16 Vascular risk factors for depression and apathy There are a number of validated scales to assess apathy across populations, of which the Neuropsychiatric Inventory (NPI) and the Apathy Evaluation Scale (AES) are the most robust 33. One of the problems that arise from the use in research, however, is that respondents with minimal cognitive impairment (MCI) or dementia tend to report lower apathy levels than peers without these health problems, which tendency is most likely attributable to less cognitive insight 34. Most researchers investigating cognitively impaired populations hence prefer to use clinician or caregiver reported scales. Research into apathy has also benefitted from more uniformity through the recent consensus on the diagnostic criteria for apathy 35, which can be used in neuropsychiatric as well as healthy populations. Applying these well-defined criteria 35 in a range of neuropsychiatric disorders, researchers documented apathy prevalences of 55% for Alzheimer’s disease, 70% for mixed dementia, 43% for minimal cognitive impairment, 27% for Parkinson’s disease, 53% for schizophrenia and 94% for major depressive disorder 26. Given that in the general population it is seen in 2-6%, apathy is predominantly a syndrome of old age, with the prevalence increasing with age, especially in men 36. Treatment options for apathy are primarily aimed at raising the activity level through external stimuli and at relieving the caregiver burden 37 since the evidence for the efficacy of pharmacological interventions in apathy is not well established and confined to specific populations. Thus, there is some evidence for the usefulness of methylphenidate for the treatment of apathy in patients with Alzheimer’s disease 38 and of dopamine agonists and rivastigmine in patients with Parkinson’s disease 39. The neuroscience of apathy Neuroimaging studies show that, across brain disorders, apathy is associated with abnormalities in the fronto-striatal pathways, most notably disruptions of the dorsal anterior cingulate cortex, the ventral striatum and connected brain regions 40. Functional MRI and diffusion tensor imaging (DTI) studies have revealed that when the disruption in these fronto-striatal pathways leads to disruption of the underlying reward network, higher levels of apathy are seen 41 (See Figure 1). Research into this reward network and its function in the motivation process is emerging 42. Studies combining functional MRI or DTI and behavioural paradigms show that the reward network plays a role in effortbased decision-making, i.e. the process in which a person decides whether to expend effort to gain a reward or not 42. In people with CSVD, apathy is associated with reduced connectivity in this specific network of the brain 43. CSVD and the vascular apathy hypothesis The prevalence of CSVD increases with age, from 5% in people aged 50 to almost 100% in those older than 90 years 44, with 52% of those with CSVD on neuroimaging showing apathy 24. CSVD refers to a group of atherosclerotic diseases of the small vessels of the brain causing ischaemic changes in the surrounding brain tissue. MRI-markers of CVSD include white matter hyperintensities (WMH), cerebral microbleeds, lacunar infarcts
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