Relationship between cortical microinfarcts and cognitive impairment in Alzheimer's disease

Abstract

Cerebrovascular disease and AD pathology co-exist in most dementia cases, and microinfarcts (MIs), particularly if cortical and multiple, play an additive and independent role in AD cognitive impairment. The main cause of cortical MIs is chronic cerebral hypoperfusion but occlusive vascular diseases, embolism and blood-brain barrier disruptions, isolated or combined, may also play a role. The precise mechanisms by which MIs cause cognitive impairment are not well known, but one plausible explanation is that they are widespread and accompanied by diffuse hypoperfusion, hypoxia, oxidative stress and inflammation, particularly in the watershed areas of the tertiary association cortex, and hence could damage cognition networks and explain many of AD's cognitive and behavioral disturbances. Therefore, it is crucial to control vascular risk factors and avoid uncontrolled use of the antihypertensives, neuroleptics and other sedative drugs frequently prescribed to AD patients.

Chronic cerebral hypoperfusion alters amyloid-β peptide pools leading to cerebral amyloid angiopathy, microinfarcts and haemorrhages in Tg-SwDI mice

“…Previous studies have shown a significant association between oxidative stress and the development of microinfarcts [23][24][25][26][27][28]. Consequently, to further investigate the potential mechanistic basis of our current finding of increased microinfarction following chronic cerebral hypoperfusion, we studied the levels of NOX2.…”

“…Additionally, microinfarction has been shown to occur regionally in areas of brain hypoperfusion in AD patients [19] and, as indicated, in models of cerebral hypoperfusion [10,20]. Importantly, cerebral microinfarcts have been implicated as important contributors to cognitive impairment [21][22][23]. Although the mechanisms leading to microinfarct formation remain unknown, oxidative stress and inflammation, as the result of cerebrovascular alterations, have been suggested as possible contributors [24,25].…”

Brain Stimulation in Alzheimer's Disease

“…In summary, current invasive DBS studies aimed at the subcortical areas such as NBM and fornix, while non-invasive DBS studies aimed the cortical areas such as DLFPC, temporal cortex, Broca's are, Wernicke's area, and PSAC. Generally speaking, the subcortical area is associated with emotion and behavior ( 122 ), whereas cortical function is related to cognition ( 123 ). However, whether the stimulated regions meet the outcome variables are not clearly evaluated and understood.…”

Identification of hippocampal cortical microinfarcts on postmortem 3-T magnetic resonance imaging

“…Cortical microinfarcts (CMI) correspond to small ischemic events of 0.05–4 mm in size, mostly measuring ≤ 1 mm [ 1 ]. They are associated with ß-amyloid deposits (57.1% of cases in one study [ 2 ]) and, depending on the affected brain region, atherosclerotic microangiopathy [ 2 ].…”