, 2013). Microscopic infarcts (microinfarcts) and hemorrhages (microbleeds) (Figure 5) are independent predictors of cognitive dysfunction, but are commonly associated with

other vascular pathologies, such as leukoaraiosis, lacunar infarcts, large infarcts, and hemorrhage (Smith et al., 2012 and van Norden et al., 2013), as well as CADASIL and AD (Table 1). Microinfarcts are sharply delineated lesions consisting PLX4032 purchase of pallor, necrosis, cavitation, and inflammation (astrocytosis, microgliosis, and macrophage infiltration) (Thal et al., 2012), caused by the small vessel pathology described above (Table 1). Microbleeds are microscopic areas of blood extravasation from leaky arterioles, which are restricted to the perivascular space and do not disrupt the brain parenchyma (De Reuck, 2012). Observed in 17% of demented patients (Cordonnier and van der Flier, 2011), cortical microbleeds are frequently associated with cerebral amyloid angiopathy (CAA), whereas microbleeds in deep regions tend to be associated with white matter disease secondary to vascular risk factors (De Reuck, 2012 and Park et al., 2013a). It is well known that deposits of Aβ in cerebral

blood vessels or CAA are associated with vascular cognitive impairment. Although inherited forms of CAA have been described, CAA is most prevalent selleck chemicals in AD, being present in over 90% of cases (Attems et al., 2011 and Charidimou et al., 2012). CAA is also observed in demented (50%–60%) and nondemented

(20%–40%) elderly people (Attems et al., 2011 and Charidimou et al., 2012). The major risk factor for CAA is advanced age, and cardiovascular risk factors seem to play a lesser role (Charidimou et al., 2012). CAA is a major cause of microbleeds and large hemorrhages, typically located in the cortex (lobar hemorrhages) (Auriel and Greenberg, isothipendyl 2012). The amyloid accumulation occurs in the media and the adventitia of cerebral vessels, leading to degeneration of smooth muscle cells and pericytes (Thal et al., 2012). In extreme cases, the vascular wall develops fibrinoid necrosis and the vessels assume a characteristic double barrel appearance (Thal et al., 2012). Overlap of AD neuropathology (amyloid plaques and neurofibrillary tangles) with cerebrovascular lesions is observed in up to 50% of cases of dementia (Jellinger, 2013). These lesions include atherosclerosis of the circle of Willis and its branches, leukoaraiosis, and lacunar infarcts, microbleeds, microinfarcts, and CAA (Benedictus et al., 2013, Charidimou et al., 2012, Honig et al., 2005, Jellinger, 2013, Richardson et al., 2012, Roher et al., 2004, Toledo et al., 2013 and Yarchoan et al., 2012). Ischemic lesions in regions between arterial territories (watershed infarcts) have also been reported in AD, implicating hypoperfusion and CAA in their mechanisms (Miklossy, 2003 and Suter et al., 2002).