For many years, doctors have considered memory loss to be the first clear sign of Alzheimer’s disease. A new study suggests that the brain may actually show problems much earlier in a different way.
Scientists from Texas A&M Health report that difficulty adapting to change could appear before noticeable memory problems. The research was published in Nature Communications.
Alzheimer’s disease develops slowly. Harmful proteins gradually build up inside the brain, damaging nerve cells over many years. Because the disease progresses quietly, researchers are trying to find warning signs that appear before serious memory loss begins.
In this study, scientists investigated a mental skill called cognitive flexibility. This ability allows people to adjust when plans change, learn from mistakes, solve new problems, and switch between different tasks. These skills are important for everyday life, from driving to following new instructions at work.
The researchers studied mice that develop Alzheimer’s-like brain changes. They first trained the animals to receive a reward after making the correct choice. Later, they changed the rules.
Healthy mice quickly learned the new pattern, while the Alzheimer’s model mice continued making the old choice even when it no longer earned a reward. Despite this difficulty adapting, the animals still remembered locations normally, showing that flexibility declined before memory.
Further investigation revealed that one important decision-making area of the brain, called the medial prefrontal cortex, had become unusually active. Another connected brain region, the striatum, also showed abnormal activity. At the same time, certain nerve cells that normally help control learning and flexible behavior became less active.
Scientists have known that overactive brain cells can increase production of amyloid-beta, one of the proteins linked to Alzheimer’s disease. Unfortunately, amyloid-beta can then make brain cells even more active, creating a damaging cycle.
To interrupt this process, the researchers used a targeted method to quiet the overactive brain pathway. The treatment improved the animals’ ability to adapt to new situations, normalized brain activity, and reduced amyloid-beta levels.
These findings suggest that abnormal brain activity may actively drive Alzheimer’s disease rather than simply resulting from it. If confirmed in people, doctors may eventually add cognitive flexibility testing to current memory assessments, allowing much earlier diagnosis.
Early diagnosis matters because current and future treatments are likely to work best before large numbers of brain cells have been lost. Finding Alzheimer’s disease earlier could give patients more time to receive treatment, plan for the future, and participate in clinical trials.
The study provides strong biological evidence that executive function may decline before memory in Alzheimer’s disease. It also demonstrates that correcting abnormal brain activity can improve brain function in experimental models.
However, because the research was performed in mice, it cannot yet prove that the same sequence occurs in humans. Large human studies will be needed before these findings can be translated into routine medical care.
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Source: Texas A&M Health.
