NUS researchers discover brain connectome phenotype tied to cerebrovascular disease can track cognitive decline

SINGAPORE: Researchers at the National University of Singapore (NUS) have made significant strides in understanding the complex interplay between cerebrovascular disease (CeVD) and Alzheimer’s disease (AD) in contributing to neurodegeneration and cognitive decline in older adults.

The study, led by Associate Professor Juan Helen Zhou, Director of the Centre for Translational Magnetic Resonance Research at NUS Medicine, has identified a unique brain functional connectome phenotype associated with multiple CeVD markers.

This phenotype adds to cognitive decline and neurodegeneration alongside AD pathology, redefining how CeVD’s role in dementia is understood.

CeVD, a group of conditions affecting blood flow in the brain, includes stroke, cerebral atherosclerosis, and small vessel disease. These disorders can impair oxygen and nutrient delivery, leading to brain damage.

Previous research has established CeVD as a common comorbidity in AD, but the new findings position CeVD as a global disruptor of brain connectivity, emphasizing its critical role in dementia progression.

The study, published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, analyzed brain functional organization in 529 older adults, from those with healthy cognition to individuals with AD.

By correlating CeVD markers with brain activity patterns, the team uncovered a global functional connectome phenotype linked to a high burden of four CeVD markers.

This phenotype revealed distinct impacts on cognitive decline and brain atrophy when compared to p-tau181, a blood biomarker for AD.

While both CeVD-related brain network patterns and p-tau181 independently contributed to cognitive decline and brain atrophy, the study found no synergistic interaction between them.

This suggests that CeVD and AD markers influence neurodegeneration through separate pathways.

“We discovered that a CeVD-related brain network phenotype, along with a key Alzheimer’s disease blood biomarker, can provide powerful insights into the future trajectory of cognitive decline and neurodegeneration,” said A/Prof Zhou, adding:

“These findings highlight the potential of brain connectome-based markers to track cognitive decline, particularly for individuals at risk of dementia.”

Dr Joanna Su Xian Chong, senior research fellow and first author of the study, noted the widespread influence of CeVD markers on brain function.

She explained that the combination of CeVD-related patterns and p-tau181 had independent yet additive effects on cognitive decline and brain atrophy, both at baseline and over time.

The research team plans to investigate how the severity, cause, and location of CeVD markers influence the brain’s communication patterns over time.

They also aim to examine interactions between CeVD-related brain network changes and other AD markers, exploring their combined impact on cognitive decline across various domains.

Additionally, the researchers hope to establish these brain network features as reliable biomarkers for predicting and monitoring cognitive decline in at-risk individuals. Such biomarkers could enhance early detection and lead to more targeted interventions.

The study highlights the importance of integrating neuroimaging and blood biomarkers to deepen understanding of dementia pathophysiology.

By developing advanced imaging tools, the research paves the way for earlier detection and better disease monitoring, offering new hope for individuals at risk of dementia.

The research was supported by the National Research Foundation, Singapore, under the NMRC Open Fund – Large Collaborative Grant. Study participants were recruited from the National University Hospital and St Luke’s Hospital.