Biomarkers.

Area of Science:

• Neuroscience
• Gerontology
• Psychiatry

Background:

• Mild behavioral impairment (MBI) is an early indicator of increased dementia risk.
• The underlying mechanisms of MBI are not fully understood.
• Altered functional connectivity (FC) in cortical networks is observed in MBI.

Purpose of the Study:

• To investigate the cortical-subcortical FC correlates of MBI.
• To examine the relationship between MBI, Alzheimer's disease biomarkers, and cerebrovascular disease biomarkers.

Main Methods:

• 238 dementia-free participants underwent neuropsychological testing and resting-state functional MRI.
• Resting-state functional connectivity (RSFC) was analyzed between subcortical limbic regions and cortical networks (DMN, FPCN, SN).
• Regression models examined associations between MBI and RSFC, and their interaction with white matter hyperintensities volume (WMHV), p-Tau181, and GFAP.

Main Results:

• Reduced left hippocampus-DMN RSFC was associated with higher global MBI scores, particularly motivation and affective dysregulation.
• White matter hyperintensities volume (WMHV) and glial fibrillary acidic protein (GFAP) significantly moderated the association between left hippocampus-DMN RSFC and MBI.
• The association was significant only with high WMHV or high GFAP, suggesting a role for cerebrovascular pathology and neuroinflammation.

Conclusions:

• Cortical-subcortical functional alterations in the DMN are associated with MBI.
• Cerebrovascular pathology and neuroinflammation may modulate the brain-behavior relationship in MBI.
• Further research is warranted to explore these modulating factors in dementia risk.