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Prediction of dementia in MCI patients based on core diagnostic markers for Alzheimer disease
Open accessAbstract
OBJECTIVES: The current model of Alzheimer disease (AD) stipulates that brain amyloidosis biomarkers turn abnormal earliest, followed by cortical hypometabolism, and finally brain atrophy ones. The aim of this study is to provide clinical evidence of the model in patients with mild cognitive impairment (MCI). METHODS: A total of 73 patients with MCI from 3 European memory clinics were included. Brain amyloidosis was assessed by CSF Aβ42 concentration, cortical metabolism by an index of temporoparietal hypometabolism on FDG-PET, and brain atrophy by automated hippocampal volume. Patients were divided into groups based on biomarker positivity: 1) Aβ42- FDG-PET- Hippo-, 2) Aβ42+ FDG-PET- Hippo-, 3) Aβ42 + FDG-PET + Hippo-, 4) Aβ42 + FDG-PET+ Hippo+, and 5) any other combination not in line with the model. Measures of validity were prevalence of group 5, increasing incidence of progression to dementia with increasing biological severity, and decreasing conversion time. RESULTS: When patients with MCI underwent clinical follow-up, 29 progressed to dementia, while 44 remained stable. A total of 26% of patients were in group 5. Incident dementia was increasing with greater biological severity in groups 1 to 5 from 4% to 27%, 64%, and 100% (p for trend < 0.0001), and occurred increasingly earlier (p for trend = 0.024). CONCLUSIONS: The core biomarker pattern is in line with the current pathophysiologic model of AD. Fully normal and fully abnormal pattern is associated with exceptional and universal development of dementia. Cases not in line might be due to atypical neurobiology or inaccurate thresholds for biomarker (ab)normality.
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The finding of no significant influence of Aβ on subfield atrophy pattern is in line with recent studies showing that AD-type atrophy and/or hypometabolism can be found in both Aβ-negative healthy controls and Aβ-negative MCI patients.
“Yet, this finding is in line with recent studies showing that AD-type atrophy and/or hypometabolism can be found in both Aβ-negative healthy controls (Jack et al., 2012) and Aβ-negative MCI patients (Prestia et al., 2013).”
From Hippocampal subfield volumetry in mild cognitive impairment, Alzheimer's disease and semantic dementia (2013) · cites this paper as Prestia et al., 2013
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Metadata
- Authors
- Prestia, A., Caroli, A., van der Flier, W. M., Ossenkoppele, R., Van Berckel, B., Barkhof, F., Teunissen, C. E., Wall, A. E., Carter, S. F., Schöll, M., Choo, I. H., Nordberg, A., Scheltens, P., & Frisoni, G. B.
- Affiliations
- Uppsala University (SE)
- From LENITEM–Laboratory of Epidemiology Neuroimaging and Telemedicine (A.P., A.C., G.B.F.), IRCCS Centro San Giovanni di Dio FBF, Brescia; Medical Imaging Unit (A.C.), Biomedical Engineering Department, Mario Negri Institute for Pharmacological Research, Bergamo, Italy; Alzheimer Center and Department of Neurology (W.M.v.d.F., R.O., P.S.) and Departments of Epidemiology & Biostatistics (W.M.v.d.F.), Nuclear Medicine and PET Research (R.O., B.V.B.), Radiology (F.B.), and Clinical Chemistry (C.E.T...
- ORCID
- Venue
- Neurology
- Published
- 2013-03-12
- Volume
- 80
- Issue
- 11
- Pages
- 1048-1056
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W1981636437
- Cited by
- 184
- References
- 40
- Citations by year
- 2026: 3 · 2025: 12 · 2024: 5 · 2023: 8 · 2022: 10 · 2021: 8 · 2020: 11 · 2019: 16 · 2018: 21 · 2017: 15 · 2016: 14 · 2015: 19 · 2014: 23 · 2013: 18
- FWCI
- 17.48
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- UCL Discovery (University College London) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Oncology › Cancer-related cognitive impairment studies
- Keywords
- Alzheimer's disease, mild cognitive impairment, dementia progression, amyloid-beta 42, cerebrospinal fluid biomarkers, FDG-PET hypometabolism, hippocampal atrophy, biomarker patterns, conversion to dementia, amyloid hypothesis, temporal lobe
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Atrophy, Brain, Dementia, Female, Follow-Up Studies, Humans, Male, Middle Aged, Peptide Fragments, Predictive Value of Tests, Biomarkers, Amyloid beta-Peptides, tau Proteins, Disease Progression, Cognitive Dysfunction
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