Evidence map›Paper›PMID 41891380›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026

Spatially and temporally progressive hypoperfusion in Alzheimer's disease revealed by normative modeling.

Xinglin Zeng, Yiran Li, Lin Hua, Ruoxi Lu, Lucas Lemos Franco, Peter Kochunov, Shuo Chen, John A Detre, Ze Wang, Alzheimer's Disease Neuroimaging Initiative

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Spatially and temporally progressive hypoperfusion in Alzheimer's disease revealed by normative modeling.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  2. 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.

Xinglin ZengDepartment of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Yiran LiDepartment of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Lin HuaDepartment of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Ruoxi LuDepartment of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Lucas Lemos FrancoDepartment of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Peter KochunovDepartment of Psychiatry and Behavioral Science, University of Texas Health Science, San Antonio, Texas, USA.
Shuo ChenMaryland Psychitric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA.
John A DetreDepartments of Neurology and Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Ze WangDepartment of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0002-8339-5567
Alzheimer's Disease Neuroimaging Initiative

Funding

QAQC Johns Hopkins Institute for Clinical and Translational ResearchUL1TR003098 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2019 to 2023
$57.7M
Academic Industrial Partnership on Advanced Perfusion MRIR01EB031080 · NIBIB · UNIVERSITY OF PENNSYLVANIA · PI Yulin V Chang, JOHN A DETRE · 2022 to 2026
$2.7M
Diversity Supplement to Brain entropy mapping in Alzheimer's DiseaseR01AG070227 · NIA · UNIVERSITY OF MARYLAND BALTIMORE · PI WANG, ZE · 2021 to 2024
$2.5M
Deep-Learning Enhanced ASL MRI For Early AD AssessmentR01AG081693 · NIA · UNIVERSITY OF MARYLAND BALTIMORE · PI Ze Wang · 2024 to 2026
$2.3M
Automated Quality Evaluation and Harmonization for Multisite ASL MRI DataR33AG080518 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Sudipto Dolui, Ze Wang · 2025 to 2026
$1.5M
Automated Quality Evaluation and Harmonization for Multisite ASL MRI DataR21AG080518 · NIA · UNIVERSITY OF PENNSYLVANIA · PI DOLUI, SUDIPTO, WANG, ZE · 2023 to 2024
$453k
Institute for Clinical and Translational Research, University of Maryland, Baltimore 1UL1TR003098NCATS NIH HHS UL1 TR003098NIA NIH HHS R01 AG070227NIA NIH HHS R01AG070227NIA NIH HHS R01 AG081693NIA NIH HHS R01AG081693NIA NIH HHS R21 AG080518NIA NIH HHS R33 AG080518NIA NIH HHS R33AG080518NIBIB NIH HHS R01 EB031080the University of Maryland Baltimore
6 · The paper itself

Abstract

introductionCerebral perfusion is implicated in Alzheimer's disease (AD), but its development in AD and mild cognitive impairment (MCI) is not well characterized.

methodsWe constructed a normative model using > 12,000 arterial spin labeling MRI scans and applied generalized additive models for location, scale, and shape (GAMLSS). Individual deviation z scores were derived by normative model, and outlier regions (z ≤ 2.3) were quantified as the total negative proportion (TNP) of extreme hypoperfusion. These metrics were then related to other AD biomarkers through linear modeling.

resultsCompared to cognitively normal controls, AD showed higher TNP and greater longitudinal increases (p = 0.003), indicating progressive hypoperfusion. Progressive MCI exhibited greater perfusion decline than stable MCI (p = 0.01). Perfusion changes correlated with cognition, brain volume, amyloid, and apolipoprotein E status (all p < 0.05). DISCUSSION: Normative modeling revealed inter-individual heterogeneity in cerebral perfusion trajectories, underscoring its potential relevance for AD development.

Indexed as

Alzheimer DiseaseBrainCerebrovascular CirculationCognitive DysfunctionAgedAged, 80 and overDisease ProgressionFemaleHumansLongitudinal StudiesMagnetic Resonance ImagingMalePerfusion Magnetic Resonance ImagingSpin LabelsSpin LabelsAlzheimer's diseasearterial spin labelingcerebral perfusionlongitudinal studymild cognitive impairmentneuroimagingnormative model

Identifiers

PMID41891380
PMCPMC13093283

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.