More than 6 million Americans are living with Alzheimer's. By 2050, this number is projected to rise to nearly 13 million. (© Orawan - stock.adobe.com)
LONDON — With many diseases, there are predictable stages that follow a similar path with all patients. In the case of Alzheimer’s disease, however, a game-changing new study is shifting everything scientists thought they knew about the condition.
Researchers in the United Kingdom suggest that the way Alzheimer’s reshapes our brains is as unique as our fingerprints, challenging long-held beliefs about the disease’s progression. A team from University College London (UCL) and Radboud University in the Netherlands have unveiled a revolutionary approach to tracking Alzheimer’s disease using what they call “brain fingerprints.” By comparing individual brain scans to a vast database of healthy brains, they’ve discovered that each person’s journey with Alzheimer’s is surprisingly distinct.
The study, published in the journal Alzheimer’s & Dementia, analyzed 3,233 MRI brain scans from 1,181 individuals with mild cognitive impairment (MCI) or Alzheimer’s disease. These scans were compared to a benchmark created from 58,836 healthy brain scans, allowing researchers to create personalized maps of brain changes over time.
Astonishingly, the team found that there is no one-size-fits-all pattern to how Alzheimer’s shrinks the brain. Instead, each person’s brain tells its own unique story of decline.
“We know that Alzheimer’s affects everyone differently. Understanding and quantifying this variability has important implications for the design and interpretation of clinical trials, and potentially in due course for counseling patients and developing personalized approaches to treatment,” says Professor Jonathan Schott from UCL Queen Square Institute of Neurology in a media release.
The researchers developed a measure called the total outlier count (tOC), which essentially tallies up the number of brain regions showing unusual shrinkage compared to healthy brains. They found that people with Alzheimer’s disease typically had 15 to 20 outlier regions at the start of the study, increasing to around 30 after three years. In comparison, those with mild cognitive impairment started with only five to 10 outliers, accumulating just two to three more over the same period.
Intriguingly, among people with mild cognitive impairment, those who went on to develop dementia within three years accumulated an average of four new outliers every year. This suggests that tracking these personalized brain maps over time could help predict who is most likely to develop Alzheimer’s.
The study authors also revealed connections between their brain mapping technique and cognitive performance. People with more rapidly accumulating outliers tended to perform worse on memory and executive function tests.
“While it’s true that some regions of the brain, such as the hippocampus, are particularly important in Alzheimer’s disease, we wanted to avoid focusing on specific regions in this study. Our results confirm that everyone is different, the regions affected by disease in one person may not be the same in the next,” explains Dr. Serena Verdi, the study’s first author.
This personalized approach to tracking brain changes offers several potential benefits. It could help doctors identify patients at high risk of developing Alzheimer’s earlier, allowing for more timely interventions. It might also prove useful in clinical trials, helping researchers select appropriate participants and measure the effectiveness of new treatments more precisely.
“Hopefully, this is a step towards a more personalized approach to diagnosis and treatment,” concludes Professor James Cole, the study’s senior author.
While the study represents a significant advance in our understanding of Alzheimer’s progression, the researchers caution that more work is necessary before this technique can be widely applied in clinical settings. The current study population was primarily of European ancestry and included mostly individuals in the early to intermediate stages of Alzheimer’s. Future research will need to include more diverse populations and individuals at various stages of the disease to ensure the method’s broad applicability.
Paper Summary
Methodology
The researchers used a technique called neuroanatomical normative modeling. They created a reference database of healthy brain scans from nearly 59,000 individuals. Then, they compared brain scans from the study participants to this database, looking for areas that showed more shrinkage than expected for a person’s age and sex. They did this for 168 different brain regions, creating a personalized map of unusual brain changes for each participant. By repeating this process over time, they could track how these changes progressed.
Key Results
The study found that people with Alzheimer’s disease and those with mild cognitive impairment who later developed Alzheimer’s showed a faster increase in the number of brain regions with unusual shrinkage (outliers). This increase was associated with worse performance on cognitive tests. The patterns of brain shrinkage varied significantly between individuals, with no uniform pattern of progression.
Study Limitations
The study primarily included people of European ancestry and those in the early to middle stages of Alzheimer’s. This limits how well the findings might apply to more diverse populations or people in later stages of the disease. The researchers also noted that some of the variability in their measurements might be due to differences in how the brain scans were processed or normal fluctuations between scans.
Discussion & Takeaways
This study introduces a new way to track Alzheimer’s progression that accounts for individual differences. The ability to create personalized brain maps could lead to earlier detection of Alzheimer’s risk and more tailored treatment approaches. The researchers suggest that this method could be particularly useful in clinical trials, both for selecting participants and measuring treatment effects. However, they emphasize the need for further validation and testing in more diverse populations before the technique can be widely adopted in clinical practice.
Funding & Disclosures
The study was funded by multiple organizations, including the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and various pharmaceutical companies. One of the authors is an employee of Eli Lilly and Company. The researchers used data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a large-scale study aimed at developing biomarkers for the early detection and tracking of AD.
