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

Stephanie J. B. Vos; Frans Verhey; Lutz Froelich; Johannes Kornhuber; Jens Wiltfang; Wolfgang Maier; Oliver Peters; Eckart Ruether; Flavio Nobili; Silvia Morbelli; Giovanni B. Frisoni; Alexander Drzezga; Mira Didic; Bart N. M. van Berckel; Andrew Simmons; Hilkka Soininen; Iwona Kloszewska; Patrizia Mecocci; Magda Tsolaki; Bruno Vellas; Simon Lovestone; Cristina Muscio; Sanna-Kaisa Herukka; Eric Salmon; Christine Bastin; Anders Wallin; Arto Nordlund; Alexandre de Mendonca; Dina Silva; Isabel Santana; Raquel Lemos; Sebastiaan Engelborghs; Stefan Van der Mussele; Yvonne Freund-Levi; Asa 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

Stephanie J. B. Vos^*, Frans Verhey, Lutz Froelich, Johannes Kornhuber, Jens Wiltfang, Wolfgang Maier, Oliver Peters, Eckart Ruether, Flavio Nobili, Silvia Morbelli, Giovanni B. Frisoni, Alexander Drzezga, Mira Didic, Bart N. M. van Berckel, Andrew Simmons, Hilkka Soininen, Iwona Kloszewska, Patrizia Mecocci, Magda Tsolaki, Bruno VellasSimon Lovestone, Cristina Muscio, Sanna-Kaisa Herukka, Eric Salmon, Christine Bastin, Anders Wallin, Arto Nordlund, Alexandre de Mendonca, Dina Silva, Isabel Santana, Raquel Lemos, Sebastiaan Engelborghs, Stefan Van der Mussele, Yvonne Freund-Levi, Asa K. Wallin, Harald Hampel, Wiesje van der Flier, Philip Scheltens, Pieter Jelle Visser

^*Corresponding author for this work

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

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.

Original language	English
Pages (from-to)	1327-1338
Journal	Brain
Volume	138
DOIs	https://doi.org/10.1093/brain/awv029
Publication status	Published - 1 May 2015

Keywords

Alzheimer's disease
MCI
biomarkers
diagnostic criteria
prognosis

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10.1093/brain/awv029

Cite this

Vos, S. J. B., Verhey, F., Froelich, L., Kornhuber, J., Wiltfang, J., Maier, W., Peters, O., Ruether, E., Nobili, F., Morbelli, S., Frisoni, G. B., Drzezga, A., Didic, M., van Berckel, B. N. M., Simmons, A., Soininen, H., Kloszewska, I., Mecocci, P., Tsolaki, M., ... Visser, P. J. (2015). Prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage. Brain, 138, 1327-1338. https://doi.org/10.1093/brain/awv029

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title = "Prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage",

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.",

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author = "Vos, {Stephanie J. B.} and Frans Verhey and Lutz Froelich and Johannes Kornhuber and Jens Wiltfang and Wolfgang Maier and Oliver Peters and Eckart Ruether and Flavio Nobili and Silvia Morbelli and Frisoni, {Giovanni B.} and Alexander Drzezga and Mira Didic and {van Berckel}, {Bart N. M.} and Andrew Simmons and Hilkka Soininen and Iwona Kloszewska and Patrizia Mecocci and Magda Tsolaki and Bruno Vellas and Simon Lovestone and Cristina Muscio and Sanna-Kaisa Herukka and Eric Salmon and Christine Bastin and Anders Wallin and Arto Nordlund and {de Mendonca}, Alexandre and Dina Silva and Isabel Santana and Raquel Lemos and Sebastiaan Engelborghs and {Van der Mussele}, Stefan and Yvonne Freund-Levi and Wallin, {Asa K.} and Harald Hampel and {van der Flier}, Wiesje and Philip Scheltens and Visser, {Pieter Jelle}",

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Vos, SJB , Verhey, F, Froelich, L, Kornhuber, J, Wiltfang, J, Maier, W, Peters, O, Ruether, E, Nobili, F, Morbelli, S, Frisoni, GB, Drzezga, A, Didic, M, van Berckel, BNM, Simmons, A, Soininen, H, Kloszewska, I, Mecocci, P, Tsolaki, M, Vellas, B, Lovestone, S, Muscio, C, Herukka, S-K, Salmon, E, Bastin, C, Wallin, A, Nordlund, A, de Mendonca, A, Silva, D, Santana, I, Lemos, R, Engelborghs, S, Van der Mussele, S, Freund-Levi, Y, Wallin, AK, Hampel, H, van der Flier, W, Scheltens, P & Visser, PJ 2015, 'Prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage', Brain, vol. 138, pp. 1327-1338. https://doi.org/10.1093/brain/awv029

TY - JOUR

T1 - Prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage

AU - Vos, Stephanie J. B.

AU - Verhey, Frans

AU - Froelich, Lutz

AU - Kornhuber, Johannes

AU - Wiltfang, Jens

AU - Maier, Wolfgang

AU - Peters, Oliver

AU - Ruether, Eckart

AU - Nobili, Flavio

AU - Morbelli, Silvia

AU - Frisoni, Giovanni B.

AU - Drzezga, Alexander

AU - Didic, Mira

AU - van Berckel, Bart N. M.

AU - Simmons, Andrew

AU - Soininen, Hilkka

AU - Kloszewska, Iwona

AU - Mecocci, Patrizia

AU - Tsolaki, Magda

AU - Vellas, Bruno

AU - Lovestone, Simon

AU - Muscio, Cristina

AU - Herukka, Sanna-Kaisa

AU - Salmon, Eric

AU - Bastin, Christine

AU - Wallin, Anders

AU - Nordlund, Arto

AU - de Mendonca, Alexandre

AU - Silva, Dina

AU - Santana, Isabel

AU - Lemos, Raquel

AU - Engelborghs, Sebastiaan

AU - Van der Mussele, Stefan

AU - Freund-Levi, Yvonne

AU - Wallin, Asa K.

AU - Hampel, Harald

AU - van der Flier, Wiesje

AU - Scheltens, Philip

AU - Visser, Pieter Jelle

PY - 2015/5/1

Y1 - 2015/5/1

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - MCI

KW - biomarkers

KW - diagnostic criteria

KW - prognosis

U2 - 10.1093/brain/awv029

DO - 10.1093/brain/awv029

M3 - Article

C2 - 25693589

SN - 0006-8950

VL - 138

SP - 1327

EP - 1338

JO - Brain

JF - Brain

ER -