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ATN classification and clinical progression in subjective cognitive decline: The SCIENCe project
OBJECTIVE: To investigate the relationship between the ATN classification system (amyloid, tau, neurodegeneration) and risk of dementia and cognitive decline in individuals with subjective cognitive decline (SCD). METHODS: We classified 693 participants with SCD (60 ± 9 years, 41% women, Mini-Mental...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371376/ https://www.ncbi.nlm.nih.gov/pubmed/32522798 http://dx.doi.org/10.1212/WNL.0000000000009724 |
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author | Ebenau, Jarith L. Timmers, Tessa Wesselman, Linda M.P. Verberk, Inge M.W. Verfaillie, Sander C.J. Slot, Rosalinde E.R. van Harten, Argonde C. Teunissen, Charlotte E. Barkhof, Frederik van den Bosch, Karlijn A. van Leeuwenstijn, Mardou Tomassen, Jori den Braber, Anouk Visser, Pieter Jelle Prins, Niels D. Sikkes, Sietske A.M. Scheltens, Philip van Berckel, Bart N.M. van der Flier, Wiesje M. |
author_facet | Ebenau, Jarith L. Timmers, Tessa Wesselman, Linda M.P. Verberk, Inge M.W. Verfaillie, Sander C.J. Slot, Rosalinde E.R. van Harten, Argonde C. Teunissen, Charlotte E. Barkhof, Frederik van den Bosch, Karlijn A. van Leeuwenstijn, Mardou Tomassen, Jori den Braber, Anouk Visser, Pieter Jelle Prins, Niels D. Sikkes, Sietske A.M. Scheltens, Philip van Berckel, Bart N.M. van der Flier, Wiesje M. |
author_sort | Ebenau, Jarith L. |
collection | PubMed |
description | OBJECTIVE: To investigate the relationship between the ATN classification system (amyloid, tau, neurodegeneration) and risk of dementia and cognitive decline in individuals with subjective cognitive decline (SCD). METHODS: We classified 693 participants with SCD (60 ± 9 years, 41% women, Mini-Mental State Examination score 28 ± 2) from the Amsterdam Dementia Cohort and Subjective Cognitive Impairment Cohort (SCIENCe) project according to the ATN model, as determined by amyloid PET or CSF β-amyloid (A), CSF p-tau (T), and MRI-based medial temporal lobe atrophy (N). All underwent extensive neuropsychological assessment. For 342 participants, follow-up was available (3 ± 2 years). As a control population, we included 124 participants without SCD. RESULTS: Fifty-six (n = 385) participants had normal Alzheimer disease (AD) biomarkers (A–T–N–), 27% (n = 186) had non-AD pathologic change (A–T–N+, A–T+N–, A–T+N+), 18% (n = 122) fell within the Alzheimer continuum (A+T–N–, A+T–N+, A+T+N–, A+T+N+). ATN profiles were unevenly distributed, with A–T+N+, A+T–N+, and A+T+N+ containing very few participants. Cox regression showed that compared to A–T–N–, participants in A+ profiles had a higher risk of dementia with a dose–response pattern for number of biomarkers affected. Linear mixed models showed participants in A+ profiles showed a steeper decline on tests addressing memory, attention, language, and executive functions. In the control group, there was no association between ATN and cognition. CONCLUSIONS: Among individuals presenting with SCD at a memory clinic, those with a biomarker profile A–T+N+, A+T–N–, A+T+N–, and A+T+N+ were at increased risk of dementia, and showed steeper cognitive decline compared to A–T–N– individuals. These results suggest a future where biomarker results could be used for individualized risk profiling in cognitively normal individuals presenting at a memory clinic. |
format | Online Article Text |
id | pubmed-7371376 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-73713762020-08-13 ATN classification and clinical progression in subjective cognitive decline: The SCIENCe project Ebenau, Jarith L. Timmers, Tessa Wesselman, Linda M.P. Verberk, Inge M.W. Verfaillie, Sander C.J. Slot, Rosalinde E.R. van Harten, Argonde C. Teunissen, Charlotte E. Barkhof, Frederik van den Bosch, Karlijn A. van Leeuwenstijn, Mardou Tomassen, Jori den Braber, Anouk Visser, Pieter Jelle Prins, Niels D. Sikkes, Sietske A.M. Scheltens, Philip van Berckel, Bart N.M. van der Flier, Wiesje M. Neurology Article OBJECTIVE: To investigate the relationship between the ATN classification system (amyloid, tau, neurodegeneration) and risk of dementia and cognitive decline in individuals with subjective cognitive decline (SCD). METHODS: We classified 693 participants with SCD (60 ± 9 years, 41% women, Mini-Mental State Examination score 28 ± 2) from the Amsterdam Dementia Cohort and Subjective Cognitive Impairment Cohort (SCIENCe) project according to the ATN model, as determined by amyloid PET or CSF β-amyloid (A), CSF p-tau (T), and MRI-based medial temporal lobe atrophy (N). All underwent extensive neuropsychological assessment. For 342 participants, follow-up was available (3 ± 2 years). As a control population, we included 124 participants without SCD. RESULTS: Fifty-six (n = 385) participants had normal Alzheimer disease (AD) biomarkers (A–T–N–), 27% (n = 186) had non-AD pathologic change (A–T–N+, A–T+N–, A–T+N+), 18% (n = 122) fell within the Alzheimer continuum (A+T–N–, A+T–N+, A+T+N–, A+T+N+). ATN profiles were unevenly distributed, with A–T+N+, A+T–N+, and A+T+N+ containing very few participants. Cox regression showed that compared to A–T–N–, participants in A+ profiles had a higher risk of dementia with a dose–response pattern for number of biomarkers affected. Linear mixed models showed participants in A+ profiles showed a steeper decline on tests addressing memory, attention, language, and executive functions. In the control group, there was no association between ATN and cognition. CONCLUSIONS: Among individuals presenting with SCD at a memory clinic, those with a biomarker profile A–T+N+, A+T–N–, A+T+N–, and A+T+N+ were at increased risk of dementia, and showed steeper cognitive decline compared to A–T–N– individuals. These results suggest a future where biomarker results could be used for individualized risk profiling in cognitively normal individuals presenting at a memory clinic. Lippincott Williams & Wilkins 2020-07-07 /pmc/articles/PMC7371376/ /pubmed/32522798 http://dx.doi.org/10.1212/WNL.0000000000009724 Text en Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | Article Ebenau, Jarith L. Timmers, Tessa Wesselman, Linda M.P. Verberk, Inge M.W. Verfaillie, Sander C.J. Slot, Rosalinde E.R. van Harten, Argonde C. Teunissen, Charlotte E. Barkhof, Frederik van den Bosch, Karlijn A. van Leeuwenstijn, Mardou Tomassen, Jori den Braber, Anouk Visser, Pieter Jelle Prins, Niels D. Sikkes, Sietske A.M. Scheltens, Philip van Berckel, Bart N.M. van der Flier, Wiesje M. ATN classification and clinical progression in subjective cognitive decline: The SCIENCe project |
title | ATN classification and clinical progression in subjective cognitive decline: The SCIENCe project |
title_full | ATN classification and clinical progression in subjective cognitive decline: The SCIENCe project |
title_fullStr | ATN classification and clinical progression in subjective cognitive decline: The SCIENCe project |
title_full_unstemmed | ATN classification and clinical progression in subjective cognitive decline: The SCIENCe project |
title_short | ATN classification and clinical progression in subjective cognitive decline: The SCIENCe project |
title_sort | atn classification and clinical progression in subjective cognitive decline: the science project |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371376/ https://www.ncbi.nlm.nih.gov/pubmed/32522798 http://dx.doi.org/10.1212/WNL.0000000000009724 |
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