Mild Cognitive Impairment: At the Crossroad of Neurodegeneration and Vascular Dysfunction.

The concept of mild cognitive impairment (MCI) was first introduced for the purpose of identifying individuals in an intermediate state between no cognitive impairment and Alzheimer's disease (AD). Recently, the heterogeneity of MCI has attracted attention as it has become clear that other diseases, such as cerebrovascular disease and Parkinson disease can also cause mild cognitive deficits, prompting a redefinition of MCI. Heterogeneity of MCI has been confirmed by neuropathological examinations. Most MCI patients not only possess amyloid plaques and neurofibrillary tau tangles, but also cerebral vascular pathology such as arteriosclerosis and cerebral amyloid angiopathy (CAA). CAA induces cerebral infarcts or hemorrhage of varying size and type, attributing to further cognitive impairment. Sporadic AD and CAA has been suggested to be the consequence of Aβ elimination failure, mainly caused by disturbance of the perivascular drainage system. Since severe CAA is an independent risk factor for dementia, facilitation of Aβ clearance has been suggested as a potential treatment of AD and MCI. Many epidemiological studies have shown that vascular risk factors increase incidence of MCI and its progression to AD. Accordingly, control of such factors has been shown to reduce risk of conversion to AD and ameliorate cognitive impairment in AD patients. Neurovascular approaches may therefore hold promise for the treatment of dementia in an era of preventive neurology.