Study uncovers three hidden patterns of Alzheimer’s cognitive decline

A new study has identified three distinct pathways in how Alzheimer’s develops, offering fresh insight into how Alzheimer’s cognitive decline may progress differently across patients over time

Researchers found that Alzheimer’s cognitive decline develops in three separate patterns, indicating the disease does not progress uniformly. The findings show that people with Alzheimer’s may experience different trajectories of memory and thinking changes, with variation in both speed and severity. Scientists say this could improve early disease detection and may guide more personalised treatment approaches in the future.

These findings, which add to the understanding of disease progression, are published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

Biomarkers help predict trajectories of Alzheimer’s cognitive decline

The researchers analysed data from a series of cognitive tests measuring memory, attention, and thinking, administered before and during the trial. Scores were used to track their rate of cognitive decline. The researchers also collected brain scans and blood tests, including phosphorylated tau (P-tau217), a marker of the protein tau, one of the hallmarks of Alzheimer’s disease.

The analysis revealed three distinct patterns of Alzheimer’s cognitive decline: stable (no change or improvement); slow decline (gradual decline in test scores); and fast decline (rapid, more pronounced decline in test scores).

Participants who showed either a gradual or rapid decline in thinking and memory had higher levels of P-tau217 at the start of the study, as well as increased tau levels on brain scans, compared with those whose cognition remained stable.

They also tended to have a smaller hippocampus — a part of the brain important for memory and one of the first areas affected in Alzheimer’s disease.

Using these biomarkers, researchers were able to correctly predict whether someone would remain stable or experience worsening symptoms about 70% of the time.

“These results suggest we may need to rethink how we design clinical trials in preclinical Alzheimer’s disease,” said Runpeng (Tony) Li, PhD, a postdoctoral scholar at the Keck School of Medicine and the study’s first author. “Many people with Alzheimer’s remain stable over the course of a study, which can make it hard to tell if a treatment is working. Identifying those who are more likely to decline could make trials more efficient and more informative.”

Researchers aim to improve prediction of Alzheimer’s progression patterns

The next step in the research is to enhance the predictive model, aiming to determine more precisely which patients are likely to experience rapid cognitive decline due to Alzheimer’s. The researchers plan to analyse additional data and refine their biomarkers for increased accuracy.

The findings highlight the major challenge in Alzheimer’s prevention research: many individuals remain stable during early disease, making it difficult to detect whether medication is working. The researchers say future trials should focus less on average results and more on different patterns of decline.

The researchers also plan to investigate why certain individuals, predicted to remain stable, showed decline, and why some, predicted to decline, stayed symptom-free. This could reveal protective factors against cognitive decline.

“What is different about certain patients that makes them more resilient—and can these insights be leveraged to slow down Alzheimer’s disease in others?” Donohue said.