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Duration of preclinical, prodromal, and dementia stages of Alzheimer's disease in relation to age, sex, and APOE genotype

Journal article
Authors L. Vermunt
S. A. M. Sikkes
A. van den Hout
R. Handels
I. Bos
W. M. van der Flier
Silke Kern
P. J. Ousset
P. Maruff
Ingmar Skoog
F. R. J. Verhey
Y. Freund-Levi
M. Tsolaki
A. K. Wallin
M. O. Rikkert
H. Soininen
L. Spiru
Henrik Zetterberg
Kaj Blennow
P. Scheltens
G. Muniz-Terrera
P. J. Visser
B. Vellas
E. Reynish
P. J. Ousset
S. Andrieu
A. Burns
F. Pasquier
G. Frisoni
E. Salmon
J. P. Michel
D. S. Zekry
M. Boada
J. F. Dartigues
M. G. M. Olde-Rikkert
A. S. Rigaud
B. Winblad
A. Malick
A. Sinclair
L. Frolich
P. Scheltens
C. Ribera
J. Touchon
P. Robert
A. Salva
G. Waldemar
R. Bullock
M. Tsolaki
G. Rodriguez
L. Spiru
R. W. Jones
G. Stiens
G. Stoppe
M. E. Jonhagen
A. Cherubini
P. M. Lage
T. Gomezisla
V. Camus
E. Aguera-Morales
F. Lopez
S. Savy
C. Cantet
N. Coley
Published in Alzheimers & Dementia
Volume 15
Issue 7
Pages 888-898
ISSN 1552-5260
Publication year 2019
Published at Institute of Neuroscience and Physiology
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 888-898
Language en
Keywords Alzheimer's disease, Disease duration, Preclinical, Prodromal, Dementia, APOE, Clinical setting, Progression, Multistate model, mild cognitive impairment, beta-amyloid 1-42, association workgroups, diagnostic guidelines, national institute, risk-factors, decline, prevalence, neurodegeneration, recommendations, Neurosciences & Neurology, khann g, 1984, neurology, v34, p939
Subject categories Neurosciences


Introduction: We estimated the age-specific duration of the preclinical, prodromal, and dementia stages of Alzheimer's disease (AD) and the influence of sex, setting, apolipoprotein E (APOE) genotype, and cerebrospinal fluid tau on disease duration. Methods: We performed multistate modeling in a combined sample of 6 cohorts (n = 3268) with death as the end stage and estimated the preclinical, prodromal, and dementia stage duration. Results: The overall AD duration varied between 24 years (age 60) and 15 years (age 80). For individuals presenting with preclinical AD, age 70, the estimated preclinical AD duration was 10 years, prodromal AD 4 years, and dementia 6 years. Male sex, clinical setting, APOE epsilon 4 allele carriership, and abnormal cerebrospinal fluid tau were associated with a shorter duration, and these effects depended on disease stage. Discussion: Estimates of AD disease duration become more accurate if age, sex, setting, APOE, and cerebrospinal fluid tau are taken into account. This will be relevant for clinical practice and trial design. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

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