J Psychiatry Neurosci 2016;41(3):162-168
Thomas T. van Sloten, MD, PhD; Gary F. Mitchell, MD; Sigurdur Sigurdsson, MSc; Mark A. van Buchem, MD, PhD; Palmi V. Jonsson, MD; Melissa E. Garcia, MPH; Tamara B. Harris, MD, MS; Ronald M.A. Henry, MD, PhD; Andrew S. Levey, MD; Coen D.A. Stehouwer, MD, PhD; Vilmundur Gudnason, MD, PhD; Lenore J. Launer, PhD
Background: Arterial stiffness may contribute to depression via cerebral microvascular damage, but evidence for this is scarce. We therefore investigated whether arterial stiffness is associated with depressive symptoms and whether cerebral small vessel disease contributes to this association.
Methods: This cross-sectional study included a subset of participants from the AGES-Reykjavik study second examination round, which was conducted from 2007 to 2011. Arterial stiffness (carotid–femoral pulse wave velocity [CFPWV]), depressive symptoms (15-item geriatric depression scale [GDS-15]) and cerebral small vessel disease (MRI) were determined. Manifestations of cerebral small vessel disease included higher white matter hyperintensity volume, subcortical infarcts, cerebral microbleeds, Virchow–Robin spaces and lower total brain parenchyma volume.
Results: We included 2058 participants (mean age 79.6 yr; 59.0% women) in our analyses. Higher CFPWV was associated with a higher GDS-15 score, after adjustment for potential confounders (β 0.096, 95% confidence interval [CI] 0.005–0.187). Additional adjustment for white matter hyperintensity volume or subcortical infarcts attenuated the association between CFPWV and the GDS-15 score, which became nonsignificant (p > 0.05). Formal mediation tests showed that the attenuating effects of white matter hyperintensity volume and subcortical infarcts were statistically significant. Virchow–Robin spaces, cerebral microbleeds and cerebral atrophy did not explain the association between CFPWV and depressive symptoms.
Limitations: Our study was limited by its cross-sectional design, which precludes any conclusions about causal mediation. Depressive symptoms were assessed by a self-report questionnaire.
Conclusion: Greater arterial stiffness is associated with more depressive symptoms; this association is partly accounted for by white matter hyperintensity volume and subcortical infarcts. This study supports the hypothesis that arterial stiffness leads to depression in part via cerebral small vessel disease.
Submitted Nov. 8, 2014; Revised Apr. 22, 2015; Revised June 14, 2015; Accepted June 24, 2015; Early-released Oct. 20, 2015
Acknowledgements: The AGES-Reykjavik Study was funded by National Institutes of Health (NIH) (contract N01-AG-12100) and the Intramural Research Program of the National Institute on Aging, USA; the Icelandic Heart Association and the Icelandic Parliament, Iceland; and by grants from the National Institutes of Health, National Heart, Lung and Blood Institute (HL094898) and the National Institute of Diabetes and Digestive and Kidney Diseases (DK082447).
Affiliations: From the Cardiovascular Research Institute Maastricht, Limburg, Netherlands (VanSloten, Henry, Stehouwer); the School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands (VanSloten); Cardiovascular Engineering Inc, Norwood, MA, USA (Mitchell) the Icelandic Heart Association, Kopavogur, Iceland (Sigurdsson, Gudnason); the Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands (Buchem); the Department of Geriatrics, Landspitali University Hospital, Reykjavik, Iceland (Jonsson); the Faculty of Medicine, University of Iceland, Reykjavik, Iceland (Jonsson, Gudnason); the Intramural Research Program, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA (Garcia, Harris, Launer); and the William B Schwartz Division of nephrology, Tufts Medical Center, Boston, MA, USA (Levey).
Competing interests: G. Mitchell is owner of Cardiovascular Engineering, Inc., a company that designs and manufactures devices that measure vascular stiffness. The company uses these devices in studies that evaluate the effects of diseases and interventions on vascular stiffness. He has served as a consultant for Novartis, Servier and Merck, and has a patent (6331162) for a pulse wave velocity measurement device. A. Levey has a patent application pending for precise estimation of GFR using a panel of filtration markers. No other competing interests declared.
Contributors: T. van Sloten, G. Mitchell, M. van Buchem, P. Jonsson, T. Harris, V. Gudnason and L. Launer designed the study. G. Mitchell, S. Sigurdsson, M. Garcia, A. Levey and V. Gudnason acquired the data, which T. van Sloten, G. Mitchell, R. Henry and C. Stehouwer analyzed. T. van Sloten and L. Launer wrote the article, which all authors reviewed and approved for publication.
Correspondence to: L.J. Launer, Intramural Research Program, National Institute on Aging, Bethesda, MD; LaunerL@nia.nih.gov