Normal brain aging and Alzheimer's disease pathology reshape the brain's functional connectivity along two distinct, separable patterns rather than a single shared one, according to a study published October 1, 2026 in Nature Neuroscience. Researchers led by Jonathan Rittmo and Jacob W. Vogel at Lund University, with collaborators including Nicolai Franzmeier at Ludwig Maximilian University of Munich, analyzed resting-state fMRI scans from 973 adults in the Swedish BioFINDER-2 study who also had cerebrospinal fluid amyloid and tau PET measurements, then checked their findings in 129 participants from the United States-based Alzheimer's Disease Neuroimaging Initiative. Connectivity changes that tracked chronological age followed what the team labeled a representation-executive axis of brain organization, and did so steadily across adulthood regardless of disease status. Connectivity changes tied to the accumulation of Alzheimer's pathology, and to later cognitive decline, instead followed a separate sensory-association axis running through higher-order association cortex involved in memory and other complex processing.
The cross-sectional analysis, which modeled connectivity trajectories against a continuous measure of biomarker-based pathology rather than diagnostic categories alone, found that the disease-linked pattern on the sensory-association axis was present in cognitively unimpaired participants who already had elevated tau, before any measurable cognitive symptoms. The researchers described the shifts not as isolated changes in single brain regions but as coordinated patterns, writing that connectivity increases and decreases need to be understood as "parts of larger patterns shaped by the brain's underlying organization." The pattern held up across both the Swedish and American cohorts, which used different scanners and recruitment criteria.
The researchers were careful to frame the work as a starting point rather than a diagnostic tool. Blood tests for p-tau217 can already flag Alzheimer's pathology before symptoms appear, and the authors noted that before connectivity patterns could be used to tell an individual's aging brain from an individual's Alzheimer's-affected brain, the group-level patterns identified here would need to be confirmed using measurements taken from single people, and tested for whether they actually predict who goes on to decline cognitively. The analysis was cross-sectional for most participants, meaning it compared different people at different ages and disease stages rather than following the same individuals over many years throughout.