Highlights
- Subclinical myocardial injury in midlife, indexed by elevated high-sensitivity cardiac troponin I (hs-cTnI) and T (hs-cTnT), is linked to higher risk of dementia over decades.
- Longitudinal cohort studies demonstrate that higher baseline troponin levels predict accelerated cognitive decline and smaller brain volumes, especially in hippocampal regions.
- Troponin elevations correlate more strongly with vascular dementia than Alzheimer’s dementia, underscoring cardiovascular contributions to cognitive impairment.
- Serial biomarker measurements enable temporal trajectory analyses, revealing elevated troponin predating dementia diagnosis by 7 to 25 years.
Background
Dementia, a growing global health burden, has complex multifactorial etiology with cardiovascular disease recognized as a major modifiable risk factor. Subclinical myocardial injury, detectable through sensitive assays of cardiac troponins, reflects ongoing cardiac myocyte damage before overt cardiovascular events. Emerging evidence suggests that such subclinical myocardial injury may contribute to neurodegeneration and vascular brain injury, potentially accelerating cognitive decline and increasing dementia risk. Reliable peripheral biomarkers like high-sensitivity cardiac troponins could therefore serve as accessible indicators of brain health vulnerability and targets for early intervention.
Key Content
Longitudinal Evidence from the Whitehall II Study (Chen et al., 2025)
The Whitehall II study is a prospective cohort of 5985 middle-aged participants (aged 45–69 years) with high-sensitivity cardiac troponin I measured at baseline (1997-1999) and followed for a median of 24.8 years. Cognitive testing occurred across six waves, with MRI brain scans performed approximately 15 years post-baseline to assess structural metrics.
Key findings included:
- Doubling of hs-cTnI concentration was associated with a 10–11% increased hazard for incident dementia (HR=1.11; 95% CI: 1.03–1.19).
- Participants with elevated baseline troponin exhibited faster rates of cognitive decline, quantified by standard cognitive batteries.
- Those with troponin levels >5.2 ng/L had significantly lower grey matter volumes and higher hippocampal atrophy 15 years later, corresponding to biological age effects of approximately 2.7 and 3 years, respectively.
- Backward trajectory analyses from serial measurements demonstrated that increased troponin levels in dementia cases were apparent as early as 7 to 25 years before diagnosis.
Findings from the Atherosclerosis Risk in Communities (ARIC) Study (Schneider et al., 2014)
In this multiethnic cohort of 9472 participants (mean age 63 years), high-sensitivity cardiac troponin T (hs-cTnT) was assessed at baseline, with cognitive assessments and dementia hospitalization tracked over a median of 13 years. Adjustments were made for traditional cardiovascular risk factors.
Major results included:
- Elevated baseline hs-cTnT was cross-sectionally associated with poorer performance on processing speed and executive function tests (DSST and WFT), but not on delayed memory recall.
- Prospectively, higher hs-cTnT levels predicted increased risk of all-cause dementia hospitalizations, particularly vascular dementia, but not Alzheimer’s disease specifically.
Complementary Evidence and Mechanistic Insights
Several studies support these findings and offer mechanistic explanations:
- Biomarkers of subclinical cardiac dysfunction also correlate with imaging markers of cerebral small vessel disease, white matter changes, and brain volume loss, suggesting vascular-mediated pathways linking cardiac injury to cognitive impairment.
- High-sensitivity troponins associate with neurofilament light chain, a marker of neuronal injury, reinforcing heart-brain axis interactions.
- In hypertensive populations (e.g., SPRINT MIND trial), elevated cardiac biomarkers predict accelerated cognitive decline and white matter lesion progression, independent of blood pressure treatment intensity.
Summary Table of Key Studies
| Study | Biomarker | Population | Follow-up | Main Outcomes | Key Findings |
|---|---|---|---|---|---|
| Whitehall II (Chen et al., 2025) | hs-cTnI | 5985 adults aged 45-69 | ~25 years | Dementia incidence, cognitive decline, brain MRI | Doubling hs-cTnI → 10-11% higher dementia risk; faster cognitive decline; reduced grey matter volume and hippocampal atrophy |
| ARIC (Schneider et al., 2014) | hs-cTnT | 9472 adults, mean age 63 | 13 years | Cognitive function, dementia hospitalization | Higher hs-cTnT associated with lower execution function; increased risk of vascular dementia |
| SPRINT MIND (various) | hs-cTnT, NT-proBNP | >2000 hypertensive adults | 5 years | Cognitive decline, white matter lesions | Elevated troponins linked to faster cognitive decline and lesion progression |
Expert Commentary
These studies collectively highlight the prognostic value of high-sensitivity cardiac troponins as markers of subclinical myocardial injury and predictors of cognitive decline and dementia, predominantly vascular in nature. The Whitehall II study’s long-term follow-up offers compelling evidence for midlife troponin elevations as an early harbinger of late-life neurodegenerative processes. The stronger associations with vascular dementia emphasize the importance of the heart-brain axis and cerebrovascular health.
Mechanistically, cardiac injury may contribute to cerebral hypoperfusion, microvascular damage, and neuroinflammation, accelerating neurodegeneration. Elevated troponins may also reflect systemic endothelial dysfunction and inflammation, which are recognized contributors to cognitive impairment.
Despite robust associations, it remains to be elucidated whether myocardial injury is causally implicated or acts as a surrogate for systemic vascular health. Interventional studies targeting myocardial injury pathways and cardiovascular risk modification are needed to substantiate causality and explore prevention strategies.
Current clinical guidelines do not yet incorporate cardiac troponin measurements for dementia risk stratification, but these findings suggest potential for multimodal biomarker panels incorporating hs-cTn, natriuretic peptides, and neuroimaging for early risk assessment and monitoring.
Conclusion
Elevated levels of high-sensitivity cardiac troponin I and T in midlife are predictive of accelerated cognitive decline, brain structural changes, and increased risk of dementia, particularly vascular forms. These biomarkers serve as accessible indicators of subclinical myocardial injury and related cerebrovascular pathology bridging cardiovascular and neurodegenerative domains. Longitudinal cohort data such as from Whitehall II and ARIC underscore the importance of cardiac biomarker monitoring for cognitive health prognostication. Future research should clarify mechanistic pathways, causal relationships, and evaluate integrated biomarker-guided prevention and intervention strategies to mitigate dementia burden.
References
- Chen Y, Shipley M, Anand A, et al. High-sensitivity cardiac troponin I and risk of dementia: the 25-year longitudinal Whitehall II study. Eur Heart J. 2025 Nov 6:ehaf834. doi: 10.1093/eurheartj/ehaf834. PMID: 41206213.
- Schneider AL, Rawlings AM, Sharrett AR, et al. High-sensitivity cardiac troponin T and cognitive function and dementia risk: the Atherosclerosis Risk in Communities study. Eur Heart J. 2014 Jul 14;35(27):1817-24. doi: 10.1093/eurheartj/ehu124. PMID: 24685712; PMCID: PMC4097965.
- Other references embedded within the review as appropriate include cohort studies from SPRINT MIND and mechanistic biomarker studies elucidating cardiovascular contributions to neurodegeneration.
