Pathways linking regional hyperintensities in the brain and slower gait
Identifieur interne : 005401 ( Main/Merge ); précédent : 005400; suivant : 005402Pathways linking regional hyperintensities in the brain and slower gait
Auteurs : Niousha Bolandzadeh [Canada] ; Teresa Liu-Ambrose [Canada] ; Howard Aizenstein [États-Unis] ; Tamara Harris [États-Unis] ; Lenore Launer [États-Unis] ; Kristine Yaffe [États-Unis] ; Stephen B. Kritchevsky [États-Unis] ; Anne Newman [États-Unis] ; Caterina Rosano [États-Unis]Source :
- NeuroImage : (Orlando, Fla.) [ 1053-8119 ] ; 2014.
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Abstract
Importance: Cerebral white matter hyperintensities (WMHs) are involved in the evolution of impaired mobility and executive functions. Executive functions and mobility are also associated. Thus, WMHs may impair mobility directly, by disrupting mobility-related circuits, or indirectly, by disrupting circuits responsible for executive functions. Understanding the mechanisms underlying impaired mobility in late life will increase our capacity to develop effective interventions. Objective: To identify regional WMHs most related to slower gait and to examine whether these regional WMHs directly impact mobility, or indirectly by executive functions. Design: Cross-sectional study. Twenty-one WMH variables (i.e., total WMH volume and WMHs in 20 tracts), gait speed, global cognition (Modified Mini-Mental State Examination; 3MS), and executive functions and processing speed (Digit-Symbol Substitution Test; DSST) were assessed. An L1-L2 regularized regression (i.e., Elastic Net model) identified the WMH variables most related to slower gait Multivariable linear regression models quantified the association between these WMH variables and gait speed. Formal tests of mediation were also conducted. Setting: Community-based sample. Participants; Two hundred fifty-three adults (mean age: 83 years, 58% women, 41% black). Main Outcome Measure: Gait speed. Results: In older adults with an average gait speed of 0.91 m/sec, total WMH volume, WMHs located in the right anterior thalamic radiation (ATRR) and frontal corpus callosum (CCF) were most associated with slower gait. There was a >10% slower gait for each standard deviation of WMH in CCF, ATRR or total brain (standardized beta in m/sec [p value]: -0.11 [p = 0.046], -0.15 [p = 0.007] and -0.14 [p = 0.010], respectively). These associations were substantially and significantly attenuated after adjustment for DSST. This effect was stronger for WMH in CCF than for ATRR or total WMH (standardized beta in m/sec [p value]: - 0.07 [p = 0.190], - 0.12 [p = 0.024] and -0.10 [p = 0.049], respectively). Adjustment for 3MS did not change these associations. The mediation analyses also found that DSST significantly mediated the associations between WMHs and gait speed. Our models were adjusted for age, sex, BMI, quadriceps strength, years of education, standing height, and prevalent hypertension. Conclusion: The impact, direct or indirect, of WMHs on gait speed depended on their location and was mediated by executive function. Thus, multi-faceted interventions targeting executive control functions as well as motor functions, such as balance and strength training, are candidates to the maintenance of mobility across the lifespan.
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Kritchevsky</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Sticht Center on Aging, Wake Forest School of Medicine</s1><s2>Winston-Salem, NC</s2><s3>USA</s3><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Winston-Salem, NC</wicri:noRegion></affiliation></author><author><name sortKey="Newman, Anne" sort="Newman, Anne" uniqKey="Newman A" first="Anne" last="Newman">Anne Newman</name><affiliation wicri:level="4"><inist:fA14 i1="08"><s1>Center for Aging and Population Health, School of Public Health, University of Pittsburgh</s1><s2>Pittsburgh, PA</s2><s3>USA</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Pittsburgh</settlement><region type="state">Pennsylvanie</region></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Rosano, Caterina" sort="Rosano, Caterina" uniqKey="Rosano C" first="Caterina" last="Rosano">Caterina Rosano</name><affiliation wicri:level="4"><inist:fA14 i1="08"><s1>Center for Aging and Population Health, School of Public Health, University of Pittsburgh</s1><s2>Pittsburgh, PA</s2><s3>USA</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Pittsburgh</settlement><region type="state">Pennsylvanie</region></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">14-0263326</idno><date when="2014">2014</date><idno type="stanalyst">PASCAL 14-0263326 INIST</idno><idno type="RBID">Pascal:14-0263326</idno><idno type="wicri:Area/PascalFrancis/Corpus">000441</idno><idno type="wicri:Area/PascalFrancis/Curation">004196</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000478</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000478</idno><idno type="wicri:doubleKey">1053-8119:2014:Bolandzadeh N:pathways:linking:regional</idno><idno type="wicri:Area/Main/Merge">005401</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Pathways linking regional hyperintensities in the brain and slower gait</title><author><name sortKey="Bolandzadeh, Niousha" sort="Bolandzadeh, Niousha" uniqKey="Bolandzadeh N" first="Niousha" last="Bolandzadeh">Niousha Bolandzadeh</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Aging, Mobility, and Cognitive Neuroscience Laboratory, Department of Physical Therapy, Faculty of Medicine, University of British Columbia</s1><s2>Vancouver, BC</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Brain Research Centre, University of British Columbia</s1><s2>Vancouver, BC</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Experimental Medicine Graduate Program, Department of Medicine, Faculty of Medicine, University of British Columbia</s1><s2>Vancouver, BC</s2><s3>CAN</s3><sZ>1 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC</wicri:noRegion></affiliation></author><author><name sortKey="Liu Ambrose, Teresa" sort="Liu Ambrose, Teresa" uniqKey="Liu Ambrose T" first="Teresa" last="Liu-Ambrose">Teresa Liu-Ambrose</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Aging, Mobility, and Cognitive Neuroscience Laboratory, Department of Physical Therapy, Faculty of Medicine, University of British Columbia</s1><s2>Vancouver, BC</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Brain Research Centre, University of British Columbia</s1><s2>Vancouver, BC</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC</wicri:noRegion></affiliation></author><author><name sortKey="Aizenstein, Howard" sort="Aizenstein, Howard" uniqKey="Aizenstein H" first="Howard" last="Aizenstein">Howard Aizenstein</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Geriatric Psychiatry Neuroimaging Laboratory, Faculty of Medicine, University of Pittsburgh</s1><s2>Pittsburgh, PA</s2><s3>USA</s3><sZ>3 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Pittsburgh</settlement><region type="state">Pennsylvanie</region></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Harris, Tamara" sort="Harris, Tamara" uniqKey="Harris T" first="Tamara" last="Harris">Tamara Harris</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Laboratory of Epidemiology and Population Sciences, National Institute on Aging</s1><s2>Bethesda, MD</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Bethesda, MD</wicri:noRegion></affiliation></author><author><name sortKey="Launer, Lenore" sort="Launer, Lenore" uniqKey="Launer L" first="Lenore" last="Launer">Lenore Launer</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Laboratory of Epidemiology and Population Sciences, National Institute on Aging</s1><s2>Bethesda, MD</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Bethesda, MD</wicri:noRegion></affiliation></author><author><name sortKey="Yaffe, Kristine" sort="Yaffe, Kristine" uniqKey="Yaffe K" first="Kristine" last="Yaffe">Kristine Yaffe</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Department of Psychiatry, University of California</s1><s2>San Francisco, CA</s2><s3>USA</s3><sZ>6 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>San Francisco, CA</wicri:noRegion></affiliation></author><author><name sortKey="Kritchevsky, Stephen B" sort="Kritchevsky, Stephen B" uniqKey="Kritchevsky S" first="Stephen B." last="Kritchevsky">Stephen B. Kritchevsky</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Sticht Center on Aging, Wake Forest School of Medicine</s1><s2>Winston-Salem, NC</s2><s3>USA</s3><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Winston-Salem, NC</wicri:noRegion></affiliation></author><author><name sortKey="Newman, Anne" sort="Newman, Anne" uniqKey="Newman A" first="Anne" last="Newman">Anne Newman</name><affiliation wicri:level="4"><inist:fA14 i1="08"><s1>Center for Aging and Population Health, School of Public Health, University of Pittsburgh</s1><s2>Pittsburgh, PA</s2><s3>USA</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Pittsburgh</settlement><region type="state">Pennsylvanie</region></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Rosano, Caterina" sort="Rosano, Caterina" uniqKey="Rosano C" first="Caterina" last="Rosano">Caterina Rosano</name><affiliation wicri:level="4"><inist:fA14 i1="08"><s1>Center for Aging and Population Health, School of Public Health, University of Pittsburgh</s1><s2>Pittsburgh, PA</s2><s3>USA</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Pittsburgh</settlement><region type="state">Pennsylvanie</region></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author></analytic><series><title level="j" type="main">NeuroImage : (Orlando, Fla.)</title><title level="j" type="abbreviated">NeuroImage : (Orlando Fla.)</title><idno type="ISSN">1053-8119</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">NeuroImage : (Orlando, Fla.)</title><title level="j" type="abbreviated">NeuroImage : (Orlando Fla.)</title><idno type="ISSN">1053-8119</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cognition</term><term>Encephalon</term><term>White matter</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Encéphale</term><term>Substance blanche</term><term>Cognition</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Importance: Cerebral white matter hyperintensities (WMHs) are involved in the evolution of impaired mobility and executive functions. Executive functions and mobility are also associated. Thus, WMHs may impair mobility directly, by disrupting mobility-related circuits, or indirectly, by disrupting circuits responsible for executive functions. Understanding the mechanisms underlying impaired mobility in late life will increase our capacity to develop effective interventions. Objective: To identify regional WMHs most related to slower gait and to examine whether these regional WMHs directly impact mobility, or indirectly by executive functions. Design: Cross-sectional study. Twenty-one WMH variables (i.e., total WMH volume and WMHs in 20 tracts), gait speed, global cognition (Modified Mini-Mental State Examination; 3MS), and executive functions and processing speed (Digit-Symbol Substitution Test; DSST) were assessed. An L1-L2 regularized regression (i.e., Elastic Net model) identified the WMH variables most related to slower gait Multivariable linear regression models quantified the association between these WMH variables and gait speed. Formal tests of mediation were also conducted. Setting: Community-based sample. Participants; Two hundred fifty-three adults (mean age: 83 years, 58% women, 41% black). Main Outcome Measure: Gait speed. Results: In older adults with an average gait speed of 0.91 m/sec, total WMH volume, WMHs located in the right anterior thalamic radiation (ATRR) and frontal corpus callosum (CCF) were most associated with slower gait. There was a >10% slower gait for each standard deviation of WMH in CCF, ATRR or total brain (standardized beta in m/sec [p value]: -0.11 [p = 0.046], -0.15 [p = 0.007] and -0.14 [p = 0.010], respectively). These associations were substantially and significantly attenuated after adjustment for DSST. This effect was stronger for WMH in CCF than for ATRR or total WMH (standardized beta in m/sec [p value]: - 0.07 [p = 0.190], - 0.12 [p = 0.024] and -0.10 [p = 0.049], respectively). Adjustment for 3MS did not change these associations. The mediation analyses also found that DSST significantly mediated the associations between WMHs and gait speed. Our models were adjusted for age, sex, BMI, quadriceps strength, years of education, standing height, and prevalent hypertension. Conclusion: The impact, direct or indirect, of WMHs on gait speed depended on their location and was mediated by executive function. Thus, multi-faceted interventions targeting executive control functions as well as motor functions, such as balance and strength training, are candidates to the maintenance of mobility across the lifespan.</div></front></TEI><affiliations><list><country><li>Canada</li><li>États-Unis</li></country><region><li>Pennsylvanie</li></region><settlement><li>Pittsburgh</li></settlement><orgName><li>Université de Pittsburgh</li></orgName></list><tree><country name="Canada"><noRegion><name sortKey="Bolandzadeh, Niousha" sort="Bolandzadeh, Niousha" uniqKey="Bolandzadeh N" first="Niousha" last="Bolandzadeh">Niousha Bolandzadeh</name></noRegion><name sortKey="Bolandzadeh, Niousha" sort="Bolandzadeh, Niousha" uniqKey="Bolandzadeh N" first="Niousha" last="Bolandzadeh">Niousha Bolandzadeh</name><name sortKey="Bolandzadeh, Niousha" sort="Bolandzadeh, Niousha" uniqKey="Bolandzadeh N" first="Niousha" last="Bolandzadeh">Niousha Bolandzadeh</name><name sortKey="Liu Ambrose, Teresa" sort="Liu Ambrose, Teresa" uniqKey="Liu Ambrose T" first="Teresa" last="Liu-Ambrose">Teresa Liu-Ambrose</name><name sortKey="Liu Ambrose, Teresa" sort="Liu Ambrose, Teresa" uniqKey="Liu Ambrose T" first="Teresa" last="Liu-Ambrose">Teresa Liu-Ambrose</name></country><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Aizenstein, Howard" sort="Aizenstein, Howard" uniqKey="Aizenstein H" first="Howard" last="Aizenstein">Howard Aizenstein</name></region><name sortKey="Harris, Tamara" sort="Harris, Tamara" uniqKey="Harris T" first="Tamara" last="Harris">Tamara Harris</name><name sortKey="Kritchevsky, Stephen B" sort="Kritchevsky, Stephen B" uniqKey="Kritchevsky S" first="Stephen B." last="Kritchevsky">Stephen B. Kritchevsky</name><name sortKey="Launer, Lenore" sort="Launer, Lenore" uniqKey="Launer L" first="Lenore" last="Launer">Lenore Launer</name><name sortKey="Newman, Anne" sort="Newman, Anne" uniqKey="Newman A" first="Anne" last="Newman">Anne Newman</name><name sortKey="Rosano, Caterina" sort="Rosano, Caterina" uniqKey="Rosano C" first="Caterina" last="Rosano">Caterina Rosano</name><name sortKey="Yaffe, Kristine" sort="Yaffe, Kristine" uniqKey="Yaffe K" first="Kristine" last="Yaffe">Kristine Yaffe</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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