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Trajectories of depressive symptoms in older adults and associated health outcomes


With the progressive aging of the world’s population, prolongation of a healthy lifespan in old age has become a medical research priority. The presence of depressive symptoms in later life is associated with poor health prognosis and increased mortality1,2. Here we explore distinct trajectories of depressive symptoms in later life and their association with several health-related outcomes in 19,110 older individuals followed for a median of 4.7 years. Using a latent class, mixed-modeling approach we identified four distinct trajectories of depressive symptoms with scoring patterns of consistently low, moderate, emerging and persistently high. Compared to those with minimal depressive symptoms, membership of any other class was associated with specific patterns of baseline sociodemographic and medical factors. Membership of any group with depressive symptoms was associated with a higher likelihood of health events, including physical disability, cancer and major bleeding episodes. Membership of the persistently depressed class was associated with increased mortality, while a diagnosis of dementia was generally limited to the class with initially low and progressively rising symptoms. The course of depressive symptoms in older individuals can vary widely and depend on several factors. The presence of depressive symptoms, including those that do not meet criteria for major depression, can flag a poor prognosis and risk for specific health conditions. Systematic assessment of depressive symptoms may facilitate early identification of at-risk populations.

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Fig. 1: Trajectory of depressive symptoms.
Fig. 2: Association between latent class membership and medical comorbidities at baseline.

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Data availability

The individual participant data that underlie the results reported in this article will be made available after deidentification. Requests for data access will be via the ASPREE Principal Investigators, with details for applications provided through the website,, and in accordance with the NIH policy on data sharing: details available at Data availability will commence on publication of this article. The supporting Protocol and Statistical Analysis Plan is already available as an independently published article53. These data will be available upon request to investigators whose proposed use of the data, registered as a project through the ASPREE Access Management Site:, has been approved by a review committee. These data will be available through a web-based data portal safe haven, based at Monash University, Australia.

Code availability

Codes are stored in the ASPREE web-based data portal safe haven, based at Monash University. They are available upon request following the procedures described above and on


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The ASPREE trial was supported by grants from the National Institute on Aging and the National Cancer Institute at the US National Institutes of Health (NIH, nos. U01AG029824 and U19AG062682); the National Health and Medical Research Council of Australia (NHMRC) (nos. 334047, 1081901 and 1127060); Monash University (Australia); and the Victorian Cancer Agency (Australia). M.B. is supported by a NHMRC Senior Principal Research Fellowship (no. 1156072), C.M.R. by a NHMRC Principal Research Fellowship (no. 1136372) and L.J.W. by a NHMRC Emerging Leadership Fellowship (no. 1174060). M.L. is funded by the Alfred Deakin Postdoctoral Research Fellowship. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. We thank the ASPREE participants who volunteered for this study, the general practitioners and staff of the medical clinics who support the study participants and the trial staff and management team of the ASPREE study in Australia and the United States (

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Authors and Affiliations



Study design and grant application were performed by M.B., M.M., J.J.M., R.L.W., R.C.S., A.M.M., C.M.R., M.R.N., A.T., B.A. and M.L. Data were collected by M.B., R.L.W., M.R.N., R.C.S., C.M.R., A.M.M. and J.J.M. Statistical analysis was carried out by M.L., M.M. and B.A. Manuscript preparation and editing were the responsibility of B.A., M.L., M.B., C.M.R., R.L.W., M.R.N., R.C.S., A.M.M., J.J.M., M.L., M.M., J.R., L.J.W. and M.P.F.

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Correspondence to Bruno Agustini.

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Competing interests

The authors declare the following potential competing interests. M.B. has received grant/research support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, Medical Benefits Fund, NHMRC, Medical Research Futures Fund, Beyond Blue, Rotary Health, A2 milk company, Meat and Livestock Board, Woolworths, Avant and the Harry Windsor Foundation; has been a speaker for AstraZeneca, Lundbeck, Merck and Pfizer; and served as a consultant to Allergan, AstraZeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Lundbeck Merck, Pfizer and Servier—all unrelated to this work. M.R.N. is member of the Novartis lipids advisory board and received travel and advisory board support from Bayer AG, who provided product for the ASPREE study. A.T. has received honoraria for Safety Monitoring Committee or Advisory Board participation, or lectures from Amgen, Boehringer-Ingelheim, The Medicines Group, Novartis, Pfizer and Merck; and research support from Bayer for materials in ASPREE—all unrelated to this work. These funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

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Nature Aging thanks Gindo Tampubolon, Mark Ward and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Agustini, B., Lotfaliany, M., Mohebbi, M. et al. Trajectories of depressive symptoms in older adults and associated health outcomes. Nat Aging 2, 295–302 (2022).

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