A study led by a team from Johns Hopkins University in the United States suggests that 22%-44% of dementia cases – by the age of 80 – may be due to poor vascular health for at least the preceding six years.
They said maintaining optimal vascular health throughout late life can significantly lower the risk of developing dementia before 80, after estimating the proportion of new dementia cases linked to modifiable vascular risk factors, reports Medscape.
Their findings highlighted the “potentially immense value of early detection of vascular risk factors and primordial prevention (e.g, vis-à-vis promotion of physical activity and healthy body weight management) beginning in midlife”, wrote the study team, led by Jason Smith, PhD, with Johns Hopkins Bloomberg School of Public Health in Baltimore.
The study was published online in JAMA Neurology.
Vascular health equals brain health
Hypertension, diabetes and smoking are widely recognised modifiable vascular risk factors for dementia. While their roles have been studied individually, the cumulative impact of these risk factors across the lifespan – and how this varies by genetic background, race, and sex – has been less clear.
Smith and colleagues used data from the Atherosclerosis Risk in Communities Neurocognitive Study, with 33 years of follow-up, to assess the fraction of dementia attributable to hypertension, diabetes and smoking measured at different life stages.
A total of 7 731 participants were included in the analysis of risk factors measured at 45-54 years (58% women, 71% white, 29% black); 12 274 contributed data at age 55-64 (55% women, 76% white, 24% black); and 6 787 contributed data at 65-74 (56% women, 80% white, 20% black). Overall, a total of 2 218 people developed dementia by their 80th birthday.
By 80, the population attributable fraction of dementia attributable to at least one vascular risk factor measured at age 45-54 was 22%; at 55-64, it was 26%, and at 65-74, it was 44%.
Only 2%-8% of dementia cases occurring after 80 were attributable to these vascular risk factors.
Subgroup differences emerged. For example, the attributable fractions for the vascular risk factors were higher in APOE-ε4 non-carriers aged 55 or older (range, 33%-61%). “This reflects the fact that in populations with lower genetic Alzheimer risk, the extent of the relative contribution of vascular disease to dementia risk is greater,” the study team said.
Attributable fractions for the vascular risk factors were also higher in black individuals aged 45 or older (range, 26%-53%) and women 55 or older (range, 29%-51%).
Risk factor clusters such as hypertension plus diabetes and smoking plus diabetes significantly increased dementia risk, with hazard ratios ranging from 2.00 to 3.54, depending on age and risk factor combination. The importance of hypertension and diabetes increased with age, whereas the importance of smoking decreased with age.
“Given the contribution of vascular disease to dementia and the overlap in risk factors between CVD and dementia, interventions that address these underlying risk factors have the potential to reduce the risk of both outcomes,” the co-authors of a linked editorial said.
These results also suggest that “to be optimally effective, interventions to reduce dementia risk by addressing vascular risk factors may need to be individualised and targeted based on factors such as age, genetics, race, and sex”, wrote Roch Nianogo, MD, PhD, with the University of California-Los Angeles, and Deborah Barnes, PhD, MPH, University of California-San Francisco.
Study details
Contribution of Modifiable Midlife and Late-Life Vascular Risk Factors to Incident Dementia
Jason Smith, James Russell Pike, Rebecca Gottesman, et al.
Published in JAMA Neurology on 2 June 2025
Abstract
Importance
Midlife vascular risk factors are associated with an elevated risk of dementia. However, the total contribution of vascular risk factors in midlife and late life with incident dementia is uncertain.
Objective
To quantify the proportion of incident dementia attributable to modifiable vascular risk factors measured in midlife and late life and to examine differences by apolipoprotein ε4 genotype, self-reported race, and sex.
Design, Setting, and Participants
This was a prospective cohort analysis of the Atherosclerosis Risk in Communities (ARIC) study using 33 years of follow-up (1987-2020). The setting included ARIC field centres (Jackson, Mississippi; Forsyth County, North Carolina; Minneapolis suburbs, Minnesota; Washington County, Maryland). Study baseline in Black and White participants with complete exposure and covariate data was set by age at risk factor measurement (45-54 years, 55-64 years, and 65-74 years). Data were analysed from August 2023 to December 2024.
Exposures
Hypertension (systolic blood pressure [BP] ≥130 mm Hg, diastolic BP ≥80 mm Hg, or use of medication for BP), diabetes (fasting glucose ≥126 mg/dL, non-fasting glucose ≥200 mg/dL, self-reported physician’s diagnosis, or use of any diabetes medication), and current smoking (self-reported).
Main Outcomes and Measures
Incident dementia. Population attributable fractions were estimated by age 80 years, and separately after 80 years, from having at least one vascular risk factor by age at risk factor measurement.
Results
A total of 7731 participants were included in analysis of risk factors measured at age 45 to years (4494 female [58%]; 2207 black [29%]; 5524 white [71%]), 12 274 contributed to analysis of risk factors measured at age 55 to 64 years (6698 female [55%]; 2886 black [24%]; 9388 white [76%]), and 6787 contributed to analysis of risk factors measured at age 65 to 74 years (3764 female [56%], 1375 black [20%]; 5412 white [80%]). There were 801, 995, and 422 dementia cases by 80, respectively. The fraction of dementia by 80 attributable to at least 1 vascular factor at age 45 to 54 years was 21.8% (95% CI, 14.3%-29.3%), at 55 to 64 years was 26.4% (95% CI, 19.1%-33.6%), and at 65 to 74 years was 44.0% (95% CI, 30.9%-57.2%). Attributable fractions for these factors were higher in apolipoprotein ε4 non-carriers at 55 and older (range, 33.3%-61.4%), Black individuals at 45 and older (range, 25.5%-52.9%), and females at 55 and older (range, 29.2%-51.3%). Only 2% to 8% of dementia cases after 80 were attributable to these factors.
Conclusions and Relevance
Results of this cohort study suggest that between 22% and 44% of incident dementia cases by 80 in the ARIC study were attributed to midlife and late-life vascular risk factors. Assuming causal relationships, maintaining optimal vascular health across the life course could mitigate a sizeable proportion of dementia risk by 80
Medscape article – Up to 44% of Dementia Cases Preventable (Open access)
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