Three Midlife Risk Factors Linked to Earlier Dementia Onset

Three major vascular risk factors in middle age — smoking, diabetes, and high blood pressure — were associated with nearly 13 fewer years of dementia-free survival.In a prospective cohort study of 12,409 adults followed for a median of 26.3 years, participants with none of the three risk factors averaged 30.1 dementia-free years between ages 55 and 95 compared with 17.5 years among those with all three.Dementia-free survival also declined progressively as vascular risk burden increased, and varied by sex and race, with women living longer without dementia than men and Black participants experiencing fewer dementia-free years than White participants.“Our findings argue that people need to actively avert these factors in midlife as a strategy for preserving brain health for more than a decade,” study investigator Josef Coresh, MD, PhD, said in a news release.“Discovering new ways to delay dementia is crucial with 42 percent of Americans at risk for developing the condition at any time after age 55,” Coresh, who is the founding director of the Optimal Aging Institute and Terry and Mel Karmazin Professor of Population Health at NYU Grossman School of Medicine in New York City, said.The study was published online on August 5 in Neurology Open Access.Tackling Vascular Health to Delay DementiaAlmost half of US middle-aged adults are at risk of developing dementia. Modifiable risk factors like physical inactivity and smoking are associated with an increased risk of developing dementia.Previous research has shown that up to 44% of dementia cases are linked to midlife and late-life vascular health. In this study, the researchers set out to assess the link between midlife vascular risk factors and dementia-free years.Using data from the Atherosclerosis Risk in Communities Study, the researchers analyzed data from 12,409 middle-aged adults who were dementia-free at age 55 (mean age, 56.2 years; 56% women).Participants were followed for an average of 26.3 years and assessed for vascular risk factors. Diabetes was defined by a history of diagnosis, use of diabetes drugs or a A1c level of 6.5% or more.Hypertension was defined as a systolic blood pressure of 140 mm Hg or higher, a diastolic blood pressure of 90 mm Hg or higher, or the use of antihypertensives. Smoking status was based on self-report responses.Dementia was assessed by reviewing participants’ medical and death records as well as cognitive testing and interviews using measures including the Clinical Dementia Rating scale and the Functional Activities Questionnaire.Death without dementia was identified using the National Death Index and participant records.The investigators estimated cumulative incidence, cause-specific hazards, and restricted mean survival time of dementia. Statistical analyses were grouped by sex, race, and APOE4 gene.Early Prevention Is KeyOver 26 years, 3008 participants developed dementia. A combination of high blood pressure, smoking, and diabetes was associated with fewer dementia-free years.Compared with participants who had no risk factors, those with all three had a higher likelihood of dementia (hazard ratio [HR], 2.69; 95% CI, 1.94-3.73) and death without dementia (HR, 5.61; 95% CI, 4.67-6.74).Participants with no risk factors had an average of 30.1 dementia-free years (95% CI, 29.9-30.4), compared with 26.3 years among those with one risk factor and 21.0 years among those with two.Study participants with all three risk factors had the fewest dementia-free years, averaging 17.5 years (95% CI, 16.3-18.7) — nearly 13 fewer years than those with none.Among those with all three risk factors, the probability of developing dementia increased with age, from 23% at age 55 to 37% at age 75.Sensitivity analyses of dementia-free survival were consistent with the primary findings.Women with all three risk factors had more dementia-free years than men with the same risk burden (18.1 vs 16.6 years). Black participants with all three risk factors had fewer dementia-free years than White participants (16.0 vs 19.6 years). APOE epsilon 4 carriers also had shorter dementia-free survival than noncarriers.“These results suggest that vascular risk reduction may benefit all groups, but that certain populations, such as Black adults, may especially benefit from targeted prevention efforts,” Coresh said. “Hopefully, these results will encourage people to stop smoking and watch their vascular health closely from age 45 on.”Study limitations included the lack of longitudinal data on changes in vascular risk factors and potential differences in dementia assessment across participants.The researchers reported no relevant disclosures. The study was supported by National Institutes of Health (NIH) grants K24HL152440 and K01DK138273, and the ARIC study was funded by grants NIH U01HL096812, U01HL096814, U01HL096899, U01HL096902, and U01HL096917.