Evidence map›Paper›PMID 41023472›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Catecholaminergic nucleus integrity and Alzheimer's pathology, symptoms, and progression.

Michael C B David, Magdalena A Kolanko, Thomas D Parker, Ramin Nilforooshan, Karl A Zimmerman, Cristina Bonet Olivares, Karen Hoang, Johanna Brandt, Charikleia Triantafyllou, Peter J Lally and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Attenuated pupillary response during visual search in preclinical Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  2. Review
  3. Catecholaminergic nucleus integrity and Alzheimer's pathology, symptoms, and progression.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    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

14 authors.

Michael C B DavidUK Dementia Research Institute Care Research and Technology Centre, Imperial College London, London, UK.
Magdalena A KolankoUK Dementia Research Institute Care Research and Technology Centre, Imperial College London, London, UK.
Thomas D ParkerUK Dementia Research Institute Care Research and Technology Centre, Imperial College London, London, UK.
Ramin NilforooshanUK Dementia Research Institute Care Research and Technology Centre, Imperial College London, London, UK.
Karl A ZimmermanUK Dementia Research Institute Care Research and Technology Centre, Imperial College London, London, UK.
Cristina Bonet OlivaresImperial College London, Brain Sciences, South Kensington, London, UK.
Karen HoangImperial College London, Brain Sciences, South Kensington, London, UK.
Johanna BrandtImperial College London, Brain Sciences, South Kensington, London, UK.
Charikleia TriantafyllouImperial College London, Brain Sciences, South Kensington, London, UK.
Peter J LallyUK Dementia Research Institute Care Research and Technology Centre, Imperial College London, London, UK.
Gregory ScottUK Dementia Research Institute Care Research and Technology Centre, Imperial College London, London, UK.
CR&T Group of UKDRIUK Dementia Research Institute Care Research and Technology Centre, Imperial College London, London, UK.
David J SharpUK Dementia Research Institute Care Research and Technology Centre, Imperial College London, London, UK.
Paresh A MalhotraUK Dementia Research Institute Care Research and Technology Centre, Imperial College London, London, UK.

Funding

Alzheimer's Research UKAlzheimer's Society 608 AS-CTF-22-013Dementias Platform UKLifeArcMedical Research Council MR/W016095/1National Institute for Health and Care Research NIHR302971National Institute for Health and Care Research (NIHR) Advanced Fellow NIHR302971NIHR Imperial Biomedical Research Centrethe UK DRI UKDRI-7202
6 · The paper itself

Abstract

backgroundThe noradrenergic locus coeruleus (LC) accumulates pathology early in Alzheimer's disease (AD), with LC dysfunction contributing to symptoms and disease progression. We investigated LC and substantia nigra (SN) integrity in healthy controls and AD participants.

methodsNinety-three AD participants and 29 controls underwent neuromelanin magnetic resonance imaging. LC and SN contrast, reflecting nucleus integrity, related to cognitive and neuropsychiatric symptoms, as well as cognitive decline and atrophy rates.

resultsLC - but not SN - integrity was reduced in AD versus controls (b = -0.39, p = 0.001) and within AD was associated with global cognition (b = 8.53, p = 0.04) and neuropsychiatric symptoms, accounting for SN. An AD subgroup with reduced SN integrity had worse cognition. LC integrity predicted plasma phosphorylated tau protein 217 (b = -0.30, p = 0.03). Lower LC and SN integrities were both related to faster cognitive decline (LC: b = -4.74, p = 0.048; SN: b = -2.27, p = 0.03), accounting for one another. DISCUSSION: Catecholaminergic nucleus integrity plays an important role in AD. Both systems are relevant to cognitive performance and decline. LC, in particular, relates closely to symptoms, pathology, and rate of progression. HIGHLIGHTS: In symptomatic AD, LC integrity reflects cortical AD pathology, measured by pTau217. LC integrity predicts cognitive function in AD, independent of cortical atrophy. LC and SN integrity independently relate to attentional performance. Symptoms of anxiety, depression, and apathy are associated with lower LC integrity. LC and SN relate to cognitive decline rate and left LC predicts atrophy rate.

Indexed as

Alzheimer DiseaseLocus CoeruleusSubstantia NigraAgedAged, 80 and overAtrophyCognitive DysfunctionDisease ProgressionFemaleHumansMagnetic Resonance ImagingMaleMelaninsNeuropsychological Teststau ProteinsMelaninsneuromelanintau Proteinscatecholaminescognitiondisease progressiondopaminelocus coeruleusneuromelaninneuropsychiatric symptomsnoradrenalinenorepinephrinesubstantia nigra

Identifiers

PMID41023472
PMCPMC12479218

What Socratic holds

Textmetadata
LicenceCC BY
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.