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Apathy and depressive symptoms in older people and incident myocardial infarction, stroke, and mortality: a systematic review and meta-analysis of individual participant data

Authors Eurelings LSM, van Dalen JW, ter Riet G, Moll van Charante EP, Richard E, van Gool WA

Received 5 September 2017

Accepted for publication 15 January 2018

Published 4 April 2018 Volume 2018:10 Pages 363—379

DOI https://doi.org/10.2147/CLEP.S150915

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 4

Editor who approved publication: Professor Vera Ehrenstein


Lisa SM Eurelings,1,* Jan Willem van Dalen,1,* Gerben ter Riet,2 Eric P Moll van Charante,2 Edo Richard,1,3 Willem A van Gool1


On behalf of the ICARA Study Group

1Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 2Department of General Practice, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 3Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Radboud University Medical Centre, Nijmegen, the Netherlands

*These authors contributed equally to this work


Background: Previous findings suggest that apathy symptoms independently of depressive symptoms measured using the Geriatric Depression Scale (GDS) are associated with cardiovascular disease (CVD) in older individuals.
Aims: To study whether apathy and depressive symptoms in older people are associated with future CVD, stroke, and mortality using individual patient-data meta-analysis.
Methods: Medline, Embase, and PsycInfo databases up to September 3, 2013, were systematically searched without language restrictions. We sought prospective studies with older (mean age ≥65 years) community-dwelling populations in which the GDS was employed and subsequent stroke and/or CVD were recorded to provide individual participant data. Apathy symptoms were defined as the three apathy-related subitems of the GDS, with depressive symptoms the remaining items. We used myocardial infarction (MI), stroke, and all-cause mortality as main outcomes. Analyses were adjusted for age, sex, and MI/stroke history. An adaptation of the Newcastle–Ottawa scale was used to evaluate bias. Hazard ratios were calculated using one-stage random-effect Cox regression models.
Results: Of the 52 eligible studies, 21 (40.4%) were included, comprising 47,625 older people (mean age [standard deviation] 74 [7.4] years), over a median follow-up of 8.8 years. Participants with apathy symptoms had a 21% higher risk of MI (95% confidence interval [CI] 1.08–1.36), a 37% higher risk of stroke (95% CI 1.18–1.59), and a 47% higher risk of all-cause mortality (95% CI 1.38–1.56). Participants with depressive symptoms had a comparably higher risk of stroke (HR 1.36, 95% CI 1.18–1.56) and all-cause mortality (HR 1.44, 95% CI 1.35–1.53), but not of MI (HR 1.08, 95% CI 0.91–1.29). Associations for isolated apathy and isolated depressive symptoms were comparable. Sensitivity analyses according to risk of bias yielded similar results.
Conclusion: Our findings stress the clinical importance of recognizing apathy independently of depressive symptoms, and could help physicians identify persons at increased risk of vascular disease.

Keywords: apathy, older people, depression, cardiovascular disease, meta-analysis, stroke, myocardial infarction

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