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Lithium therapy and delayed progression of Alzheimer’s disease and related dementias in patients with bipolar disorder and mild neurocognitive disorders
Weckstein AR, Carr S, Wang P, Krüger N, Danaei G, Schneeweiss S, Desai RJ.. medRxiv, 2026-01-13
Topic: Drug trials: efficacy and safety
Plain-language summary
Recent mechanistic evidence identifies lithium deficiency as a driver of Alzheimer’s disease and related dementias (ADRD) pathogenesis. To evaluate this hypothesis in a population-based setting, we emulated a target trial comparing ADRD progression after initiation of lithium versus antiepileptic mood stabilizers among adults ≥55 years with bipolar disorder and mild neurocognitive disorder, using US Medicare claims with replication in two commercial databases. Lithium initiation was associated with a lower 5-year risk of progression to advanced ADRD (risk ratio 0.87; 95% CI 0.78-0.99) and long-term care stay with ADRD (0.75; 0.56-0.97). Lower risks were most pronounced in patients with later stages of mild cognitive impairment. Results were consistent across sensitivity analyses and replications. Validations using linked cognitive assessments from standardized instruments strengthened confidence in findings. While results may be susceptible to residual bias, this study supports investigating lithium’s potential to delay ADRD progression with randomized trials of optimized lithium formulations.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Weckstein, A. R., Carr, S., Wang, P., Krüger, N., Danaei, G., Schneeweiss, S., et al. (2026). Lithium therapy and delayed progression of Alzheimer’s disease and related dementias in patients with bipolar disorder and mild neurocognitive disorders. medRxiv. https://doi.org/10.64898/2026.01.12.26343472
Vancouver
Weckstein AR, Carr S, Wang P, Krüger N, Danaei G, Schneeweiss S, et al. Lithium therapy and delayed progression of Alzheimer’s disease and related dementias in patients with bipolar disorder and mild neurocognitive disorders. medRxiv. 2026. doi:10.64898/2026.01.12.26343472.
BibTeX
@article{weckstein2026-20b0989e,
author = {Weckstein, A. R. and Carr, S. and Wang, P. and Krüger, N. and Danaei, G. and Schneeweiss, S. and Desai, R. J.},
title = {{Lithium therapy and delayed progression of Alzheimer’s disease and related dementias in patients with bipolar disorder and mild neurocognitive disorders}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.01.12.26343472},
url = {https://doi.org/10.64898/2026.01.12.26343472}
}
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 7 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.
Key findings
- To evaluate this hypothesis in a population-based setting, we emulated a target trial comparing ADRD progression after initiation of lithium versus antiepileptic mood stabilizers among adults ≥55 years with bipolar disorder and mild neurocognitive disorder, using US Medicare claims with replication in two commercial databases.
- Lithium initiation was associated with a lower 5-year risk of progression to advanced ADRD (risk ratio 0.87; 95% CI 0.78-0.99) and long-term care stay with ADRD (0.75; 0.56-0.97).
- Results were consistent across sensitivity analyses and replications.
- While results may be susceptible to residual bias, this study supports investigating lithium’s potential to delay ADRD progression with randomized trials of optimized lithium formulations.
Study details
- Evidence strengthHigh
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 27 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported, studied in people and randomized / 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 multicenter collaboration, so those were left out: it earned 17 of the 62 points we could judge it on, which is 27 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 | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 5 / 5 | Rated “high” 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 | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization 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 |
| Multicenter 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 | 17 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 17 of the 62 points we could judge it on is 27 out of 100. |
| Total | 27 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
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