Evidence map›Paper›PMID 34116150›Full record

ArticleNeuroImage2021

T2 heterogeneity as an in vivo marker of microstructural integrity in medial temporal lobe subfields in ageing and mild cognitive impairment.

Alfie R Wearn, Volkan Nurdal, Esther Saunders-Jennings, Michael J Knight, Christopher R Madan, Sean-James Fallon, Hanna K Isotalus, Risto A Kauppinen, Elizabeth J Coulthard

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NeuroImage, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
0.4field-weighted citation impact, top 46% of its field
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

5 citing papers in PubMed, 1 synthesis or guideline pooled it, 6 citations in OpenAlex.

  1. Pooled it
  2. Longitudinal MRI Characterization of TNMR in biomedicine · 2026
    Article
  3. Quantitative MRI of the hippocampus reveals microstructural trajectories of aging and Alzheimer's disease pathology.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  4. Review
  5. 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

9 authors at 4 institutions in 1 country.

Alfie R WearnBristol Medical School, University of Bristol, Institute of Clinical Neurosciences, Learning & Research Building at Southmead Hospital, Bristol BS10 5NB, UK. Electronic address: Alfie.wearn@bristol.ac.uk.
Volkan NurdalBristol Medical School, University of Bristol, Institute of Clinical Neurosciences, Learning & Research Building at Southmead Hospital, Bristol BS10 5NB, UK.
Esther Saunders-JenningsBristol Medical School, University of Bristol, Institute of Clinical Neurosciences, Learning & Research Building at Southmead Hospital, Bristol BS10 5NB, UK.
Michael J KnightSchool of Psychological Science, University of Bristol, Bristol, UK.
Christopher R MadanSchool of Psychology, University of Nottingham, Nottingham, UK.
Sean-James FallonNational Institute for Health Research Bristol Biomedical Research Centre, University Hospitals Bristol, NHS Foundation Trust and University of Bristol, Bristol, UK.
Hanna K IsotalusBristol Medical School, University of Bristol, Institute of Clinical Neurosciences, Learning & Research Building at Southmead Hospital, Bristol BS10 5NB, UK.
Risto A KauppinenFaculty of Engineering, University of Bristol, Bristol, UK.
Elizabeth J CoulthardBristol Medical School, University of Bristol, Institute of Clinical Neurosciences, Learning & Research Building at Southmead Hospital, Bristol BS10 5NB, UK; Clinical Neurosciences, North Bristol NHS Trust, Bristol, UK.
Southmead Hospital · GBUniversity of Bristol · GBNational Institute for Health Research · GBUniversity of Nottingham · GB

Funding

Wellcome Trust 109067/Z/15/AI
6 · The paper itself

Abstract

A better understanding of early brain changes that precede loss of independence in diseases like Alzheimer's disease (AD) is critical for development of disease-modifying therapies. Quantitative MRI, such as T2 relaxometry, can identify microstructural changes relevant to early stages of pathology. Recent evidence suggests heterogeneity of T2 may be a more informative MRI measure of early pathology than absolute T2. Here we test whether T2 markers of brain integrity precede the volume changes we know are present in established AD and whether such changes are most marked in medial temporal lobe (MTL) subfields known to be most affected early in AD. We show that T2 heterogeneity was greater in people with mild cognitive impairment (MCI; n = 49) compared to healthy older controls (n = 99) in all MTL subfields, but this increase was greatest in MTL cortices, and smallest in dentate gyrus. This reflects the spatio-temporal progression of neurodegeneration in AD. T2 heterogeneity in CA1-3 and entorhinal cortex and volume of entorhinal cortex showed some ability to predict cognitive decline, where absolute T2 could not, however further studies are required to verify this result. Increases in T2 heterogeneity in MTL cortices may reflect localised pathological change and may present as one of the earliest detectible brain changes prior to atrophy. Finally, we describe a mechanism by which memory, as measured by accuracy and reaction time on a paired associate learning task, deteriorates with age. Age-related memory deficits were explained in part by lower subfield volumes, which in turn were directly associated with greater T2 heterogeneity. We propose that tissue with high T2 heterogeneity represents extant tissue at risk of permanent damage but with the potential for therapeutic rescue. This has implications for early detection of neurodegenerative diseases and the study of brain-behaviour relationships.

Indexed as

AgingAgedAged, 80 and overAlzheimer DiseaseCognitionCognitive DysfunctionEarly DiagnosisFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedNeuropsychological TestsTemporal LobeAgeingAlzheimer's diseaseEarly diagnosisHippocampal subfieldsMagnetic resonance imagingMedial temporal lobeT2 heterogeneityT2 relaxometry

Identifiers

PMID34116150
PMCPMC8350145
OpenAlexW3168545690

What OpenQuestion 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 OpenQuestion graph.