**5.1 Vascular dementia and poststroke depression**

Alexopoulos and colleagues found that elderly stroke patients that suffered ischemic strokes demonstrated increased encephalomalacia and MRI hyperintensities that would predispose these patients to develop depression [33]. Their study suggested that these changes were not seen in elderly patients that had depression without vascular risk factors. Elderly patients that have been observed to have signs of depression, but do not have any vascular risk factors were found to have less white matter hyperintensities on MRI, which were similar to the nondepressed controls [31]. It has also been demonstrated that patients that suffered from depression without vascular insult had phenotypically different depression with features of more agitation, aggression, feelings of guilt and dysphoria. This is the theory of vascular depression in the elderly [33]. The hypothesis behind vascular depression states that chronic small vessel changes or non-symptomatic cerebrovascular events accumulate over time, resulting in the disruption of cortico-striato-pallido-thalamo-cortical (CSPTC) pathways [31]. Vascular dementia is described as a subcortical phenomenon. This type of depression differs from poststroke depression, in that they are silent, and the patient is not aware that they have suffered a stroke [31]. In a Japanese sample, greater than 80% of the patients that had major depression had MRI evidence of multiple silent infarcts [32]. Up to 75% of these depressed patients had lesions in the basal ganglia and thalamus [31, 33].

Three pathways associated with CSPTC were proposed in the way that vascular depression can present phenotypically. Within the CSPTC are the orbitofrontal pathway, the cingulate pathway, and the dorsolateral pathway. Injury over time to the orbitofrontal pathway can result in irritability and disinhibition [31]. The cingulate pathway can cause apathy, and lack of initiative if injured, and lastly, injury to the dorsolateral pathway can result in poor speech productions, and inability to learn. These symptoms can all be seen in elderly depression. Prefrontal dysfunction has shown to have a poor or delayed response to antidepressants in elderly patients [31, 33]. However, early administration of antidepressants, particularly selective serotonin reuptake inhibitors have been shown to improve neuropsychological rehabilitation in elderly stroke patients.

Lacunar infarcts have been seen to result in more depression among Alzheimer patients especially basal ganglia strokes and cortical strokes were found to have more cognitive impairment [31]. Severe cognitive impairment was also seen to be one of the leading causes of depression in the elderly. There are some questions of whether cognitive impairment or dementia can increase the risk of stroke, and thus poststroke depression among the elderly, or do strokes result in cognitive decline and vascular depression [31]. Dementia and depression can be difficult to differentiate. In the elderly, pseudodementia can be secondary to depression however, the opposite is also true. This is a "what came first" type of scenario with dementia, stroke and vascular depression [31].

Although vascular depression and poststroke depression are different in the way they affect a patient, they likely lay on a continuum. Both are secondary to a vascular event, and both result in depression. Vascular depression has a higher incidence in elderly patients as they have an accumulation of more subcortical white matter changes that are seen as hyperintensities on MRI FLAIR. Poststroke depression is less subtle since the patient is usually aware that they have had a stroke [31, 33]. There may be a growing incidence of vascular depression among young patients,

due to poorly controlled hypertension, tobacco, diabetes, drug use, and poor diet and lifestyle choices causing small vessel disease. These risk factors put all patients at risk for an acute stroke, and chronic small vessel disease.
