Neuropathologic substrate of mild cognitive impairment.

Area of Science:

• Neuropathology
• Neuroscience
• Gerontology

Background:

• Mild cognitive impairment (MCI) is a transitional stage between normal aging and dementia.
• Distinguishing MCI from early Alzheimer disease (AD) at a neuropathologic level is crucial for understanding disease progression.

Purpose of the Study:

• To define and compare the neuropathologic findings in amnestic MCI and early AD.
• To correlate neuropathologic markers with memory performance.

Main Methods:

• Quantified diffuse plaques, neuritic plaques (NPs), and neurofibrillary tangles (NFTs) in neocortical and ventromedial temporal lobe regions.
• Compared 10 amnestic MCI patients, 10 early AD patients, and 23 controls longitudinally.
• Correlated neuropathologic findings with memory performance.

Main Results:

• MCI patients showed elevated NPs in neocortical regions and amygdala compared to controls.
• NFTs were significantly increased in MCI ventromedial temporal lobe structures and parietal lobe compared to controls.
• Both NPs and NFTs were significantly elevated in early AD compared to controls.
• Memory function correlated with NFTs in the hippocampus (CA1) and entorhinal cortex.

Conclusions:

• Amnestic MCI exhibits early neuropathologic changes characteristic of Alzheimer disease.
• Neurofibrillary tangles (NFTs) appear more prominent than beta-amyloid plaques in the progression from normal aging to MCI to early AD.
• Ventromedial temporal lobe NFTs are likely responsible for memory decline in MCI, suggesting amnestic MCI is an early form of AD.