Late-Life Depressive Symptoms as Partial Mediators in the Associations between Subclinical Cardiovascular Disease with Onset of Mild Cognitive Impairment and Dementia

https://doi.org/10.1016/j.jagp.2017.11.004Get rights and content

Highlights

  • •

    Subclinical cardiovascular disease leads to earlier MCI/dementia onset.

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    Late-life depressive symptoms partially mediate the association between subclinical cardiovascular disease and MCI/dementia onset.

  • •

    Subclinical cardiovascular disease, late-life depressive symptoms, and MCI/dementia may lie on same pathway.

Objective

To study whether depression contributes to the association between subclinical cardiovascular disease (CVD) and dementia, and identify the contribution's magnitude.

Methods

Among participants from the Cardiovascular Health Study Cognition Study who did not have baseline CVD-related events (N = 2,450), causal mediation methodology was implemented to examine whether late-life depressive symptoms, defined as 10-item Center for Epidemiologic Studies-Depression (mCES-D) Scale scores ≥8 from 2 to 3 years after baseline, partially mediated the association of baseline subclinical CVD (CAC, carotid intimal medial thickness, stenosis, and ankle brachial index) with mild cognitive impairment (MCI)/dementia onset occurring between 5 and 10 years from baseline. The total effect was decomposed into direct and indirect effects (via late-life depressive symptoms), obtained from an accelerated failure time model with weights derived from multivariable logistic regression of late-life depressive symptoms on subclinical CVD. Analyses were adjusted by baseline covariates: age, race, sex, poverty status, marital status, body mass index, smoking status, ApoE4 status, and mCES-D.

Results

Participants contributed 20,994 person-years of follow-up with a median follow-up time of 9.4 years. Subclinical CVD was associated with 12% faster time to MCI/dementia (time ratio [TR]: 0.88; 95% CI: 0.83, 0.93). The total effect of subclinical CVD on MCI/dementia onset was decomposed into a direct effect (TR: 0.95, 95% CI: 0.92, 0.98) and indirect effect (TR: 0.92, 95% CI: 0.88, 0.97); 64.5% of the total effect was mediated by late-life depressive symptoms.

Conclusions

These data suggest late-life depressive symptoms partially mediate the association of subclinical CVD with MCI/dementia onset.

Section snippets

Study Participants

The Cardiovascular Health Study (CHS) Cognition Study is an ancillary study of the Cardiovascular Health Study, an ongoing, prospective cohort of older adults across four sites that started in 1989.21 The CHS Cognition Study was initiated between 1992 and 1993 to identify dementia cases and followed participants at risk for developing dementia through 1999–2000. Additional details about the CHS Cognition Study are described in detail elsewhere.21 All participants provided informed consent for

Sample Characteristics

Table 1 shows the sample characteristics for each model for the mediating effect of LLD symptoms on the association between subclinical CVD and MCI/dementia onset. Those with baseline subclinical CVD were likely to be older, male, current smokers, and impoverished as well as have diabetes, treated hypertension, higher systolic blood pressure, lower HDL cholesterol, and shorter time on study, as compared to those without baseline subclinical CVD (Table 1). Also, those with baseline subclinical

Discussion

Subclinical CVD was associated with elevated risk of MCI/dementia. Late-life depressive symptoms partially mediated the association of subclinical CVD with MCI/dementia onset even after propensity score adjustment. Late-life depressive symptoms accounted for 64.5% of the total association between subclinical CVD and MCI/dementia onset. There was an indirect effect of LLD symptoms on the association between any baseline CVD and MCI/dementia, and results were similar with models adjusted by

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    © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.