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

Author:

Frenzel Stefan1,Bis Joshua C.2,Gudmundsson Elias F.3,O’Donnell Adrienne45,Simino Jeannette67,Yaqub Amber8,Bartz Traci M.29,Brusselle Guy G. O.10,Bülow Robin11,DeCarli Charles S.1213,Ewert Ralf14,Gharib Sina A.15,Ghosh Saptaparni416,Gireud-Goss Monica17,Gottesman Rebecca F.18,Ikram M. Arfan8,Knopman David S.19,Launer Lenore J.20,London Stephanie J.21,Longstreth W.T.2223,Lopez Oscar L.24,Melo van Lent Debora41617,O’Connor George425,Satizabal Claudia L.1726,Shrestha Srishti627,Sigurdsson Sigurdur3,Stubbe Beate14,Talluri Rajesh7,Vasan Ramachandran S.42829,Vernooij Meike W.830,Völzke Henry31,Wiggins Kerri L.2,Yu Bing32,Beiser Alexa S.4533,Gudnason Vilmundur334,Mosley Thomas62735,Psaty Bruce M.22336,Wolters Frank J.830,Grabe Hans J.137,Seshadri Sudha4161738

Affiliation:

1. Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany

2. Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA

3. Icelandic Heart Association, Kopavogur, Iceland

4. Framingham Heart Study, Framingham, MA, USA

5. Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA

6. Gertrude C. Ford Memory Impairment and Neurodegenerative Dementia (MIND) Center, University of Mississippi Medical Center, Jackson, MS, USA

7. Department of Data Science, John D. Bower School of Population Health, University of Mississippi Medical Center, Jackson, MS, USA

8. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands

9. Department of Biostatistics, University of Washington, Seattle, WA, USA

10. Department of Respiratory Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands

11. Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany

12. Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, CA, USA

13. Imaging of Dementia and Aging (IDeA) Laboratory, Department of Neurology, University of California-Davis, Davis, CA, USA

14. Department of Internal Medicine B, Cardiology, Intensive Care, Pulmonary Medicine and Infectious Diseases, University Medicine Greifswald, Greifswald, Germany

15. Center for Lung Biology, Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA, USA

16. Department of Neurology, Boston University Schoolof Medicine, Boston, MA, USA

17. Glenn Biggs Institute for Alzheimer and Neurodegenerative Diseases, The University of Texas Health Science Center at San Antonio, SanAntonio, TX, USA

18. Stroke, Cognition, and Neuroepidemiology (SCAN) section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA

19. Department of Neurology, Mayo Clinic, Rochester, MN, USA

20. Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, MD, USA

21. Epidemiology Branch, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Research Triangle Park, NC, USA

22. Department of Neurology, University of Washington, Seattle, WA, USA

23. Department of Epidemiology, University of Washington, Seattle, WA, USA

24. Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA

25. Department of Medicine, Boston University School of Medicine, Boston, MA, USA

26. Department of Population Health Sciences, The University of Texas Health Science Center at San Antonio, SanAntonio, TX, USA

27. Department of Neurology, School of Medicine, University of Mississippi Medical Center, Jackson, MS, USA

28. Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston, MA, USA

29. Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA

30. Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands

31. Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany

32. Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA

33. Department of Neurology, Boston School of Medicine, Boston, MA, USA

34. Faculty of Medicine, University of Iceland, Reykjavik, Iceland

35. Department of Medicine, School of Medicine, University of Mississippi Medical Center, Jackson, MS, USA

36. Department of Health Systems and Population Health, University of Washington, Seattle, WA, USA

37. German Center for Neurodegenerative Disease (DZNE), partner site Rostock/Greifswald, Germany

38. Department of Neurology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

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.

Publisher

IOS Press

Subject

Psychiatry and Mental health,Geriatrics and Gerontology,Clinical Psychology,General Medicine,General Neuroscience

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