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56/100

✓ Peer-reviewed alzhub usefulness score 56 out of 100. Long-term cohort studies

Topic: Brain proteins, microglia and lab models

Plain-language summary

Background Cysteine-altering NOTCH3 variants identical to those causing the rare monogenic form of stroke, CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), have been reported more common than expected in the general population, but their clinical significance and contribution to stroke and dementia risk in the community remain unclear. Methods Cysteine-altering NOTCH3 variants were identified in UK Biobank whole-exome sequencing data (N=200 632). Frequency of stroke, vascular dementia and other clinical features of CADASIL, and MRI white matter hyperintensity volume were compared between variant carriers and non-carriers.

What this study adds

Evidence grade: Low

The record lists 200 participants. In UK Biobank whole-exome data from 200,632 people, cysteine-altering NOTCH3 variants were found in about 1 in 450 participants, more common than expected. Reported effect size: OR: 2.33; OR: 5.00.

Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.

Cite this study APA, Vancouver, BibTeX · download .bib or .ris

APA 7th

Cho, B. P. H., Nannoni, S., Harshfield, E. L., Tozer, D., Gräf, S., Bell, S., et al. (2021). NOTCH3 variants are more common than expected in the general population and associated with stroke and vascular dementia: an analysis of 200 000 participants. Journal of neurology, neurosurgery, and psychiatry. https://doi.org/10.1136/jnnp-2020-325838

Vancouver

Cho BPH, Nannoni S, Harshfield EL, Tozer D, Gräf S, Bell S, et al. NOTCH3 variants are more common than expected in the general population and associated with stroke and vascular dementia: an analysis of 200 000 participants. Journal of neurology, neurosurgery, and psychiatry. 2021. doi:10.1136/jnnp-2020-325838. PMID: 33712516.

BibTeX

@article{cho2021-33712516,
  author  = {Cho, B. P. H. and Nannoni, S. and Harshfield, E. L. and Tozer, D. and Gräf, S. and Bell, S. and Markus, H. S.},
  title   = {{NOTCH3 variants are more common than expected in the general population and associated with stroke and vascular dementia: an analysis of 200 000 participants}},
  journal = {Journal of neurology, neurosurgery, and psychiatry},
  year    = {2021},
  doi     = {10.1136/jnnp-2020-325838},
  pmid    = {33712516},
  url     = {https://doi.org/10.1136/jnnp-2020-325838}
}

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.

How to read this study

Design: our record does not state a study design, so check the methods section of the original before weighing the result.
Size: the record lists 200 participants. Ask whether that is enough for the question, and who they were.
Effect: the record reports “OR: 2.33; OR: 5.00”. A statistically significant result can still be small in daily life.

What the evidence grade means here

This page is graded low. alzhub.org assigns the grade automatically from keywords in the abstract, not from reading the paper. Low means the abstract matched neither pattern. It is the default label, and it does not mean the work is poor; many sound lab and imaging papers land here. It can add at most 5 of the 100 points in the study score, and it is a label about design, not a verdict on whether the findings are true.

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Key findings

Methods Cysteine-altering NOTCH3 variants were identified in UK Biobank whole-exome sequencing data (N=200 632).
Frequency of stroke, vascular dementia and other clinical features of CADASIL, and MRI white matter hyperintensity volume were compared between variant carriers and non-carriers.
MRIs from those with variants were visually rated, each matched with three controls.
Results Of 200 632 participants with exome sequencing data available, 443 (~1 in 450) carried 67 different cysteine-altering NOTCH3 variants.

Why it matters

In UK Biobank whole-exome data from 200,632 people, cysteine-altering NOTCH3 variants were found in about 1 in 450 participants, more common than expected. Carriers had higher frequencies of stroke and vascular dementia compared with non-carriers, indicating these variants may contribute to these conditions in the general population.

Study details

Participants200
Effect sizeOR: 2.33; OR: 5.00
Evidence strengthLow

How this study scored 56/100

Published in a peer-reviewed journal. Scored zero for study design and randomized / blinded because the record does not state it.

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (Journal of neurology, neurosurgery, and psychiatry)
Journal's citation record	3 / 4	Journal of Neurology Neurosurgery & Psychiatry: journal h-index 336 (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	3 / 5	2021 — within 6 year(s) of the newest study here
Sample size	2 / 4	200 participants
Effect reported	3 / 3	Effect reported with a statistic (interval, p-value, ratio or similar)
Studied in people	3 / 3	Studied in people (participant count stated)
Randomized / blinded	0 / 2	No randomization or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	4 / 7	Cited 75 times (OpenAlex, 2026-10-10)
Citations per year	3 / 5	10.7 citations a year over 7 year(s) since 2021
Impact for its field and year	3 / 6	Cited 5.7× 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 38 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	4 / 4	Last-listed author Hugh Stephen Markus: h-index 137 (OpenAlex, whole career)
Institution's track record	2 / 3	University of Cambridge: institution h-index 1,973 (OpenAlex)
Multicenter 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 33712516)
Free to read	2 / 2	Free to read
Total	56 / 100	—

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