Alzheimer's Disease: Cognitive Decline Varies Significantly, Study Finds

A new study reveals that cognitive decline in Alzheimer's disease varies significantly among patients, highlighting the need for personalised approaches in prevention and treatment.

A study has revealed three trajectories of cognitive decline in Alzheimer's disease -- stable or no change, slow decline, and fast decline -- based on scans of over 1,100 people in the US who had an elevated level of amyloid protein clumps in the brain, a hallmark feature of Alzheimer's disease, but were cognitively unimpaired.

Understanding Alzheimer's Disease and Cognitive Decline

Alzheimer's disease is a neurodegenerative condition in which memory and cognition (thought processes) steadily declines with age, eventually interfering with one's abilities to perform daily activities. Scans of patients commonly show agglomerates or clumps of brain proteins, such as amyloid and tau.

Researchers from the University of Southern California's school of medicine found higher levels of tau and phosphorylated tau (P-tau217, a modified form of tau) among participants who showed a gradual or a fast cognitive decline, compared to those who remained stable.

Key Biomarkers and Brain Regions Affected

Findings published in the Alzheimer's and Dementia: The Journal of the Alzheimer's Association also showed a smaller hippocampus among the participants with cognitive decline, a brain region involved in memory formation and among the first affected due to the neurodegenerative disease.

"Most studies look at the average across participants, which can make it seem like everyone is slowly getting worse at the same rate," said author Michael Donohue, professor of neurology and associate director of biostatistics at the University of Southern California's Keck School of Medicine.

"But we found that this approach masks major differences between people, suggesting that Alzheimer's disease is more variable than often depicted," Donohue said.

Implications for Alzheimer's Research and Treatment

The researchers said while previous studies suggest that people with the neurodegenerative condition suffer cognitive decline at differing rates, the study is among the first to tie the patterns of cognitive decline to biomarkers, including phosphorylated tau.

The team also found that using blood tests and brain scans, they could predict and classify participants into 'stable' and 'cognitive decline' groups with about 70 per cent accuracy.

The findings also point to a major challenge in Alzheimer's prevention research -- during early stages of the disease, participants may remain stable even without treatment, making it harder to detect whether a drug is working, the researchers said.

They added future trials should focus less on average results and more on different patterns of decline.

Study Methodology and Data Sources

Data for the analysis was taken from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study, a clinical trial of the monoclonal antibody solanezumab, and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration Extension (LEARN), a companion study of people without the elevated levels of amyloid in the brain.

Scores of cognitive tests measuring memory, attention and thinking were used to assess cognitive decline among the participants.