Alzheimer’s: What Are the Real Early Signs?

It is undoubtedly a major advance in understanding and early diagnosis of Alzheimer’s disease: a redefinition of its earliest symptoms.

The emergence of cognitive rigidity

While Alzheimer’s disease has historically and systematically been associated with memory losses (such as missing appointments or forgetting names), a recent study published in Nature Communications reveals that these memory problems actually appear late, once brain lesions are already well established. The researchers highlight another early, subtler warning signal: a disruption of cognitive flexibility.

What is cognitive flexibility? It is our ability to adapt our behavior in the face of an unexpected event or a change in the situation. To identify this phenomenon, the Texas A&M Health team conducted experiments on mice genetically engineered to develop beta-amyloid plaques, the hallmark of Alzheimer’s disease. The scientists first conditioned the rodents to follow a simple rule to obtain a reward, before altering that rule. While healthy mice immediately changed their behavior to adapt, the mice carrying early brain lesions persisted in applying the old, now ineffective method, demonstrating early behavioral rigidity.

A prelude to memory troubles

The major finding of this experiment lies in the chronology of symptoms. Indeed, when the sick mice failed to adapt to the rule change, the tests showed that their spatial memory was nonetheless perfectly intact. This “loss of flexibility” therefore predates the first memory lapses observed in Alzheimer’s disease. Thus, a subtle daily attitude change could actually be the very first clinical indicator of the disease.

By analyzing the brains of the mice, researchers uncovered the biological origin of this cognitive rigidity: an abnormal hyperactivity in the neural circuit connecting the prefrontal cortex (the decision-making area) to the striatum (involved in learning and adapting behavior). By experimentally damping this excessive activity, they not only restored the animals’ ability to adapt, but also observed a decrease in beta-amyloid plaque deposits.

The importance of early diagnosis

This study fuels new hope because it validates the possibility of detecting Alzheimer’s disease years before the first memory ravages occur. Scientists agree that an extremely early diagnosis is the key to future treatments. The earlier this disease is addressed, the better the chances that therapies aimed at slowing the progressive neurodegeneration will be effective.

Alongside the loss of cognitive flexibility, researchers are exploring other early warning signals that appear well before memory losses. Subtle language changes, episodes of spatial disorientation, pronounced sleep disturbances (insomnia, frequent awakenings), or a reduced ability to identify odors (loss of smell) are among the various avenues currently studied to design tomorrow’s screening tests.