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Functional connectivity in autosomal dominant and late-onset Alzheimer disease
Thomas JB, Brier MR, Bateman RJ, Snyder AZ, Benzinger TL, Xiong C, Raichle M, Holtzman DM et al.. JAMA neurology, 2014-09-01
Topic: Amyloid, tau and blood-test diagnosis
Importance Autosomal dominant Alzheimer disease (ADAD) is caused by rare genetic mutations in 3 specific genes in contrast to late-onset Alzheimer disease (LOAD), which has a more polygenetic risk profile. Objective To assess the similarities and differences in functional connectivity changes owing to ADAD and LOAD. Design, setting, and participants We analyzed functional connectivity in multiple brain resting state networks (RSNs) in a cross-sectional cohort of participants with ADAD (n = 79) and LOAD (n = 444), using resting-state functional connectivity magnetic resonance imaging at multiple international academic sites. Main outcomes and measures For both types of AD, we quantified and compared functional connectivity changes in RSNs as a function of dementia severity measured by the Clinical Dementia Rating Scale. In ADAD, we qualitatively investigated functional connectivity changes with respect to estimated years from onset of symptoms within 5 RSNs. Results A decrease in functional connectivity with increasing Clinical Dementia Rating scores were similar for both LOAD and ADAD in multiple RSNs. Ordinal logistic regression models constructed in one type of Alzheimer disease accurately predicted clinical dementia rating scores in the other, further demonstrating the similarity of functional connectivity loss in each disease type. Among participants with ADAD, functional connectivity in multiple RSNs appeared qualitatively lower in asymptomatic mutation carriers near their anticipated age of symptom onset compared with asymptomatic mutation noncarriers. Conclusions and relevance Resting-state functional connectivity magnetic resonance imaging changes with progressing AD severity are similar between ADAD and LOAD. Resting-state functional connectivity magnetic resonance imaging may be a useful end point for LOAD and ADAD therapy trials. Moreover, the disease process of ADAD may be an effective model for the LOAD disease process.
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APA 7th
Thomas, J. B., Brier, M. R., Bateman, R. J., Snyder, A. Z., Benzinger, T. L., Xiong, C., et al. (2014). Functional connectivity in autosomal dominant and late-onset Alzheimer disease. JAMA neurology. https://doi.org/10.1001/jamaneurol.2014.1654
Vancouver
Thomas JB, Brier MR, Bateman RJ, Snyder AZ, Benzinger TL, Xiong C, et al. Functional connectivity in autosomal dominant and late-onset Alzheimer disease. JAMA neurology. 2014. doi:10.1001/jamaneurol.2014.1654. PMID: 25069482.
BibTeX
@article{thomas2014-25069482,
author = {Thomas, J. B. and Brier, M. R. and Bateman, R. J. and Snyder, A. Z. and Benzinger, T. L. and Xiong, C. and Raichle, M. and Holtzman, D. M. and others},
title = {{Functional connectivity in autosomal dominant and late-onset Alzheimer disease}},
journal = {JAMA neurology},
year = {2014},
doi = {10.1001/jamaneurol.2014.1654},
pmid = {25069482},
url = {https://doi.org/10.1001/jamaneurol.2014.1654}
}
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Key findings
- Results A decrease in functional connectivity with increasing Clinical Dementia Rating scores were similar for both LOAD and ADAD in multiple RSNs.
- Among participants with ADAD, functional connectivity in multiple RSNs appeared qualitatively lower in asymptomatic mutation carriers near their anticipated age of symptom onset compared with asymptomatic mutation noncarriers.
Why it matters
This cross-sectional imaging study found that loss of functional connectivity in brain networks was similar in inherited and late-onset Alzheimer's disease, and that a model built on one type could predict dementia severity in the other. It does not test any treatment, so it offers no direct path to curing or preventing the disease.
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Study details
- Study designcross-sectional
- Participants79
- Evidence strengthModerate
How this study scored 60/100
Published in a leading specialty journal, and it is a snapshot of people at one point in time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA neurology) |
| Journal's citation record | 2 / 4 | JAMA Neurology: journal h-index 235 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2014 — within 20 year(s) of the newest study here |
| Sample size | 1 / 4 | 79 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 | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 131 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 9.4 citations a year over 14 year(s) since 2014 |
| Impact for its field and year | 3 / 6 | Cited 6.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 11 other studies in this library |
| Still being cited | 2 / 4 | Cited 23 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Beau M. Ances: h-index 81 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 22 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25069482) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 60 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1001/jamaneurol.2014.1654
- PubMed: 25069482
- Original source →
- Free full text: UNSWorks (University of New South Wales, Sydney, Australia) →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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