ATN classification and clinical progression in subjective cognitive decline: The SCIENCe project.


Journal

Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060

Informations de publication

Date de publication:
07 07 2020
Historique:
received: 22 07 2019
accepted: 12 12 2019
pubmed: 12 6 2020
medline: 29 9 2020
entrez: 12 6 2020
Statut: ppublish

Résumé

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). 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. 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. 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.

Identifiants

pubmed: 32522798
pii: WNL.0000000000009724
doi: 10.1212/WNL.0000000000009724
pmc: PMC7371376
doi:

Substances chimiques

Amyloid beta-Peptides 0
Biomarkers 0
tau Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e46-e58

Informations de copyright

Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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Auteurs

Jarith L Ebenau (JL)

From the Alzheimer Center, Department of Neurology (J.L.E., T.T., L.M.P.W., I.M.W.V., R.E.R.S., A.C.v.H., K.A.v.d.B., M.v.L., J.T., A.d.B., P.J.V., N.D.P., S.A.M.S., P.S., B.N.M.v.B., W.M.v.d.F.), and Department of Radiology & Nuclear Medicine (S.C.J.V., F.B., B.N.v.B.), Amsterdam Neuroscience, Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK; Department of Biological Psychology (A.d.B.), Neuroscience Amsterdam, VU University Amsterdam; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; and Department of Neurobiology, Care Sciences and Society (P.J.V.), Division of Neurogeriatrics, Karolinska Institutet, Stockholm Sweden. j.ebenau@amsterdamumc.nl.

Tessa Timmers (T)

From the Alzheimer Center, Department of Neurology (J.L.E., T.T., L.M.P.W., I.M.W.V., R.E.R.S., A.C.v.H., K.A.v.d.B., M.v.L., J.T., A.d.B., P.J.V., N.D.P., S.A.M.S., P.S., B.N.M.v.B., W.M.v.d.F.), and Department of Radiology & Nuclear Medicine (S.C.J.V., F.B., B.N.v.B.), Amsterdam Neuroscience, Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK; Department of Biological Psychology (A.d.B.), Neuroscience Amsterdam, VU University Amsterdam; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; and Department of Neurobiology, Care Sciences and Society (P.J.V.), Division of Neurogeriatrics, Karolinska Institutet, Stockholm Sweden.

Linda M P Wesselman (LMP)

From the Alzheimer Center, Department of Neurology (J.L.E., T.T., L.M.P.W., I.M.W.V., R.E.R.S., A.C.v.H., K.A.v.d.B., M.v.L., J.T., A.d.B., P.J.V., N.D.P., S.A.M.S., P.S., B.N.M.v.B., W.M.v.d.F.), and Department of Radiology & Nuclear Medicine (S.C.J.V., F.B., B.N.v.B.), Amsterdam Neuroscience, Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK; Department of Biological Psychology (A.d.B.), Neuroscience Amsterdam, VU University Amsterdam; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; and Department of Neurobiology, Care Sciences and Society (P.J.V.), Division of Neurogeriatrics, Karolinska Institutet, Stockholm Sweden.

Inge M W Verberk (IMW)

From the Alzheimer Center, Department of Neurology (J.L.E., T.T., L.M.P.W., I.M.W.V., R.E.R.S., A.C.v.H., K.A.v.d.B., M.v.L., J.T., A.d.B., P.J.V., N.D.P., S.A.M.S., P.S., B.N.M.v.B., W.M.v.d.F.), and Department of Radiology & Nuclear Medicine (S.C.J.V., F.B., B.N.v.B.), Amsterdam Neuroscience, Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK; Department of Biological Psychology (A.d.B.), Neuroscience Amsterdam, VU University Amsterdam; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; and Department of Neurobiology, Care Sciences and Society (P.J.V.), Division of Neurogeriatrics, Karolinska Institutet, Stockholm Sweden.

Sander C J Verfaillie (SCJ)

From the Alzheimer Center, Department of Neurology (J.L.E., T.T., L.M.P.W., I.M.W.V., R.E.R.S., A.C.v.H., K.A.v.d.B., M.v.L., J.T., A.d.B., P.J.V., N.D.P., S.A.M.S., P.S., B.N.M.v.B., W.M.v.d.F.), and Department of Radiology & Nuclear Medicine (S.C.J.V., F.B., B.N.v.B.), Amsterdam Neuroscience, Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK; Department of Biological Psychology (A.d.B.), Neuroscience Amsterdam, VU University Amsterdam; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; and Department of Neurobiology, Care Sciences and Society (P.J.V.), Division of Neurogeriatrics, Karolinska Institutet, Stockholm Sweden.

Rosalinde E R Slot (RER)

From the Alzheimer Center, Department of Neurology (J.L.E., T.T., L.M.P.W., I.M.W.V., R.E.R.S., A.C.v.H., K.A.v.d.B., M.v.L., J.T., A.d.B., P.J.V., N.D.P., S.A.M.S., P.S., B.N.M.v.B., W.M.v.d.F.), and Department of Radiology & Nuclear Medicine (S.C.J.V., F.B., B.N.v.B.), Amsterdam Neuroscience, Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK; Department of Biological Psychology (A.d.B.), Neuroscience Amsterdam, VU University Amsterdam; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; and Department of Neurobiology, Care Sciences and Society (P.J.V.), Division of Neurogeriatrics, Karolinska Institutet, Stockholm Sweden.

Argonde C van Harten (AC)

From the Alzheimer Center, Department of Neurology (J.L.E., T.T., L.M.P.W., I.M.W.V., R.E.R.S., A.C.v.H., K.A.v.d.B., M.v.L., J.T., A.d.B., P.J.V., N.D.P., S.A.M.S., P.S., B.N.M.v.B., W.M.v.d.F.), and Department of Radiology & Nuclear Medicine (S.C.J.V., F.B., B.N.v.B.), Amsterdam Neuroscience, Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK; Department of Biological Psychology (A.d.B.), Neuroscience Amsterdam, VU University Amsterdam; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; and Department of Neurobiology, Care Sciences and Society (P.J.V.), Division of Neurogeriatrics, Karolinska Institutet, Stockholm Sweden.

Charlotte E Teunissen (CE)

From the Alzheimer Center, Department of Neurology (J.L.E., T.T., L.M.P.W., I.M.W.V., R.E.R.S., A.C.v.H., K.A.v.d.B., M.v.L., J.T., A.d.B., P.J.V., N.D.P., S.A.M.S., P.S., B.N.M.v.B., W.M.v.d.F.), and Department of Radiology & Nuclear Medicine (S.C.J.V., F.B., B.N.v.B.), Amsterdam Neuroscience, Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK; Department of Biological Psychology (A.d.B.), Neuroscience Amsterdam, VU University Amsterdam; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; and Department of Neurobiology, Care Sciences and Society (P.J.V.), Division of Neurogeriatrics, Karolinska Institutet, Stockholm Sweden.

Frederik Barkhof (F)

From the Alzheimer Center, Department of Neurology (J.L.E., T.T., L.M.P.W., I.M.W.V., R.E.R.S., A.C.v.H., K.A.v.d.B., M.v.L., J.T., A.d.B., P.J.V., N.D.P., S.A.M.S., P.S., B.N.M.v.B., W.M.v.d.F.), and Department of Radiology & Nuclear Medicine (S.C.J.V., F.B., B.N.v.B.), Amsterdam Neuroscience, Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK; Department of Biological Psychology (A.d.B.), Neuroscience Amsterdam, VU University Amsterdam; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; and Department of Neurobiology, Care Sciences and Society (P.J.V.), Division of Neurogeriatrics, Karolinska Institutet, Stockholm Sweden.

Karlijn A van den Bosch (KA)

From the Alzheimer Center, Department of Neurology (J.L.E., T.T., L.M.P.W., I.M.W.V., R.E.R.S., A.C.v.H., K.A.v.d.B., M.v.L., J.T., A.d.B., P.J.V., N.D.P., S.A.M.S., P.S., B.N.M.v.B., W.M.v.d.F.), and Department of Radiology & Nuclear Medicine (S.C.J.V., F.B., B.N.v.B.), Amsterdam Neuroscience, Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK; Department of Biological Psychology (A.d.B.), Neuroscience Amsterdam, VU University Amsterdam; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; and Department of Neurobiology, Care Sciences and Society (P.J.V.), Division of Neurogeriatrics, Karolinska Institutet, Stockholm Sweden.

Mardou van Leeuwenstijn (M)

From the Alzheimer Center, Department of Neurology (J.L.E., T.T., L.M.P.W., I.M.W.V., R.E.R.S., A.C.v.H., K.A.v.d.B., M.v.L., J.T., A.d.B., P.J.V., N.D.P., S.A.M.S., P.S., B.N.M.v.B., W.M.v.d.F.), and Department of Radiology & Nuclear Medicine (S.C.J.V., F.B., B.N.v.B.), Amsterdam Neuroscience, Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK; Department of Biological Psychology (A.d.B.), Neuroscience Amsterdam, VU University Amsterdam; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; and Department of Neurobiology, Care Sciences and Society (P.J.V.), Division of Neurogeriatrics, Karolinska Institutet, Stockholm Sweden.

Jori Tomassen (J)

From the Alzheimer Center, Department of Neurology (J.L.E., T.T., L.M.P.W., I.M.W.V., R.E.R.S., A.C.v.H., K.A.v.d.B., M.v.L., J.T., A.d.B., P.J.V., N.D.P., S.A.M.S., P.S., B.N.M.v.B., W.M.v.d.F.), and Department of Radiology & Nuclear Medicine (S.C.J.V., F.B., B.N.v.B.), Amsterdam Neuroscience, Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK; Department of Biological Psychology (A.d.B.), Neuroscience Amsterdam, VU University Amsterdam; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; and Department of Neurobiology, Care Sciences and Society (P.J.V.), Division of Neurogeriatrics, Karolinska Institutet, Stockholm Sweden.

Anouk den Braber (AD)

From the Alzheimer Center, Department of Neurology (J.L.E., T.T., L.M.P.W., I.M.W.V., R.E.R.S., A.C.v.H., K.A.v.d.B., M.v.L., J.T., A.d.B., P.J.V., N.D.P., S.A.M.S., P.S., B.N.M.v.B., W.M.v.d.F.), and Department of Radiology & Nuclear Medicine (S.C.J.V., F.B., B.N.v.B.), Amsterdam Neuroscience, Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK; Department of Biological Psychology (A.d.B.), Neuroscience Amsterdam, VU University Amsterdam; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; and Department of Neurobiology, Care Sciences and Society (P.J.V.), Division of Neurogeriatrics, Karolinska Institutet, Stockholm Sweden.

Pieter Jelle Visser (PJ)

From the Alzheimer Center, Department of Neurology (J.L.E., T.T., L.M.P.W., I.M.W.V., R.E.R.S., A.C.v.H., K.A.v.d.B., M.v.L., J.T., A.d.B., P.J.V., N.D.P., S.A.M.S., P.S., B.N.M.v.B., W.M.v.d.F.), and Department of Radiology & Nuclear Medicine (S.C.J.V., F.B., B.N.v.B.), Amsterdam Neuroscience, Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK; Department of Biological Psychology (A.d.B.), Neuroscience Amsterdam, VU University Amsterdam; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; and Department of Neurobiology, Care Sciences and Society (P.J.V.), Division of Neurogeriatrics, Karolinska Institutet, Stockholm Sweden.

Niels D Prins (ND)

From the Alzheimer Center, Department of Neurology (J.L.E., T.T., L.M.P.W., I.M.W.V., R.E.R.S., A.C.v.H., K.A.v.d.B., M.v.L., J.T., A.d.B., P.J.V., N.D.P., S.A.M.S., P.S., B.N.M.v.B., W.M.v.d.F.), and Department of Radiology & Nuclear Medicine (S.C.J.V., F.B., B.N.v.B.), Amsterdam Neuroscience, Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK; Department of Biological Psychology (A.d.B.), Neuroscience Amsterdam, VU University Amsterdam; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; and Department of Neurobiology, Care Sciences and Society (P.J.V.), Division of Neurogeriatrics, Karolinska Institutet, Stockholm Sweden.

Sietske A M Sikkes (SAM)

From the Alzheimer Center, Department of Neurology (J.L.E., T.T., L.M.P.W., I.M.W.V., R.E.R.S., A.C.v.H., K.A.v.d.B., M.v.L., J.T., A.d.B., P.J.V., N.D.P., S.A.M.S., P.S., B.N.M.v.B., W.M.v.d.F.), and Department of Radiology & Nuclear Medicine (S.C.J.V., F.B., B.N.v.B.), Amsterdam Neuroscience, Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK; Department of Biological Psychology (A.d.B.), Neuroscience Amsterdam, VU University Amsterdam; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; and Department of Neurobiology, Care Sciences and Society (P.J.V.), Division of Neurogeriatrics, Karolinska Institutet, Stockholm Sweden.

Philip Scheltens (P)

From the Alzheimer Center, Department of Neurology (J.L.E., T.T., L.M.P.W., I.M.W.V., R.E.R.S., A.C.v.H., K.A.v.d.B., M.v.L., J.T., A.d.B., P.J.V., N.D.P., S.A.M.S., P.S., B.N.M.v.B., W.M.v.d.F.), and Department of Radiology & Nuclear Medicine (S.C.J.V., F.B., B.N.v.B.), Amsterdam Neuroscience, Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK; Department of Biological Psychology (A.d.B.), Neuroscience Amsterdam, VU University Amsterdam; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; and Department of Neurobiology, Care Sciences and Society (P.J.V.), Division of Neurogeriatrics, Karolinska Institutet, Stockholm Sweden.

Bart N M van Berckel (BNM)

From the Alzheimer Center, Department of Neurology (J.L.E., T.T., L.M.P.W., I.M.W.V., R.E.R.S., A.C.v.H., K.A.v.d.B., M.v.L., J.T., A.d.B., P.J.V., N.D.P., S.A.M.S., P.S., B.N.M.v.B., W.M.v.d.F.), and Department of Radiology & Nuclear Medicine (S.C.J.V., F.B., B.N.v.B.), Amsterdam Neuroscience, Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK; Department of Biological Psychology (A.d.B.), Neuroscience Amsterdam, VU University Amsterdam; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; and Department of Neurobiology, Care Sciences and Society (P.J.V.), Division of Neurogeriatrics, Karolinska Institutet, Stockholm Sweden.

Wiesje M van der Flier (WM)

From the Alzheimer Center, Department of Neurology (J.L.E., T.T., L.M.P.W., I.M.W.V., R.E.R.S., A.C.v.H., K.A.v.d.B., M.v.L., J.T., A.d.B., P.J.V., N.D.P., S.A.M.S., P.S., B.N.M.v.B., W.M.v.d.F.), and Department of Radiology & Nuclear Medicine (S.C.J.V., F.B., B.N.v.B.), Amsterdam Neuroscience, Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK; Department of Biological Psychology (A.d.B.), Neuroscience Amsterdam, VU University Amsterdam; Alzheimer Center Limburg (P.J.V.), School for Mental Health and Neuroscience, Maastricht University, the Netherlands; and Department of Neurobiology, Care Sciences and Society (P.J.V.), Division of Neurogeriatrics, Karolinska Institutet, Stockholm Sweden.

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