Functional Connectivity Changes in the Aging Brain are Different in Alzheimer's Disease Patients
Functional connectivity is a measure of neuronal activity over time in different parts of the brain, assessed using MRI to detect the increased blood flow that accompanies increased neuronal activity. Researchers here demonstrate that changes in functional connectivity observed in Alzheimer's disease patients differ from age-related changes observed in individuals without dementia. As is the case for many measures of aging, there is some debate within the scientific community with regard to whether any specific change is dysfunction or an adaptive, compensatory reaction to dysfunction. This will likely remain the case until effective rejuvenation therapies or effective treatments for specific neurodegenerative conditions such as Alzheimer's exist, can be used in sizable patient populations, and the results measured.
Aging and Alzheimer's disease (AD) are both associated with changes in functional brain networks - groups of regions that typically communicate with one another and support cognition. However, the precise nature of these changes - their spatio-temporal dynamics and whether they reflect compensatory adaptations, pathological disruptions, or both - remains a topic of active debate. Functional connectivity (FC), the temporal synchrony of activity between brain regions, may be a mechanism facilitating the spread of pathology, a system affected by pathology, or an interplay of both.
Here, in two independent cohorts (BioFINDER-2, N = 973; Alzheimer's Disease Neuroimaging Initiative, N = 129), we show that functional connectivity changes associated with aging and AD are strongly aligned with separate fundamental axes of hierarchical brain communication. Early accumulation of AD pathology and subsequent cognitive decline are both linked to functional change along the sensory-association axis. Meanwhile, age-related functional changes occur along the representation-executive axis consistently throughout the adult lifespan. These findings together suggest that both AD and aging alter major but orthogonal functional pathways in the brain.