And, of course, I am also profoundly thankful to all of our co-authors and collaborators for their wisdom and insights, and everyone involved in the @biofinder.bsky.social and ADNI studies who made this work possible! 13/

There’s still a lot to understand about why these patterns emerge, how they relate to cognition, what they mean at the individual level, and whether they may have clinical relevance. These are questions we are actively working on 11/

For me, the most striking part is that these findings highlight the value of looking at the whole cortex for functional changes. What can seem like unrelated regional connectivity changes form coordinated patterns shaped by the brain’s underlying functional organization 10/

Why different axes? One idea we explore is differential cognitive pressures. In general, aging is more associated with executive decline while AD hits memory harder. Better executive performance aligned numerically more with the RE axis, better memory more with the SA axis 9/

Is this just structure or vascular damage in disguise? It seems not. The signatures survive adjusting for cortical thickness, white matter hyperintensities, lacunes, microbleeds and α-synuclein. In fact, those factors show their own axis-aligned effects, independently 8/

There was also a shift in what the signature relates to. Before symptom onset it closely tracks AD pathology. Among cognitively impaired individuals, however, the same pattern is more strongly related to cognitive performance 7/

We then asked where the Alzheimer's-related signature sits in the disease trajectory. And found that it emerges early during pathology accumulation, and then weakens at more advanced stages 6/

We replicated the findings in an independent cohort (ADNI, n = 129), and also found that the same pattern held longitudinally: within the same individuals, increasing tau was accompanied by connectivity changes along the sensory-association axis 5/

In 973 BioFINDER-2 participants with fMRI + CSF/PET biomarkers, we modelled age- and AD-related connectivity changes across the cortex. Two distinct patterns emerged: AD pathology → sensory-association axis (r=.74); age → representational-executive axis (r=.75) 4/

The brain's functional organization can be described by several large-scale axes. Two of the dominant ones are the sensory-association (SA) axis and the representational-executive (RE) axis. We asked if these axes could help us interpret the effects 3/

Functional connectivity captures how activity in different brain regions relates over time. Studies suggest this may be affected early in Alzheimer’s, but findings have been difficult to interpret, with a mix of increases and decreases across regions and networks 2/