Prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage

Stephanie J B Vos; Frans Verhey; Lutz Frölich; Johannes Kornhuber; Jens Wiltfang; Wolfgang Maier; Oliver Peters; Eckart Rüther; Flavio Nobili; Silvia Morbelli; Giovanni B Frisoni; Alexander Drzezga; Mira Didic; Bart N M van Berckel; Andrew Simmons; Hilkka Soininen; Iwona Kłoszewska; Patrizia Mecocci; Magda Tsolaki; Bruno Vellas; Simon Lovestone; Cristina Muscio; Sanna-Kaisa Herukka; Eric Salmon; Christine Bastin; Anders Wallin; Arto Nordlund; Alexandre de Mendonça; Dina Silva; Isabel Santana; Raquel Lemos; Sebastiaan Engelborghs; Stefan Van der Mussele; Alzheimer’s Disease Neuroimaging Initiative; Yvonne Freund-Levi; Åsa K Wallin; Harald Hampel; Wiesje van der Flier; Philip Scheltens; Pieter Jelle Visser

doi:10.1093/brain/awv029

Prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage

Brain. 2015 May;138(Pt 5):1327-38. doi: 10.1093/brain/awv029. Epub 2015 Feb 17.

Authors

Stephanie J B Vos¹, Frans Verhey², Lutz Frölich³, Johannes Kornhuber⁴, Jens Wiltfang⁵, Wolfgang Maier⁶, Oliver Peters⁷, Eckart Rüther⁸, Flavio Nobili⁹, Silvia Morbelli¹⁰, Giovanni B Frisoni¹¹, Alexander Drzezga¹², Mira Didic¹³, Bart N M van Berckel¹⁴, Andrew Simmons¹⁵, Hilkka Soininen¹⁶, Iwona Kłoszewska¹⁷, Patrizia Mecocci¹⁸, Magda Tsolaki¹⁹, Bruno Vellas²⁰, Simon Lovestone²¹, Cristina Muscio²², Sanna-Kaisa Herukka¹⁶, Eric Salmon²³, Christine Bastin²⁴, Anders Wallin²⁵, Arto Nordlund²⁵, Alexandre de Mendonça²⁶, Dina Silva²⁶, Isabel Santana²⁷, Raquel Lemos²⁸, Sebastiaan Engelborghs²⁹, Stefan Van der Mussele³⁰; Alzheimer’s Disease Neuroimaging Initiative; Yvonne Freund-Levi³¹, Åsa K Wallin³², Harald Hampel³³, Wiesje van der Flier³⁴, Philip Scheltens³⁴, Pieter Jelle Visser³⁵

Affiliations

¹ 1 Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht, The Netherlands [email protected].
² 1 Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht, The Netherlands.
³ 2 Department of Geriatric Psychiatry, Zentralinstitut für Seelische Gesundheit, University of Heidelberg, Mannheim, Germany.
⁴ 3 Department of Psychiatry and Psychotherapy, Friedrich-Alexander University of Erlangen, Erlangen, Germany.
⁵ 4 Department of Psychiatry and Psychotherapy, University Medical Centre (UMG), Georg-August-University, Göttingen, Germany.
⁶ 5 Department of Psychiatry and Psychotherapy, University of Bonn, German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany.
⁷ 6 Department of Psychiatry and Psychotherapy, Charité Berlin, Berlin, Germany.
⁸ 7 Department of Psychiatry and Psychotherapy, University of Göttingen, Göttingen, Germany.
⁹ 8 Clinical Neurophysiology Service, Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Genoa, Italy.
¹⁰ 9 Nuclear Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.
¹¹ 10 IRCCS San Giovanni di Dio Fatebenefratelli, Brescia, Italy 11 University Hospitals and University of Geneva, Geneva, Switzerland.
¹² 12 Department of Nuclear Medicine, University of Cologne, Cologne, Germany.
¹³ 13 Service de Neurologie et Neuropsychologie, Pôle de neurosciences cliniques, AP-HM Timone, Aix Marseille Université, INS UMR_S 1106, 13005, Marseille, France.
¹⁴ 14 Department of Nuclear Medicine and PET Research, VU University Medical CentRE, Amsterdam, The Netherlands.
¹⁵ 15 Department of Neuroimaging, Centre for Neuroimaging Science, King's College London, Institute of Psychiatry, London, UK.
¹⁶ 16 Institute of Clinical Medicine, Neurology, University of Eastern Finland and Neurocenter, Neurology, Kuopio University Hospital, Kuopio, Finland.
¹⁷ 17 Medical University of Lodz, Lodz, Poland.
¹⁸ 18 Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy.
¹⁹ 19 Aristotle University of Thessaloniki, Memory and Dementia Center, 3rd Department of Neurology, "G Papanicolaou" General Hospital, Thessaloniki, Greece.
²⁰ 20 UMR INSERM 1027, CHU Toulouse, Toulouse, France.
²¹ 21 University of Oxford, Department of Psychiatry, Oxford, UK.
²² 10 IRCCS San Giovanni di Dio Fatebenefratelli, Brescia, Italy 22 Fondazione Europea Ricerca Biomedica (FERB), Centro di Eccellenza Alzheimer, Ospedale Briolini, Gazzaniga, Bergamo, Italy 23 Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
²³ 24 Memory Clinic, Department of Neurology, CHU Liège, Belgium 25 Cyclotron Research Centre, University of Liège, Liège, Belgium.
²⁴ 25 Cyclotron Research Centre, University of Liège, Liège, Belgium.
²⁵ 26 Department of Psychiatry and Neurochemistry, Institute for Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
²⁶ 27 Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon, Portugal.
²⁷ 28 Department of Neurology, Coimbra University Hospital, Coimbra, Portugal.
²⁸ 29 Faculty of Psychology and Educational Sciences, University of Coimbra, Coimbra, Portugal.
²⁹ 30 Reference Centre for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium 31 Department of Neurology and Memory Clinic, Hospital Network Antwerp, Middelheim and Hoge Beuken, Antwerp, Belgium.
³⁰ 30 Reference Centre for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
³¹ 32 Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, and Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
³² 33 Lund University, Clinical Sciences Malmö, Clinical Memory Research Unit, Lund, Sweden.
³³ 34 Centre des Maladies Cognitives et Comportementales, Institut du Cerveau et de la Moelle épinière, Paris, France; Université Pierre et Marie Curie-Paris 6, AP-HP, Hôpital de la Salpêtrière, Paris, France.
³⁴ 35 Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
³⁵ 1 Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht, The Netherlands 35 Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.

Abstract

Three sets of research criteria are available for diagnosis of Alzheimer's disease in subjects with mild cognitive impairment: the International Working Group-1, International Working Group-2, and National Institute of Aging-Alzheimer Association criteria. We compared the prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage according to these criteria. Subjects with mild cognitive impairment (n = 1607), 766 of whom had both amyloid and neuronal injury markers, were recruited from 13 cohorts. We used cognitive test performance and available biomarkers to classify subjects as prodromal Alzheimer's disease according to International Working Group-1 and International Working Group-2 criteria and in the high Alzheimer's disease likelihood group, conflicting biomarker groups (isolated amyloid pathology or suspected non-Alzheimer pathophysiology), and low Alzheimer's disease likelihood group according to the National Institute of Ageing-Alzheimer Association criteria. Outcome measures were the proportion of subjects with Alzheimer's disease at the mild cognitive impairment stage and progression to Alzheimer's disease-type dementia. We performed survival analyses using Cox proportional hazards models. According to the International Working Group-1 criteria, 850 (53%) subjects had prodromal Alzheimer's disease. Their 3-year progression rate to Alzheimer's disease-type dementia was 50% compared to 21% for subjects without prodromal Alzheimer's disease. According to the International Working Group-2 criteria, 308 (40%) subjects had prodromal Alzheimer's disease. Their 3-year progression rate to Alzheimer's disease-type dementia was 61% compared to 22% for subjects without prodromal Alzheimer's disease. According to the National Institute of Ageing-Alzheimer Association criteria, 353 (46%) subjects were in the high Alzheimer's disease likelihood group, 49 (6%) in the isolated amyloid pathology group, 220 (29%) in the suspected non-Alzheimer pathophysiology group, and 144 (19%) in the low Alzheimer's disease likelihood group. The 3-year progression rate to Alzheimer's disease-type dementia was 59% in the high Alzheimer's disease likelihood group, 22% in the isolated amyloid pathology group, 24% in the suspected non-Alzheimer pathophysiology group, and 5% in the low Alzheimer's disease likelihood group. Our findings support the use of the proposed research criteria to identify Alzheimer's disease at the mild cognitive impairment stage. In clinical settings, the use of both amyloid and neuronal injury markers as proposed by the National Institute of Ageing-Alzheimer Association criteria offers the most accurate prognosis. For clinical trials, selection of subjects in the National Institute of Ageing-Alzheimer Association high Alzheimer's disease likelihood group or the International Working Group-2 prodromal Alzheimer's disease group could be considered.

Keywords: Alzheimer’s disease; MCI; biomarkers; diagnostic criteria; prognosis.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adult
Aged
Aged, 80 and over
Alzheimer Disease / complications
Alzheimer Disease / epidemiology*
Biomarkers / metabolism
Cognitive Dysfunction / epidemiology*
Cognitive Dysfunction / etiology
Disease Progression
Female
Humans
Male
Middle Aged
Neuropsychological Tests
Prevalence
Prognosis
Survival Analysis

Substances

Biomarkers

Grants and funding

U01 AG024904/AG/NIA NIH HHS/United States