Mounting evidence suggests that the brain and heart share far more than a circulatory connection. Cardiovascular health, once regarded solely as a cardiac concern, is increasingly recognised as a major determinant of cognitive ageing. Researchers at Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), together with partners across Singapore, are investigating this heart–brain axis through advanced imaging and biomarker approaches, uncovering how cardiac function shapes brain integrity and cognitive trajectories across the lifespan.

Targeting the heart–brain connection in middle-aged and older adults

Understanding how cardiac health influences brain ageing is especially critical as individuals transition from midlife into older adulthood. Physiological changes such as declining cardiac output, increasing arterial stiffness, and microvascular alterations may affect cerebral microstructure and neural function, making this connection essential for identifying early markers of cognitive vulnerability.

Our lab’s recent studies support this link. In our Neurology paper (2023), we showed that blood biomarkers associated with cardiovascular stress—high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and growth differentiation factor 15 (GDF‑15)—were strongly associated with brain microstructural alterations measured via diffusion MRI in pre-dementia older adults. Individuals with elevated biomarker levels exhibited higher free water (FW), a sensitive marker of microvascular injury and inflammation, across major white-matter pathways and key cortical networks, including the default-mode and executive-control networks. Importantly, baseline FW changes mediated the associations between cardiac biomarkers and domain-specific cognitive decline over five years, suggesting that subtle cardiovascular dysfunction may quietly influence the brain long before dementia manifests.

Extending these findings, our second study, published in Journal of Cerebral Blood Flow and Metabolism (2024), demonstrated that even mild left-atrial dysfunction was linked to higher FW in orbitofrontal and temporal regions as well as major white-matter tracts in cognitively normal, community-dwelling older adults without known cardiovascular disease. These microstructural changes correlated with poorer executive function and higher circulating BNP levels, highlighting that the heart–brain axis may operate silently, with cardiac performance reflected in the brain’s microenvironment well before clinical symptoms appear.

To deepen this work, we are now collaborating with colleagues across the NUHS and SingHealth communities in both clinical and population-based studies. For example, together with Professor Roger Foo and his team in the Cardiovascular-Metabolic Disease Translational Research Programme at NUS Medicine, we are conducting neuroimaging and cognitive assessments in participants from Project RESET, an ongoing study identifying cardio-liver-metabolic risk markers in asymptomatic adults aged 40–70. By integrating cardiac, metabolic, brain, and cognitive measures, we aim to identify early indicators linking cardiovascular and brain health, ultimately guiding timely preventive strategies.

Lifestyle interventions to enhance cardiovascular function and protect the ageing brain

Together with collaborators across NUHS and SingHealth, our group is examining brain and cognitive outcomes in two lifestyle intervention studies funded by the National Medical Research Council (NMRC), Ministry of Health, Singapore.

Non-pharmacological strategies involving exercise, diet, and cognitive engagement have been shown to benefit both cardiovascular and cognitive function. Building on this knowledge, the first trial evaluates a three-month diet and exercise intervention in 140 older adults with reduced cardiac function. The study assesses changes in MRI-based cardiac and cerebrovascular markers, alongside cognitive outcomes. The primary endpoint is change in MRI-derived cardiac and cerebrovascular measures following intervention. The second trial focuses on adults aged 40–70 with hypertensive heart disease. This study tests the effectiveness of a 12-month health-coach–guided digital lifestyle programme on a wide spectrum of outcomes, encompassing cardiac, liver, and brain health; health behaviours; cognitive performance and quality of life. Together, these trials may shift the field from association to causation, asking whether interventions that rejuvenate cardiac function can, in turn, protect the ageing brain.

Leveraging Artificial Intelligence (AI) to predict health trajectories

In tandem with these biological and clinical studies, our lab is harnessing AI to map and forecast individual health trajectories. AI provides a powerful means to integrate multimodal brain health measures with clinical, behavioural and molecular data in unified predictive frameworks.

Recently, we developed Brain Harmony, the first multimodal brain foundation model capable of being adapted to diverse downstream tasks, including predicting cognitive performance, behavioural outcomes, and disease conversion. Built using large-scale neuroimaging datasets (N > 80,000), Brain Harmony learns generalisable representations that transfer robustly across tasks. Our next step is to extend this framework by jointly modelling both heart and brain measures, enabling deeper investigation of shared mechanisms and improving personalised prediction of long‑term cardiometabolic and cognitive outcomes.

Looking ahead

As population ageing accelerates, the Heart–Brain Connection Research Programme at NUS Medicine—together with partners in academia, healthcare, and industry—exemplifies the power of interdisciplinary science. Our vision is to integrate longitudinal imaging, physiological, molecular, digital health, behavioural, and clinical data from large-scale cohort and patient studies across the lifespan to pinpoint modifiable risk factors and develop targeted interventions that shift the trajectory early. In parallel, we aim to develop digital twins—personalised computational models of an individual’s evolving cardiac and brain health—capable of simulating the effects of lifestyle changes or treatments to guide precision prevention. Collectively, these efforts represent a pivotal step toward extending not only lifespan, but healthspan.