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Alzheimers Dement. 2019 Jun 1. pii: S1552-5260(19)30084-6. doi: 10.1016/j.jalz.2019.04.001. [Epub ahead of print]

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

Author information

1
Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. Electronic address: l.vermunt@vumc.nl.
2
Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
3
Department of Statistical Science, University College London, London, UK.
4
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Alzheimer Centrum Limburg, Maastricht University, Maastricht, The Netherlands.
5
Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands; Department of Epidemiology and Biostatistics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
6
Department of Psychiatry and Neurochemistry, Neuropsychiatric Epidemiology Unit, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
7
CHU Toulouse, Gérontopôle and INSERM UMR 1027, Toulouse, France.
8
Cogstate Ltd, Florey Institute, University of Melbourne, Melbourne, Australia.
9
Department of Neurobiology, Caring Sciences and Society (NVS), Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Old Age Psychiatry, Psychology and Neuroscience, King's College London, London, UK; School of Medical Sciences, Orebro University Campus USÖ, Örebro, Sweden.
10
3rd Department of Neurology, Aristotle University of Thessaloniki, Memory and Dementia Center, "G Papanicolau" General Hospital, Thessaloniki, Greece.
11
Department of Clinical Sciences, Clinical Memory Research Unit, Lund University, Malmö, Sweden.
12
Department of Geriatric Medicine, Radboudumc Alzheimer Centre, Radboud University Medical Center, Nijmegen, The Netherlands.
13
Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland.
14
"Carol Davila" University of Medicine and Pharmacy, Geriatrics-Gerontology and Old Age Psychiatry Clinical Department -"Elias" University Clinical Hospital, Bucarest, Romenia; "Ana Aslan" International Academy of Aging - The Memory Clinic and Longevity Medicine, Bucarest, Romenia.
15
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK; UK Dementia Research Institute at UCL, London, UK.
16
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
17
Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
18
Centre for Dementia Prevention, University of Edinburgh, Edinburgh, UK.
19
Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Alzheimer Centrum Limburg, Maastricht University, Maastricht, The Netherlands.

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.

KEYWORDS:

APOE; Alzheimer's disease; Clinical setting; Dementia; Disease duration; Multistate model; Preclinical; Prodromal; Progression

PMID:
31164314
DOI:
10.1016/j.jalz.2019.04.001

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