Associations of Pulmonary Function with MRI Brain Volumes: A Coordinated Multi-Study Analysis

Stefan Frenzel, Joshua C. Bis, Elias F. Gudmundsson, Adrienne O'Donnell, Jeannette Simino, Amber Yaqub, Traci M. Bartz, Guy G.O. Brusselle, Robin Bülow, Charles S. DeCarli, Ralf Ewert, Sina A. Gharib, Saptaparni Ghosh, Monica Gireud-Goss, Rebecca F. Gottesman, M. Arfan Ikram, David S. Knopman, Lenore J. Launer, Stephanie J. London, W. T. LongstrethOscar L. Lopez, Debora Melo van Lent, George O'Connor, Claudia L. Satizabal, Srishti Shrestha, Sigurdur Sigurdsson, Beate Stubbe, Rajesh Talluri, Ramachandran S. Vasan, Meike W. Vernooij, Henry Völzke, Kerri L. Wiggins, Bing Yu, Alexa S. Beiser, Vilmundur Gudnason, Thomas Mosley, Bruce M. Psaty, Frank J. Wolters, Hans J. Grabe, Sudha Seshadri

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Abstract

BACKGROUND: Previous studies suggest poor pulmonary function is associated with increased burden of cerebral white matter hyperintensities and brain atrophy among elderly individuals, but the results are inconsistent. OBJECTIVE: To study the cross-sectional associations of pulmonary function with structural brain variables. METHODS: Data from six large community-based samples (N = 11,091) were analyzed. Spirometric measurements were standardized with respect to age, sex, height, and ethnicity using reference equations of the Global Lung Function Initiative. Associations of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and their ratio FEV1/FVC with brain volume, gray matter volume, hippocampal volume, and volume of white matter hyperintensities were investigated using multivariable linear regressions for each study separately and then combined using random-effect meta-analyses. RESULTS: FEV1 and FVC were positively associated with brain volume, gray matter volume, and hippocampal volume, and negatively associated with white matter hyperintensities volume after multiple testing correction, with little heterogeneity present between the studies. For instance, an increase of FVC by one unit was associated with 3.5 ml higher brain volume (95% CI: [2.2, 4.9]). In contrast, results for FEV1/FVC were more heterogeneous across studies, with significant positive associations with brain volume, gray matter volume, and hippocampal volume, but not white matter hyperintensities volume. Associations of brain variables with both FEV1 and FVC were consistently stronger than with FEV1/FVC, specifically with brain volume and white matter hyperintensities volume. CONCLUSION: In cross-sectional analyses, worse pulmonary function is associated with smaller brain volumes and higher white matter hyperintensities burden.

Original languageEnglish
Pages (from-to)1073-1083
Number of pages11
JournalJournal of Alzheimer's disease : JAD
Volume90
Issue number3
DOIs
Publication statusPublished - 22 Nov 2022

Bibliographical note

Funding Information:
This study was supported by National Institute of Health (NIH) grant AG059421. Additional study-specific acknowledgements can be found in the Supplementary Material.

Publisher Copyright:
© 2022 - The authors. Published by IOS Press.

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