Review

. 2018 Apr 4:10:363-379.

doi: 10.2147/CLEP.S150915. eCollection 2018.

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

Lisa Sm Eurelings^#¹, Jan Willem van Dalen^#¹, Gerben Ter Riet², Eric P Moll van Charante², Edo Richard^{1

3}, Willem A van Gool¹, Osvaldo P Almeida^{4

5}, Tiago S Alexandre⁶, Bernhard T Baune⁷, Horst Bickel⁸, Francesco Cacciatore^{9

10}, Cyrus Cooper^{11

12

13}, Ton Ajm de Craen¹⁴, Jean-Marie Degryse^{15

16}, Mauro Di Bari^{17

18}, Yeda A Duarte¹⁹, Liang Feng^{20

21}, Nicola Ferrara^{9

10}, Leon Flicker^{22

23

24}, Maurizio Gallucci^{25

26}, Antonio Guaita²⁷, Stephanie L Harrison²⁸, Mindy J Katz²⁹, Maria L Lebrão³⁰, Jason Leung³¹, Richard B Lipton^{29

32

29}, Marta Mengoni¹⁷, Tze Pin Ng²¹, Truls Østbye^{33

34}, Francesco Panza³⁵, Letizia Polito²⁷, Dirk Sander³⁶, Vincenzo Solfrizzi³⁷, Holly E Syddall¹¹, Roos C van der Mast^{38

39}, Bert Vaes^{15

16}, Jean Woo⁴⁰, Kristine Yaffe^{30

41}; ICARA Study Group

Collaborators, Affiliations

Collaborators

ICARA Study Group:
Sujuan Gao, Suzanne C Ho, Joan Lindsay, Aprille Sham, Simone Reppermund, Frederick W Unverzagt

Affiliations

¹ Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands j.vandalen@amc.nl.
² Department of General Practice, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
³ Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Radboud University Medical Centre, Nijmegen, the Netherlands.
⁴ Department of Psychiatry and Clinical Neurosciences, Royal Perth Hospital, University of Western Australia, Perth, Australia.
⁵ Harry Perkins Institute for Medical Research, Western Australian Centre for Health & Ageing, Royal Perth Hospital, University of Western Australia, Perth, Australia.
⁶ Department of Gerontology, Center for Biological and Health Sciences, Federal University of São Carlos, São Carlos, Brazil.
⁷ Discipline of Psychiatry, Royal Adelaide Hospital, University of Adelaide, Adelaide, Australia.
⁸ Department of Psychiatry and Psychotherapy, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.
⁹ Department of Translational Medical Sciences, University of Naples "Federico II", Naples, Italy.
¹⁰ Salvatore Maugeri Foundation, Scientific Institute of Telese Terme, Telese Terme, Italy.
¹¹ Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
¹² National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
¹³ National Institute for Health Research Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK.
¹⁴ Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
¹⁵ Department of Public Health and Primary Care, Katholieke Universiteit Leuven, Leuven, Belgium.
¹⁶ Institut de Recherche Santé et Société, Université Catholique de Louvain, Brussels, Belgium.
¹⁷ Department of Experimental and Clinical Medicine, Research Unit of Medicine of Aging, University of Florence, Florence, Italy.
¹⁸ Department of Geriatrics, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
¹⁹ Department of Medical-Surgical Nursing, University of São Paulo, São Paulo, Brazil.
²⁰ Department of Health Sciences and System Research, Duke NUS Medical School, National University of Singapore, Singapore.
²¹ Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
²² Centre Medical Research, Western Australian Centre for Health & Ageing, University of Western Australia, Perth, Australia.
²³ Department of Geriatric Medicine, Royal Perth Hospital, Perth, Australia.
²⁴ School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
²⁵ Cognitive Impairment Center, Health District of Treviso, Local Health Authority 9 of Treviso, Treviso, Italy.
²⁶ Interdisciplinary Geriatric Research Foundation, Treviso, Italy.
²⁷ Golgi Cenci Foundation, Abbiategrasso, Italy.
²⁸ Department of Epidemiology and Biostatistics, California Pacific Medical Center Research Institute, University of California, San Francisco, CA, USA.
²⁹ Department of Neurology, Albert Einstein College of Medicine, New York, NY, USA.
³⁰ Department of Epidemiology, Faculty of Public Health, University of São Paulo, São Paulo, Brazil.
³¹ Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong.
³² Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY, USA.
³³ Center for Aging Research and Education, Duke NUS Medical School, Singapore.
³⁴ Duke Global Health Institute, Duke University, Durham, NC, USA.
³⁵ Department of Basic Medicine, Neuroscience, and Sense Organs, Neurodegenerative Disease Unit, Pia Fondazione Cardinale G Panico, University of Bari Aldo Moro, Tricase, Italy.
³⁶ Department of Neurology, Benedictus Krankenhaus Tutzing, Technische Universität München, Tutzing, Germany.
³⁷ Interdisciplinary Department of Medicine, Geriatric Medicine and Memory Unit, Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, University of Bari Aldo Moro, Bari, Italy.
³⁸ Department of Psychiatry, Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Antwerp, Belgium.
³⁹ Department of Psychiatry, Leiden University Medical Center, Leiden, Netherlands.
⁴⁰ Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong.
⁴¹ Departments of Psychiatry and Neurology, University of California, San Francisco, CA, USA.

^# Contributed equally.

PMID: 29670402
PMCID: PMC5894652
DOI: 10.2147/CLEP.S150915

Review

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

Lisa Sm Eurelings et al. Clin Epidemiol. 2018.

. 2018 Apr 4:10:363-379.

doi: 10.2147/CLEP.S150915. eCollection 2018.

Authors

Collaborators

ICARA Study Group:
Sujuan Gao, Suzanne C Ho, Joan Lindsay, Aprille Sham, Simone Reppermund, Frederick W Unverzagt

Affiliations

¹ Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands j.vandalen@amc.nl.
² Department of General Practice, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
³ Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Radboud University Medical Centre, Nijmegen, the Netherlands.
⁴ Department of Psychiatry and Clinical Neurosciences, Royal Perth Hospital, University of Western Australia, Perth, Australia.
⁵ Harry Perkins Institute for Medical Research, Western Australian Centre for Health & Ageing, Royal Perth Hospital, University of Western Australia, Perth, Australia.
⁶ Department of Gerontology, Center for Biological and Health Sciences, Federal University of São Carlos, São Carlos, Brazil.
⁷ Discipline of Psychiatry, Royal Adelaide Hospital, University of Adelaide, Adelaide, Australia.
⁸ Department of Psychiatry and Psychotherapy, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.
⁹ Department of Translational Medical Sciences, University of Naples "Federico II", Naples, Italy.
¹⁰ Salvatore Maugeri Foundation, Scientific Institute of Telese Terme, Telese Terme, Italy.
¹¹ Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
¹² National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
¹³ National Institute for Health Research Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK.
¹⁴ Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
¹⁵ Department of Public Health and Primary Care, Katholieke Universiteit Leuven, Leuven, Belgium.
¹⁶ Institut de Recherche Santé et Société, Université Catholique de Louvain, Brussels, Belgium.
¹⁷ Department of Experimental and Clinical Medicine, Research Unit of Medicine of Aging, University of Florence, Florence, Italy.
¹⁸ Department of Geriatrics, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
¹⁹ Department of Medical-Surgical Nursing, University of São Paulo, São Paulo, Brazil.
²⁰ Department of Health Sciences and System Research, Duke NUS Medical School, National University of Singapore, Singapore.
²¹ Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
²² Centre Medical Research, Western Australian Centre for Health & Ageing, University of Western Australia, Perth, Australia.
²³ Department of Geriatric Medicine, Royal Perth Hospital, Perth, Australia.
²⁴ School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
²⁵ Cognitive Impairment Center, Health District of Treviso, Local Health Authority 9 of Treviso, Treviso, Italy.
²⁶ Interdisciplinary Geriatric Research Foundation, Treviso, Italy.
²⁷ Golgi Cenci Foundation, Abbiategrasso, Italy.
²⁸ Department of Epidemiology and Biostatistics, California Pacific Medical Center Research Institute, University of California, San Francisco, CA, USA.
²⁹ Department of Neurology, Albert Einstein College of Medicine, New York, NY, USA.
³⁰ Department of Epidemiology, Faculty of Public Health, University of São Paulo, São Paulo, Brazil.
³¹ Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong.
³² Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY, USA.
³³ Center for Aging Research and Education, Duke NUS Medical School, Singapore.
³⁴ Duke Global Health Institute, Duke University, Durham, NC, USA.
³⁵ Department of Basic Medicine, Neuroscience, and Sense Organs, Neurodegenerative Disease Unit, Pia Fondazione Cardinale G Panico, University of Bari Aldo Moro, Tricase, Italy.
³⁶ Department of Neurology, Benedictus Krankenhaus Tutzing, Technische Universität München, Tutzing, Germany.
³⁷ Interdisciplinary Department of Medicine, Geriatric Medicine and Memory Unit, Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, University of Bari Aldo Moro, Bari, Italy.
³⁸ Department of Psychiatry, Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Antwerp, Belgium.
³⁹ Department of Psychiatry, Leiden University Medical Center, Leiden, Netherlands.
⁴⁰ Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong.
⁴¹ Departments of Psychiatry and Neurology, University of California, San Francisco, CA, USA.

^# Contributed equally.

PMID: 29670402
PMCID: PMC5894652
DOI: 10.2147/CLEP.S150915

Erratum in

Erratum: Apathy and depressive symptoms in older people and incident myocardial infarction, stroke, and mortality: a systematic review and meta-analysis of individual participant data [Erratum].
[No authors listed] [No authors listed] Clin Epidemiol. 2019 Mar 15;11:229. doi: 10.2147/CLEP.S206812. eCollection 2019. Clin Epidemiol. 2019. PMID: 30992683 Free PMC article.

Abstract

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; cardiovascular disease; depression; meta-analysis; myocardial infarction; older people; stroke.

PubMed Disclaimer

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

**Figure 1**
PRISMA diagram of study selection. **Notes:** ^aDissertation/conference abstract, ≤100 study participants, no longitudinal data, case–control study, no original data, no geriatric depression scale or geriatric depression scale version without apathy items; ^bone dissertation, one study with ≤100 participants, and full text not available for one study.

**Figure 2**
HRs for myocardial infarction, stroke, and all-cause mortality by apathy score in individuals without depressive symptoms. **Notes:** Results from Cox proportional-hazard analyses with GDS3A score as predictor adjusted for baseline age, sex, and history of myocardial infarction and/or stroke in individuals without depressive symptoms (GDS12 score ≤1). **Abbreviation:** GDS, Geriatric Depression Scale.

See this image and copyright information in PMC

References

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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

Collaborators

Affiliations

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

Collaborators

Affiliations

Erratum in

Abstract

Conflict of interest statement

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References

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