Directed Functional Brain Connectivity is Altered in Sub-threshold Amyloid-β Accumulation in Cognitively Normal...

Area of Science:

• Neuroscience
• Biomarkers
• Alzheimer's Disease Research

Background:

• Amyloid-beta (Aβ) deposition below clinical thresholds is linked to cognitive changes and increased Alzheimer's disease (AD) risk.
• Functional MRI (fMRI) detects early AD alterations, but sub-threshold Aβ changes haven't been linked to functional connectivity.
• Early detection of AD pathology is crucial for timely intervention.

Purpose of the Study:

• To apply directed functional connectivity to identify early network function changes in cognitively unimpaired individuals with sub-threshold Aβ accumulation.
• To investigate if network properties can detect preclinical AD pathology.
• To explore the relationship between Aβ accumulation, network function, and cognitive performance.

Main Methods:

• Analysis of baseline fMRI data from 113 cognitively unimpaired participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort.
• Classification of participants into Aβ- non-accumulators, Aβ- accumulators, and Aβ+ accumulators based on longitudinal ¹⁸F-florbetapir-PET data.
• Calculation of whole-brain directed functional connectivity networks using an anti-symmetric correlation method and evaluation of global/nodal properties (clustering coefficient, global efficiency).

Main Results:

• Aβ- accumulators showed a lower global clustering coefficient compared to Aβ- non-accumulators.
• Aβ+ accumulators exhibited reduced global efficiency and clustering coefficient, particularly in the superior frontal gyrus, anterior cingulate cortex, and caudate nucleus.
• In Aβ- accumulators, network measures correlated with baseline PET uptake and cognitive scores (Modified Preclinical Alzheimer Cognitive Composite).

Conclusions:

• Directed functional connectivity network properties are sensitive to subtle changes associated with very early Aβ accumulation, preceding clinical thresholds.
• These network properties show potential as viable biomarkers for detecting the downstream effects of preclinical AD pathology.
• Findings highlight the utility of network analysis in understanding early neurobiological changes in Alzheimer's disease.