Brain structure, amyloid, and behavioral features for predicting clinical progression in subjective cognitive decline

Area of Science:

• Neurology
• Neuroimaging
• Geriatrics

Background:

• Subjective cognitive decline (SCD) is a preclinical stage of Alzheimer's dementia, associated with higher risks of cognitive decline and dementia.
• The influence of SCD on clinical progression, considering amyloid deposition, cerebrovascular disease (CeVD), and psychiatric symptoms, remains unclear.

Purpose of the Study:

• To investigate the longitudinal effects of SCD on cerebrovascular disease (CeVD) and cognitive decline.
• To determine if SCD status, age, and depressive symptoms predict clinical outcomes in older adults.

Main Methods:

• Utilized data from the ADNI database, comparing normal controls (NC), SCD individuals who progressed (P-SCD), and SCD individuals who did not (S-SCD).
• Assessed white matter hyperintensities (WMH), including deep (DWMH) and periventricular (PWMH) regions, and grey matter volumes.
• Employed structural equation modeling to analyze longitudinal changes and relationships between SCD, CeVD, depressive symptoms, and cognitive outcomes.

Main Results:

• Both SCD groups exhibited higher baseline and increased longitudinal PWMH volumes compared to NC; P-SCD also showed higher baseline and increased DWMH volumes.
• SCD status was linked to future WMH progression, and baseline SCD predicted cognitive decline mediated by PWMH.
• Depressive symptoms directly contributed to clinical outcomes, independent of CeVD.

Conclusions:

• SCD is associated with increased CeVD burden, with a more pronounced increase in those progressing to mild cognitive impairment.
• SCD status influences future cognitive decline primarily through CeVD pathologies, specifically white matter hyperintensities.
• Multi-modal longitudinal studies are crucial for understanding SCD heterogeneity and enabling early interventions.