Cortical changes in incipient Alzheimer's disease.

Area of Science:

• Neuroimaging
• Neurology
• Alzheimer's Disease Research

Background:

• Mild cognitive impairment (MCI) is a transitional stage between normal aging and Alzheimer's disease (AD).
• Structural brain changes preceding AD conversion are not fully understood.
• Previous research focused more on cortical changes in diagnosed AD patients.

Purpose of the Study:

• To investigate longitudinal gray matter changes in MCI patients who convert to AD (cMCI) versus those who remain stable (sMCI).
• To identify specific brain regions affected early in the progression from MCI to AD.
• To compare gray matter volume and loss over time between cMCI, sMCI, and healthy controls.

Main Methods:

• Structural MRI scans (1.0T) were acquired at baseline and follow-up for 46 MCI patients and 20 healthy controls.
• Subjects were assessed yearly for up to 4 years using a comprehensive neuropsychological battery.
• Voxel-based statistical mesh-model technique (cortical pattern matching) and region-of-interest analysis were employed to map gray matter changes.

Main Results:

• At baseline, cMCI patients exhibited 10-30% less gray matter than controls in AD-vulnerable regions (entorhinal, temporoparietal, posterior cingulate, orbitofrontal cortex).
• Over time, cMCI patients experienced significantly greater gray matter loss (>8%) than sMCI patients, especially in olfactory and polysynaptic hippocampal networks.
• sMCI patients showed reduced gray matter volume in posterior cingulate and orbitofrontal cortex compared to controls, but with slower progression.

Conclusions:

• MCI patients who convert to AD demonstrate accelerated gray matter loss in key brain networks, including olfactory and hippocampal regions, years prior to clinical diagnosis.
• These findings highlight the utility of longitudinal neuroimaging in identifying early AD-related brain changes.
• The observed patterns of gray matter loss align with known neuropathological hallmarks of Alzheimer's disease.