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Cited by 383Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCancer-related cognitive impairment studies

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

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Vos, Stephanie J. B., Verhey, Frans, Frölich, Lutz, Kornhuber, Johannes, Wiltfang, Jens, Maier, Wolfgang, Peters, Oliver, Rüther, Eckart +32 more·2015·Brain
DOI 10.1093/brain/awv029PMC PMC5013930
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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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  • MCI patients with biomarker-based evidence of Alzheimer's disease have a high risk of approximately 70% to develop Alzheimer's dementia within 3 years.

    “However, MCI patients with a biomarker-based evidence of AD have a high risk of approximately 70% to develop Alzheimer’s dementia within 3 years [9].”

    From Psychotherapeutic interventions in individuals at risk for Alzheimer’s dementia: a systematic review (2022) · cites this paper as [9]

    The Abstract reports a high 3-year risk of Alzheimer’s disease-type dementia in biomarker-defined MCI groups, but the rates are 61% under IWG-2 criteria and 59% in the NIA-AA high-likelihood group, not approximately 70%. A table reproduced in the Discussion reports 68% for a more narrowly defined biomarker subgroup, but that figure is for progression at last follow-up, not specifically within three years. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • In a pooled memory clinic cohort, the median prodromal Alzheimer's disease duration was three years, with no age-specific estimates and no adjustment for mortality.

    “The median duration of prodromal AD was three years in a pooled memory clinic cohort study, but no age-specific estimates were provided and mortality was not taken into account [18].”

    From Duration of preclinical, prodromal, and dementia stages of Alzheimer's disease in relation to age, sex, and <i>APOE</i> genotype (2019) · cites this paper as [18]

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Authors
Vos, S. J. B., Verhey, F., Frölich, L., Kornhuber, J., Wiltfang, J., Maier, W., Peters, O., Rüther, E., Nobili, F., Morbelli, S., Frisoni, G. B., Drzezga, A., Didic, M., van Berckel, B. N. M., Simmons, A., Soininen, H., Kłoszewska, I., Mecocci, P., Tsolaki, M., Vellas, B., Lovestone, S., Muscio, C., Herukka, S.-K., Salmon, E., Bastin, C., Wallin, A., Nordlund, A., de Mendonça, A., Silva, D., Santana, I., Lemos, R., Engelborghs, S., Van der Mussele, S., Initiative, T. A. D. N., Freund-Levi, Y., Wallin, Å. K., Hampel, H., van der Flier, W., Scheltens, P., & Visser, P. J.
Affiliations
  • Maastricht University (NL)
  • Heidelberg University (DE)
  • Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
  • Universitätsmedizin Göttingen (DE)
  • University of Bonn (DE)
  • Stiftung Charité (DE)
  • University of Göttingen (DE)
  • University of Genoa (IT)
  • University of Geneva (CH)
  • University of Cologne (DE)
  • Aix-Marseille Université (FR)
  • King's College London (GB)
  • University of Eastern Finland (FI)
  • Medical University of Lodz (PL)
  • University of Perugia (IT)
  • Aristotle University of Thessaloniki (GR)
  • Inserm (FR)
  • University of Oxford (GB)
  • Centro San Giovanni di Dio Fatebenefratelli (IT)
  • University of Liège (BE)
  • Lund University (SE)
  • University of Gothenburg (SE)
  • University of Lisbon (PT)
  • Unidade Local de Saúde de Coimbra (PT)
  • University of Coimbra (PT)
  • University of Antwerp (BE)
  • Karolinska University Hospital (SE)
  • Assistance Publique – Hôpitaux de Paris (FR)
ORCID
Venue
Brain
Publisher
Oxford University Press (OUP)
Published
2015-02-17
Volume
138
Issue
5
Pages
1327-1338
ISSN
  • 0006-8950 (ISSN-L)
  • 1460-2156
DOI
10.1093/brain/awv029
PMC
PMC5013930
OpenAlex
W2152163581
Cited by
383
References
34
Citations by year
2026: 18 · 2025: 23 · 2024: 35 · 2023: 26 · 2022: 43 · 2021: 40 · 2020: 39 · 2019: 40 · 2018: 33 · 2017: 37 · 2016: 32 · 2015: 17
FWCI
32.17
Type
journal article
Language
en
Open access
Locations
  • Brain (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Research Publications (Maastricht University) (publishedVersion, other-oa)
  • Pure Amsterdam UMC (publishedVersion, other-oa)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
  • Archive ouverte UNIGE (University of Geneva) (publishedVersion)
  • reroDoc Digital Library (submittedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
  • CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion, other-oa)
  • Research Portal (King's College London) (submittedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
  • ORBi (University of Liège) (submittedVersion)
  • DZNE Pub (submittedVersion)
  • GRO (submittedVersion)
  • Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion)
  • OPUS FAU (Kooperativer Bibliotheksverbund Berlin-Brandenburg (KOBV), on behalf of the Universitätsbibliothek Erlangen-Nürnberg) (submittedVersion)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
  • VUBIR (Vrije Universiteit Brussel) (submittedVersion)
  • Research Publications (Maastricht University) (submittedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Funders
  • U.S. Department of Defense (U01 AG024904, W81XWH, W81XWH-12-2-, W81XWH-12, W81XWH1220012, AG024904)
  • Foundation for the National Institutes of Health (W81XWH-12-2-0012, U01AG024904, Grant U01 AG024904, AG024904)
  • Alzheimer's Association (U01 AG024904, W81XWH-12-2-0012)
  • Bristol-Myers Squibb (U01 AG024904, AG024904, W81XWH-12-2-0012)
  • Eli Lilly and Company (FP6-2004-LIFESCIHEALTH-5, U01 AG024904, AG024904, W81XWH-12-2-0012)
  • Pfizer (AG024904, W81XWH-12-2-0012, 115372, U01 AG024904)
  • Biogen (W81XWH-12-2-0012, U01 AG024904, AG024904)
  • University of Southern California (W81XWH-12-2-0012, U01 AG024904)
  • F. Hoffmann-La Roche (W81XWH-12-2-0012, AG024904, U01 AG024904)
  • Medpace (U01 AG024904)
  • Meso Scale Diagnostics (U01 AG024904, AG024904, W81XWH-12-2-0012)
  • Synarc (U01 AG024904)
  • Alzheimer's Disease Neuroimaging Initiative (W81XWH-12-2–0012, U01AG024904, AG024904, W81XWH-12-2-, Department of Defense award number W81XWH-12-2-0012)
  • BioClinica (U01 AG024904, W81XWH-12-2-0012, AG024904)
  • Novartis Pharmaceuticals Corporation (W81XWH-12-2-0012, U01 AG024904, AG024904)
  • Northern California Institute for Research and Education (U01 AG024904, W81XWH-12-2-0012)
  • European Federation of Pharmaceutical Industries and Associations (115372)
  • National Institute for Health and Care Research (NF-SI-0512-10053)
  • European Commission (U01 AG024904, 2007–2013, W81XWH-12-2-0012, QLRT-2001-2455, FP6-2004-LIFESCIHEALTH-5, 115372)
  • Eisai (W81XWH-12-2-0012, U01 AG024904, AG024904)
  • Center for Translational Molecular Medicine (02N-101)
  • Stichting Dioraphte
  • Innovative Medicines Initiative (#115372)
  • Alzheimer Nederland
  • Servier (AG024904, W81XWH-12-2-0012, U01 AG024904)
  • IXICO (AG024904, W81XWH-12-2-0012, U01 AG024904)
  • National Institutes of Health (3u01ag024904-10s2, W81XWH, W81XWH-12-2-0012, U01-AG024904, Grant U01 AG024904, AG024904)
  • Genentech (W81XWH-12-2-0012, AG024904, U01 AG024904)
  • University of California, San Diego
  • Canadian Institutes of Health Research (U01 AG024904, W81XWH-12-2-0012)
  • National Institute on Aging (U01-AG-024904, W81XWH-12-2–0012, AG 024904)
  • National Institute of Biomedical Imaging and Bioengineering (W81XWH-12-2-0012, U01 AG024904, AG024904)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
Keywords
Alzheimer's disease, mild cognitive impairment, prodromal Alzheimer's disease, diagnostic criteria, NIA-AA criteria, amyloid biomarkers, conversion to dementia, prevalence, prognosis, amyloid pathology, survival analysis, cohort studies, cognitive test performance
MeSH terms
Adult, Aged, Aged, 80 and over, Alzheimer Disease, Female, Humans, Male, Middle Aged, Neuropsychological Tests, Prognosis, Biomarkers, Prevalence, Survival Analysis, Disease Progression, Cognitive Dysfunction

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