Part II | Vascular risk factors for depression and apathy 103 6 Introduction Apathy, or diminished motivation, has traditionally been regarded as a symptom of psychiatric and neurological disorders, such as major depressive disorder 1 and Parkinson’s disease 2. Apathy has increasingly come to be regarded as an independent syndrome for which diagnostic criteria have been proposed in a consensus paper 3 4. With its prevalence in the general population (≥50 years) being estimated at 23.7% 5, the impact of apathy on both individuals and the society is extensive. The apathy syndrome negatively affects motivational decision making 6 and is associated with functional decline 5, reduced engagement in activities of daily living, and a poorer quality of life 7. Understandably, apathy is very distressing for family and other caregivers 8. The hypothesis of vascular apathy assumes a relationship between the generally widespread cerebrovascular damage caused by small vessel disease (SVD) and apathy 9 10. Whether cerebrovascular damage due to small vessel disease, is associated with apathy, -even in the general population without prior knowledge of cerebrovascular damage-, is the main subject of this study. Various brain circuits play a role in planning, motivation and, auto activation, among which are the frontal regions with their projections to prefrontal regions and the basal ganglia, the parietal regions, and the anterior cingulate 11. The vascular apathy hypothesis then supposes that SVD can cause apathy by damaging these tracts. However, the relationship between vascular disease and apathy could well be bidirectional: a recent systematic review and meta-analysis showed that apathy increases the risk of myocardial infarction by 21 %, stroke by 37%, and even mortality by 47% 12. In the populations evaluated, these risks might additionally or alternatively be raised due to the participants’ adverse health behaviours and low adherence to treatment regimens for vascular disease 13 14 15. Moreover, apathy and vascular disease might have a shared aetiology 16, while apathy could well be a marker of subclinical SVD (SSVD) 14. Early evidence for the vascular apathy hypothesis was reported in studies in clinical samples with established cerebrovascular disease (e.g. vascular dementia and stroke), where apathy appeared related to the general effect (or severity) of cerebrovascular damage given that, associations with specific cerebral circuitries and regions were inconsistent 17 18. Particularly the stroke subtype of SVD (lacunar infarcts and white matter hyperintensities) was found to be related to apathy in several other studies, independent of depression 19 20 21. Indirect and also contradictory evidence came from research into late-life depression, where chronicity of late-life depression was found to be associated with the severity of the risk factors for cerebrovascular disease and apathy 22. Still, although the presence of apathy was predicted by vascular factors in several elderly depressed populations 23, other studies found no such associations 24 12. Moreover, depression itself could be related to vascular factors, as the so-called vascular depression hypothesis postulates 25 which
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