CoChat
Sign Up
Cited by 114Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCancer-related cognitive impairment studies

The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.

The implications of different approaches to define AT(N) in Alzheimer disease

Open access
Mattsson-Carlgren, Niklas, Leuzy, Antoine, Janelidze, Shorena, Palmqvist, Sebastian, Stomrud, Erik, Strandberg, Olof, Smith, Ruben, Hansson, Oskar·2020·Neurology
DOI 10.1212/wnl.0000000000009485PMC PMC7357296
Open this paper in CoChat — free accountOpen PDF

Abstract

Objective To compare different β-amyloid (Aβ), tau, and neurodegeneration (AT[N]) variants within the Swedish BioFINDER studies. Methods A total of 490 participants were classified into AT(N) groups. These include 53 cognitively unimpaired (CU) and 48 cognitively impaired (CI) participants (14 mild cognitive impairment [MCI] and 34 Alzheimer disease [AD] dementia) from BioFINDER-1 and 389 participants from BioFINDER-2 (245 CU and 144 CI [138 MCI and 6 AD dementia]). Biomarkers for A were CSF Aβ42 and amyloid-PET ([18F]flutemetamol); for T, CSF phosphorylated tau (p-tau) and tau PET ([18F]flortaucipir); and for (N), hippocampal volume, temporal cortical thickness, and CSF neurofilament light (NfL). Binarization of biomarkers was achieved using cutoffs defined in other cohorts. The relationship between different AT(N) combinations and cognitive trajectories (longitudinal Mini-Mental State Examination scores) was examined using linear mixed modeling and coefficient of variation. Results Among CU participants, A−T−(N)− or A+T−(N)− variants were most common. However, more T+ cases were seen using p-tau than tau PET. Among CI participants, A+T+(N)+ was more common; however, more (N)+ cases were seen for MRI measures relative to CSF NfL. Tau PET best predicted longitudinal cognitive decline in CI and p-tau in CU participants. Among CI participants, continuous T (especially tau PET) and (N) measures improved the prediction of cognitive decline compared to binary measures. Conclusions Our findings show that different AT(N) variants are not interchangeable, and that optimal variants differ by clinical stage. In some cases, dichotomizing biomarkers may result in loss of important prognostic information.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1212/wnl.0000000000009485

Cites

34 of 34 references verified0 citation errors · 0 not checkable

Statistics

Figures

Figure 1 Pairwise scatterplots for A, T, and (N) variables in BioFINDER-1 Scatterplots show the association between continuous measures for amyloid (A), tau (B–D), and (N) (E–G) biomarkers. Dashed lines indicate cutoff points. Spearman correlations (ρ) with p values, Cohen kappa statistic (κ), and concordance (percentage showing both biomarkers positive or negative) are shown at the top of each panel. For A and T comparisons, the upper right and lower left quadrants indicate concordance positive (+/+) and negative (−/−), respectively. For the comparisons (N)1 vs (N)2, the lower left and upper right quadrants indicate concordance positive and negative, respectively. For the 2 remaining (N) comparisons, concordant positive is in the lower right quadrant while concordant negative is in the upper left. Percentage figures across quadrants indicate distribution (percentage-wise) of participants. Aβ = β-amyloid; AT(N) = β-amyloid, tau, and neurodegeneration classification system; CI = cognitively impaired; CU = cognitively unimpaired; ITC = inferior temporal cortex; NfL = neurofilament light; p-tau = tau phosphorylated at Thr181; ROI = region of interest; SUVR = standardized uptake value ratio.
Figure 1 Pairwise scatterplots for A, T, and (N) variables in BioFINDER-1 Scatterplots show the association between continuous measures for amyloid (A), tau (B–D), and (N) (E–G) biomarkers. Dashed lines indicate cutoff points. Spearman correlations (ρ) with p values, Cohen kappa statistic (κ), and concordance (percentage showing both biomarkers positive or negative) are shown at the top of each panel. For A and T comparisons, the upper right and lower left quadrants indicate concordance positive (+/+) and negative (−/−), respectively. For the comparisons (N)1 vs (N)2, the lower left and upper right quadrants indicate concordance positive and negative, respectively. For the 2 remaining (N) comparisons, concordant positive is in the lower right quadrant while concordant negative is in the upper left. Percentage figures across quadrants indicate distribution (percentage-wise) of participants. Aβ = β-amyloid; AT(N) = β-amyloid, tau, and neurodegeneration classification system; CI = cognitively impaired; CU = cognitively unimpaired; ITC = inferior temporal cortex; NfL = neurofilament light; p-tau = tau phosphorylated at Thr181; ROI = region of interest; SUVR = standardized uptake value ratio.CC BY · PubMed Central
Figure 2 Prevalence of different AT(N) categories in different AT(N) variants among cognitively unimpaired (CU) and cognitively impaired (CI) participants in BioFINDER-1 Prevalence is reported without (A,C) and with (B, D) consideration for the (N) component. CSF Aβ42 (A1); amyloid PET neocortical standardized uptake value ratio (SUVR) (A2); CSF tau phosphorylated at Thr181 (T1); tau PET inferior temporal cortex SUVR (T2); tau PET Braak V/VI SUVR (T3); hippocampal volume, adjusted for intracranial volume ([N]1); cortical thickness with a temporal meta–region of interest ([N]2); CSF neurofilament light ([N]3). AT(N) = β-amyloid, tau, and neurodegeneration classification system.
Figure 2 Prevalence of different AT(N) categories in different AT(N) variants among cognitively unimpaired (CU) and cognitively impaired (CI) participants in BioFINDER-1 Prevalence is reported without (A,C) and with (B, D) consideration for the (N) component. CSF Aβ42 (A1); amyloid PET neocortical standardized uptake value ratio (SUVR) (A2); CSF tau phosphorylated at Thr181 (T1); tau PET inferior temporal cortex SUVR (T2); tau PET Braak V/VI SUVR (T3); hippocampal volume, adjusted for intracranial volume ([N]1); cortical thickness with a temporal meta–region of interest ([N]2); CSF neurofilament light ([N]3). AT(N) = β-amyloid, tau, and neurodegeneration classification system.CC BY · PubMed Central
Figure 3 Prevalence of T and (N) positivity across cognitively unimpaired (CU) and cognitively impaired (CI) participants in BioFINDER-1 and BioFINDER-2 Prevalence estimates for CU participants are shown in (A) (BioFINDER, n = 101: 53 CU and 48 CI participants) and (B) (BioFINDER-2, n = 389: 245 CU and 144 CI participants) and for CI participants in (C) (BioFINDER-1) and (D) (BioFINDER-2). AT(N) = β-amyloid, tau, and neurodegeneration classification system.
Figure 3 Prevalence of T and (N) positivity across cognitively unimpaired (CU) and cognitively impaired (CI) participants in BioFINDER-1 and BioFINDER-2 Prevalence estimates for CU participants are shown in (A) (BioFINDER, n = 101: 53 CU and 48 CI participants) and (B) (BioFINDER-2, n = 389: 245 CU and 144 CI participants) and for CI participants in (C) (BioFINDER-1) and (D) (BioFINDER-2). AT(N) = β-amyloid, tau, and neurodegeneration classification system.CC BY · PubMed Central
Figure 4 AT(N) variants and longitudinal cognition (A, D) R2 for different AT(N) variants to predict longitudinal Mini-Mental State Examination (MMSE) for cognitively unimpaired (CU) and cognitively impaired (CI) participants, respectively (divided by A biomarkers). The selected models in (B,C) and (E, F) are the top 2 best for CU and CI participants, respectively; 25 and 75 refer to 25th and 75th quartiles, where higher indicates a more abnormal biomarker. All CI participants were positive using CSF Aβ42 in ratio with Aβ40. AT(N) = β-amyloid, tau, and neurodegeneration classification system. ITC = inferior temporal cortex; p-tau = phosphorylated at Thr181; ROI = region of interest.
Figure 4 AT(N) variants and longitudinal cognition (A, D) R2 for different AT(N) variants to predict longitudinal Mini-Mental State Examination (MMSE) for cognitively unimpaired (CU) and cognitively impaired (CI) participants, respectively (divided by A biomarkers). The selected models in (B,C) and (E, F) are the top 2 best for CU and CI participants, respectively; 25 and 75 refer to 25th and 75th quartiles, where higher indicates a more abnormal biomarker. All CI participants were positive using CSF Aβ42 in ratio with Aβ40. AT(N) = β-amyloid, tau, and neurodegeneration classification system. ITC = inferior temporal cortex; p-tau = phosphorylated at Thr181; ROI = region of interest.CC BY · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Research works printed but not linked: 4

  1. American Psychiatric Association. Diagnostic Criteria from DSM-5. Washington, DC: American Psychiatric Association; 2013.
  2. 10.1001/jamaneurol.2017.4026 · DOI
  3. 10.1212/WNL.0000000000004667 · DOI · Paper page
  4. 10.1212/WNL.0000000000001238 · DOI

Cited by

Sorted by citations

See all 114

Metadata

Authors
Mattsson-Carlgren, N., Leuzy, A., Janelidze, S., Palmqvist, S., Stomrud, E., Strandberg, O., Smith, R., & Hansson, O.
Affiliations
  • From the Clinical Memory Research Unit, Department of Clinical Sciences (N.M.-C., A.L., S.J., S.P., E.S., O.S., R.S., O.H.), and Wallenberg Centre for Molecular Medicine (N.M.-C.), Lund University, Malmö; and Department of Neurology (N.M.-C., S.P., R.S.) and Memory Clinic (E.S., O.H.), Skåne University Hospital, Lund, Sweden.
  • Lund University (SE)
Corresponding author
Hansson, Oskar
ORCID
Venue
Neurology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2020-05-26
Volume
94
Issue
21
Pages
e2233-e2244
ISSN
  • 0028-3878 (ISSN-L)
  • 1526-632X
DOI
10.1212/wnl.0000000000009485
PMC
PMC7357296
OpenAlex
W3025228866
Cited by
114
References
34
Citations by year
2026: 6 · 2025: 12 · 2024: 18 · 2023: 28 · 2022: 19 · 2021: 27 · 2020: 4
FWCI
14.23
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Neurology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Oncology › Cancer-related cognitive impairment studies
Keywords
Alzheimer's disease, amyloid PET, tau PET, neurodegeneration biomarkers, phosphorylated tau, hippocampal volume, cortical thickness, mild cognitive impairment, cognitive decline, longitudinal cognitive trajectories
MeSH terms
Mental Status and Dementia Tests, Aged, Alzheimer Disease, Aniline Compounds, Brain, Carbolines, Female, Humans, Longitudinal Studies, Male, Middle Aged, Nerve Degeneration, Sweden, Biomarkers, Case-Control Studies, Amyloid beta-Peptides, tau Proteins, Neurofilament Proteins, Positron-Emission Tomography, Benzothiazoles, Cognitive Dysfunction

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review