Vascular risk factors for depression and apathy | Part II 102 Abstract Objectives A systematic review of the relationship between subclinical small vessel disease (SSVD) in the general population and apathy to examine the hypothesis that apathy has a vascular basis. Methods We searched for studies on associations between apathy and SSVD, operationalized as white matter hyperintensities (WMH) or white matter diffusivity changes, lacunar infarcts, cerebral microbleeds, decreasing cortical thickness, and perivascular spaces, while also peripheral proxies for SSVD were considered, operationalized as ankle brachial pressure index (ABI), intima media thickness, arterial stiffness, cardio-femoral pulse wave velocity, hypertension or cardiovascular disease. Only eligible retrospective and prospective observational studies conducted in the general population were included. Results The 14 studies eligible for review examined the associations between apathy and hypertension (3), ABI (1), arterial stiffness (1), cardiovascular disease (2), WMH (3), white matter diffusivity (2), cerebral microbleeds (1), or cortical thickness (3). Arterial stiffness and white matter diffusivity were not related to apathy, while the associations with cortical thickness were contradictory. Cross-sectional studies in the general population did find evidence of apathy being associated with WMH, CM, cardiovascular disease, hypertension and ABI and cardiovascular disease was prospectively associated with apathy. The methodologies of the studies reviewed were too heterogeneous to perform meta-analyses. Conclusions Although more prospective evidence is needed and vascular depression needs to be controlled for, cardiovascular disease, hypertension and ABI as proxies for SSVD, andWMH and cerebral microbleeds as direct measures of SSVD have been found to be associated with apathy in the general population, supporting the hypothesis of vascular apathy.
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