Does Sex or Frailty Modify the Relationship Between Antidepressant Exposure and Dementia Risk: A Scoping Review
Bibliographic record
Abstract
BACKGROUND: Depression is a modifiable risk factor for dementia. Prior studies on antidepressant use and dementia yielded conflicting results, potentially due to unmeasured potential confounding or potential effect modification by sex or frailty. This scoping review aimed to determine whether existing literature on antidepressant-dementia relationship explored sex or frailty as confounders or modifiers in the antidepressant-dementia relationship in adults over 55. METHODS: We searched PubMed, MEDLINE, Embase, CINAHL, and Cochrane Library databases. Eligibility criteria were revised during screening due to the lack of eligible studies and to reduce ambiguity. Studies were included if sex or frailty of participants was described. RESULTS: After screening 7803 titles/abstracts and 47 full texts, we included 21 observational studies. None explicitly defined or investigated sex or frailty as primary objectives. Frailty was not described or measured in any of the included studies. As for exploring sex as an effect modifier, two studies (9%) included sex as an interaction term, but one included interaction term between gender and time, rather than gender and antidepressant use. Another assessed interaction between different sexes with regards to anticholinergic-dementia relationship but not antidepressant-dementia relationship. As for exploring sex as a confounder, twelve studies (57%) adjusted for sex as a covariate, and the studies differed widely with regards to study characteristics, participant characteristics, and methods for analysis, including effect measures. Sex/gender binary framework predominated. CONCLUSION: Frailty was not explored as an effect modifier or confounder in the relationship between antidepressant use and dementia. Sex was also not explored as an effect modifier in the antidepressant-dementia relationship. Two studies (9%) included sex as an interaction term, but they were included in such a way that the findings did not answer our research question. As for exploring sex as a confounder in the antidepressant-dementia relationship, inconsistencies in study characteristics, participant characteristics, and methodologies (including effect measures) hinder a generalized conclusion as to whether or not sex is a confounder in the antidepressant-dementia relationship. Future research could incorporate validated frailty measures, explore sex as an effect modifier, and include sex and gender definitions beyond the binary.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.011 | 0.071 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.006 | 0.008 |
| Bibliometrics | 0.009 | 0.009 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.004 | 0.003 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.003 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".