Posterior Cingulate Cortex Network Predicts Alzheimer's Disease Progression.

Area of Science:

• Neuroscience
• Neurology
• Radiology

Background:

• Alzheimer's disease (AD) is a progressive neurodegenerative disorder linked to toxic protein accumulation propagating through brain networks.
• Previous studies identified potential AD epicenters and networks, but their association with disease progression remained unclear.
• Understanding early-stage AD pathophysiology and network involvement is crucial for developing effective interventions.

Purpose of the Study:

• To identify vulnerable brain epicenters and large-scale structural networks in early Alzheimer's disease (AD).
• To evaluate the association of these networks with disease progression and cognitive decline using a longitudinal design.
• To investigate the role of network degeneration in AD pathophysiology.

Main Methods:

• Longitudinal study involving 23 AD patients, 37 amnestic mild cognitive impairment (MCI) patients, and 33 healthy controls (HC) over 3 years.
• Annual MRI and neuropsychological assessments were conducted.
• Candidate epicenters were identified by gray matter volume (GMV) decline rates in MCI patients who progressed to AD; synchronized degeneration networks (SDNs) were mapped in HCs.

Main Results:

• Hippocampus and posterior cingulate cortex (PCC) identified as vulnerable AD-associated epicenters.
• The PCC-synchronized degeneration network (PCC-SDN) showed significant spatial association with GMV atrophy rates, particularly in advanced AD stages.
• Higher GMV atrophy rates in the PCC-SDN correlated with faster decline in multiple cognitive domains.

Conclusions:

• The PCC and hippocampus are early vulnerable regions in Alzheimer's disease (AD) pathophysiology.
• The PCC-SDN, not the hippocampus-SDN, demonstrated a closer association with AD progression.
• Findings offer insights into AD pathophysiology from a large-scale network perspective, highlighting the PCC-SDN's role in disease advancement.