Evidence mapPaperPMID 33023653Full record

ArticleAlzheimer's research & therapy2020

Quantitative detection and staging of presymptomatic cognitive decline in familial Alzheimer's disease: a retrospective cohort analysis.

Antoinette O'Connor, Philip S J Weston, Ivanna M Pavisic, Natalie S Ryan, Jessica D Collins, Kirsty Lu, Sebastian J Crutch, Daniel C Alexander, Nick C Fox, Neil P Oxtoby

Open access · goldAbstract read
In one paragraph

Article in Alzheimer's research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

19 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Observational
  17. Article
  18. Article
  19. Investigating cognition in midlife.Alzheimer's & dementia (New York, N. Y.) · 2021
    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 at 4 institutions in 1 country.

Antoinette O'ConnorDementia Research Centre, UCL Queen Square Institute Of Neurology, 8-11 Queen Square, London, WC1N 3AR, UK. antoinette.o'connor@ucl.ac.uk.ORCID 0000-0003-4467-128X
Philip S J WestonDementia Research Centre, UCL Queen Square Institute Of Neurology, 8-11 Queen Square, London, WC1N 3AR, UK.
Ivanna M PavisicDementia Research Centre, UCL Queen Square Institute Of Neurology, 8-11 Queen Square, London, WC1N 3AR, UK.
Natalie S RyanDementia Research Centre, UCL Queen Square Institute Of Neurology, 8-11 Queen Square, London, WC1N 3AR, UK.
Jessica D CollinsDementia Research Centre, UCL Queen Square Institute Of Neurology, 8-11 Queen Square, London, WC1N 3AR, UK.
Kirsty LuDementia Research Centre, UCL Queen Square Institute Of Neurology, 8-11 Queen Square, London, WC1N 3AR, UK.
Sebastian J CrutchDementia Research Centre, UCL Queen Square Institute Of Neurology, 8-11 Queen Square, London, WC1N 3AR, UK.
Daniel C AlexanderDepartment of Computer Science, UCL Centre for Medical Image Computing, 1st Floor, 90 High Holborn, London, WC1V 6LJ, UK.
Nick C FoxDementia Research Centre, UCL Queen Square Institute Of Neurology, 8-11 Queen Square, London, WC1N 3AR, UK.
Neil P OxtobyDepartment of Computer Science, UCL Centre for Medical Image Computing, 1st Floor, 90 High Holborn, London, WC1V 6LJ, UK. n.oxtoby@ucl.ac.uk.
NIHR Queen Square Dementia Biomedical Research Unit · GBUK Dementia Research Institute · GBUCL Biomedical Research Centre · GBUniversity College London · GB

Funding

Medical Research Council G0900421Medical Research Council MR/M003108/1Medical Research Council MR/S03546X/1
6 · The paper itself

Abstract

backgroundUnderstanding the earliest manifestations of Alzheimer's disease (AD) is key to realising disease-modifying treatments. Advances in neuroimaging and fluid biomarkers have improved our ability to identify AD pathology in vivo. The critical next step is improved detection and staging of early cognitive change. We studied an asymptomatic familial Alzheimer's disease (FAD) cohort to characterise preclinical cognitive change.

methodsData included 35 asymptomatic participants at 50% risk of carrying a pathogenic FAD mutation. Participants completed a multi-domain neuropsychology battery. After accounting for sex, age and education, we used event-based modelling to estimate the sequence of cognitive decline in presymptomatic FAD, and uncertainty in the sequence. We assigned individuals to their most likely model stage of cumulative cognitive decline, given their data. Linear regression of estimated years to symptom onset against model stage was used to estimate the timing of preclinical cognitive decline.

resultsCognitive change in mutation carriers was first detected in measures of accelerated long-term forgetting, up to 10 years before estimated symptom onset. Measures of subjective cognitive decline also revealed early abnormalities. Our data-driven model demonstrated subtle cognitive impairment across multiple cognitive domains in clinically normal individuals on the AD continuum.

conclusionsData-driven modelling of neuropsychological test scores has potential to differentiate cognitive decline from cognitive stability and to estimate a fine-grained sequence of decline across cognitive domains and functions, in the preclinical phase of Alzheimer's disease. This can improve the design of future presymptomatic trials by informing enrichment strategies and guiding the selection of outcome measures.

Indexed as

Alzheimer DiseaseCognitive DysfunctionCohort StudiesHumansNeuropsychological TestsRetrospective StudiesEvent-based modellingFamilial Alzheimer’s diseaseNeuropsychologyPreclinical

Identifiers

PMID33023653
PMCPMC7539456
OpenAlexW3092116716

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.