Long-Term Association of Cardiovascular Risk Burden With Dementia Risk: The Role of Life-Course Confounders in an Analysis of Cumulative and Specific Factors.
Riahi R, Mansournia M, Badihian N, Hosseini S • Journal of the American Heart Association • 2026
Higher cardiovascular risk factor burden over time was associated with greater dementia risk, with maintaining a low CVRF burden associated with a risk difference of -4.31% and maintaining a high CVRF burden associated with a risk difference of 10.5% compared with the natural course.
Key Findings
Results
Maintaining a low cardiovascular risk factor (CVRF) burden over time was associated with a lower estimated 20-year risk of dementia compared with the natural course.
Risk difference of -4.31% (95% compatibility interval, -7.75% to -0.80%) for maintaining low CVRF burden
Analysis used the doubly robust g-formula method to estimate 20-year risk differences under hypothetical strategies
The method explicitly accounted for competing mortality and time-varying confounding
Sample included 6,051 participants from the ARIC (Atherosclerosis Risk in Communities) study with a median follow-up of 21.9 years
Results
Maintaining a high CVRF burden over time was associated with a substantially higher estimated 20-year risk of dementia compared with the natural course.
Risk difference of 10.5% (95% compatibility interval, 5.8%-15.7%) for maintaining high CVRF burden
At baseline, 23.1% of participants had 3 or more CVRFs
During follow-up, 1,008 participants (17%) developed dementia
Results were derived under hypothetical scenarios comparing different levels of sustained CVRF burden
Results
Under model assumptions, approximately 41.3% of dementia cases were estimated to be associated with the presence of CVRFs.
This estimate was derived using the doubly robust g-formula approach
The analysis accounted for both cumulative CVRF burden and changes in CVRFs over time
The study analyzed longitudinal changes in CVRF burden rather than single time-point measurements
Median follow-up was 21.9 years across 6,051 ARIC study participants
Results
Low birth weight, midlife depression, and poor oral health emerged as important life-course confounders in the relationship between CVRF burden and dementia risk.
These factors were identified as early-life and psychological confounders that had not been well characterized in prior research on CVRFs and dementia
The study explicitly incorporated time-varying confounding into its analytical framework using the doubly robust g-formula
The role of these life-course confounders was described as 'poorly understood' prior to this analysis
Accounting for these confounders was highlighted as important for accurately estimating the CVRF-dementia association
Methods
The study used a doubly robust g-formula method to estimate dementia risk under different hypothetical intervention scenarios while accounting for competing mortality.
The g-formula method was chosen to handle time-varying confounding across the longitudinal follow-up period
Competing mortality was explicitly modeled to avoid bias in dementia risk estimation
Hypothetical strategies maintained CVRF burden at different levels (low versus high) over time
The analytical sample comprised 6,051 participants from the ARIC cohort study with a median follow-up of 21.9 years
Discussion
The study found that both cumulative CVRF burden and changes in CVRFs over time are relevant to dementia risk, rather than single time-point measurements alone.
The study design specifically aimed to estimate the 'longitudinal association between changes in CVRF burden and dementia risk'
Prior research on individual CVRFs linked to dementia had not adequately captured cumulative burden or temporal changes
The findings suggest 'early and sustained management of CVRFs' may be important for dementia prevention
The study population came from the ARIC study, a well-established cardiovascular and dementia cohort
What This Means
This research suggests that the accumulation of cardiovascular risk factors (such as high blood pressure, diabetes, obesity, and smoking) over many years is strongly linked to a person's risk of developing dementia. Using data from more than 6,000 adults followed for nearly 22 years, the researchers estimated that keeping cardiovascular risk factors low throughout life could reduce the 20-year probability of dementia by about 4 percentage points, while having a persistently high number of cardiovascular risk factors could increase the probability by about 10.5 percentage points compared to what would happen naturally. The study also estimated that about 41% of dementia cases in this population were associated with the presence of these cardiovascular risk factors.
An important contribution of this study was identifying factors from across a person's life that could confound or distort the relationship between cardiovascular risk and dementia. The researchers found that low birth weight, depression in midlife, and poor oral health were notable confounders that needed to be accounted for to get accurate estimates — factors that previous studies often overlooked. The analytical method used (the doubly robust g-formula) was designed to handle the complexity of risk factors and confounders that change over time, as well as the fact that some people die before developing dementia, which can bias simpler analyses.
This research suggests that managing cardiovascular risk factors early and consistently throughout life, rather than only in old age, may be an important strategy for reducing dementia risk at the population level. It also highlights that a fuller picture of dementia prevention needs to consider early-life circumstances and mental health, not just traditional cardiovascular measures. These findings reinforce public health messages about the brain-heart connection and point to potential value in integrated approaches to chronic disease prevention.
Riahi R, Mansournia M, Badihian N, Hosseini S. (2026). Long-Term Association of Cardiovascular Risk Burden With Dementia Risk: The Role of Life-Course Confounders in an Analysis of Cumulative and Specific Factors.. Journal of the American Heart Association. https://doi.org/10.1161/JAHA.125.045217