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White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer's disease
Araque Caballero MÁ, Suárez-Calvet M, Duering M, Franzmeier N, Benzinger T, Fagan AM, Bateman RJ, Jack CR et al.. Brain : a journal of neurology, 2018-10-01
Topic: Amyloid, tau and blood-test diagnosis
White matter alterations are present in the majority of patients with Alzheimer's disease type dementia. However, the spatiotemporal pattern of white matter changes preceding dementia symptoms in Alzheimer's disease remains unclear, largely due to the inherent diagnostic uncertainty in the preclinical phase and increased risk of confounding age-related vascular disease and stroke in late-onset Alzheimer's disease. In early-onset autosomal-dominantly inherited Alzheimer's disease, participants are destined to develop dementia, which provides the opportunity to assess brain changes years before the onset of symptoms, and in the absence of ageing-related vascular disease.
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APA 7th
MÁ, A. C., Suárez-Calvet, M., Duering, M., Franzmeier, N., Benzinger, T., Fagan, A. M., et al. (2018). White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer's disease. Brain : a journal of neurology. https://doi.org/10.1093/brain/awy229
Vancouver
MÁ AC, Suárez-Calvet M, Duering M, Franzmeier N, Benzinger T, Fagan AM, et al. White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer's disease. Brain : a journal of neurology. 2018. doi:10.1093/brain/awy229. PMID: 30239611.
BibTeX
@article{ma2018-30239611,
author = {MÁ, Araque Caballero and Suárez-Calvet, M. and Duering, M. and Franzmeier, N. and Benzinger, T. and Fagan, A. M. and Bateman, R. J. and Jack, C. R. and others},
title = {{White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer's disease}},
journal = {Brain : a journal of neurology},
year = {2018},
doi = {10.1093/brain/awy229},
pmid = {30239611},
url = {https://doi.org/10.1093/brain/awy229}
}
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Key findings
- However, the spatiotemporal pattern of white matter changes preceding dementia symptoms in Alzheimer's disease remains unclear, largely due to the inherent diagnostic uncertainty in the preclinical phase and increased risk of confounding age-related vascular disease and stroke in late-onset Alzheimer's disease.
- In early-onset autosomal-dominantly inherited Alzheimer's disease, participants are destined to develop dementia, which provides the opportunity to assess brain changes years before the onset of symptoms, and in the absence of ageing-related vascular disease.
- Here, we assessed mean diffusivity alterations in the white matter in 64 mutation carriers compared to 45 non-carrier family non-carriers.
- Using tract-based spatial statistics, we mapped the interaction of mutation status by estimated years from symptom onset on mean diffusivity.
Why it matters
In people with inherited, early-onset Alzheimer's, this study found white matter changes on brain scans before symptoms began. It describes an early sign of disease and does not report a treatment, cure or prevention.
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Study details
- Evidence strengthLow
How this study scored 55/100
Published in a leading specialty 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 | 9 / 10 | Tier 2 — leading specialty journal (Brain : a journal of neurology) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (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 | 2 / 5 | 2018 — within 10 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 | 5 / 7 | Cited 179 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 17.9 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 4 / 6 | Cited 12.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 9 other studies in this library |
| Still being cited | 3 / 4 | Cited 62 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Michael Ewers: h-index 74 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 19 institution(s) in 5 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30239611) |
| Free to read | 2 / 2 | Free to read |
| Total | 55 / 100 | — |
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