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Deep Brain Stimulation Targeting the Fornix for Mild Alzheimer Dementia (the ADvance Trial): A Two Year Follow-up Including Results of Delayed Activation
Leoutsakos JS, Yan H, Anderson WS, Asaad WF, Baltuch G, Burke A, Chakravarty MM, Drake KE et al.. Journal of Alzheimer's disease : JAD, 2018-01-01
Topic: Amyloid, tau and blood-test diagnosis
Background Given recent challenges in developing new treatments for Alzheimer dementia (AD), it is vital to explore alternate treatment targets, such as neuromodulation for circuit dysfunction. We previously reported an exploratory Phase IIb double-blind trial of deep brain stimulation targeting the fornix (DBS-f) in mild AD (the ADvance trial). We reported safety but no clinical benefits of DBS-f versus the delayed-on (sham) treatment in 42 participants after one year. However, secondary post hoc analyses of the one-year data suggested a possible DBS-f benefit for participants≥65 years. Objective To examine the long-term safety and clinical effects of sustained and delayed-on DBS-f treatment of mild AD after two years. Methods 42 participants underwent implantation of DBS-f electrodes, with half randomized to active DBS-f stimulation (early on) for two years and half to delayed-on (sham) stimulation after 1 year to provide 1 year of active DBS-f stimulation (delayed on). We evaluated safety and clinical outcomes over the two years of the trial. Results DBS-f had a favorable safety profile with similar rates of adverse events across both trial phases (years 1 and 2) and between treatment arms. There were no differences between treatment arms on any primary clinical outcomes. However, post-hoc age group analyses suggested a possible benefit among older (>65) participants. Conclusion DBS-f was safe. Additional study of mechanisms of action and methods for titrating stimulation parameters will be needed to determine if DBS has potential as an AD treatment. Future efficacy studies should focus on patients over age 65.
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APA 7th
Leoutsakos, J. S., Yan, H., Anderson, W. S., Asaad, W. F., Baltuch, G., Burke, A., et al. (2018). Deep Brain Stimulation Targeting the Fornix for Mild Alzheimer Dementia (the ADvance Trial): A Two Year Follow-up Including Results of Delayed Activation. Journal of Alzheimer's disease : JAD. https://doi.org/10.3233/jad-180121
Vancouver
Leoutsakos JS, Yan H, Anderson WS, Asaad WF, Baltuch G, Burke A, et al. Deep Brain Stimulation Targeting the Fornix for Mild Alzheimer Dementia (the ADvance Trial): A Two Year Follow-up Including Results of Delayed Activation. Journal of Alzheimer's disease : JAD. 2018. doi:10.3233/jad-180121. PMID: 29914028.
BibTeX
@article{leoutsakos2018-29914028,
author = {Leoutsakos, J. S. and Yan, H. and Anderson, W. S. and Asaad, W. F. and Baltuch, G. and Burke, A. and Chakravarty, M. M. and Drake, K. E. and others},
title = {{Deep Brain Stimulation Targeting the Fornix for Mild Alzheimer Dementia (the ADvance Trial): A Two Year Follow-up Including Results of Delayed Activation}},
journal = {Journal of Alzheimer's disease : JAD},
year = {2018},
doi = {10.3233/jad-180121},
pmid = {29914028},
url = {https://doi.org/10.3233/jad-180121}
}
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Key findings
- We reported safety but no clinical benefits of DBS-f versus the delayed-on (sham) treatment in 42 participants after one year.
- Results DBS-f had a favorable safety profile with similar rates of adverse events across both trial phases (years 1 and 2) and between treatment arms.
Why it matters
In 42 participants with mild Alzheimer's disease, deep brain stimulation of the fornix had a favorable safety profile but showed no clinical benefits compared with delayed stimulation after one or two years. Post-hoc analyses suggested a possible benefit in participants over 65, but this was not a primary finding and requires further study.
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Study details
- Study designpost-hoc analysis
- Participants42
- Evidence strengthHigh
How this study scored 55/100
Published in a peer-reviewed journal. Scored zero for study design and effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Alzheimer's disease : JAD) |
| Journal's citation record | 2 / 4 | Journal of Alzheimer s Disease: journal h-index 218 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | Design recorded as “post-hoc analysis”, which our rubric does not rank (not stated in the record — scored 0) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2018 — within 10 year(s) of the newest study here |
| Sample size | 1 / 4 | 42 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 1 / 2 | Randomised (as stated in the record) |
| Times cited | 5 / 7 | Cited 103 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 10.3 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 3 / 6 | Cited 6.4× 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 29 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Constantine George Lyketsos: h-index 130 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Johns Hopkins University: institution h-index 2,306 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 17 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29914028) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 55 / 100 | — |
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