TY - JOUR
T1 - ATN classification and clinical progression in subjective cognitive decline
T2 - The SCIENCe project
AU - Ebenau, Jarith L.
AU - Timmers, Tessa
AU - Wesselman, Linda M.P.
AU - Verberk, Inge M.W.
AU - Verfaillie, Sander C.J.
AU - Slot, Rosalinde E.R.
AU - Van Harten, Argonde C.
AU - Teunissen, Charlotte E.
AU - Barkhof, Frederik
AU - Van Den Bosch, Karlijn A.
AU - Van Leeuwenstijn, Mardou
AU - Tomassen, Jori
AU - Braber, Anouk Den
AU - Visser, Pieter Jelle
AU - Prins, Niels D.
AU - Sikkes, Sietske A.M.
AU - Scheltens, Philip
AU - Van Berckel, Bart N.M.
AU - Van Der Flier, Wiesje M.
N1 - Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
PY - 2020/7/7
Y1 - 2020/7/7
N2 - ObjectiveTo 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).MethodsWe 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.ResultsFifty-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.ConclusionsAmong 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.
AB - ObjectiveTo 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).MethodsWe 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.ResultsFifty-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.ConclusionsAmong 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.
UR - http://www.scopus.com/inward/record.url?scp=85088206849&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85088206849&partnerID=8YFLogxK
U2 - https://doi.org/10.1212/WNL.0000000000009724
DO - https://doi.org/10.1212/WNL.0000000000009724
M3 - Article
C2 - 32522798
SN - 0028-3878
VL - 95
SP - 46
EP - 58
JO - Neurology
JF - Neurology
IS - 1
ER -