One of the key challenges in understanding and treating Alzheimer's disease (AD) remains its heterogeneity. AD progresses at different rates in different patients, and more than half of those diagnosed also have other brain pathologies that significantly affect the decline in memory, thinking, and other cognitive functions.

A study, led by Christopher Brown and David Wolk of the Perelman School of Medicine at the University of Pennsylvania, has focused on patients with early-stage AD.

The researchers describe the findings, published in the medical journal JAMA Neurology, as the basis for more accurate prediction of the course of AD and a personalized treatment approach based not only on biomarkers, but also on the clinical manifestations of AD.

Scientists have tried to explain why some people have significantly more severe cognitive impairment than expected—based on levels of the protein tau in the brain, one of the main biological markers of AD—while others have milder symptoms.

To do this, the researchers measured levels of the protein tau using either neuroimaging or blood tests, and then compared those data with clinical assessments of memory, attention, and thinking. Based on these data, the participants were divided into three groups: “vulnerable,” whose symptoms were more severe than expected; “valid,” whose clinical manifestations were consistent with the level of tau pathology; and “stable,” whose cognitive impairment was less severe.

The study showed that people in the “vulnerable” group were more likely to have additional pathological changes in the brain, including other abnormal protein processes. Also, these patients showed a faster decline in cognitive function over time.

In contrast, participants in the resilient group experienced a significantly slower decline in cognitive abilities. This points to the possible role of so-called cognitive reserve despite AD—the brain's ability to compensate for damage and maintain function for longer.

Interestingly, the patterns found were maintained regardless of the method used to measure tau protein, whether it was a brain scan or a blood test.