Vascular risk factors for depression and apathy | Part II 104 complicates the interpretation of findings pertaining to vascular apathy in depressed populations. Other indirect evidence seems to support the existence of vascular apathy in that a negative interaction was observed between neuroticism and cerebrovascular risk factors in the prediction of depression, suggesting that apathy caused by SSVD might attenuate the depressogenic effect of neuroticism 10 26. Obviously, more convincing and direct evidence of vascular apathy could come from research investigating the apathy-SSVD relationship in the general population, given that cerebral SVD develops from a subclinical condition, increasing the risk on overt cerebrovascular disease 27 28 29 30, where, although still subclinical, SSVDmight cause subtle signs and symptoms, like mild disturbances in gait, cognitive functioning and mood 27, The aim of the present systematic review is to examine all the evidence supporting an association between SSVD and apathy in the general population, while also considering findings of associations between proxies of SSVD and apathy. Methods Literature search process All eligible articles were found using Ovid-all resources (which include the Cochrane Library, EMBASE, MEDLINE, and PSYCHINFO), limits: English, humans. The search terms were vascular apathy, and apathy combined with deep white matter hyperintensities (DWMH), white matter hyperintensities (WMH), cerebrovascular disease (not stroke) (CV disease), lacunar infarcts, cerebral microbleeds, cortical thickness, perivascular spaces, ankle brachial pressure index (ABI), intima media thickness (IMT), arterial stiffness, cardio-femoral pulse wave velocity (CFPWV), hypertension, cardiovascular disease and cerebrovascular risk factors (CVRF). Duplicates were removed. The search was conducted on the 27th of June, 2018 by the first author (LW) and checked by the second author (MvK). Differences in findings were analyzed and discrepancies were discussed between both authors (LW and MvK) and when no consensus could be reached, a third author (RM) was asked to make the final judgment. Two more eligible articles were identified while preparing a speech on apathy using the search terms “apathy” and “dementia” 31 32. On inspection these two studies also reported on the general population or populations with minimal cognitive impairment (MCI), which is why we included them in our review. Articles were included when 1. apathy was assessed by any kind of relevant instrument; 2. SSVD was based on either neuroimaging, considered a direct measure of SSVD or peripheral measures of atherosclerosis, considered as proxies for SSVD; 3. studies reported on observational epidemiological research, and 4. were performed in the general
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