Sedentary behavior, brain-derived neurotrophic factor and brain structure in midlife: A longitudinal brain MRI sub-study of the coronary artery risk development in young adults study

Brain-derived neurotrophic factor levels are higher in those who are physically active and lower in people with cognitive dysfunction. This study investigated whether brain-derived neurotrophic factor mediated or modified the association of sedentary time to MRI-estimated brain volumes in midlife. B...

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Published in:Frontiers in dementia Vol. 2; p. 1110553
Main Authors: Zhang, Xuan, Meirelles, Osorio D., Li, Zhiguang, Yaffe, Kristine, Bryan, R. Nick, Qiu, Chengxuan, Launer, Lenore J.
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 13.03.2023
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ISSN:2813-3919, 2813-3919
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Abstract Brain-derived neurotrophic factor levels are higher in those who are physically active and lower in people with cognitive dysfunction. This study investigated whether brain-derived neurotrophic factor mediated or modified the association of sedentary time to MRI-estimated brain volumes in midlife. Baseline ( = 612) and five-year follow-up ( = 418) data were drawn from the multicenter Coronary Artery Risk Development in Young Adults Brain MRI sub-study, including Black and White participants (aged 50.3 years, 51.6% females, 38.6% Black). Sedentary time (hours per day) was categorized into quartiles with low ≤ 4.3 (reference) and high > 8.4. Outcomes of the study were total brain, white matter, gray matter, hippocampal volumes, and white matter fractional anisotropy at baseline and 5-year percent change from baseline. The study used general linear regression models to examine the mediation and moderation effects of brain-derived neurotrophic factor (natural log transformed) on the associations of sedentary time to brain outcomes. The authors adjusted the regression model for age, sex, race, intracranial volume, education, and vascular factors. Cross-sectionally, baseline participants with the highest sedentary time had a lower total brain (-12.2 cc; 95%CI: -20.7, -3.7), gray matter (-7.8 cc; 95%CI: -14.3, -1.3), and hippocampal volume (-0.2 cc; 95%CI: -0.3, 0.0) compared with populations with the lowest sedentary time. The brain-derived neurotrophic factor levels did not mediate the associations between brain measures and sedentary time. Brain-derived neurotrophic factor was found to moderate associations of sedentary time to total brain and white matter volume such that the brain volume difference between high and low sedentary time decreased as brain-derived neurotrophic factor levels increased. Longitudinally, higher baseline brain-derived neurotrophic factor level was associated with less brain volume decline. The longitudinal associations did not differ by sedentary time, and brain-derived neurotrophic factor did not mediate or moderate the association of sedentary time to brain measure changes. Higher brain-derived neurotrophic factor levels may buffer the negative effects of sedentary time on the brain.
AbstractList Brain-derived neurotrophic factor levels are higher in those who are physically active and lower in people with cognitive dysfunction. This study investigated whether brain-derived neurotrophic factor mediated or modified the association of sedentary time to MRI-estimated brain volumes in midlife. Baseline ( = 612) and five-year follow-up ( = 418) data were drawn from the multicenter Coronary Artery Risk Development in Young Adults Brain MRI sub-study, including Black and White participants (aged 50.3 years, 51.6% females, 38.6% Black). Sedentary time (hours per day) was categorized into quartiles with low ≤ 4.3 (reference) and high > 8.4. Outcomes of the study were total brain, white matter, gray matter, hippocampal volumes, and white matter fractional anisotropy at baseline and 5-year percent change from baseline. The study used general linear regression models to examine the mediation and moderation effects of brain-derived neurotrophic factor (natural log transformed) on the associations of sedentary time to brain outcomes. The authors adjusted the regression model for age, sex, race, intracranial volume, education, and vascular factors. Cross-sectionally, baseline participants with the highest sedentary time had a lower total brain (-12.2 cc; 95%CI: -20.7, -3.7), gray matter (-7.8 cc; 95%CI: -14.3, -1.3), and hippocampal volume (-0.2 cc; 95%CI: -0.3, 0.0) compared with populations with the lowest sedentary time. The brain-derived neurotrophic factor levels did not mediate the associations between brain measures and sedentary time. Brain-derived neurotrophic factor was found to moderate associations of sedentary time to total brain and white matter volume such that the brain volume difference between high and low sedentary time decreased as brain-derived neurotrophic factor levels increased. Longitudinally, higher baseline brain-derived neurotrophic factor level was associated with less brain volume decline. The longitudinal associations did not differ by sedentary time, and brain-derived neurotrophic factor did not mediate or moderate the association of sedentary time to brain measure changes. Higher brain-derived neurotrophic factor levels may buffer the negative effects of sedentary time on the brain.
Brain-derived neurotrophic factor levels are higher in those who are physically active and lower in people with cognitive dysfunction. This study investigated whether brain-derived neurotrophic factor mediated or modified the association of sedentary time to MRI-estimated brain volumes in midlife.BackgroundBrain-derived neurotrophic factor levels are higher in those who are physically active and lower in people with cognitive dysfunction. This study investigated whether brain-derived neurotrophic factor mediated or modified the association of sedentary time to MRI-estimated brain volumes in midlife.Baseline (n = 612) and five-year follow-up (n = 418) data were drawn from the multicenter Coronary Artery Risk Development in Young Adults Brain MRI sub-study, including Black and White participants (aged 50.3 years, 51.6% females, 38.6% Black). Sedentary time (hours per day) was categorized into quartiles with low ≤ 4.3 (reference) and high > 8.4. Outcomes of the study were total brain, white matter, gray matter, hippocampal volumes, and white matter fractional anisotropy at baseline and 5-year percent change from baseline. The study used general linear regression models to examine the mediation and moderation effects of brain-derived neurotrophic factor (natural log transformed) on the associations of sedentary time to brain outcomes. The authors adjusted the regression model for age, sex, race, intracranial volume, education, and vascular factors.MethodsBaseline (n = 612) and five-year follow-up (n = 418) data were drawn from the multicenter Coronary Artery Risk Development in Young Adults Brain MRI sub-study, including Black and White participants (aged 50.3 years, 51.6% females, 38.6% Black). Sedentary time (hours per day) was categorized into quartiles with low ≤ 4.3 (reference) and high > 8.4. Outcomes of the study were total brain, white matter, gray matter, hippocampal volumes, and white matter fractional anisotropy at baseline and 5-year percent change from baseline. The study used general linear regression models to examine the mediation and moderation effects of brain-derived neurotrophic factor (natural log transformed) on the associations of sedentary time to brain outcomes. The authors adjusted the regression model for age, sex, race, intracranial volume, education, and vascular factors.Cross-sectionally, baseline participants with the highest sedentary time had a lower total brain (-12.2 cc; 95%CI: -20.7, -3.7), gray matter (-7.8 cc; 95%CI: -14.3, -1.3), and hippocampal volume (-0.2 cc; 95%CI: -0.3, 0.0) compared with populations with the lowest sedentary time. The brain-derived neurotrophic factor levels did not mediate the associations between brain measures and sedentary time. Brain-derived neurotrophic factor was found to moderate associations of sedentary time to total brain and white matter volume such that the brain volume difference between high and low sedentary time decreased as brain-derived neurotrophic factor levels increased. Longitudinally, higher baseline brain-derived neurotrophic factor level was associated with less brain volume decline. The longitudinal associations did not differ by sedentary time, and brain-derived neurotrophic factor did not mediate or moderate the association of sedentary time to brain measure changes.ResultsCross-sectionally, baseline participants with the highest sedentary time had a lower total brain (-12.2 cc; 95%CI: -20.7, -3.7), gray matter (-7.8 cc; 95%CI: -14.3, -1.3), and hippocampal volume (-0.2 cc; 95%CI: -0.3, 0.0) compared with populations with the lowest sedentary time. The brain-derived neurotrophic factor levels did not mediate the associations between brain measures and sedentary time. Brain-derived neurotrophic factor was found to moderate associations of sedentary time to total brain and white matter volume such that the brain volume difference between high and low sedentary time decreased as brain-derived neurotrophic factor levels increased. Longitudinally, higher baseline brain-derived neurotrophic factor level was associated with less brain volume decline. The longitudinal associations did not differ by sedentary time, and brain-derived neurotrophic factor did not mediate or moderate the association of sedentary time to brain measure changes.Higher brain-derived neurotrophic factor levels may buffer the negative effects of sedentary time on the brain.ConclusionsHigher brain-derived neurotrophic factor levels may buffer the negative effects of sedentary time on the brain.
Author Meirelles, Osorio D.
Zhang, Xuan
Yaffe, Kristine
Li, Zhiguang
Qiu, Chengxuan
Launer, Lenore J.
Bryan, R. Nick
AuthorAffiliation 1 Laboratory of Epidemiology and Population Sciences Intramural Research Program, National Institute on Aging , Baltimore, MD , United States
2 Departments of Psychiatry and Behavioral Sciences, Neurology, and Epidemiology, University of California, San Francisco , San Francisco, CA , United States
3 Department of Radiology, University of Pennsylvania , Philadelphia, PA , United States
4 Aging Research Center and Center for Alzheimer's Research, Karolinska Institutet , Stockholm , Sweden
AuthorAffiliation_xml – name: 4 Aging Research Center and Center for Alzheimer's Research, Karolinska Institutet , Stockholm , Sweden
– name: 3 Department of Radiology, University of Pennsylvania , Philadelphia, PA , United States
– name: 1 Laboratory of Epidemiology and Population Sciences Intramural Research Program, National Institute on Aging , Baltimore, MD , United States
– name: 2 Departments of Psychiatry and Behavioral Sciences, Neurology, and Epidemiology, University of California, San Francisco , San Francisco, CA , United States
Author_xml – sequence: 1
  givenname: Xuan
  surname: Zhang
  fullname: Zhang, Xuan
– sequence: 2
  givenname: Osorio D.
  surname: Meirelles
  fullname: Meirelles, Osorio D.
– sequence: 3
  givenname: Zhiguang
  surname: Li
  fullname: Li, Zhiguang
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  givenname: Kristine
  surname: Yaffe
  fullname: Yaffe, Kristine
– sequence: 5
  givenname: R. Nick
  surname: Bryan
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  surname: Qiu
  fullname: Qiu, Chengxuan
– sequence: 7
  givenname: Lenore J.
  surname: Launer
  fullname: Launer, Lenore J.
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Keywords sedentary time
longitudinal
brain volume
biomarkers
middle-aged
Language English
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This article was submitted to Aging and Risk Factors for Dementia, a section of the journal Frontiers in Dementia
Reviewed by: Alan W. J. Morris, University of Colorado Anschutz Medical Campus, United States; Angel Golimstok, Italian Hospital of Buenos Aires, Argentina
Edited by: Zoe Arvanitakis, Rush University, United States
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Snippet Brain-derived neurotrophic factor levels are higher in those who are physically active and lower in people with cognitive dysfunction. This study investigated...
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SubjectTerms Dementia
Title Sedentary behavior, brain-derived neurotrophic factor and brain structure in midlife: A longitudinal brain MRI sub-study of the coronary artery risk development in young adults study
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