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

AIBL Research Group, Alzheimer Disease Neuroimaging Initiative

Research output: Contribution to journalArticleAcademicpeer-review

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 ε4 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.
Original languageEnglish
JournalAlzheimer's and Dementia
DOIs
Publication statusPublished - 2019

Cite this

@article{8d944e2fd3ab45bf980d06de37ab6497,
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 ε4 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.",
author = "{AIBL Research Group} and {Alzheimer Disease Neuroimaging Initiative} and 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, {{\AA}sa K.} and {Olde Rikkert}, Marcel 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. Fr{\"o}lich 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 P. Scheltens",
year = "2019",
doi = "10.1016/j.jalz.2019.04.001",
language = "English",
journal = "Alzheimers & Dementia",
issn = "1552-5260",
publisher = "Elsevier",

}

Duration of preclinical, prodromal, and dementia stages of Alzheimer's disease in relation to age, sex, and APOE genotype. / AIBL Research Group; Alzheimer Disease Neuroimaging Initiative.

In: Alzheimer's and Dementia, 2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

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

AU - AIBL Research Group

AU - Alzheimer Disease Neuroimaging Initiative

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, Åsa K.

AU - Olde Rikkert, Marcel

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 - Frölich, 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 - Scheltens, P.

PY - 2019

Y1 - 2019

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 ε4 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.

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 ε4 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.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85066298869&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/31164314

U2 - 10.1016/j.jalz.2019.04.001

DO - 10.1016/j.jalz.2019.04.001

M3 - Article

JO - Alzheimers & Dementia

JF - Alzheimers & Dementia

SN - 1552-5260

ER -