Brain agingHumans

Aging and Alzheimer's alter separate functional brain pathways

Two human cohorts of 973 and 129 individuals revealed that aging and Alzheimer's disease disrupt separate, orthogonal functional communication axes across the brain.

Figure 1 from Nature Neuroscience
Open the figure at full size
Figure 1Rittmo et al.

Nature Neuroscience

In two independent human cohorts (BioFINDER-2, N = 973; Alzheimer's Disease Neuroimaging Initiative, N = 129), researchers analyzed whole-cortex functional connectivity changes across the adult lifespan and in Alzheimer's disease. The team found that functional connectivity alterations linked to aging and Alzheimer's disease align with separate fundamental axes of hierarchical brain communication. Early accumulation of Alzheimer's pathology and subsequent cognitive decline both link to functional changes along the sensory-association axis. In contrast, age-related functional changes occur along the representation-executive axis consistently throughout the adult lifespan. These patterns demonstrate that Alzheimer's disease and typical aging alter major but orthogonal functional pathways in the brain rather than sharing a single continuum of network breakdown.

Why it matters

The findings help clarify the biological distinction between normal brain aging and neurodegenerative disease by showing their functional impacts follow separate organizational axes. This framework provides a whole-brain model for interpreting how brain communication shifts across the adult lifespan.

Caveats

The findings rely on observational functional imaging data across two specific cohorts. The study also does not establish whether these functional connectivity changes directly cause cognitive decline or arise secondary to other neuropathological events.

The paper

Different functional connectivity gradients reflect aging and Alzheimer's disease

Lund University

Nature Neuroscience · 1 Oct 2026

doi.org/10.1038/s41593-026-02402-0PubMed 42823476

Related