Could trouble adapting to change appear before memory loss in Alzheimer’s disease?
A new study suggests the answer may be yes. Alzheimer’s disease is usually linked with forgetting names, losing important items, or becoming confused about places and events.
However, scientists are now discovering that the disease may begin affecting the brain years before these familiar symptoms appear. Researchers at Texas A&M Health have found evidence that difficulty adjusting to new situations may be one of the earliest warning signs. Their findings were published in Nature Communications.
Alzheimer’s disease is the most common cause of dementia. It slowly damages brain cells and gradually affects memory, thinking, judgment, and everyday activities. By the time memory problems become obvious, many brain cells have already been damaged. This is why researchers are searching for earlier signs that could help doctors diagnose the disease sooner.
The new study focused on cognitive flexibility, which is the brain’s ability to change plans, learn new rules, and adjust when situations change. This skill is part of executive function, which also includes planning, decision-making, attention, and problem-solving.
The research team, led by neuroscientist Dr. Jun Wang, used a well-established mouse model of Alzheimer’s disease known as 5xFAD. These animals develop amyloid-beta plaques similar to those seen in people with Alzheimer’s disease.
The scientists used a test called reversal learning. The mice first learned that one action produced a reward. After they mastered the task, the researchers changed the rule so that a different action was rewarded instead.
Healthy mice quickly adapted to the new rule, but the Alzheimer’s model mice kept repeating the old behavior even when it no longer worked. Surprisingly, these same mice still performed normally on memory tests that measured their ability to remember locations.
The researchers then examined what was happening inside the brain. They found unusually high activity in the medial prefrontal cortex, an area involved in planning, decision-making, and flexible thinking. This overactivity also spread through a network connecting the prefrontal cortex and the striatum, another brain region that helps control behavior.
The team also discovered reduced activity in special nerve cells called cholinergic interneurons, which help people learn and adapt. Together, these changes appeared to explain why the animals struggled to adjust to new situations.
The researchers wondered whether calming this overactive brain circuit could help. Using a highly targeted technique, they temporarily reduced activity in the affected pathway.
The treatment improved the animals’ ability to adapt, restored more normal brain activity, and even reduced the buildup of amyloid-beta. Some of these improvements continued after treatment had stopped.
Although this work was carried out in animals, it provides an exciting new direction for Alzheimer’s research.
If future human studies find the same pattern, simple tests that measure cognitive flexibility could help identify people years before memory loss becomes obvious. Earlier diagnosis would give doctors a better chance to begin treatment while more brain cells remain healthy.
This is a carefully designed preclinical study that links changes in brain circuits with early thinking problems before memory loss appears. The results are encouraging because they identify both a possible early warning sign and a potential treatment target.
However, the findings have not yet been confirmed in humans, so more research and clinical trials will be needed before these discoveries change medical practice.
If you care about Alzheimer’s, please read studies about the likely cause of Alzheimer’s disease , and new non-drug treatment that could help prevent Alzheimer’s.
For more health information, please see recent studies about diet that may help prevent Alzheimer’s, and results showing some dementia cases could be prevented by changing these 12 things.
Source: Texas A&M Health.
