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Evaluating resting-state BOLD variability in relation to biomarkers of preclinical Alzheimer's disease
Millar PR, Ances BM, Gordon BA, Benzinger TLS, Fagan AM, Morris JC, Balota DA.. Neurobiology of aging, 2020-08-18
Topic: Amyloid, tau and blood-test diagnosis
Recent functional magnetic resonance imaging studies have demonstrated that moment-to-moment variability in the blood oxygen level-dependent (BOLD) signal is related to age differences, cognition, and symptomatic Alzheimer's disease (AD). However, no studies have examined BOLD variability in the context of preclinical AD. We tested relationships between resting-state BOLD variability and biomarkers of amyloidosis, tauopathy, and neurodegeneration in a large (N = 321), well-characterized sample of cognitively normal adults (age = 39-93), using multivariate machine learning techniques. Furthermore, we controlled for cardiovascular health factors, which may contaminate resting-state BOLD variability estimates. BOLD variability, particularly in the default mode network, was related to cerebrospinal fluid (CSF) amyloid-β42 but was not related to CSF phosphorylated tau-181. Furthermore, BOLD variability estimates were also related to markers of neurodegeneration, including CSF neurofilament light protein, hippocampal volume, and a cortical thickness composite. Notably, relationships with hippocampal volume and cortical thickness survived correction for cardiovascular health and also contributed to age-related differences in BOLD variability. Thus, BOLD variability may be sensitive to preclinical pathology, including amyloidosis and neurodegeneration in AD-sensitive areas.
Key findings
- Recent functional magnetic resonance imaging studies have demonstrated that moment-to-moment variability in the blood oxygen level-dependent (BOLD) signal is related to age differences, cognition, and symptomatic Alzheimer's disease (AD).
Why it matters
In 321 cognitively normal adults, resting-state BOLD variability, especially in the default mode network, was related to spinal fluid amyloid-β42 and to markers of neurodegeneration, but not to phosphorylated tau-181. This suggests a possible marker of preclinical change, not a treatment, cure or prevention.
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Study details
- Participants321
- Evidence strengthLow
How this study scored 44/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurobiology of aging) |
| Journal's citation record | 3 / 4 | Neurobiology of Aging: journal h-index 263 (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 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 321 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 35 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.4 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 3 / 6 | Cited 3.4× 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 | 1 / 4 | Cited 14 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author David A. Balota: h-index 90 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33039901) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 44 / 100 | — |
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Read the original
- DOI: 10.1016/j.neurobiolaging.2020.08.007
- PubMed: 33039901
- Original source →
- Free full text: PubMed Central →
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 names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Millar, P. R., Ances, B. M., Gordon, B. A., Benzinger, T. L. S., Fagan, A. M., Morris, J. C., et al. (2020). Evaluating resting-state BOLD variability in relation to biomarkers of preclinical Alzheimer's disease. Neurobiology of aging. https://doi.org/10.1016/j.neurobiolaging.2020.08.007
Vancouver
Millar PR, Ances BM, Gordon BA, Benzinger TLS, Fagan AM, Morris JC, et al. Evaluating resting-state BOLD variability in relation to biomarkers of preclinical Alzheimer's disease. Neurobiology of aging. 2020. doi:10.1016/j.neurobiolaging.2020.08.007. PMID: 33039901.
BibTeX
@article{millar2020-33039901,
author = {Millar, P. R. and Ances, B. M. and Gordon, B. A. and Benzinger, T. L. S. and Fagan, A. M. and Morris, J. C. and Balota, D. A.},
title = {{Evaluating resting-state BOLD variability in relation to biomarkers of preclinical Alzheimer's disease}},
journal = {Neurobiology of aging},
year = {2020},
doi = {10.1016/j.neurobiolaging.2020.08.007},
pmid = {33039901},
url = {https://doi.org/10.1016/j.neurobiolaging.2020.08.007}
}
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