Vascular risk factors for depression and apathy | Part II 84 The vascular apathy hypothesis poses that the generally widespread cerebrovascular damage due to small vessel disease causes damage to the frontolimbic networks, even if no other symptoms of cerebrovascular disease are yet present and the cerebrovascular damage is still subclinical 21 22 23. While empirical evidence for this hypothesis is still scarce, it might explain the structural damage found in apathy persisting after depression 19 20. The objective of the present study is to assess the association between comorbid vascular risk factors and vascular diseases and the severity of apathy at 6-year follow-up among a large cohort of well-phenotyped depressed patients who had achieved a full remission according to DSM criteria. Within this unique study design, we hypothesize that apathy in remitted depression is associated with vascular risk factors and vascular disease, and we hypothesize that this association is not explained by the residual symptom of a depressed mood. Methods Design and participants The present study was embedded in the Netherlands Study of Depression and Anxiety (NESDA) 24 25 and the Netherlands Study of Depression in Older Persons (NESDO) 26. NESDA and NESDO are multi-site naturalistic prospective clinical cohort studies that have harmonized their study design and measurements. Depressive disorder was assessed over a 6-month according to DSM-IV criteria based on the Clinical International Diagnostic Interview, version 2.1 (CIDI 2.1) at both baseline and 6-year follow-up 27 28. From the 1523 patients with a past 6-month depressive disorder at baseline we selected all patients that had no past 6-month depressive disorder according to DSM-IV criteria at 6-year follow-up (n=663). We have chosen the 6-year follow-up assessment for our analyses as both cohort studies had included the Starkstein Apathy Scale at this assessment. For details of patient recruitment, attrition rates and study design we refer to previous papers of both cohort studies 25 24 26. Of particular relevance for the present study, however, is that dementia was specifically an exclusion criterion of the NESDO study, defined as an established diagnosis of dementia, a Mini Mental State Examination (MMSE) <18 (allowing to include also severely depressed patients), and a suspected diagnosis of dementia underlying the depression by the referring geriatric psychiatrist. Since these latter criteria were not applied in the NESDA study due to an upper age-limit of 65 years, we additionally checked the general practitioner’s information of the NESDA participants for a diagnosis of either Alzheimer’s disease or multi-site infarct dementia (these were not found).
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