Early detection of dementia through default-mode network connectivity: A breakthrough study
In a groundbreaking study published in Nature Mental Health [1], researchers from Queen Mary University of London, University College London, and Monash University have unveiled a promising method for the early detection of dementia.
Utilizing advanced neuroimaging techniques and dynamic causal modelling, the team demonstrated that changes in the effective connectivity within the brain’s default-mode network (DMN) could predict the onset of dementia years before clinical symptoms appear. This innovative approach holds significant potential for early intervention and personalized dementia-prevention strategies.
Study overview
The study focused on the DMN, a network of brain regions known to be affected in Alzheimer’s disease (AD), the leading cause of dementia. The DMN is involved in various high-level cognitive functions, including self-referential thinking and social cognition, making it a critical area of study for neurodegenerative diseases.
Researchers applied spectral dynamic causal modelling (DCM) to resting-state functional magnetic resonance imaging (rs-fMRI) data from the UK Biobank. The dataset included 81 individuals who developed dementia up to nine years after imaging and 1,030 matched controls. By analyzing the effective connectivity within the DMN, the team aimed to identify neural patterns predictive of future dementia diagnosis.
Key findings
- Predictive power of DMN dysconnectivity: The study found that dysconnectivity within the DMN could predict dementia incidence with an area under the curve (AUC) of 0.82. This model outperformed traditional approaches based on brain structure and general functional connectivity, highlighting the superior predictive power of effective connectivity measures.
- Time to diagnosis: Effective connectivity patterns were also significantly correlated with the time until dementia diagnosis, with a Spearman’s correlation coefficient of 0.53. This finding suggests that changes in DMN connectivity not only indicate who will develop dementia but also provide insights into when the diagnosis might occur.
- Associations with risk factors: The study revealed strong associations between DMN dysconnectivity and major risk factors for dementia, including polygenic risk scores for Alzheimer’s disease and social isolation. These relationships underscore the complex interplay between genetic predisposition, environmental factors, and neural connectivity in the pathogenesis of dementia.
Methodological advancements
Dynamic causal modelling offers a more nuanced analysis of neural connectivity compared to traditional functional connectivity methods. By distinguishing between neural, hemodynamic, and noise components of the BOLD signal, DCM provides a detailed map of the causal influences between brain regions. This level of detail is crucial for identifying subtle changes in neural circuitry that precede clinical symptoms.
The study employed a rigorous nested case-control design and extensive cross-validation to ensure the robustness of their findings. Bayesian model reduction and averaging were used to identify the most parsimonious connectivity parameters, enhancing the model’s interpretability and clinical applicability.
Clinical implications
The ability to detect dementia years before the onset of symptoms has profound implications for public health and clinical practice. Early identification of individuals at high risk for dementia allows for timely intervention, potentially slowing disease progression through lifestyle modifications, targeted therapies, and enhanced monitoring.
Moreover, understanding the specific patterns of DMN dysconnectivity associated with dementia can inform the development of new therapeutic strategies aimed at preserving neural connectivity and cognitive function. Personalized prevention plans based on an individual’s connectivity profile and risk factors could become a reality, transforming the landscape of dementia care.
Commenting on the research, Samuel Ereira, lead author and Academic Foundation Programme Doctor at the Centre for Preventive Neurology, Wolfson Institute of Population Health, said: ”Using these analysis techniques with large datasets we can identify those at high dementia risk, and also learn which environmental risk factors pushed these people into a high-risk zone. Enormous potential exists to apply these methods to different brain networks and populations, to help us better understand the interplays between environment, neurobiology and illness, both in dementia and possibly other neurodegenerative diseases. fMRI is a non-invasive medical imaging tool, and it takes about 6 minutes to collect the necessary data on an MRI scanner, so it could be integrated into existing diagnostic pathways, particularly where MRI is already used.”
Charles Marshall, Professor and Honorary Consultant Neurologist, who led the research team within the Centre for Preventive Neurology at Queen Mary’s Wolfson Institute of Population Health, commented: “Predicting who is going to get dementia in the future will be vital for developing treatments that can prevent the irreversible loss of brain cells that causes the symptoms of dementia. Although we are getting better at detecting the proteins in the brain that can cause Alzheimer’s disease, many people live for decades with these proteins in their brain without developing symptoms of dementia. We hope that the measure of brain function that we have developed will allow us to be much more precise about whether someone is actually going to develop dementia, and how soon, so that we can identify whether they might benefit from future treatments.”
Conclusion
This study represents a significant advance in the early detection of dementia, demonstrating that effective connectivity within the DMN is a powerful biomarker for predicting dementia onset and progression. The integration of advanced neuroimaging techniques with dynamic causal modeling offers a promising avenue for early intervention and personalized prevention strategies, potentially reducing the growing burden of dementia on individuals and society.
The research team’s innovative approach and robust findings pave the way for future studies to validate and refine these predictive models, ultimately bringing us closer to a future where dementia can be detected and managed more effectively at its earliest stages.
Reference:
- Ereira, S., Waters, S., Razi, A. et al. Early detection of dementia with default-mode network effective connectivity. Mental Health (2024). https://doi.org/10.1038/s44220-024-00259-5
