ratio  of  approximately  3:1.  Increased  susceptibility  of  females  occurs  in  many  autoimmune  diseases,  suggestive  of  a  fundamental  sex-dependent  immune  mechanism  as  its  etiology.  Gray  matter  (GM)  atrophy,  a  strong  predictor  of  disability  progression  in  MS,  is  not  uniformly  distributed  across  the  brain  and  differs  by  sex.  Brain  atrophy,  specifically  gray  matter  (GM)  atrophy,  serves  as  a  putative  surrogate  for  neurodegeneration  in  MS.  Regional  gray  matter  atrophy  has  been  observed  in  MS  with  clinical  disabilities  correlating  strongly  with  atrophy  in  disability-specific  neuroanatomical  regions.  Sensitive  neuroimaging  tools  capable  of  detecting  early,  region-specific  GM  changes  are  needed  to  identify  predictive  biomarkers  of  clinical  progression  in  MS.The  primary  aim  of  this  dissertation  was  to  investigate  sex  differences  in  the  progression  of  gray  matter  (GM)  atrophy  during  early  multiple  sclerosis  (MS)  and  to  identify  region-specific  predictors  of  clinical  impairment.  Sex  differences  in  regional  GM  atrophy  in  MS  were  evaluated  using  a  cohort  of  female  and  male  MS  subjects  with  age-  and  disease-  matched  healthy  controls  to  reveal  insights  relevant  to  sex  differences  in  neurodegeneration.  In  the  third  chapter,  we  employed  voxel-based  morphometry  (VBM)  and  FreeSurfer-based  cortical  thickness  analysis  of  cross-sectional  data  between  MS  patients  and  healthy  controls.  We  found  that  while  whole-brain  GM  volume  did  not  differ  significantly  between  patients  and  controls,  region-specific  GM  loss  was  evident  in  both  sexes.  Females  exhibited  focal  atrophy  in  the  cerebellum,  while  males  showed  a  broader  pattern  of  neurodegeneration  involving  the  cerebellum,  thalamus,  and  medial  frontal  cortex-regions  associated  with  motor  control  and  executive  function.  Notably,  males  also  demonstrated  significantly  worse  performance  on  the  9-Hole  Peg  Test  (9HPT),  and  cortical  volume  was  positively  correlated  with  PASAT3  cognitive  scores  in  males  but  not  females.  In  the  fourth  chapter,  we  conducted  a  longitudinal  analysis  of  the  same  MS  cohort  to  evaluate  sex-specific  trajectories  of  GM  atrophy  over  time.  Using  voxel-wise  analyses  and  regression  analyses,  we  generated  disability-specific  GM  atrophy  maps  and  identified  deep  GM  structures-particularly  the  cortex,  thalamus  and  cerebellum-as  vulnerable  regions  in  both  sexes.  However,  males  displayed  more  statistically  significant  declines  in  GM  volume  and  more  pronounced  associations  between  regional  atrophy  and  measures  of  cognitive  and  motor  disability.Together,  these  findings  suggest  that  GM  atrophy  manifests  differently  between  sexes  early  in  the  disease,  with  men  exhibiting  statistically  significant  widespread  neurodegeneration  and  stronger  structure-function  correlations.  Understanding  these  sex-based  patterns  of  atrophy  may  provide  critical  insight  into  MS  pathophysiology  and  help  guide  the  development  of  more  personalized  and  neuroprotective  treatment  strategies.
■590    ▼aSchool  code:  0031.
■650  4▼aMedicine
■650  4▼aNeurosciences
■650  4▼aPathology
■650  4▼aMedical  imaging
■653    ▼aMultiple  sclerosis
■653    ▼aGray  matter  atrophy
■653    ▼aVoxel-based  morphometry
■653    ▼aBrain  atrophy
■653    ▼aSex  differences
■690    ▼a0564
■690    ▼a0574
■690    ▼a0317
■690    ▼a0571
■71020▼aUniversity  of  California,  Los  Angeles▼bPhysics  and  Biology  in  Medicine  009Y.
■7730  ▼tDissertations  Abstracts  International▼g86-11B.
■790    ▼a0031
■791    ▼aPh.D.
■792    ▼a2025
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17357990▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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