Evidence map›Paper›PMID 39051173›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024

Locus coeruleus integrity and neuropsychiatric symptoms in a cohort of early- and late-onset Alzheimer's disease.

Neus Falgàs, Marta Peña-González, Andrea Val-Guardiola, Agnès Pérez-Millan, Núria Guillén, Jordi Sarto, Diana Esteller, Beatriz Bosch, Guadalupe Fernández-Villullas, Adrià Tort-Merino and 10 more

Abstract read
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing 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

26 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Impact of early locus coeruleus lesions in the TgF344 Alzheimer's disease rat model.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  7. Review
  8. Neurotransmitter Systems in Alzheimer's Disease.Current issues in molecular biology · 2026
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. CTE neuropathology alone is associated with dementia and cognitive symptoms.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  15. Article
  16. Article
  17. Article
  18. Catecholaminergic nucleus integrity and Alzheimer's pathology, symptoms, and progression.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  19. Review
  20. 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

20 authors.

Neus FalgàsAlzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Barcelona, Catalonia, Spain.ORCID 0000-0002-3404-2765
Marta Peña-GonzálezMagnetic Resonance Imaging Core Facility, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
Andrea Val-GuardiolaAlzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Barcelona, Catalonia, Spain.
Agnès Pérez-MillanAlzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Barcelona, Catalonia, Spain.
Núria GuillénAlzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Barcelona, Catalonia, Spain.
Jordi SartoAlzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Barcelona, Catalonia, Spain.
Diana EstellerAlzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Barcelona, Catalonia, Spain.
Beatriz BoschAlzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Barcelona, Catalonia, Spain.
Guadalupe Fernández-VillullasAlzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Barcelona, Catalonia, Spain.
Adrià Tort-MerinoAlzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Barcelona, Catalonia, Spain.
Gerard MayàNeurology Service, Hospital Clínic de Barcelona, IDIBAPS, CIBERNED, Universitat de Barcelona, Barcelona, Spain.
Josep Maria AugéBiochemistry and Molecular Genetics Department-CDB, Hospital Clinic, IDIBAPS, CIBERehd, Barcelona, Spain.
Alex IranzoNeurology Service, Hospital Clínic de Barcelona, IDIBAPS, CIBERNED, Universitat de Barcelona, Barcelona, Spain.
Mircea BalasaAlzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Barcelona, Catalonia, Spain.
Albert LladóAlzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Barcelona, Catalonia, Spain.
Manuel Morales-RuizBiochemistry and Molecular Genetics Department-CDB, Hospital Clinic, IDIBAPS, CIBERehd, Barcelona, Spain.
Núria BargallóMagnetic Resonance Imaging Core Facility, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
Emma Muñoz-MorenoMagnetic Resonance Imaging Core Facility, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
Lea T GrinbergGlobal Brain Health Institute, University of California, San Francisco, California, USA.
Raquel Sánchez-ValleAlzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Barcelona, Catalonia, Spain.

Funding

Early Onset AD Consortium - the LEAD Study (LEADS)U01AG057195 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI APOSTOLOVA, LIANA G, CARRILLO, MARIA C · 2018 to 2023
$70.3M
Research Education ComponentP30AG062422 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Gil Dan Rabinovici · 2019 to 2026
$36.9M
Clinical Features and Neuropathological Basis of Sleep Wake Behavior in Alzheimer's and PSPR01AG060477 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Lea Tenenholz Grinberg, Thomas C Neylan · 2019 to 2026
$8.2M
Linking Sleep Dysfunction to Tau-related Degeneration across AD ProgressionR01AG064314 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRINBERG, LEA TENENHOLZ, NEYLAN, THOMAS C · 2019 to 2023
$4.0M
Neuropathological changes underlying clinical heterogeneity in Alzheimer diseaseK24AG053435 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRINBERG, LEA TENENHOLZ · 2016 to 2025
$1.8M
Alzheimer's Association AACSF_21_723056European Union, ISCIII AC21_2/00007Global Brain Health Institute, Alzheimer's Association, Alzheimer's Society UK GBHIALZUK-21-723831Instituto de Salud Carlos III (ISCIII) JR22/00014Instituto de Salud Carlos III (ISCIII) PI19/00198Instituto de Salud Carlos III (ISCIII) PI19/00449Instituto de Salud Carlos III (ISCIII) PI22/000343Instituto de Salud Carlos III (ISCIII) PI22/00343NIA NIH HHS K24 AG053435NIA NIH HHS P30 AG062422NIA NIH HHS R01 AG060477NIA NIH HHS R01 AG064314NIA NIH HHS U01 AG057195
6 · The paper itself

Abstract

introductionEarly-onset Alzheimer's disease (EOAD) shows a higher burden of neuropsychiatric symptoms than late-onset Alzheimer's disease (LOAD). We aim to determine the differences in the severity of neuropsychiatric symptoms and locus coeruleus (LC) integrity between EOAD and LOAD accounting for disease stage.

methodsOne hundred four subjects with AD diagnosis and 32 healthy controls were included. Participants underwent magnetic resonance imaging (MRI) to measure LC integrity, measures of noradrenaline levels in cerebrospinal fluid (CSF) and Neuropsychiatric Inventory (NPI). We analyzed LC-noradrenaline measurements and clinical and Alzheimer's disease (AD) biomarker associations.

resultsEOAD showed higher NPI scores, lower LC integrity, and similar levels of CSF noradrenaline compared to LOAD. Notably, EOAD exhibited lower LC integrity independently of disease stage. LC integrity negatively correlated with neuropsychiatric symptoms. Noradrenaline levels were increased in AD correlating with AD biomarkers. DISCUSSION: Decreased LC integrity negatively contributes to neuropsychiatric symptoms. The higher LC degeneration in EOAD compared to LOAD could explain the more severe neuropsychiatric symptoms in EOAD. HIGHLIGHTS: LC degeneration is greater in early-onset AD (EOAD) compared to late-onset AD. Tau-derived LC degeneration drives a higher severity of neuropsychiatric symptoms. EOAD harbors a more profound selective vulnerability of the LC system. LC degeneration is associated with an increase of cerebrospinal fluid noradrenaline levels in AD.

Indexed as

Alzheimer DiseaseBiomarkersLocus CoeruleusMagnetic Resonance ImagingNorepinephrineAgedAge of OnsetCohort StudiesFemaleHumansMaleMiddle AgedNeuropsychological TestsBiomarkersNorepinephrineAlzheimer's diseaseearly‐onset Alzheimer's diseaselocus coeruleusneuromodulatory subcortical systemsneuropsychiatric symptomsselective vulnerability

Identifiers

PMID39051173
PMCPMC11497680

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LicenceCC BY-NC-ND
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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.