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

Lisa Vermunt; Sietske A. M. Sikkes; Ardo van den Hout; Ron Handels; Isabelle Bos; Wiesje M. van der Flier; Silke Kern; Pierre-Jean Ousset; Paul Maruff; Ingmar Skoog; Frans R. J. Verhey; Yvonne Freund-Levi; Magda Tsolaki; Asa K. Wallin; Marcel Olde Rikkert; Hilkka Soininen; Luisa Spiru; Henrik Zetterberg; Kaj Blennow; Philip Scheltens; Graciela Muniz-Terrera; Pieter Jelle 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. Froelich; P. Scheltens; C. Ribera; J. Touchon; P. Robert; A. Salva; G. Waldemar; R. Bullock; M. Tsolaki; G. Rodriguez; L. Spiru; Alzheimer's Disease Neuroimaging Initiative; AIBL Research Group; ICTUS study group; DSA Study Group

doi:10.1016/j.jalz.2019.04.001

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

Lisa Vermunt^*, Sietske A. M. Sikkes, Ardo van den Hout, Ron Handels, Isabelle Bos, Wiesje M. van der Flier, Silke Kern, Pierre-Jean Ousset, Paul Maruff, Ingmar Skoog, Frans R. J. Verhey, Yvonne Freund-Levi, Magda Tsolaki, Asa K. Wallin, Marcel Olde Rikkert, Hilkka Soininen, Luisa Spiru, Henrik Zetterberg, Kaj Blennow, Philip ScheltensGraciela Muniz-Terrera, Pieter Jelle 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. Froelich, P. Scheltens, C. Ribera, J. Touchon, P. Robert, A. Salva, G. Waldemar, R. Bullock, M. Tsolaki, G. Rodriguez, L. Spiru, Alzheimer's Disease Neuroimaging Initiative, AIBL Research Group, ICTUS study group, DSA Study Group

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

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.

Original language	English
Pages (from-to)	888-898
Number of pages	11
Journal	Alzheimer's & Dementia
Volume	15
Issue number	7
DOIs	https://doi.org/10.1016/j.jalz.2019.04.001
Publication status	Published - Jul 2019

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

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Vermunt, L., Sikkes, S. A. M., van den Hout, A., Handels, R., Bos, I., van der Flier, W. M., Kern, S., Ousset, P-J., Maruff, P., Skoog, I., Verhey, F. R. J., Freund-Levi, Y., Tsolaki, M., Wallin, A. K., Rikkert, M. O., Soininen, H., Spiru, L., Zetterberg, H., Blennow, K., ... DSA Study Group (2019). Duration of preclinical, prodromal, and dementia stages of Alzheimer's disease in relation to age, sex, and APOE genotype. Alzheimer's & Dementia, 15(7), 888-898. https://doi.org/10.1016/j.jalz.2019.04.001

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

abstract = "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.",

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",

author = "Lisa Vermunt and Sikkes, {Sietske A. M.} and {van den Hout}, Ardo and Ron Handels and Isabelle Bos and {van der Flier}, {Wiesje M.} and Silke Kern and Pierre-Jean Ousset and Paul Maruff and Ingmar Skoog and Verhey, {Frans R. J.} and Yvonne Freund-Levi and Magda Tsolaki and Wallin, {Asa K.} and Rikkert, {Marcel Olde} and Hilkka Soininen and Luisa Spiru and Henrik Zetterberg and Kaj Blennow and Philip Scheltens and Graciela Muniz-Terrera and Visser, {Pieter Jelle} and B. Vellas and E. Reynish and Ousset, {P. J.} and S. Andrieu and A. Burns and F. Pasquier and G. Frisoni and E. Salmon and Michel, {J. P.} and Zekry, {D. S.} and M. Boada and Dartigues, {J. F.} and Olde-Rikkert, {M. G. M.} and Rigaud, {A. S.} and B. Winblad and A. Malick and A. Sinclair and L. Froelich and P. Scheltens and C. Ribera and J. Touchon and P. Robert and A. Salva and G. Waldemar and R. Bullock and M. Tsolaki and G. Rodriguez and L. Spiru and {Alzheimer's Disease Neuroimaging Initiative} and {AIBL Research Group} and {ICTUS study group} and {DSA Study Group}",

year = "2019",

month = jul,

doi = "10.1016/j.jalz.2019.04.001",

language = "English",

volume = "15",

pages = "888--898",

journal = "Alzheimer's & Dementia",

issn = "1552-5260",

publisher = "Elsevier Science",

number = "7",

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Vermunt, L, Sikkes, SAM, van den Hout, A, Handels, R, Bos, I, van der Flier, WM, Kern, S, Ousset, P-J, Maruff, P, Skoog, I, Verhey, FRJ, Freund-Levi, Y, Tsolaki, M, Wallin, AK, Rikkert, MO, Soininen, H, Spiru, L, Zetterberg, H, Blennow, K, Scheltens, P, Muniz-Terrera, G, Visser, PJ, Vellas, B, Reynish, E, Ousset, PJ, Andrieu, S, Burns, A, Pasquier, F, Frisoni, G, Salmon, E, Michel, JP, Zekry, DS, Boada, M, Dartigues, JF, Olde-Rikkert, MGM, Rigaud, AS, Winblad, B, Malick, A, Sinclair, A, Froelich, L, Scheltens, P, Ribera, C, Touchon, J, Robert, P, Salva, A, Waldemar, G, Bullock, R, Tsolaki, M, Rodriguez, G, Spiru, L, Alzheimer's Disease Neuroimaging Initiative, AIBL Research Group, ICTUS study group & DSA Study Group 2019, 'Duration of preclinical, prodromal, and dementia stages of Alzheimer's disease in relation to age, sex, and APOE genotype', Alzheimer's & Dementia, vol. 15, no. 7, pp. 888-898. https://doi.org/10.1016/j.jalz.2019.04.001

TY - JOUR

T1 - Duration of preclinical, prodromal, and dementia stages of Alzheimer's disease in relation to age, sex, and APOE genotype

AU - Vermunt, Lisa

AU - Sikkes, Sietske A. M.

AU - van den Hout, Ardo

AU - Handels, Ron

AU - Bos, Isabelle

AU - van der Flier, Wiesje M.

AU - Kern, Silke

AU - Ousset, Pierre-Jean

AU - Maruff, Paul

AU - Skoog, Ingmar

AU - Verhey, Frans R. J.

AU - Freund-Levi, Yvonne

AU - Tsolaki, Magda

AU - Wallin, Asa K.

AU - Rikkert, Marcel Olde

AU - Soininen, Hilkka

AU - Spiru, Luisa

AU - Zetterberg, Henrik

AU - Blennow, Kaj

AU - Scheltens, Philip

AU - Muniz-Terrera, Graciela

AU - Visser, Pieter Jelle

AU - Vellas, B.

AU - Reynish, E.

AU - Ousset, P. J.

AU - Andrieu, S.

AU - Burns, A.

AU - Pasquier, F.

AU - Frisoni, G.

AU - Salmon, E.

AU - Michel, J. P.

AU - Zekry, D. S.

AU - Boada, M.

AU - Dartigues, J. F.

AU - Olde-Rikkert, M. G. M.

AU - Rigaud, A. S.

AU - Winblad, B.

AU - Malick, A.

AU - Sinclair, A.

AU - Froelich, L.

AU - Scheltens, P.

AU - Ribera, C.

AU - Touchon, J.

AU - Robert, P.

AU - Salva, A.

AU - Waldemar, G.

AU - Bullock, R.

AU - Tsolaki, M.

AU - Rodriguez, G.

AU - Spiru, L.

AU - Alzheimer's Disease Neuroimaging Initiative

AU - AIBL Research Group

AU - ICTUS study group

AU - DSA Study Group

PY - 2019/7

Y1 - 2019/7

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Disease duration

KW - Preclinical

KW - Prodromal

KW - Dementia

KW - APOE

KW - Clinical setting

KW - Progression

KW - Multistate model

KW - MILD COGNITIVE IMPAIRMENT

KW - BETA-AMYLOID 1-42

KW - ASSOCIATION WORKGROUPS

KW - DIAGNOSTIC GUIDELINES

KW - NATIONAL INSTITUTE

KW - RISK-FACTORS

KW - DECLINE

KW - PREVALENCE

KW - NEURODEGENERATION

KW - RECOMMENDATIONS

U2 - 10.1016/j.jalz.2019.04.001

DO - 10.1016/j.jalz.2019.04.001

M3 - Article

VL - 15

SP - 888

EP - 898

JO - Alzheimer's & Dementia

JF - Alzheimer's & Dementia

SN - 1552-5260

IS - 7

ER -