ATN profiles among cognitively normal individuals and longitudinal cognitive outcomes.

Aged Alzheimer Disease / cerebrospinal fluid Amyloid beta-Peptides / cerebrospinal fluid Cognition Cohort Studies Disease Progression Female Humans Longitudinal Studies Male Middle Aged Peptide Fragments / cerebrospinal fluid Phosphoproteins / cerebrospinal fluid tau Proteins / cerebrospinal fluid

Journal

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

Informations de publication

Date de publication:
02 04 2019
Historique:
received: 09 04 2018
accepted: 27 11 2018
pubmed: 8 3 2019
medline: 18 12 2019
entrez: 8 3 2019
Statut: ppublish

Résumé

To examine the long-term cognitive trajectories of individuals with normal cognition at baseline and distinct amyloid/tau/neurodegeneration (ATN) profiles. Pooling data across 4 cohort studies, 814 cognitively normal participants (mean baseline age = 59.6 years) were classified into 8 ATN groups using baseline CSF levels of β-amyloid 1-42 as a measure of amyloid (A), phosphorylated tau 181 as a measure of tau (T), and total tau as a measure of neurodegeneration (N). Cognitive performance was measured using a previously validated global factor score and with the Mini-Mental State Examination. We compared the cognitive trajectories across groups using growth curve models (mean follow-up time = 7 years). Using different model formulations and cut points for determining biomarker abnormality, only the group with abnormal levels of amyloid, tau, and neurodegeneration (A+T+N+) showed consistently greater cognitive decline than the group with normal levels of all biomarkers (A-T-N-). Replicating prior findings using the 2011 National Institute on Aging-Alzheimer's Association/suspected non-Alzheimer disease pathophysiology schema, only individuals with abnormal levels of both amyloid and phosphorylated tau 181 or total tau (stage 2) showed greater cognitive decline than those with normal biomarker levels (stage 0). The results are consistent with the hypothesis that both elevated brain amyloid and neurofibrillary tangles are necessary to observe accelerated neurodegeneration, which in turn leads to cognitive decline.

Identifiants

DOI: 10.1212/WNL.0000000000007248 PMID: 30842300 PMC: PMC6448449
pubmed: 30842300
pii: WNL.0000000000007248
doi: 10.1212/WNL.0000000000007248
pmc: PMC6448449
doi:

Substances chimiques

Amyloid beta-Peptides 0
MAPT protein, human 0
Peptide Fragments 0
Phosphoproteins 0
amyloid beta-protein (1-42) 0
tau Proteins 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1567-e1579

Subventions

Organisme : NIA NIH HHS
ID : P30 AG066507
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG058676
Pays : United States
Organisme : NIA NIH HHS
ID : K23 AG053426
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG059869
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062715
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG033514
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG026276
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG033655
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2019 American Academy of Neurology.

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Auteurs

Anja Soldan (A)

From the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. asoldan1@jhmi.edu.

Corinne Pettigrew (C)

From the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
ORCID: 0000-0003-4264-275X

Anne M Fagan (AM)

From the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Suzanne E Schindler (SE)

From the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Abhay Moghekar (A)

From the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Christopher Fowler (C)

From the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Qiao-Xin Li (QX)

From the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Steven J Collins (SJ)

From the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Cynthia Carlsson (C)

From the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Sanjay Asthana (S)

From the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Colin L Masters (CL)

From the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Sterling Johnson (S)

From the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

John C Morris (JC)

From the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Marilyn Albert (M)

From the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Alden L Gross (AL)

From the Department of Neurology (A.S., C.P., A.M., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (A.M.F., S.E.S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Florey Institute of Neuroscience and Mental Health (C.F., Q.-X.L., S.J.C., C.L.M.), the University of Melbourne, Australia; Geriatric Research Education and Clinical Center (C.C., S.A., S.J.), Wm. S. Middleton Memorial VA Hospital and Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison; and Center on Aging and Health and Department of Epidemiology (A.L.G.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › ATN profiles among cognitively normal...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie d'Alzheimer › ATN profiles among cognitively normal...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Peptides bêta-amyloïdes › ATN profiles among cognitively normal...
questionsmedicales.fr › Phénomènes psychologiques › Processus mentaux › Cognition › ATN profiles among cognitively normal...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › ATN profiles among cognitively normal...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › ATN profiles among cognitively normal...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › ATN profiles among cognitively normal...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études longitudinales › ATN profiles among cognitively normal...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › ATN profiles among cognitively normal...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Fragments peptidiques › ATN profiles among cognitively normal...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Phosphoprotéines › ATN profiles among cognitively normal...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Protéines associées aux microtubules › Protéines tau › ATN profiles among cognitively normal...