Adults with no major midlife vascular risk factors lived nearly 13 years longer without dementia than those with all three, while greater vascular burden was also linked to markedly higher mortality.

Study: Midlife Vascular Risk Burden and Dementia-Free Survival Years. Image Credit: dan quiet life / Shutterstock

In a recent study published in the journal Neurology Open Access, a group of researchers examined how the number of modifiable vascular risk factors present during midlife affects dementia-free survival between 55 and 95 years of age.

Background

Almost 42% of middle-aged Americans may develop dementia during their life, which makes dementia prevention one of the most important issues in public health. Although treatments are still limited, several vascular risk factors, including diabetes, hypertension, and smoking, can be identified and managed years before symptoms appear. These risk factors can emerge during midlife and contribute to brain damage over time, as well as an increased risk of premature death.

Understanding how vascular health influences dementia-free survival can help patients and healthcare professionals make informed decisions about long-term health goals. Further research is needed to better understand how vascular health throughout life influences dementia-free survival across different populations.

About the study

The investigators conducted a prospective cohort study using data from the Atherosclerosis Risk in Communities (ARIC) Study, a community-based study that enrolled adults from four communities across the United States. The study involved individuals who were alive and free of dementia at age 55 years and had completed the second ARIC visit in the period from 1990 to 1992. Participants with missing data, prevalent dementia, insufficient follow-up, or race categories represented by small numbers were excluded, resulting in a final study population of 12,409 participants.

Midlife vascular risk burden was assessed at ARIC visit 2 using three modifiable risk factors: diabetes, hypertension, and current smoking. Diabetes was defined by self-reported physician diagnosis, diabetes medications, or hemoglobin A1c (HbA1c)≥6.5%.

Hypertension was defined based on elevated blood pressure readings or the use of antihypertensive medication, while smoking status was self-reported. Participants were categorized by the number of vascular risk factors present: 0, 1, 2, or 3. Dementia was determined through cognitive tests, interviews with informants, phone evaluations, hospital records, death records, and expert evaluations. 

Mortality information was obtained from multiple sources, including the National Death Index. Statistical analyses included estimation of cumulative incidence, hazard ratios (HRs), and restricted mean survival time (RMST) while accounting for the competing risk of death. The analyses were also stratified by sex, race, and apolipoprotein E (APOE) ε4 carrier status.

Study results

Over a median follow-up time of 26.3 years, 3,008 cases of dementia were recorded along with 5,238 deaths without dementia in 12,409 participants. People with more midlife vascular risk factors had higher body mass index (BMI), lower physical activity level, less educational attainment, and a higher prevalence of stroke. They were also more likely to be Black participants and to carry at least one apolipoprotein E (APOE) ε4 allele.

The incidence rate of dementia increased progressively with vascular risk burden. Participants with no risk factors had an incidence rate of 8.8 per 1,000 person-years, whereas those with three vascular risk factors had the highest incidence rate, at 12.5 per 1,000 person-years. However, the increase in dementia-free mortality was even more pronounced, climbing from 10.5 to 42.3 per 1,000 person-years across the same groups.

Individuals with more vascular risk factors developed dementia at younger ages, yet they showed a lower cumulative dementia incidence by age 95 because substantially more participants died before developing dementia.

The cumulative incidence of dementia reached 10% in participants with three vascular risk factors, while those without vascular risk factors saw the incidence at 3% at age 75. By age 95, the cumulative incidence of dementia was 42% among participants with no vascular risk factors compared with 23% among those with three risk factors, reflecting the substantially higher competing risk of death in the higher-risk group.

Dementia-free mortality also increased consistently with vascular risk burden, reaching 74% by age 95 among participants with three risk factors compared with 44% among those with no vascular risk factors.

Researchers found an association between vascular risk burden and dementia-free survival. Analysis showed that, from age 55 onward, those with no vascular risk factors had approximately 30.1 dementia-free years, while those with one, two, or three risk factors had 26.3, 21.0, and 17.5 dementia-free years, respectively. 

Among participants who developed dementia, those who had more vascular risk factors spent a greater proportion of their remaining life living with the disease. The association between vascular risk burden and dementia-free years remained consistent across participant subgroups.

Women had longer dementia-free survival than men, while Black participants lived for shorter periods without the disease. Similarly, APOE-ε4 carriers experienced fewer dementia-free years than noncarriers. Sensitivity analyses produced findings consistent with the primary analyses.

Compared with participants who had no vascular risk factors, those with three vascular risk factors had 2.69 times the hazard of developing dementia and 5.61 times the hazard of dying without dementia. The combined outcome of dementia or dementia-free mortality also increased steadily with vascular risk burden, demonstrating a strong association between poorer midlife vascular health and shorter dementia-free survival.

The authors noted that vascular risk factors were assessed only once in midlife, limiting the analysis's ability to capture changes in diabetes, hypertension, or smoking over time. They also noted potential differences in dementia ascertainment and residual confounding, while the simple count of 3 risk factors did not reflect a comprehensive cardiometabolic risk profile.

Conclusion

The study demonstrated that better vascular health during midlife was strongly associated with longer dementia-free survival. Individuals with no vascular risk factors experienced approximately 13 additional dementia-free years compared with those who had all three major vascular risk factors.

People with fewer vascular risk factors also had lower mortality and longer dementia-free survival. Importantly, their higher cumulative incidence of dementia by age 95 reflected longer survival and greater opportunity to reach ages at which dementia develops, rather than a higher dementia hazard. 

The findings highlight the potential importance of preventing or managing diabetes and hypertension and avoiding smoking during midlife to support brain health and promote longer dementia-free survival.

Journal reference:

• Hu, J., Coresh, J., Smith, J. R., Sharrett, A. R., Gottesman, R. F., Lutsey, P. L., Mosley, T. H., Selvin, E., Fang, M., & Weiss, J. (2026). Midlife vascular risk burden and dementia-free survival years: The Atherosclerosis Risk in Communities Neurocognitive Study. Neurology Open Access. 2. DOI:10.1212/WN9.0000000000000152, https://www.neurology.org/doi/10.1212/WN9.0000000000000152