Convergent and Discriminant Validity of Default Mode Network and Limbic Network Perfusion in Amnestic Mild Cognitive Impairment Patients

Background: Previous studies reported default mode network (DMN) and limbic network (LIN) brain perfusion deficits in patients with amnestic mild cognitive impairment (aMCI), frequently a prodromal stage of Alzheimer's disease (AD). However, the validity of these measures as AD markers has not yet been tested using MRI arterial spin labeling (ASL). Objective: To investigate the convergent and discriminant validity of DMN and LIN perfusion in aMCI. Methods: We collected core AD markers (amyloid-beta 42 [A beta(42)], phosphorylated tau 181 levels in cerebrospinal fluid [CSF]), neurodegenerative (hippocampal volumes and CSF total tau), vascular (white matter hyperintensities), genetic (apolipoprotein E [APOE] status), and cognitive features (memory functioning on Paired Associate Learning test [PAL]) in 14 aMCI patients. Cerebral blood flow (CBF) was extracted from DMN and LIN using ASL and correlated with AD features to assess convergent validity. Discriminant validity was assessed carrying out the same analysis with AD-unrelated features, i.e., somatomotor and visual networks' perfusion, cerebellar volume, and processing speed. Results: Perfusion was reduced in the DMN (F = 5.486, p= 0.039) and LIN (F = 12.678, p= 0.004) in APOE epsilon 4 carriers compared to non-carriers. LIN perfusion correlated with CSF A beta(42) levels (r= 0.678, p= 0.022) and memory impairment (PAL, number of errors, r = -0.779, p = 0 .002). No significant correlation was detected with tau, neurodegeneration, and vascular features, nor with AD-unrelated features. Conclusion: Our results support the validity of DMN and LIN ASL perfusion as AD markers in aMCI, indicating a significant correlation between CBF and amyloidosis, APOE epsilon 4, and memory impairment.

Automated summary

The study investigated the validity of DMN and LIN perfusion as Alzheimer's disease markers in patients with aMCI. The results showed a significant correlation between decreased perfusion in DMN and LIN with amyloidosis, APOE epsilon 4 status, and memory impairment, supporting their potential as markers for AD in aMCI patients.