The association between cardiovascular disease and cognitive decline varies by long-term depressive symptom trajectories in older adults

Q: What are the key findings of this study?

Baseline CVD accelerated global cognitive decline (β = -0.045 SD/year, P<0.001), an effect strongest in low-stable depression (β = -0.051) and attenuated in higher depression trajectories.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Cardiovascular disease and depressive symptoms in older adults (n=5423). Intervention: Baseline cardiovascular disease moderated by long-term depressive symptom trajectories (moderate-stable and high-stable vs low-stable) vs. No baseline cardiovascular disease and low-stable depressive symptom trajectory. Primary outcome: Longitudinal rate of change in global cognition z-score (SD/year) (beta -0.045 SD/year, 95% CI -0.057 to -0.034, p=<0.001).

Q: What does this research mean for the field?

The association between cardiovascular disease and accelerated cognitive decline is strongest among older adults with low-stable depressive symptoms and attenuates in those with persistent moderate or high depressive symptom trajectories. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To determine whether long-term depressive symptom trajectories modify the association between baseline cardiovascular disease and subsequent cognitive decline in older adults.

Yujin Bao; Sida Wang; Yun Lu; Feng Chang

doi:10.1038/s41598-026-78420-6

November 2, 2026Scientific ReportsOpen Access

The association between cardiovascular disease and cognitive decline varies by long-term depressive symptom trajectories in older adults

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Key result

Baseline CVD is linked to faster cognitive decline, particularly in adults with low depressive symptoms.

beta -0.045 SD/year
95% CI -0.057 to -0.034
P<0.001
n=5,423

Why the study?

Cardiovascular disease and depressive symptoms are established risk factors for late-life cognitive decline, but whether long-term depressive symptom burden modifies the association between CVD and cognitive ageing remains unclear.

Does long-term depressive symptom trajectory modify the association between baseline cardiovascular disease and subsequent cognitive decline in adults aged 50 years and older?

Key Points

To determine whether long-term depressive symptom trajectories modify the association between baseline cardiovascular disease and subsequent cognitive decline in older adults.
Longitudinal cohort study using data from 5423 adults aged 50 years and older from the English Longitudinal Study of Ageing followed between 2004 and 2018.
Depressive symptoms were measured repeatedly via the eight-item Center for Epidemiologic Studies Depression Scale, with growth mixture modelling applied to identify longitudinal symptom trajectories.
Linear mixed-effects models examined the associations of baseline cardiovascular disease, depressive symptom trajectories, and their interactions with longitudinal changes in global cognition, memory, semantic fluency, and orientation.
Baseline cardiovascular disease was associated with longitudinal decline across all participants in global cognition (β = −0.045, 95% CI −0.057 to −0.034, P < 0.001), semantic fluency (β = −0.034, 95% CI −0.044 to −0.024, P < 0.001), memory (β = −0.034, 95% CI −0.044 to −0.025, P < 0.001), and orientation (β = −0.018, 95% CI −0.032 to −0.004, P < 0.05).
Growth mixture modelling identified three distinct symptom trajectories: low-stable (76.8%), moderate-stable (18.1%), and high-stable (5.1%).
The cardiovascular-related decline in global cognition was steepest in the low-stable group (β = −0.051 SD/year, 95% CI −0.064 to −0.038, P < 0.001) and was significantly attenuated in the moderate-stable (interaction β = 0.031, 95% CI 0.002 to 0.060, P = 0.036) and high-stable groups (interaction β = 0.059, 95% CI 0.011 to 0.107, P = 0.017).

Study Design

Type

Cohort (n=5,423)

Multicenter

Yes

Structured PICO

Does long-term depressive symptom trajectory modify the association between baseline cardiovascular disease and subsequent cognitive decline in adults aged 50 years and older?

P

Population

5,423 adults aged >=50 years (mean age 65.2, 56% female) from the English Longitudinal Study of Ageing, stratified by baseline CVD and long-term depressive symptom trajectories, followed for 14 years (2004-2018).

E

Exposure

Baseline cardiovascular disease (CVD) and long-term depressive symptom trajectories (low-stable, moderate-stable, and high-stable) assessed repeatedly using the 8-item Center for Epidemiologic Studies Depression Scale (CES-D)

C

Comparator

No baseline cardiovascular disease (n=4,343) and low-stable depressive symptom trajectory (reference group)

O

Outcome

Longitudinal rate of change in global cognition z-score (standardized average of memory, orientation, and semantic fluency domain z-scores) over a 14-year follow-up period (2004–2018)surrogate

Main Result

Standardized Mean Difference: -0.045 (95% CI -0.057–-0.034)

p-value: p=<0.001

Long-term depressive symptom burden independently predicts faster cognitive decline and attenuates the observable difference in cognitive decline associated with baseline cardiovascular disease in older adults.

Limitations

Excluded participants with missing follow-up or incomplete depression assessments were older, had higher baseline prevalence of CVD, hypertension, and diabetes, and had lower baseline cognitive scores (potential attrition/selection bias).
Baseline CVD was based on five self-reported conditions (angina, heart attack, heart failure, stroke, other heart problems) and did not directly assess subclinical cerebrovascular disease, disease severity, or extent of brain injury.
The orientation score ranged from 0 to 4 and was concentrated near the upper limit at baseline, introducing a potential ceiling effect that may influence estimates of change over time.
Neurovascular and neural pathways (such as cerebral small-vessel disease or default-mode network activity) were not directly measured.

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Answers are grounded in this paper and cite their sources.

Implication

CVD-cognitive decline link strongest in low-stable depression; leaves open trajectory modification for targeted prevention trials.

Abstract

Cardiovascular disease (CVD) and depressive symptoms are established risk factors for cognitive decline in later life, but it remains unclear whether long-term depressive symptom burden modifies the association between CVD and cognitive ageing. We used data from 5423 adults aged 50 years and older in the English Longitudinal Study of Ageing between 2004 and 2018. Depressive symptoms were assessed repeatedly using the eight-item Center for Epidemiologic Studies Depression Scale, and growth mixture modelling was used to identify long-term symptom trajectories. Linear mixed-effects models examined associations between baseline CVD, depressive symptom trajectories, and changes in global cognition, memory, semantic fluency, and orientation. Three trajectories were identified: low-stable, moderate-stable, and high-stable. Participants with moderate-stable and high-stable depressive symptoms had poorer baseline cognitive performance and faster decline in global cognition, memory, and semantic fluency than those with low-stable symptoms. Baseline CVD was associated with faster cognitive decline, but the CVD-related difference was most evident in the low-stable group and attenuated among participants with higher depressive symptom burden. These findings suggest that persistent depressive symptoms may shape the observable association between CVD and cognitive ageing, highlighting the importance of considering long-term mental health burden in cognitive risk assessment.

Discussion

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Cite This Study

Bao et al. (2026) conducted a cohort in Cardiovascular disease and depressive symptoms in older adults (n=5,423). Baseline cardiovascular disease moderated by long-term depressive symptom trajectories (moderate-stable and high-stable vs low-stable) vs. No baseline cardiovascular disease and low-stable depressive symptom trajectory was evaluated on Longitudinal rate of change in global cognition z-score (SD/year) (beta -0.045 SD/year, 95% CI -0.057 to -0.034, p=<0.001). Baseline CVD accelerated global cognitive decline (β = -0.045 SD/year, P<0.001), an effect strongest in low-stable depression (β = -0.051) and attenuated in higher depression trajectories.

synapsesocial.com/papers/6aebc8ba3e63ca1b6c315e04 https://doi.org/10.1038/s41598-026-78420-6

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The association between cardiovascular disease and cognitive decline varies by long-term depressive symptom trajectories in older adults

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

The association between cardiovascular disease and cognitive decline varies by long-term depressive symptom trajectories in older adults

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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