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Location and progression of cerebral small-vessel disease and atrophy, and depressive symptom profiles: The Second Manifestations of ARTerial disease (SMART)-Medea study

  • A. M. Grool (a1), Y. van der Graaf (a1), W. P. Th. M. Mali (a2), Th. D. Witkamp (a2), K. L. Vincken (a3) and M. I. Geerlings (a1)...



The ‘vascular depression’ hypothesis states that brain changes located in frontal-subcortical pathways increase vulnerability for specific depressive symptom profiles, but studies examining locations of small-vessel and degenerative changes with individual symptoms are scarce. We examined whether location and progression of white-matter lesions (WMLs), lacunar infarcts and atrophy were associated with motivational and mood symptoms in patients with symptomatic atherosclerotic disease.


In 578 patients [63 (s.d.=8) years] of the Second Manifestations of ARTerial disease (SMART)-Medea study, volumes of WMLs and atrophy and visually rated infarcts were obtained with 1.5 T magnetic resonance imaging at baseline and after 3.9 (s.d.=0.4) years' follow-up. Depressive symptoms were assessed with Patient Health Questionnaire-9 at follow-up and categorized into motivational and mood symptoms.


Regression analyses adjusted for age, gender, education, Mini-Mental State Examination, physical functioning, antidepressant use and vascular risk factors showed that location in mainly deep white-matter tracts and progression of WMLs were associated with symptoms of anhedonia, concentration problems, psychomotor retardation and appetite disturbance. Lacunar infarcts in deep white matter were associated with greater motivational [Incidence rate ratio (IRR) 1.7, 95% confidence interval (CI) 1.2–2.4] and mood (IRR 1.7, 95% CI 1.1–2.6) sumscores, and with symptoms of psychomotor retardation, energy loss and depressed mood; lacunar infarcts in the thalamus were associated with psychomotor retardation only. Cortical atrophy was associated with symptoms of anhedonia and appetite disturbance. Excluding patients with major depression did not materially change the results.


Our findings suggest that disruption of frontal-subcortical pathways by small-vessel lesions leads to a symptom profile that is mainly characteristic of motivational problems, also in the absence of major depression.


Corresponding author

*Address for correspondence: M. I. Geerlings, Ph.D., University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Stratenum 6.131, PO Box 85500, 3508 GA Utrecht, The Netherlands. (Email:


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Location and progression of cerebral small-vessel disease and atrophy, and depressive symptom profiles: The Second Manifestations of ARTerial disease (SMART)-Medea study

  • A. M. Grool (a1), Y. van der Graaf (a1), W. P. Th. M. Mali (a2), Th. D. Witkamp (a2), K. L. Vincken (a3) and M. I. Geerlings (a1)...


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