A Causal Association Between Drug Use and Cognitive Impairment: A Two‐Sample Mendelian Randomization Study
Bing Yan, Zhugui Chen, Dan Yang. Brain and Behavior, 2025-11-01
Topic: Risk, prevention and care in population studies
The IVW analysis indicated that antithrombotic agents (odds ratio [OR] = 2.12, 95% confidence interval [CI] = 1.03-4.34, p = 0.04), HMG CoA reductase inhibitors (OR = 1.36, 95% CI = 1.07-1.72, p = 0.01), and salicylic acid and derivatives (OR = 2.77, 95% CI = 1.44-5.32, p = 0.002) are a strong risk factor for dementia with Lewy bodies (DLB); diuretics (OR = 1.13, 95% CI = 1-1.27, p = 0.047) and calcium channel blockers (OR = 1.16, 95% CI = 1.04-1.29, p = 0.007) might be a risk factor for vascular dementia; thyroid preparations (OR = 1.03, 95% CI = 1.01-1.06, p = 0.01), diuretics (OR = 1.06, 95% CI = 1.02-1.11, p = 0.004), and immunosuppressants (OR = 1.07, 95% CI = 1.01-1.12, p = 0.001), are a risk factor for frontotemporal dementia; HMG CoA reductase inhibitors is a risk factor for dementia in Alzheimer disease (OR = 1.32, 95% CI = 1.05-1.65, p = 0.01). Moreover, antihistamines for systemic use showed some causal effect on cognitive performance (p < 0.05). The MR-Egger regression indicated that results were unaffected by horizontal pleiotropy. Moreover, no heterogeneity was detected. However, power analyses revealed that several associations had relatively low statistical power, suggesting that these findings should be interpreted with caution. Our findings suggest that certain drugs may causally affect dementia. Larger, well-designed MR studies may help establish the causal status of these dementia risk factors.
Key findings
- The IVW analysis indicated that antithrombotic agents (odds ratio [OR] = 2.12, 95% confidence interval [CI] = 1.03-4.34, p = 0.04), HMG CoA reductase inhibitors (OR = 1.36, 95% CI = 1.07-1.72, p = 0.01), and salicylic acid and derivatives (OR = 2.77, 95% CI = 1.44-5.32, p = 0.002) are a strong risk factor for dementia with Lewy bodies (DLB); diuretics (OR = 1.13, 95% CI = 1-1.27, p = 0.047) and calcium channel blockers (OR = 1.16, 95% CI = 1.04-1.29, p = 0.007) might be a risk factor for vascular dementia; thyroid preparations (OR = 1.03, 95% CI = 1.01-1.06, p = 0.01), diuretics (OR = 1.06, 95% CI = 1.02-1.11, p = 0.004), and immunosuppressants (OR = 1.07, 95% CI = 1.01-1.12, p = 0.001), are a risk factor for frontotemporal dementia; HMG CoA reductase inhibitors is a risk factor for dementia in Alzheimer disease (OR = 1.32, 95% CI = 1.05-1.65, p = 0.01).
- Moreover, antihistamines for systemic use showed some causal effect on cognitive performance (p < 0.05).
- The MR-Egger regression indicated that results were unaffected by horizontal pleiotropy.
- However, power analyses revealed that several associations had relatively low statistical power, suggesting that these findings should be interpreted with caution.
- Our findings suggest that certain drugs may causally affect dementia.
Why it matters
This Mendelian randomization study found that certain drugs, including antithrombotic agents, HMG CoA reductase inhibitors, and salicylic acid derivatives, were associated with increased risk of dementia with Lewy bodies, and HMG CoA reductase inhibitors with increased Alzheimer's disease dementia risk. The authors note that several associations had relatively low statistical power and should be interpreted with caution, so these findings do not establish that these drugs cause dementia.
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Study details
- Effect sizeOR = 1.36; OR = 2.77; OR = 1.13
- Evidence strengthLow
How this study scored 34/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Brain and Behavior) |
| Journal's citation record | 1 / 4 | Brain and Behavior: journal h-index 92 (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 | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 2 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 1.1× 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 | 0 / 4 | Cited 2 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Dan Yang: h-index 7 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Central People's Hospital of Zhanjiang: institution h-index 47 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41220200) |
| Free to read | 2 / 2 | Free to read |
| Total | 34 / 100 | — |
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Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Yan, B., Chen, Z., & Yang, D. (2025). A Causal Association Between Drug Use and Cognitive Impairment: A Two‐Sample Mendelian Randomization Study. Brain and Behavior. https://doi.org/10.1002/brb3.71057
Vancouver
Yan B, Chen Z, Yang D. A Causal Association Between Drug Use and Cognitive Impairment: A Two‐Sample Mendelian Randomization Study. Brain and Behavior. 2025. doi:10.1002/brb3.71057. PMID: 41220200.
BibTeX
@article{yan2025-41220200,
author = {Yan, Bing and Chen, Zhugui and Yang, Dan},
title = {{A Causal Association Between Drug Use and Cognitive Impairment: A Two‐Sample Mendelian Randomization Study}},
journal = {Brain and Behavior},
year = {2025},
doi = {10.1002/brb3.71057},
pmid = {41220200},
url = {https://doi.org/10.1002/brb3.71057}
}
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