Low Values for Blood Pressure, BMI, and Non-HDL Cholesterol and the Risk of Late-Life Dementia

Abstract

Background and objectives: Low values of blood pressure, body mass index (BMI), and non-high-density lipoprotein (HDL) cholesterol have all been associated with increased dementia risk in late life, but whether these risk factors have an additive effect is unknown. This study assessed whether a combination of late-life low values for systolic blood pressure (SBP), BMI, and non-HDL cholesterol is associated with a higher dementia risk than individual low values of these risk factors.

Methods: This is a post hoc analysis based on an observational extended follow-up of the Prevention of Dementia by Intensive Vascular Care (preDIVA) trial, including community-dwelling individuals, aged 70-78 years and free from dementia at baseline. We assessed the association of baseline low values of SBP, BMI, and non-HDL cholesterol with incident dementia using Cox regression analyses. First, we assessed the respective associations between quintiles of each risk factor and dementia. Second, we explored whether combinations of low values for cardiovascular risk factors increased dementia risk, adjusted for interaction and potential confounders.

Results: During a median follow-up of 10.3 years (interquartile range 7.0-10.9 years), 308 of 2,789 participants (11.0%) developed dementia, and 793 (28.4%) died. For all risk factors, the lowest quintile was associated with the highest adjusted risk for dementia. Individuals with 1, 2, and 3 low values had adjusted HRs of 1.18 (95% CI 0.93-1.51), 1.28 (95% CI 0.85-1.93), and 4.02 (95% CI 2.04-7.93), respectively, compared with those without any low values. This effect was not driven by any specific combination of 2 risk factors and could not be explained by competing risk of death.

Discussion: Older individuals with low values for SBP, BMI, or non-HDL cholesterol have a higher dementia risk compared with individuals without any low values. Dementia risk was substantially higher in individuals with low values for all 3 risk factors than expected based on a dose-response relationship. This suggests the presence of an overarching phenomenon that involves multiple risk factors simultaneously, rather than resulting from independent effects of each individual risk factor.

Trial registration information: ISRCTN registry preDIVA: ISRCTN29711771. Date of study submission to ISRCTN registry: February 14, 2006. Recruitment start date: January 1, 2006. doi.org/10.1186/ISRCTN29711771.

Figure 1. Flowchart

BMI = body mass index; HDL = high-density lipoprotein; POE = preDIVA observational extension; preDIVA = Prevention of Dementia by Intensive Vascular Care; SBP = systolic blood pressure.

Figure 2. Association for Quintiles of Cardiovascular Risk Factors With Dementia Incidence

These figures display the relative association compared with the lowest quintile (reference) with dementia incidence for systolic blood pressure, BMI, and non-HDL cholesterol. (A) Unadjusted. (B) Adjusted for age at baseline, sex, education, history of stroke, cardiovascular disease or diabetes mellitus, smoking status, and APOE 4 genotype. BMI = body mass index; HDL = high-density lipoprotein; HR = hazard ratio; SBP = systolic blood pressure.