The role of cognitive and brain reserve in late-life depressive events: The Rotterdam Study

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Background: Cognitive and brain reserve aim to explain individual differences in susceptibility to dementia and may also affect the risk of late-life depressive events. We assessed whether higher cognitive and brain reserve are associated with lower risk of a late-life depressive event.

Methods: This study included 4509 participants from the population-based Rotterdam Study (mean age: 63.4 ± 10.2 years, 55 % women) between 2005 and 2019. Participants completed cognitive testing and brain-MRI at baseline. Cognitive reserve was defined as the common variance across cognitive tests, while adjusting for demographic factors and brain MRI-markers. Brain reserve was defined as total brain volume divided by intracranial volume. Depressive events (depressive symptoms/depressive syndrome/major depressive disorder) were repeatedly measured (follow-up: 6.6 ± 3.9 years) with validated questionnaires, clinical interviews, and follow-up of medical records. Hazard ratios (HR) with 95 % confidence intervals (CI) were estimated using Cox-regressions.

Results: Higher cognitive (HR: 0.91/SD, 95%CI: 0.84; 1.00) and brain reserve (HR: 0.88/SD, 95%CI: 0.77; 1.00) were associated with a lower risk of a depressive event after adjustment for baseline depressive symptoms. These associations attenuated when participants with clinically relevant depressive symptoms at baseline were excluded (HR: 0.95/SD, 95%CI: 0.86; 1.05, HR: 0.89/SD, 95%CI: 0.76; 1.03, respectively).

Limitations: No data was available on depression in early-life and the number of participants with major depressive disorder was relatively low (n = 105).

Conclusions: Higher cognitive and brain reserve may be protective factors for late-life depressive events, particularly in those who have experienced clinical relevant depressive symptoms before. Further research is needed to determine whether cognitive and brain reserve could be used as targets for the prevention of late-life depression.

Original languageEnglish
Pages (from-to)211-217
Number of pages7
JournalJournal of Affective Disorders
Early online date30 Sep 2022
Publication statusPublished - 1 Jan 2023

Bibliographical note

Funding Information:
The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. This study was partly performed as part of the Netherlands Consortium of Dementia Cohorts (NCDC), which receives funding in the context of Deltaplan Dementie from ZonMW Memorabel (projectnr 73305095005) and Alzheimer Nederland. The study received further funding by the EU Joint Programme - Neurodegenerative Diseases (JPND) in the HeSoCare-call for the project Social Health and Reserve in the Dementia patient journey (SHARED) (HESOCARE-329-109) funded through the Deltaplan Dementia by ZonMW (number 733051082) and Alzheimer Nederland. MAI received funding from the European Union's Horizon 2020 research and innovation program (678543, ORACLE).

Publisher Copyright: © 2022 The Authors


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