Neuropathologic alterations in mild cognitive impairment: a review

Area of Science:

• Neurology
• Neuroscience
• Pathology

Background:

• Mild cognitive impairment (MCI) represents an early stage of dementia and Alzheimer's disease (AD).
• Understanding the neuropathological basis of MCI is crucial for early detection and prevention strategies.
• Longitudinal studies of patients with MCI are essential for defining its underlying pathology.

Purpose of the Study:

• To review clinical-pathological reports of longitudinally followed patients with MCI.
• To define the neuropathological substrates underlying amnestic MCI (aMCI).
• To explore the relationship between MCI pathology and progression to Alzheimer's disease.

Main Methods:

• Review of major clinical-pathological reports of longitudinally followed patients.
• Analysis of autopsied cases of amnestic MCI (aMCI).
• Correlation of neuropathological findings with clinical progression and Braak score.

Main Results:

• Most autopsied aMCI patients show neuropathological findings consistent with a pathway toward AD.
• Neurofibrillary pathology in the entorhinal cortex, hippocampus, and amygdala is the primary substrate for aMCI and memory decline.
• Concomitant pathologies, including strokes, argyrophilic grains, and Lewy bodies, are common in older MCI patients.

Conclusions:

• Neurofibrillary tangles, rather than amyloid plaques, are the key neuropathological hallmark of aMCI.
• MCI pathology, particularly neurofibrillary tangles, predicts progression to Alzheimer's disease.
• The presence of additional pathologies like strokes in MCI highlights the complexity of cognitive decline in older adults.