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Cerebrospinal fluid dynamics disorders: Relationship to Alzheimer biomarkers and cognition
Graff-Radford J, Gunter JL, Jones DT, Przybelski SA, Schwarz CG, Huston J, Lowe V, Elder BD et al.. Neurology, 2019-11-12
Topic: Amyloid, tau and blood-test diagnosis
Objective To determine the frequency of high-convexity tight sulci (HCTS) in a population-based sample and whether the presence of HCTS and related features influenced participants' cognitive status and classification within the new Alzheimer-biomarker framework. Methods We analyzed 684 participants ≥50 years of age who were enrolled in the prospective population-based Mayo Clinic Study of Aging and underwent structural MRI, amyloid PET imaging, and tau PET imaging. A fully automated machine-learning algorithm that had been developed previously in house was used to detect neuroimaging features of HCTS. On the basis of PET and MRI measures, participants were classified as having normal (A - ) or abnormal (A + ) amyloid, normal (T - ) or abnormal (T + ) tau, and normal (N - ) or abnormal (N + ) neurodegeneration. The neuropsychological battery assessed domain-specific and global cognitive scores. Gait speed also was assessed. Analyses were adjusted for age and sex. Results Of 684 participants, 45 (6.6%) were classified with HCTS according to the automated algorithm. Patients with HCTS were older than patients without HCTS (mean [SD] 78.0 [8.3] vs 71.9 [10.8] years; p p = 0.005). Amyloid PET status was similar with and without HCTS, but tau PET standard uptake value ratio (SUVR) was lower for those with HCTS after age and sex adjustment ( p - (N) + group, regardless of amyloid status. Conclusion The HCTS pattern represents a definable subgroup of non-AD pathophysiology (i.e., T - [N] + ) that is associated with cognitive impairment. HCTS may confound clinical and biomarker interpretation in AD clinical trials.
Key findings
- Results Of 684 participants, 45 (6.6%) were classified with HCTS according to the automated algorithm.
- Conclusion The HCTS pattern represents a definable subgroup of non-AD pathophysiology (i.e., T - [N] + ) that is associated with cognitive impairment.
Why it matters
In 684 participants from a population-based study, 6.6% had a pattern of high-convexity tight sulci, which was associated with cognitive impairment and classified as a non-Alzheimer's pattern of neurodegeneration. This describes a subgroup of non-Alzheimer pathophysiology and does not test any treatment.
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Study details
- Participants684
- Effect size6.6%
- Evidence strengthLow
How this study scored 53/100
Published in a leading specialty journal. Scored zero for study design and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (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 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 684 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | 3.9 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 2 / 6 | Cited 2.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 2 / 4 | Cited 15 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Clifford R. Jack: h-index 203 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Mayo Clinic: institution h-index 1,606 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31719134) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 53 / 100 | — |
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Read the original
- DOI: 10.1212/wnl.0000000000008616
- PubMed: 31719134
- 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'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
Graff-Radford, J., Gunter, J. L., Jones, D. T., Przybelski, S. A., Schwarz, C. G., Huston, J., et al. (2019). Cerebrospinal fluid dynamics disorders: Relationship to Alzheimer biomarkers and cognition. Neurology. https://doi.org/10.1212/wnl.0000000000008616
Vancouver
Graff-Radford J, Gunter JL, Jones DT, Przybelski SA, Schwarz CG, Huston J, et al. Cerebrospinal fluid dynamics disorders: Relationship to Alzheimer biomarkers and cognition. Neurology. 2019. doi:10.1212/wnl.0000000000008616. PMID: 31719134.
BibTeX
@article{graffradford2019-31719134,
author = {Graff-Radford, J. and Gunter, J. L. and Jones, D. T. and Przybelski, S. A. and Schwarz, C. G. and Huston, J. and Lowe, V. and Elder, B. D. and others},
title = {{Cerebrospinal fluid dynamics disorders: Relationship to Alzheimer biomarkers and cognition}},
journal = {Neurology},
year = {2019},
doi = {10.1212/wnl.0000000000008616},
pmid = {31719134},
url = {https://doi.org/10.1212/wnl.0000000000008616}
}
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