Evidence map›Paper›PMID 38703035›Full record

ArticleInternational journal of stroke : official journal of the International Stroke Society2024

Sex differences in histopathological markers of cerebral amyloid angiopathy and related hemorrhage.

Emma A Koemans, Valentina Perosa, Whitney M Freeze, Hang Lee, Mariel G Kozberg, Gillian T Coughlan, Rachel F Buckley, Marieke Jh Wermer, Steven M Greenberg, Susanne J van Veluw

Abstract read
In one paragraph

Article in International journal of stroke : official journal of the International Stroke Society, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Exploring the origins of frequent tau-PET signal in vermal and adjacent regions.European journal of nuclear medicine and molecular imaging · 2025
    Article
  6. Review
  7. Vascular cognitive impairment and dementia: Mechanisms, treatment, and future directions.International journal of stroke : official journal of the International Stroke Society · 2024
    Review
  8. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Emma A KoemansDepartment of Neurology, Leiden University Medical Center, Leiden, The Netherlands.ORCID 0000-0003-0560-8077
Valentina PerosaDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-3551-5237
Whitney M FreezeDepartment of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
Hang LeeDepartment of Biostatistics, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Mariel G KozbergDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-9358-3262
Gillian T CoughlanDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Rachel F BuckleyDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Marieke Jh WermerDepartment of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
Steven M GreenbergDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Susanne J van VeluwDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Funding

University of Washington Alzheimer's Disease Research CenterP30AG066509 · NIA · UNIVERSITY OF WASHINGTON · PI Thomas J. Grabowski · 2020 to 2026
$29.0M
Building predictive algorithms to identify resilience and resistance to Alzheimer's diseaseR01AG079142 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Rachel Frances Buckley, Michael C Donohue · 2023 to 2026
$4.0M
The inactive X: discovering sex genes that influence female vulnerability to Alzheimer's diseaseDP2AG082342 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Rachel Frances Buckley · 2022 to 2026
$2.5M
Sex differences in the progression of Alzheimer's disease: is menopause the key?R00AG061238 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI BUCKLEY, RACHEL FRANCES · 2021 to 2023
$747k
Unraveling the mechanisms of microhemorrhages in cerebral amyloid angiopathyR00AG059893 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI VAN VELUW, SUSANNE JANNEKE · 2020 to 2022
$745k
NIA NIH HHS DP2 AG082342NIA NIH HHS P30 AG066509NIA NIH HHS R00 AG059893NIA NIH HHS R00 AG061238NIA NIH HHS R01 AG079142
6 · The paper itself

Abstract

backgroundMen with cerebral amyloid angiopathy (CAA) may have an earlier onset of intracerebral hemorrhage and a more hemorrhagic disease course compared to women. In this cohort study, we investigated sex differences in histopathological markers associated with amyloid-β burden and hemorrhage in cognitively impaired individuals and patients with CAA, using neuropathological data from two autopsy databases.

methodsFirst, we investigated presence of parenchymal (Thal score) and vascular amyloid-β (CAA severity score) in cognitively impaired individuals from the National Alzheimer's Coordinating Center (NACC) neuropathology database. Next, we examined sex differences in hemorrhagic ex vivo magnetic resonance imaging (MRI) markers and local cortical iron burden and the interaction of sex on factors associated with cortical iron burden (CAA percentage area and vessel remodeling) in patients with pathologically confirmed clinical CAA from the Massachusetts General Hospital (MGH) CAA neuropathology database.

resultsIn 6120 individuals from the NACC database (45% women, mean age 80 years), the presence of parenchymal amyloid-β (odds ratio (OR) (95% confidence interval (CI)) =0.68 (0.53-0.88)) but not vascular amyloid-β was less in men compared to women. In 19 patients with definite CAA from the MGH CAA database (35% women, mean age 75 years), a lower microbleed count (p < 0.001) but a higher proportion of cortical superficial siderosis and a higher local cortical iron burden was found in men (p < 0.001) compared to women. CAA percentage area was comparable in men and women (p = 0.732). Exploratory analyses demonstrated a possible stronger negative relation between cortical CAA percentage area and cortical iron density in men compared to women (p = 0.03).

conclusionPreviously observed sex differences in hemorrhage onset and progression in CAA patients are likely not due to differences in global CAA severity between men and women. Other factors, such as vascular remodeling, may contribute, but future studies are necessary to replicate our findings in larger data sets and to further investigate the underlying mechanisms behind these complex sex differences.

Indexed as

Amyloid beta-PeptidesCerebral Amyloid AngiopathyCerebral HemorrhageMagnetic Resonance ImagingSex CharacteristicsAgedAged, 80 and overBiomarkersBrainCognitive DysfunctionCohort StudiesFemaleHumansIronMaleSex FactorsAmyloid beta-PeptidesBiomarkersIronamyloidCerebral amyloid angiopathyhistopathologyintracerebral hemorrhageMRIsexvascular remodeling

Identifiers

PMID38703035
PMCPMC11408965

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.