NUS Medicine study finds key blood proteins which predict future cognitive decline

In a study that holds significance for individuals with cerebrovascular disease, scientists from the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), have found proteins in the blood that predict future cognitive decline and dementia.

Led by Professor Christopher Chen, Deputy Chair of the Healthy Longevity Translational Research Programme (TRP) at NUS Medicine, this first-of-its-kind study in Singapore analysed more than 1,000 proteins in the blood of a local patient cohort. The study was conducted on 528 patients from memory clinics at the National University Hospital (NUH) and St Luke’s Hospital in Singapore.

Professor Arthur Mark Richards, co-senior author of the paper published in Alzheimer’s and Dementia, said, “One of our findings was the characterisation of a blood protein signature for future cognitive decline. Using advanced proteomic technologies, we profiled over a thousand blood proteins tied to neurodegeneration, inflammation, and vascular dysfunction, which are key contributors to dementia.” Prof Richards is from the Cardiovascular-Metabolic Diseases TRP at NUS Medicine.

The team found that people with dysregulated levels of these proteins were more likely to develop future dementia and cognitive deterioration, even after accounting for age and other health conditions. These proteins are also linked to changes in brain structure, such as shrinkage in brain volume and signs of small vessel disease, which are early warning signs of dementia. When these biomarkers were combined with clinical risk factors, prognosis of cognitive decline was significantly enhanced, highlighting the potential of integrating blood-based tests with routine clinical assessments for earlier and more accurate diagnosis.

The team further validated these findings in a separate group of patients of Caucasian descent, using cerebrospinal fluid—which refers to fluid that surrounds the brain and spinal cord. The replicated protein markers remained strong predictors of cognitive decline, suggesting these biomarkers may be reliable across different biological fluids and diverse populations.

Prof Chen said, “The objective of our research was to identify better ways to detect and predict dementia, especially in Southeast Asian populations, who may present with unique risk profiles due to higher rates of co-existing conditions such as cerebrovascular disease.” Prof Chen is also from the Department of Pharmacology at NUS Medicine, and is the Director of the Memory, Ageing and Cognition Centre at the National University Health System (NUHS).

Dr Sim Ming Ann, first author of the paper, added, “We hope that the outcomes of this work will lead to better prediction models for identifying individuals at risk of cognitive deterioration. With the ability to detect key blood protein changes early, doctors could be better equipped to intervene before significant cognitive decline occurs, potentially slowing disease progression and improving quality of life for patients.” Dr Sim is a PhD candidate at the Healthy Longevity TRP at NUS Medicine, and the Memory, Ageing and Cognition Centre at NUHS, as well as Associate Consultant at the Department of Anaesthesia, NUH.

In addition to predictive potential of longer-term cognitive health, the team’s findings may help uncover the biological mechanisms behind dementia, offering new possibilities for targeted therapies. These advances could greatly benefit healthcare outcomes for countries with ageing populations, helping doctors tailor care to individual needs and manage health risks more effectively. The next steps for the research team involve exploring how these blood proteins function in the body, and whether they can be harnessed for the development of novel treatments for dementia.