Researchers detected brain changes in cognitively healthy adults well before visible plaque buildup. The results may broaden the search for early Alzheimer’s markers beyond amyloid alone. Credit: Stock

A new study suggests that brain imaging could detect Alzheimer’s disease more than seven years earlier than previously thought.

Long before amyloid plaques become visible on standard brain scans, structural changes associated with Alzheimer’s disease may already be taking place. The findings suggest that the current gold standard for Alzheimer’s imaging (amyloid-PET) may not be sensitive enough to capture these earliest processes, with researchers detecting brain changes at least seven years before plaques could be seen.

“We found that structural changes in the brain occur many years before high levels of plaque are seen on PET scans, which is the brain scan currently used to identify the earliest signs of Alzheimer’s disease,” says James Michael Roe.

Roe was a postdoctoral researcher at the Center for Lifespan Changes in Brain and Cognition (LCBC) in the University of Oslo’s Department of Psychology when the research was carried out and served as the study’s main researcher while at LCBC. He is now International Scientific Lead at Cercare Medical.

Brain changes appear before visible plaques

According to Roe, the results raise the possibility that disease processes may begin in the brain well before today’s most sensitive imaging methods can detect them.

“We found the earliest signal detected on brain scans to date, which could be useful for tracking the disease before symptoms emerge and may help with earlier detection,” he says.

Dementia can be detected earlier than previously assumed, new research shows. Here is conductor Kim Wigaard during a rehearsal with the popular Dementia Choir. The NRK series received the The University of Oslo Human Rights Award. Credit: Anna Sørmarken Vestly / NTB Scanpix

Two decades of scans revealed an earlier signal

To look further back in time, the researchers followed healthy people with repeated brain scans (MRI) for nearly two decades. Those records allowed them to determine when plaques first became detectable and which participants developed them, then examine MRI scans from the previous decade to compare earlier brain changes in people who later showed plaques with those who did not.

James Michael Roe. Credit: Erik Engblad/ UiO

“The most groundbreaking aspect of this study is that we found structural changes in the brain many years before the first signs of plaque buildup, which is considered to be the earliest sign of Alzheimer’s disease,” says Anders Martin Fjell, Professor at the Department of Psychology, and head of LCBC.

“These are cognitively well-functioning older individuals. What is unique here is that we have examined changes in brain structure in the years before the first scan revealed plaques,” says Fjell.

Fjell notes that Alzheimer’s disease remains extremely difficult to treat, in part because it is closely connected with aging and is probably influenced by multiple factors.

The earliest changes may extend beyond amyloid

“These findings suggest that there are brain changes that precede the first detectable signs of plaque accumulation, which is considered the earliest phase of the disease and occurs many years before cognitive symptoms start showing,” he says.

Fjell says the results point to two possible explanations:

1. Harmful processes that either drive plaque accumulation or result from it may already be occurring before the plaques can be detected by scans.
2. Other biological processes may be producing brain changes even before amyloid plaques begin to accumulate.

“If the latter is true, it suggests it is important to continue developing drugs that target processes other than amyloid plaque accumulation. But we need more research on this,” says Anders Martin Fjell.

Reference: “Cortical thickness changes precede high levels of amyloid by at least 7 years” by James M. Roe, William J. Jagust, Susan M. Landau, Theresa M. Harrison, Håkon Grydeland, Maksim Slivka, José-Luis Alatorre-Warren, Pablo F. Garrido, Øystein Sørensen, Edvard O. S. Grødem, Tyler J. Ward, Esten H. Leonardsen, Alice Murphy, JiaQie Lee, Tormod Fladby, Atle Bjørnerud, Kristine B. Walhovd, Anders M. Fjell, Didac Vidal-Piñeiro and Yunpeng Wang, 19 August 2026, Nature Neuroscience.
DOI: 10.1038/s41593-026-02363-4

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