Preclinical Brain Network Abnormalities in Patients with Subjective Cognitive Decline

Area of Science:

• Neuroscience
• Neurology
• Radiology

Background:

• Alzheimer's disease (AD) is the leading cause of dementia globally, with no current disease-modifying treatments.
• Early detection of individuals at high risk for dementia is crucial for clinical trial development.
• Subjective cognitive decline (SCD) describes individuals perceiving cognitive decline without objective deficits, yet exhibiting AD-related cerebrospinal fluid biomarkers.

Purpose of the Study:

• To investigate alterations in brain functional connectivity (FC) within individuals experiencing subjective cognitive decline (SCD).

Main Methods:

• Twenty-three SCD subjects and 33 healthy subjects (HS) completed comprehensive neuropsychological assessments.
• 3T-MRI scans, including T1-weighted imaging and resting-state fMRI (RS-fMRI), were acquired to evaluate brain atrophy and FC.
• Analysis focused on comparing brain structure and FC between SCD and HS groups.

Main Results:

• No significant differences in grey matter volume were observed between SCD and HS groups.
• SCD subjects demonstrated both increased and decreased FC within executive and parietal brain networks compared to HS.
• Correlations between cognitive assessments (particularly working memory) and FC were identified in both SCD and HS groups.

Conclusions:

• SCD individuals exhibit altered FC in fronto-parietal networks, potentially linked to diminished visuo-spatial working memory.
• Executive-frontal network dysfunction may underlie the subjective cognitive decline experienced by SCD individuals, despite normal neuropsychological test scores.
• These findings support considering SCD as a potential early stage of AD, indicating an elevated long-term risk for disease progression.