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Concurrent Gabapentin and Dihydropyridine Calcium Channel Blocker Use and Risk of Incident Dementia: An Active-Comparator Cohort Study
Green JW, Fonseca LM, Beeri MS, Simon SS, Parrott JS, Ljubic B, Schulewski M, Tafuto B et al.. medRxiv, 2026-02-09
Topic: Drug trials: efficacy and safety
Both classes act on neuronal calcium signaling, raising the question of whether their combined use is associated with greater cognitive risk than gabapentin alone. Results Among 33,791 patients (mean [SD] age, 69.9 [11.5] years; 57.1% female; 502 dementia events; median follow-up, 1.22 years), gabapentin initiation was associated with higher dementia incidence among patients also taking a CCB than among those not taking a CCB (time-varying HR, 1.52 [95% CI, 1.23–1.89]; baseline-stratified HR, 2.22 [95% CI, 1.42–3.47]). Conclusions and Relevance In this active-comparator cohort of older adults with hypertension, concurrent CCB use — particularly with DHP agents — was associated with substantially higher gabapentin-related dementia incidence than gabapentin without CCB exposure. Key Points Question In older adults with hypertension, is concurrent calcium channel blocker (CCB) use associated with higher gabapentin-related dementia incidence than gabapentin alone? Findings In an active-comparator cohort of 33,791 adults, gabapentin initiation (vs pregabalin) was associated with higher dementia incidence among patients also taking a CCB than among those not taking a CCB (time-varying HR, 1.52 [95% CI, 1.23–1.89; P = .0003]; baselinestratified HR, 2.22 [95% CI, 1.42–3.47]; interaction P = .004).
Key findings
- Both classes act on neuronal calcium signaling, raising the question of whether their combined use is associated with greater cognitive risk than gabapentin alone.
- Results Among 33,791 patients (mean [SD] age, 69.9 [11.5] years; 57.1% female; 502 dementia events; median follow-up, 1.22 years), gabapentin initiation was associated with higher dementia incidence among patients also taking a CCB than among those not taking a CCB (time-varying HR, 1.52 [95% CI, 1.23–1.89]; baseline-stratified HR, 2.22 [95% CI, 1.42–3.47]).
- Conclusions and Relevance In this active-comparator cohort of older adults with hypertension, concurrent CCB use — particularly with DHP agents — was associated with substantially higher gabapentin-related dementia incidence than gabapentin without CCB exposure.
- Key Points Question In older adults with hypertension, is concurrent calcium channel blocker (CCB) use associated with higher gabapentin-related dementia incidence than gabapentin alone?
- Findings In an active-comparator cohort of 33,791 adults, gabapentin initiation (vs pregabalin) was associated with higher dementia incidence among patients also taking a CCB than among those not taking a CCB (time-varying HR, 1.52 [95% CI, 1.23–1.89; P = .0003]; baselinestratified HR, 2.22 [95% CI, 1.42–3.47]; interaction P = .004).
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Study details
- Study designcohort study
- Participants33,791
- Effect size57.1%
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 50 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 31 of the 62 points we could judge it on, which is 50 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 4 / 4 | 33,791 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 31 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 31 of the 62 points we could judge it on is 50 out of 100. |
| Total | 50 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Green, J. W., Fonseca, L. M., Beeri, M. S., Simon, S. S., Parrott, J. S., Ljubic, B., et al. (2026). Concurrent Gabapentin and Dihydropyridine Calcium Channel Blocker Use and Risk of Incident Dementia: An Active-Comparator Cohort Study. medRxiv. https://doi.org/10.64898/2026.02.06.26345763
Vancouver
Green JW, Fonseca LM, Beeri MS, Simon SS, Parrott JS, Ljubic B, et al. Concurrent Gabapentin and Dihydropyridine Calcium Channel Blocker Use and Risk of Incident Dementia: An Active-Comparator Cohort Study. medRxiv. 2026. doi:10.64898/2026.02.06.26345763.
BibTeX
@article{green2026-93f370c9,
author = {Green, J. W. and Fonseca, L. M. and Beeri, M. S. and Simon, S. S. and Parrott, J. S. and Ljubic, B. and Schulewski, M. and Tafuto, B. and others},
title = {{Concurrent Gabapentin and Dihydropyridine Calcium Channel Blocker Use and Risk of Incident Dementia: An Active-Comparator Cohort Study}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.02.06.26345763},
url = {https://doi.org/10.64898/2026.02.06.26345763}
}