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

Area of Science:

• Neurology
• Neuroscience
• Pathology

Background:

• Mild cognitive impairment (MCI) was initially defined as a transitional stage to Alzheimer's disease (AD).
• Recent research reveals MCI's heterogeneity, with cerebrovascular and Parkinson's diseases contributing to mild cognitive deficits.
• Neuropathological findings confirm MCI heterogeneity, showing co-occurrence of amyloid plaques, tau tangles, and cerebrovascular pathology.

Purpose of the Study:

• To redefine MCI considering its diverse etiologies.
• To explore the role of cerebral amyloid angiopathy (CAA) in cognitive impairment.
• To investigate the impact of vascular risk factors and neurovascular approaches on MCI and dementia.

Main Methods:

• Review of neuropathological examinations in MCI patients.
• Analysis of epidemiological studies on vascular risk factors and cognitive decline.
• Examination of the relationship between CAA, Aβ clearance, and dementia progression.

Main Results:

• MCI patients often exhibit both AD-related pathology (amyloid plaques, tau tangles) and cerebrovascular pathology (arteriosclerosis, CAA).
• Cerebral amyloid angiopathy (CAA) contributes to cognitive impairment through infarcts and hemorrhage.
• Vascular risk factors are linked to increased MCI incidence and progression to AD.

Conclusions:

• MCI is a heterogeneous condition with multiple underlying causes beyond AD.
• Impaired Aβ clearance, particularly via the perivascular drainage system, contributes to sporadic AD and CAA.
• Controlling vascular risk factors and exploring neurovascular treatments are crucial for managing MCI and preventing dementia.