Evidence map›Paper›PMID 40220152›Full record

ArticleGeroScience2025

Cerebral hypoperfusion, brain structural integrity, and cognitive impairment in older APOE4 carriers.

Ioannis Pappas, Trevor Lohman, Shubir Dutt, Arunima Kapoor, Allison C Engstrom, John Paul M Alitin, Samuel Barnes, Ararat Chakhoyan, Lucas Saca, Raghav Gaggar and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in GeroScience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
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

21 authors.

Ioannis PappasLaboratory of Neuro Imaging, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Trevor LohmanLeonard Davis School of Gerontology, University of Southern California, Andrus Gerontology Center, 3715 McClintock Ave, Los Angeles, CA, 90089, USA.
Shubir DuttMemory and Aging Center, University of California San Francisco, San Francisco, CA, USA.
Arunima KapoorDepartment of Psychological Science, University of California, Irvine, Irvine, CA, USA.
Allison C EngstromDepartment of Psychological Science, University of California, Irvine, Irvine, CA, USA.
John Paul M AlitinLeonard Davis School of Gerontology, University of Southern California, Andrus Gerontology Center, 3715 McClintock Ave, Los Angeles, CA, 90089, USA.
Samuel BarnesDepartment of Radiology, Loma Linda University, Loma Linda, CA, USA.
Ararat ChakhoyanDepartment of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Lucas SacaDepartment of Radiology, Loma Linda University, Loma Linda, CA, USA.
Raghav GaggarDepartment of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Elnaz NourollahimoghadamDepartment of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Danny J J WangLaboratory of Neuro Imaging, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Mark H C LaiDeparment of Psychology, Dana and David Dornsife College of Arts and Letters, University of Southern California, Los Angeles, CA, USA.
Elizabeth B JoeAlzheimer's Disease Research Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
John M RingmanAlzheimer's Disease Research Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Hussein N YassineAlzheimer's Disease Research Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Lon S SchneiderAlzheimer's Disease Research Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Helena C ChuiAlzheimer's Disease Research Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Arthur W TogaLaboratory of Neuro Imaging, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Berislav V ZlokovicDepartment of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Daniel A NationLeonard Davis School of Gerontology, University of Southern California, Andrus Gerontology Center, 3715 McClintock Ave, Los Angeles, CA, 90089, USA. danation@usc.edu.ORCID 0000-0002-9123-0658

Funding

Vascular Contributions to Dementia and Genetic Risk Factors for Alzheimer's DiseaseP01AG052350 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Daniel A Nation, ARTHUR W TOGA · 2016 to 2026
$28.4M
USCADRC Diversity Supplement PachicanoP30AG066530 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HELENA Chang CHUI, ARTHUR W TOGA · 2020 to 2026
$27.8M
Locus Coeruleus Imaging Markers in Preclinical Alzheimers disease, Cerebrovascular Disease and Cognitive DeclineR01AG082073 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BONDI, MARK W, MATHER, MARA · 2023 to 2025
$4.9M
Endothelial progenitor cells and neurovascular injury in the aging brainR01AG064228 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Daniel A Nation · 2019 to 2026
$4.5M
Cerebrovascular resistance in cognitive aging and Alzheimer's disease riskR01AG060049 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI NATION, DANIEL A · 2020 to 2023
$2.4M
Canadian Institute for Military and Veteran Health Research DFD-170763Foundation for the National Institutes of Health P01AG052350Foundation for the National Institutes of Health P30AG066530Foundation for the National Institutes of Health R01Ag060049Foundation for the National Institutes of Health R01AG064228Foundation for the National Institutes of Health R01AG082073NIA NIH HHS P01 AG052350NIA NIH HHS P30 AG066530NIA NIH HHS R01 AG060049NIA NIH HHS R01 AG064228NIA NIH HHS R01 AG082073
6 · The paper itself

Abstract

Cerebral blood flow (CBF) deficits, cognitive decline, and brain structural changes have been reported in older adults with and without apolipoprotein E-e4 (APOE4)-related risk for dementia. However, it remains unclear whether brain structural changes mediate the effects of hypoperfusion on cognitive impairment in APOE4 carriers and non-carriers. We studied 166 (60-89 years) APOE4 carriers (ε3/ε4 or ε4/ε4) and APOE3 homozygotes (e3/e3) with and without cognitive impairment by clinical dementia rating (CDR) and neuropsychological testing. Pseudocontinuous arterial spin-labeling-MRI assessed regional CBF, and T1-anatomical and diffusion-MRI assessed structural integrity. Mediation analyses examined relationships among grey matter CBF, grey matter volume, and white matter integrity in regions underlying impairment in distinct cognitive ability domains. APOE4 carriers with global/memory impairment (CDR 0.5) exhibited decreased CBF in the posterior cingulate, decreased grey matter volume in the hippocampus, parahippocampal gyrus, and posterior cingulate, and decreased white matter integrity in the cingulum relative to APOE4 carriers with no impairment (CDR 0). Mediation analysis in APOE4 carriers indicated decreased posterior cingulate CBF effects on global/memory impairment were mediated by decreased cingulum integrity. In the combined APOE4 and APOE3 carriers sample, there were direct effects of frontal and inferior parietal CBF and superior longitudinal fasciculus integrity on attention/executive impairment. There were also direct effects of left inferior frontal CBF on language impairment. Findings suggest links between hypoperfusion and brain structural integrity underlying global/memory impairment in APOE4 carriers. Independent CBF relationships with structural integrity are also identified across genotypes and impairment domains.

Indexed as

Apolipoprotein E4BrainCerebrovascular CirculationCognitive DysfunctionAgedAged, 80 and overFemaleGray MatterHeterozygoteHumansMagnetic Resonance ImagingMaleMiddle AgedNeuropsychological TestsWhite MatterApolipoprotein E4Apolipoprotein EBrain atrophyCerebral blood flowWhite matter integrity

Identifiers

PMID40220152
PMCPMC12181599

What OpenQuestion holds

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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.