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

被引：381

作者：

Vermunt, Lisa ^{[1
]}

Sikkes, Sietske A. M. ^{[1
,2
]}

van den Hout, Ardo ^{[3
]}

Handels, Ron ^{[4
]}

Bos, Isabelle ^{[4
]}

van der Flier, Wiesje M. ^{[1
,5
]}

Kern, Silke ^{[6
]}

Ousset, Pierre-Jean ^{[7
,8
]}

Maruff, Paul ^{[9
]}

Skoog, Ingmar ^{[6
]}

Verhey, Frans R. J. ^{[4
]}

Freund-Levi, Yvonne ^{[10
,11
,12
]}

Tsolaki, Magda ^{[13
]}

Wallin, Asa K. ^{[14
]}

Rikkert, Marcel Olde ^{[15
]}

Soininen, Hilkka ^{[16
]}

Spiru, Luisa ^{[17
,18
]}

Zetterberg, Henrik ^{[19
,20
,21
,22
]}

Blennow, Kaj ^{[19
,20
]}

Scheltens, Philip ^{[1
]}

Muniz-Terrera, Graciela ^{[23
]}

Visser, Pieter Jelle ^{[1
,4
]}

Vellas, B.

Reynish, E.

Ousset, P. J.

Andrieu, S.

Burns, A.

Pasquier, F.

Frisoni, G.

Salmon, E.

Michel, J. P.

Zekry, D. S.

Boada, M.

Dartigues, J. F.

Olde-Rikkert, M. G. M.

Rigaud, A. S.

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.

机构：

[1] Vrije Univ Amsterdam, Amsterdam UMC, Amsterdam Neurosci, Dept Neurol,Alzheimer Ctr Amsterdam, Amsterdam, Netherlands

[2] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA

[3] UCL, Dept Stat Sci, London, England

[4] Maastricht Univ, Alzheimer Ctr Limburg, Sch Mental Hlth & Neurosci MHeNS, Dept Psychiat & Neuropsychol, Maastricht, Netherlands

[5] Vrije Univ Amsterdam, Dept Epidemiol & Biostat, Amsterdam UMC, Amsterdam, Netherlands

[6] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem,Neuropsychiat Epidemiol, Gothenburg, Sweden

[7] CHU Toulouse, Gerontopole, Toulouse, France

[8] INSERM UMR 1027, Toulouse, France

[9] Univ Melbourne, Florey Inst, Cogstate Ltd, Melbourne, Vic, Australia

[10] Karolinska Univ Hosp Huddinge, Dept Neurobiol Caring Sci & Soc NVS, Stockholm, Sweden

[11] Kings Coll London, Dept Old Age Psychiat Psychol & Neurosci, London, England

[12] Sch Med Sci, Orebro Univ Campus USO, Orebro, Sweden

[13] Aristotle Univ Thessaloniki, Dept Neurol 3, Memory & Dementia Ctr, G Papanicolau Gen Hosp, Thessaloniki, Greece

[14] Lund Univ, Dept Clin Sci, Clin Memory Res Unit, Malmo, Sweden

[15] Radboud Univ Nijmegen, Radboudumc Alzheimer Ctr, Dept Geriatr Med, Med Ctr, Nijmegen, Netherlands

[16] Univ Eastern Finland, Inst Clin Med, Neurol, Kuopio, Finland

[17] Carol Davila Univ Med & Pharm, Geriatr Gerontol & Old Age Psychiat Clin Dept, Elias Univ Clin Hosp, Bucharest, Romania

[18] Ana Aslan Int Acad Aging, Memory Clin & Longev Med, Bucharest, Romania

[19] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden

[20] Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden

[21] UCL Inst Neurol, Dept Neurodegenerat Dis, Queen Sq, London, England

[22] UCL, UK Dementia Res Inst, London, England

[23] Univ Edinburgh, Ctr Dementia Prevent, Edinburgh, Midlothian, Scotland

来源：

ALZHEIMERS & DEMENTIA | 2019年 / 15卷 / 07期

关键词：

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;

D O I：

10.1016/j.jalz.2019.04.001

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：888 / 898

页数：11

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