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Alzheimer Combination Therapies: Overview and Scenarios
Jeffrey L. Cummings, Aaron H. Burstein, Howard M. Fillit. The Journal of Prevention of Alzheimer s Disease, 2025-10-27
Topic: Amyloid, tau and blood-test diagnosis
Progress in understanding the complexity of Alzheimer's disease informs the search for combination therapies that can successfully prevent or substantially slow the progression of the disease. Anti-amyloid monoclonal antibodies are the first approved disease targeted therapies; they slow disease progression by approximately 30 %. Building on these agents in add-on therapies is one avenue to designing combination treatments. Development of combination drugs consisting of two or more novel interventions is an alternate pathway for combination treatment development. Combination therapies can involve small molecule drugs, biological agents, devices, stem cells, gene therapies, lifestyle interventions, or cognitive training. Nonclinical assessment of drug combinations may involve animal models or new approach methodologies such as induced pluripotent stem cells or organoids. Phase 1 trials are required to characterize each member of a novel combination. Phase 2 trials may use a 2-by-2 factorial design comparing each drug to placebo and the drug combination. In Phase 3, comparison of the novel combination to standard of care may be sufficient or more complex designs may be required. Targets for combination therapies beyond amyloid-related processes include tau abnormalities, inflammation, neurodegeneration, and co-pathologies such as alpha-synuclein and TDP-43. The choice of combination therapies will depend on the strength of the information regarding the target, biomarkers to guide clinical trials, and a candidate agent with the appropriate mechanism of action. Computational strategies based on network analysis of disease and drugs, validation in non-clinical models, and use of real-world data may facilitate prioritization of candidates for combination treatments.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Cummings, J. L., Burstein, A. H., & Fillit, H. M. (2025). Alzheimer Combination Therapies: Overview and Scenarios. The Journal of Prevention of Alzheimer s Disease. https://doi.org/10.1016/j.tjpad.2025.100328
Vancouver
Cummings JL, Burstein AH, Fillit HM. Alzheimer Combination Therapies: Overview and Scenarios. The Journal of Prevention of Alzheimer s Disease. 2025. doi:10.1016/j.tjpad.2025.100328. PMID: 41145337.
BibTeX
@article{cummings2025-41145337,
author = {Cummings, Jeffrey L. and Burstein, Aaron H. and Fillit, Howard M.},
title = {{Alzheimer Combination Therapies: Overview and Scenarios}},
journal = {The Journal of Prevention of Alzheimer s Disease},
year = {2025},
doi = {10.1016/j.tjpad.2025.100328},
pmid = {41145337},
url = {https://doi.org/10.1016/j.tjpad.2025.100328}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- Phase 2 trials may use a 2-by-2 factorial design comparing each drug to placebo and the drug combination.
- In Phase 3, comparison of the novel combination to standard of care may be sufficient or more complex designs may be required.
- Targets for combination therapies beyond amyloid-related processes include tau abnormalities, inflammation, neurodegeneration, and co-pathologies such as alpha-synuclein and TDP-43.
- The choice of combination therapies will depend on the strength of the information regarding the target, biomarkers to guide clinical trials, and a candidate agent with the appropriate mechanism of action.
- Computational strategies based on network analysis of disease and drugs, validation in non-clinical models, and use of real-world data may facilitate prioritization of candidates for combination treatments.
Why it matters
This overview describes how combination therapies for Alzheimer disease could be designed and tested, noting that approved anti-amyloid monoclonal antibodies slow progression by about 30 percent. It discusses trial designs and possible targets but does not report results of any new combination treatment.
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Study details
- Study designclinical trial
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, 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 (The Journal of Prevention of Alzheimer s Disease) |
| Journal's citation record | 0 / 4 | The Journal of Prevention of Alzheimer s Disease: journal h-index 63 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | Design recorded as “clinical trial”, which our rubric does not rank (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 | 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 19 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 10.4× 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 19 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Howard M. Fillit: h-index 54 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | University of Nevada, Las Vegas: institution h-index 389 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41145337) |
| Free to read | 2 / 2 | Free to read |
| Total | 41 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.tjpad.2025.100328
- PubMed: 41145337
- Original source →
- Free full text: The Journal of Prevention of Alzheimer s Disease →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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