Biomarkers.

Area of Science:

• Neuroscience
• Medical Imaging
• Gerontology

Background:

• Alzheimer's disease (AD) pathology, including amyloid-β (Aβ) accumulation, precedes cognitive decline.
• The relationship between Aβ-associated brain atrophy and specific cognitive networks in preclinical AD remains unclear.
• Understanding early network-level atrophy is crucial for AD pathophysiology and risk stratification.

Purpose of the Study:

• To determine if Aβ-associated brain atrophy in preclinical AD maps to distinct cognitive networks.
• To identify specific brain networks linked to objective and subjective cognitive changes in early AD.
• To explore the utility of atrophy network mapping for understanding preclinical AD.

Main Methods:

• Analysis of structural MRI and amyloid-β PET scans from 1778 cognitively unimpaired older adults (65-85 years).
• Creation of individualized atrophy maps using vertex-wise general linear models.
• Estimation of functional connectivity of atrophy patterns using a normative human connectome.
• Linear regression to associate atrophy connectivity with objective (PACC) and subjective (CFI) cognitive scores.

Main Results:

• Distinct brain networks were identified for objective and subjective cognitive changes in preclinical AD.
• Atrophy patterns connected to the superior temporal gyrus were associated with objective cognitive impairment (PACC).
• Atrophy patterns connected to the mid-cingulate were associated with subjective cognitive impairment (CFI).

Conclusions:

• Atrophy network mapping successfully identified distinct brain networks linked to transitional cognitive changes in preclinical AD.
• These findings enhance understanding of early AD pathophysiology.
• The approach is valuable for localizing early cognitive signs in preclinical AD, extending its application from AD dementia.