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Depression and dementia: interrogating the causality of the relationship
Alvar Paris, Guru Amirthalingam, Tasvee Karania, Isabelle Francesca Foote, Ruth Dobson, Alastair John Noyce, Charles R. Marshall, Sheena Waters. Journal of Neurology Neurosurgery & Psychiatry, 2025-01-11
Topic: Risk, prevention and care in population studies
Depression was a strong risk factor for incident dementia with an OR of 1.76 (95% CI 1.63 to 1.90), a relationship which was found to be specific to depression rather than commonly proposed confounders. Depressive symptoms increased rapidly in the 10 years prior to dementia diagnosis. The severity of depressive symptoms showed a dose-response relationship with dementia risk. Depression at older ages correlated with reduced grey matter volume in an Alzheimer's pattern whereas younger onset depression was associated with reduced grey matter volume in the frontal lobes and cerebellum. This study provides evidence that the link between depression and dementia is due to reverse causation with a smaller component of causation with clear evidence of both mechanisms driving the association.
Key findings
- Depression was a strong risk factor for incident dementia with an OR of 1.76 (95% CI 1.63 to 1.90), a relationship which was found to be specific to depression rather than commonly proposed confounders.
- Depressive symptoms increased rapidly in the 10 years prior to dementia diagnosis.
- The severity of depressive symptoms showed a dose-response relationship with dementia risk.
- Depression at older ages correlated with reduced grey matter volume in an Alzheimer's pattern whereas younger onset depression was associated with reduced grey matter volume in the frontal lobes and cerebellum.
- This study provides evidence that the link between depression and dementia is due to reverse causation with a smaller component of causation with clear evidence of both mechanisms driving the association.
Why it matters
This study found depression was strongly linked to later dementia, but concludes the relationship is largely due to reverse causation, meaning brain changes from dementia may cause depression rather than the other way around, with a smaller causal component. This means treating depression is unlikely to be a major route to preventing dementia.
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Study details
- Participants557
- Evidence strengthLow
How this study scored 46/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Neurology Neurosurgery & Psychiatry) |
| Journal's citation record | 3 / 4 | Journal of Neurology Neurosurgery & Psychiatry: journal h-index 336 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 557 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 17 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 10.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 2 / 4 | Cited 17 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Sheena Waters: h-index 14 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Colorado Boulder: institution h-index 1,198 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39798961) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 46 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Paris, A., Amirthalingam, G., Karania, T., Foote, I. F., Dobson, R., Noyce, A. J., et al. (2025). Depression and dementia: interrogating the causality of the relationship. Journal of Neurology Neurosurgery & Psychiatry. https://doi.org/10.1136/jnnp-2024-334675
Vancouver
Paris A, Amirthalingam G, Karania T, Foote IF, Dobson R, Noyce AJ, et al. Depression and dementia: interrogating the causality of the relationship. Journal of Neurology Neurosurgery & Psychiatry. 2025. doi:10.1136/jnnp-2024-334675. PMID: 39798961.
BibTeX
@article{paris2025-39798961,
author = {Paris, Alvar and Amirthalingam, Guru and Karania, Tasvee and Foote, Isabelle Francesca and Dobson, Ruth and Noyce, Alastair John and Marshall, Charles R. and Waters, Sheena},
title = {{Depression and dementia: interrogating the causality of the relationship}},
journal = {Journal of Neurology Neurosurgery \& Psychiatry},
year = {2025},
doi = {10.1136/jnnp-2024-334675},
pmid = {39798961},
url = {https://doi.org/10.1136/jnnp-2024-334675}
}
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