Molecular, Structural, and Functional Characterization of Alzheimer's Disease: Evidence for a Relationship between Default Activity, Amyloid, and Memory

TLDR

Default‑state activity in posterior cortical regions is linked to amyloid deposition and atrophy in Alzheimer’s disease, suggesting that lifelong metabolism predisposes these regions to AD‑related changes and contributes to memory impairment. The study investigates Alzheimer’s disease and its antecedent factors by combining amyloid imaging, longitudinal atrophy measures, and reanalysis of prior metabolic and functional data. Data from 764 participants were analyzed using five in‑vivo imaging modalities, including amyloid PET and longitudinal structural MRI. Posterior cortical regions such as the posterior cingulate, retrosplenial, and lateral parietal cortex show convergent amyloid deposition, atrophy, and metabolic abnormalities early in Alzheimer’s disease, and are active during memory retrieval in young adults.

Abstract

Alzheimer's disease (AD) and antecedent factors associated with AD were explored using amyloid imaging and unbiased measures of longitudinal atrophy in combination with reanalysis of previous metabolic and functional studies. In total, data from 764 participants were compared across five in vivo imaging methods. Convergence of effects was seen in posterior cortical regions, including posterior cingulate, retrosplenial, and lateral parietal cortex. These regions were active in default states in young adults and also showed amyloid deposition in older adults with AD. At early stages of AD progression, prominent atrophy and metabolic abnormalities emerged in these posterior cortical regions; atrophy in medial temporal regions was also observed. Event-related functional magnetic resonance imaging studies further revealed that these cortical regions are active during successful memory retrieval in young adults. One possibility is that lifetime cerebral metabolism associated with regionally specific default activity predisposes cortical regions to AD-related changes, including amyloid deposition, metabolic disruption, and atrophy. These cortical regions may be part of a network with the medial temporal lobe whose disruption contributes to memory impairment.