Home › Research › Biomarkers
Resting-State Functional Connectivity Disruption as a Pathological Biomarker in Autosomal Dominant Alzheimer Disease
Smith RX, Strain JF, Tanenbaum A, Fagan AM, Hassenstab J, McDade E, Schindler SE, Gordon BA et al.. Brain connectivity, 2021-03-31
Topic: Amyloid, tau and blood-test diagnosis
The gFC was reduced in MC compared with NC participants. When MC participants were differentiated by clinical dementia rating (CDR), the gFC was significantly decreased in MC CDR >0 (demented) compared with either MC CDR 0 (cognitively normal) or NC participants. The gFC varied nonlinearly with EYO and initially decreased at EYO = -24 years, followed by a stable period followed by a further decline near EYO = 0 years. Irrespective of EYO, a lower gFC associated with values of amyloid PET, CSF Aβ 1-42 , CSF p-tau, CSF t-tau, 18F-fluorodeoxyglucose, and hippocampal volume. The gFC correlated with biomarkers used for defining the AT(N) framework. A biphasic change in the gFC suggested early changes associated with CSF amyloid and later changes associated with hippocampal volume.
Key findings
- The gFC was reduced in MC compared with NC participants.
- When MC participants were differentiated by clinical dementia rating (CDR), the gFC was significantly decreased in MC CDR >0 (demented) compared with either MC CDR 0 (cognitively normal) or NC participants.
- The gFC varied nonlinearly with EYO and initially decreased at EYO = -24 years, followed by a stable period followed by a further decline near EYO = 0 years.
- Irrespective of EYO, a lower gFC associated with values of amyloid PET, CSF Aβ 1-42 , CSF p-tau, CSF t-tau, 18F-fluorodeoxyglucose, and hippocampal volume.
- The gFC correlated with biomarkers used for defining the AT(N) framework.
Why it matters
In people with autosomal dominant Alzheimer disease, global functional connectivity was reduced compared with non-carriers and changed in a nonlinear way relative to estimated years to symptom onset, correlating with amyloid and tau markers and hippocampal volume. This describes a possible imaging marker of disease progression, not a treatment, cure or prevention.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Study designcross-sectional
- Participants171
- Evidence strengthLow
How this study scored 49/100
Published in a peer-reviewed 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. We have no data on senior author's track record, so that was left out: it earned 47 of the 96 points we could judge it on, which is 49 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Brain connectivity) |
| Journal's citation record | 1 / 4 | Brain Connectivity: journal h-index 83 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| 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 | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 171 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 | 3 / 7 | Cited 23 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.3 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 2 / 6 | Cited 2.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 8 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 2 / 3 | Massachusetts General Hospital: institution h-index 2,057 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 17 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33430685) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 47 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 47 of the 96 points we could judge it on is 49 out of 100. |
| Total | 49 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Smith, R. X., Strain, J. F., Tanenbaum, A., Fagan, A. M., Hassenstab, J., McDade, E., et al. (2021). Resting-State Functional Connectivity Disruption as a Pathological Biomarker in Autosomal Dominant Alzheimer Disease. Brain connectivity. https://doi.org/10.1089/brain.2020.0808
Vancouver
Smith RX, Strain JF, Tanenbaum A, Fagan AM, Hassenstab J, McDade E, et al. Resting-State Functional Connectivity Disruption as a Pathological Biomarker in Autosomal Dominant Alzheimer Disease. Brain connectivity. 2021. doi:10.1089/brain.2020.0808. PMID: 33430685.
BibTeX
@article{smith2021-33430685,
author = {Smith, R. X. and Strain, J. F. and Tanenbaum, A. and Fagan, A. M. and Hassenstab, J. and McDade, E. and Schindler, S. E. and Gordon, B. A. and others},
title = {{Resting-State Functional Connectivity Disruption as a Pathological Biomarker in Autosomal Dominant Alzheimer Disease}},
journal = {Brain connectivity},
year = {2021},
doi = {10.1089/brain.2020.0808},
pmid = {33430685},
url = {https://doi.org/10.1089/brain.2020.0808}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 19.
Later studies that cite this one
1 study in the alzhub library lists this one in its references.