Evidence map›Paper›PMID 36102775›Full record

ArticleThe lancet. Healthy longevity2022

Life course, genetic, and neuropathological associations with brain age in the 1946 British Birth Cohort: a population-based study.

Aaron Z Wagen, William Coath, Ashvini Keshavan, Sarah-Naomi James, Thomas D Parker, Christopher A Lane, Sarah M Buchanan, Sarah E Keuss, Mathew Storey, Kirsty Lu and 21 more

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

Article in The lancet. Healthy longevity, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
17.9field-weighted citation impact, top 1% 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

25 citing papers in PubMed, 49 citations in OpenAlex.

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  5. Unveiling the glymphatic system's role in brain aging: A comprehensive biomarker and modifiable intervention target.Proceedings of the National Academy of Sciences of the United States of America · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

31 authors at 8 institutions in 3 countries.

Aaron Z WagenDementia Research Centre, University College London Queen Square Institute of Neurology, London, UK; Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London, UK; Neurodegeneration Biology Laboratory, The Francis Crick Institute, London, UK.
William CoathDementia Research Centre, University College London Queen Square Institute of Neurology, London, UK.
Ashvini KeshavanDementia Research Centre, University College London Queen Square Institute of Neurology, London, UK.
Sarah-Naomi JamesMedical Research Council Unit for Lifelong Health and Ageing, University College London, London, UK.
Thomas D ParkerDementia Research Centre, University College London Queen Square Institute of Neurology, London, UK; Department of Brain Sciences, Imperial College London, London, UK; UK Dementia Research Institute Centre for Care Research and Technology, Imperial College London, London, UK.
Christopher A LaneDementia Research Centre, University College London Queen Square Institute of Neurology, London, UK.
Sarah M BuchananDementia Research Centre, University College London Queen Square Institute of Neurology, London, UK.
Sarah E KeussDementia Research Centre, University College London Queen Square Institute of Neurology, London, UK.
Mathew StoreyDementia Research Centre, University College London Queen Square Institute of Neurology, London, UK.
Kirsty LuDementia Research Centre, University College London Queen Square Institute of Neurology, London, UK.
Amy MacdougallDementia Research Centre, University College London Queen Square Institute of Neurology, London, UK; Department of Medical Statistics, London School of Hygiene & Tropical Medicine, London, UK.
Heidi Murray-SmithDementia Research Centre, University College London Queen Square Institute of Neurology, London, UK.
Tamar FreibergerDementia Research Centre, University College London Queen Square Institute of Neurology, London, UK.
David M CashDementia Research Centre, University College London Queen Square Institute of Neurology, London, UK; Dementia Research Institute, University College London Queen Square Institute of Neurology, London, UK.
Ian B MaloneDementia Research Centre, University College London Queen Square Institute of Neurology, London, UK.
Josephine BarnesDementia Research Centre, University College London Queen Square Institute of Neurology, London, UK.
Carole H SudreMedical Research Council Unit for Lifelong Health and Ageing, University College London, London, UK; Department of Computer Science, Centre for Medical Imaging Computing, University College London, London, UK; School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK.
Andrew WongMedical Research Council Unit for Lifelong Health and Ageing, University College London, London, UK.
Ivanna M PavisicDementia Research Centre, University College London Queen Square Institute of Neurology, London, UK.
Rebecca StreetDementia Research Centre, University College London Queen Square Institute of Neurology, London, UK.
Sebastian J CrutchDementia Research Centre, University College London Queen Square Institute of Neurology, London, UK.
Valentina Escott-PriceDivision of Neuroscience and Mental Health, Cardiff University, Cardiff, UK.
Ganna LeonenkoDementia Research Institute, Cardiff University, Cardiff, UK.
Henrik ZetterbergDementia Research Institute, University College London Queen Square Institute of Neurology, London, UK; Department of Neurodegenerative Disease, University College London Queen Square Institute of Neurology, London, UK; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
Henrietta WellingtonDementia Research Institute, University College London Queen Square Institute of Neurology, London, UK; Department of Neurodegenerative Disease, University College London Queen Square Institute of Neurology, London, UK.
Amanda HeslegraveDementia Research Institute, University College London Queen Square Institute of Neurology, London, UK; Department of Neurodegenerative Disease, University College London Queen Square Institute of Neurology, London, UK.
Frederik BarkhofDementia Research Centre, University College London Queen Square Institute of Neurology, London, UK; Department of Neurodegenerative Disease, University College London Queen Square Institute of Neurology, London, UK; Department of Computer Science, Centre for Medical Imaging Computing, University College London, London, UK; Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centre, Vrije Universiteit, Amsterdam, Netherlands.
Marcus RichardsMedical Research Council Unit for Lifelong Health and Ageing, University College London, London, UK.
Nick C FoxDementia Research Centre, University College London Queen Square Institute of Neurology, London, UK; Dementia Research Institute, University College London Queen Square Institute of Neurology, London, UK.
James H ColeDementia Research Centre, University College London Queen Square Institute of Neurology, London, UK; Department of Computer Science, Centre for Medical Imaging Computing, University College London, London, UK.
Jonathan M SchottDementia Research Centre, University College London Queen Square Institute of Neurology, London, UK; Dementia Research Institute, University College London Queen Square Institute of Neurology, London, UK. Electronic address: j.schott@ucl.ac.uk.
National Hospital for Neurology and Neurosurgery · GBUniversity College London · GBUK Dementia Research Institute · GBCardiff University · GBMedical Research Council · GBGreat Ormond Street Hospital · GBLondon School of Hygiene & Tropical Medicine · GBMRC Unit for Lifelong Health and Ageing · GB

Funding

British Heart Foundation PG/17/90/33415Department of HealthMedical Research Council CSUB19166Medical Research Council MC_UU_00019/1Medical Research Council MC_UU_00019/2Medical Research Council MC_UU_00019/3Medical Research Council MC_UU_00019/4Medical Research Council MR/L010305/1Medical Research Council MR/L023784/2Medical Research Council MR/R024790/2Medical Research Council MR/T04604X/1Wellcome Trust 200109/Z/15/Z
6 · The paper itself

Abstract

backgroundA neuroimaging-based biomarker termed the brain age is thought to reflect variability in the brain's ageing process and predict longevity. Using Insight 46, a unique narrow-age birth cohort, we aimed to examine potential drivers and correlates of brain age.

methodsParticipants, born in a single week in 1946 in mainland Britain, have had 24 prospective waves of data collection to date, including MRI and amyloid PET imaging at approximately 70 years old. Using MRI data from a previously defined selection of this cohort, we derived brain-predicted age from an established machine-learning model (trained on 2001 healthy adults aged 18-90 years); subtracting this from chronological age (at time of assessment) gave the brain-predicted age difference (brain-PAD). We tested associations with data from early life, midlife, and late life, as well as rates of MRI-derived brain atrophy.

findingsBetween May 28, 2015, and Jan 10, 2018, 502 individuals were assessed as part of Insight 46. We included 456 participants (225 female), with a mean chronological age of 70·7 years (SD 0·7; range 69·2 to 71·9). The mean brain-predicted age was 67·9 years (8·2, 46·3 to 94·3). Female sex was associated with a 5·4-year (95% CI 4·1 to 6·8) younger brain-PAD than male sex. An increase in brain-PAD was associated with increased cardiovascular risk at age 36 years (β=2·3 [95% CI 1·5 to 3·0]) and 69 years (β=2·6 [1·9 to 3·3]); increased cerebrovascular disease burden (1·9 [1·3 to 2·6]); lower cognitive performance (-1·3 [-2·4 to -0·2]); and increased serum neurofilament light concentration (1·2 [0·6 to 1·9]). Higher brain-PAD was associated with future hippocampal atrophy over the subsequent 2 years (0·003 mL/year [0·000 to 0·006] per 5-year increment in brain-PAD). Early-life factors did not relate to brain-PAD. Combining 12 metrics in a hierarchical partitioning model explained 33% of the variance in brain-PAD.

interpretationBrain-PAD was associated with cardiovascular risk, and imaging and biochemical markers of neurodegeneration. These findings support brain-PAD as an integrative summary metric of brain health, reflecting multiple contributions to pathological brain ageing, and which might have prognostic utility.

fundingAlzheimer's Research UK, Medical Research Council Dementia Platforms UK, Selfridges Group Foundation, Wolfson Foundation, Wellcome Trust, Brain Research UK, Alzheimer's Association.

Indexed as

Alzheimer DiseaseLife Change EventsAdultAgedAtrophyBrainFemaleHumansMaleProspective Studies

Identifiers

PMID36102775
PMCPMC10499760
OpenAlexW4293282436

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.