Midlife depressive symptoms, smoking status, hypertension, diabetes, dyslipidemia and obesity modify the association of long-term vascular risk factor variability from childhood with midlife cognitive function: The Bogalusa Heart Study

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Cognitive aging (n=1010). Intervention: Long-term vascular risk factor variability from childhood vs. Lowest tertile of variability. Primary outcome: Midlife global cognitive score (GCS) (β = -0.12, 95% CI -0.22, -0.02).

Q: What does this research mean for the field?

Higher long-term glucose variability from childhood is associated with poorer midlife cognitive function, particularly among individuals with hypertension and across several low-risk subgroups. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Soo Jung Kang; Jeanette Gustat; Wan Tang; Phillip H Hwang; Owen Thomas Carmichael; Ileana De Anda‐Duran; Lydia A. Bazzano

doi:10.1016/j.ijcrp.2026.200713

September 25, 2026International Journal of Cardiology Cardiovascular Risk and PreventionOpen Access

Midlife depressive symptoms, smoking status, hypertension, diabetes, dyslipidemia and obesity modify the association of long-term vascular risk factor variability from childhood with midlife cognitive function: The Bogalusa Heart Study

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Key result

Higher long-term glucose variability from childhood is linked to ~0.1-point lower midlife cognitive scores in hypertension.

β = -0.12
95% CI -0.22, -0.02
n=1,010

Figures

Graphical abstract published by International Journal of Cardiology Cardiovascular Risk and Prevention — Graphical abstract · Published by International Journal of Cardiology Cardiovascular Risk and Prevention · CC BY-NC-ND

Why the study?

Variability of vascular risk factors from childhood is linked to dementia risk, but the modifying effects of midlife depression, smoking, hypertension, diabetes, obesity, and dyslipidemia on this association with midlife cognitive function are unclear.

Does higher long-term vascular risk factor variability from childhood reduce midlife cognitive function in community-dwelling adults?

Key Points

To determine whether midlife depressive symptoms, smoking, hypertension, diabetes, obesity, and dyslipidemia modify the association between long-term vascular risk factor variability from childhood and midlife cognitive function.
Analyzed 1010 Bogalusa Heart Study participants (34% Black, 61% women; mean age 48 years; follow-up 39 years) with ≥ 3 repeated measurements of systolic blood pressure, glucose, non-HDL, and BMI across the life course.
Assessed midlife cognitive function using a global cognitive score derived from eight standardized neuropsychological tests across three cognitive domains.
Used multivariable linear regression models evaluating vascular risk factor variability (coefficient of variation) stratified by midlife depression, smoking, hypertension, type 2 diabetes, dyslipidemia, and obesity.
High glucose variability (highest vs. lowest tertile) was associated with poorer global cognitive scores in participants with hypertension (β = -0.12, 95% CI -0.22, -0.02) and in those without depression (β = -0.14, 95% CI -0.23, -0.04), never smokers (β = -0.12, 95% CI -0.22, -0.03), without obesity (β = -0.13, 95% CI -0.23, -0.02), without dyslipidemia (β = -0.18, 95% CI -0.30, -0.06), and without diabetes (β = -0.10, 95% CI -0.18, -0.02).
High systolic blood pressure variability was associated with poorer cognitive scores exclusively among former smokers (highest vs. lowest tertile, β = -0.16, 95% CI -0.30, -0.02).
Middle-tertile BMI variability was associated with better cognitive scores in individuals without depression (β = 0.11, 95% CI 0.02, 0.20), without diabetes (β = 0.10, 95% CI 0.02, 0.18), and never smokers (β = 0.09, 95% CI 0.00, 0.17), whereas middle-tertile non-HDL variability was associated with poorer scores only in individuals without depression (β = -0.11, 95% CI -0.20, -0.03).

Study Design

Type

Cohort (n=1,010)

Multicenter

No

Structured PICO

Does higher long-term vascular risk factor variability from childhood reduce midlife cognitive function in community-dwelling adults?

P

Population

1,010 midlife adults (mean age 48, 61% female) from a community-based cohort with ≥3 vascular risk factor measurements across the life course, followed for 39 years to assess cognitive function.

E

Exposure

Higher long-term variability (assessed by coefficient of variation) of vascular risk factors including glucose, SBP, BMI, and non-HDL from childhood.

C

Comparator

Lower long-term variability (lowest tertile) of the respective vascular risk factors.

O

Outcome

Midlife global cognitive score (GCS), derived from averaging eight standardized neuropsychological test scores.surrogate

Main Result

Effect estimate: β = -0.12 (95% CI -0.22, -0.02)

Tracking long-term variability of vascular risk factors from childhood may help identify individuals at risk for poorer cognitive aging and inform early personalized prevention strategies.

Limitations

Clinical diagnosis and duration of depression or smoking were unavailable
Midlife cognitive function was assessed only once
Alternative measures of adiposity such as waist circumference were not assessed
Unmeasured confounding due to unavailable data on physical activity and childhood dietary status
Information regarding antihypertensive, lipid-lowering, or glucose-lowering medication use during follow-up was unavailable
Clinical diagnosis and duration of depression or smoking unavailable
Midlife cognitive function assessed once
Alternative adiposity measures not assessed
Unmeasured confounding
Missing medication data during follow-up
Multiple subgroup analyses lacking statistical power

Implication

Glucose variability may flag cognitive risk in hypertension; extends variability-dementia links but leaves prevention trials open.

Abstract

Background: Variability of vascular risk factors (VRFs) is linked to increased dementia risk. Whether midlife depression, smoking, hypertension, diabetes, obesity, and dyslipidemia modify the association between VRF variability from childhood and midlife cognitive function (CF) is unclear. Methods: Bogalusa Heart Study participants with ≥ 3 repeated measurements of systolic blood pressure (SBP), glucose, non-HDL, and BMI across the life course and one midlife CF assessment were included. CF was evaluated using the global cognitive score (GCS), derived from averaging eight standardized neuropsychological test scores. VRF variability was assessed using coefficient of variation. Associations between VRF variability and GCS were examined using multivariable linear regression models stratified by depressive symptoms (10- item Center for Epidemiologic Studies Depression scale ≥10), smoking status, hypertension, T2DM, dyslipidemia, and obesity. Results: A total of 1010 participants were evaluated (34% Black, 61% women; mean age 48 years; follow-up 39 years). Higher glucose variability was associated with poorer GCS among individuals with hypertension (highest vs. lowest tertile, β = -0.12, 95% CI -0.22, -0.02), and among those without depression, obesity, dyslipidemia, diabetes, and among never smokers. Higher SBP variability was associated with poorer GCS only among former smokers (highest vs. lowest tertile, β = -0.16, 95% CI -0.30, -0.02). Middle-tertile BMI variability was associated with better GCS among individuals without depression, without diabetes, and among never smokers. Middle-tertile non-HDL variability was associated with poorer GCS only among individuals without depression. Conclusions: Tracking VRF variability from early life even in low-risk populations could facilitate optimal cognitive aging.

Discussion

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Cite This Study

Kang et al. (2026) conducted a cohort in Cognitive aging (n=1,010). Long-term vascular risk factor variability from childhood vs. Lowest tertile of variability was evaluated on Midlife global cognitive score (GCS) (β = -0.12, 95% CI -0.22, -0.02). Higher long-term glucose variability from childhood was associated with poorer midlife global cognitive scores among individuals with hypertension (β = -0.12) and other subgroups.

synapsesocial.com/papers/6ad0fd553afa093ea9ad03c3 https://doi.org/10.1016/j.ijcrp.2026.200713

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Midlife depressive symptoms, smoking status, hypertension, diabetes, dyslipidemia and obesity modify the association of long-term vascular risk factor variability from childhood with midlife cognitive function: The Bogalusa Heart Study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Midlife depressive symptoms, smoking status, hypertension, diabetes, dyslipidemia and obesity modify the association of long-term vascular risk factor variability from childhood with midlife cognitive function: The Bogalusa Heart Study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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