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Abstract
Background Depression has been consistently linked to the onset of dementia, but the temporality and nature of this association—whether causal, prodromal or due to shared pathophysiology—remain unresolved. Longitudinal studies with extended follow-up are necessary to clarify these relationships. This study aimed to characterise the trajectory of depressive symptoms during the 15 years preceding a dementia diagnosis, with particular attention to variations by dementia aetiology.
Methods This nested case–control study was conducted within the Three-City Study cohort, a prospective population-based study initiated in 1999. The cohort included 9294 community-dwelling individuals aged 65 and older, followed for 15 years in three French cities (Bordeaux, Dijon, Montpellier). Depressive symptoms were assessed using the Centre for Epidemiological Studies Depression scale in 1028 dementia cases and 1028 matched controls. Trajectories of depressive symptoms were analysed over the 15 years preceding the index date (dementia diagnosis).
Results No significant differences in depressive symptomatology (p=0.69) or the frequency of depressive states (OR 1.21, 95% CI 0.51 to 2.87) were observed between cases and controls 12–15 years before the index date. Gradual differences emerged over time, becoming significant 6–8 years prior to dementia onset (p<0.001) and peaking 2 years before the index date (OR 2.93, 95% CI 2.27 to 3.80). These differences were more pronounced in non-Alzheimer’s dementia cases.
Conclusions Depressive symptoms progressively increased in the years leading up to dementia diagnosis, with the most pronounced elevations occurring in non-Alzheimer’s dementia.
- DEMENTIA
- ALZHEIMER'S DISEASE
- DEPRESSION
- EPIDEMIOLOGY
- NEUROEPIDEMIOLOGY
Data availability statement
Data are available on reasonable request. Deidentified participant data used in this study are available on reasonable request. Data access is subject to approval by the 3C Study Scientific Committee. Requests should be submitted via ORCID at the following address: https://orcid.org/0000-0001-6420-1336. Only the data analysed in the present study can be shared. Reuse of the data is permitted for academic and non-commercial purposes on approval. Additional information about the 3C Study, including study protocols and background documentation, is available at: https://the-three-city-study-3c.com.
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Data availability statement
Data are available on reasonable request. Deidentified participant data used in this study are available on reasonable request. Data access is subject to approval by the 3C Study Scientific Committee. Requests should be submitted via ORCID at the following address: https://orcid.org/0000-0001-6420-1336. Only the data analysed in the present study can be shared. Reuse of the data is permitted for academic and non-commercial purposes on approval. Additional information about the 3C Study, including study protocols and background documentation, is available at: https://the-three-city-study-3c.com.
Footnotes
Contributors SH: writing–review and editing (equal); preparation; software; formal analysis; writing–review and editing; TM: writing–review and editing (equal); software; formal analysis; methodology; conceptualisation; supervision; writing–review and editing; guarantor. JN: Writing–review and editing; software; formal analysis; supervision; data curation; MM, J-FD, CH, CT and TA: Writing–review and editing; project administration.
Funding The 3C Study is carried out under a partnership agreement between the Institut National de la Santé et de la Recherche Médicale (INSERM), Victor-Segalen Bordeaux-2 University, and Sanofi-Aventis. The Fondation pour la Recherche Médicale supported the preparation and initiation of the study. The 3C study was also supported by the Caisse Nationale Maladie des Travailleurs Salaries; Direction Générale de la Santé; MGEN; the Institut de la Longévité; Agence Nationale de la Recherche ANR PNRA 2006 (06-01-01) and Longvie 2007 (LVIE-003-01); Agence Française de Sécurité Sanitaire des Produits de Santé; the Regional Governments of Aquitaine, Bourgogne and Languedoc-Roussillon; the Fondation de France; the Ministry of Research-INSERM Programme Cohorts and collection of biological material; Fondation Plan Alzheimer (FCS 2009–2012); the Caisse Nationale de Solidarité pour l’Autonomie (CNSA); Roche Pharma; and the Agence nationale de sécurité sanitaire de l’alimentation, de l’environnement et du travail (Anses, grant No 2019/1/116).
Disclaimer The funders had no role in the design and conduct of the study, collection, management, analysis and interpretation of the data; and preparation, review or approval of the manuscript.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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