Home › Research › Risk genes beyond APOE
Neurophysiological markers of cholinergic dysfunction in pre‐symptomatic autosomal dominant Alzheimer´s disease using Transcranial Magnetic Stimulation (TMS): research design and preliminary results
Daniel Martín Jiménez, José Manuel Matamala. Alzheimer s & Dementia, 2025-12-01
Topic: Brain proteins, microglia and lab models
Here we present our research design and preliminary results in ADAD mutation carriers and controls. We implemented an SAI protocol using various interstimulus intervals (ISIs) relative to the latency of the N20 component of the somatosensory evoked potential of the median nerve (-4, 0, +4, +8 milliseconds). We also recorded measures such as resting motor threshold (RMT), short-interval intracortical inhibition and facilitation (SICI-ICF), motor-evoked potential amplitude and latency (MEP), compound muscle action potential (CMAP), cortical silent period duration (CSP), and central motor conduction time (CMCT). To our knowledge, this is the first study to use TMS to assess early cortical cholinergic dysfunction in ADAD mutation carriers during the preclinical stages of the disease. We hope that identifying neurophysiological markers of cholinergic dysfunction in the preclinical phases of the AD spectrum will contribute to understanding the mechanisms underlying disease progression from preclinical to clinical stages.
Key findings
- Here we present our research design and preliminary results in ADAD mutation carriers and controls.
- We implemented an SAI protocol using various interstimulus intervals (ISIs) relative to the latency of the N20 component of the somatosensory evoked potential of the median nerve (-4, 0, +4, +8 milliseconds).
- We also recorded measures such as resting motor threshold (RMT), short-interval intracortical inhibition and facilitation (SICI-ICF), motor-evoked potential amplitude and latency (MEP), compound muscle action potential (CMAP), cortical silent period duration (CSP), and central motor conduction time (CMCT).
- To our knowledge, this is the first study to use TMS to assess early cortical cholinergic dysfunction in ADAD mutation carriers during the preclinical stages of the disease.
- We hope that identifying neurophysiological markers of cholinergic dysfunction in the preclinical phases of the AD spectrum will contribute to understanding the mechanisms underlying disease progression from preclinical to clinical stages.
Why it matters
This report presents the design and preliminary results of a TMS study measuring cholinergic dysfunction in presymptomatic autosomal dominant Alzheimer's disease mutation carriers. It is early preliminary work aimed at understanding disease progression, not at treating or preventing Alzheimer's disease.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Evidence strengthLow
How this study scored 31/100
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 (Alzheimer s & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (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 | 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 | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 0 / 6 | Cited 0.0× 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 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author José Manuel Matamala: h-index 25 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | University of Chile: institution h-index 541 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41434363) |
| Free to read | 2 / 2 | Free to read |
| Total | 31 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1002/alz70861_108702
- PubMed: 41434363
- Original source →
- Free full text: Alzheimer s & Dementia →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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.
APA 7th
Jiménez, D. M., & Matamala, J. M. (2025). Neurophysiological markers of cholinergic dysfunction in pre‐symptomatic autosomal dominant Alzheimer´s disease using Transcranial Magnetic Stimulation (TMS): research design and preliminary results. Alzheimer s & Dementia. https://doi.org/10.1002/alz70861_108702
Vancouver
Jiménez DM, Matamala JM. Neurophysiological markers of cholinergic dysfunction in pre‐symptomatic autosomal dominant Alzheimer´s disease using Transcranial Magnetic Stimulation (TMS): research design and preliminary results. Alzheimer s & Dementia. 2025. doi:10.1002/alz70861_108702. PMID: 41434363.
BibTeX
@article{jimenez2025-41434363,
author = {Jiménez, Daniel Martín and Matamala, José Manuel},
title = {{Neurophysiological markers of cholinergic dysfunction in pre‐symptomatic autosomal dominant Alzheimer´s disease using Transcranial Magnetic Stimulation (TMS): research design and preliminary results}},
journal = {Alzheimer s \& Dementia},
year = {2025},
doi = {10.1002/alz70861_108702},
pmid = {41434363},
url = {https://doi.org/10.1002/alz70861_108702}
}