Associations between arterial stiffness, depressive symptoms and cerebral small vessel disease: cross-sectional findings from the AGES-Reykjavik Study.
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.



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.



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.



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.



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.
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).
Thomas T
TT
van Sloten
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).
Gary F
GF
Mitchell
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).
Sigurdur
S
Sigurdsson
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).
Mark A
MA
van Buchem
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).
Palmi V
PV
Jonsson
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).
Melissa E
ME
Garcia
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).
Tamara B
TB
Harris
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).
Ronald M A
RM
Henry
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).
Andrew S
AS
Levey
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).
Coen D A
CD
Stehouwer
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).
Vilmundur
V
Gudnason
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).
Lenore J
LJ
Launer
D000368:Aged; D001284:Atrophy; D001921:Brain / Q000000981:diagnostic imaging; D002339:Carotid Arteries / Q000503:physiopathology; D002543:Cerebral Hemorrhage / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000523:psychology; D059345:Cerebral Small Vessel Diseases / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000523:psychology*; D003430:Cross-Sectional Studies; D003863:Depression / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D005263:Femoral Artery / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D063177:Pulse Wave Analysis; D057566:Self Report; D059289:Vascular Stiffness; D066127:White Matter / Q000000981:diagnostic imaging