Single-Domain Amnestic Mild Cognitive Impairment Identified by Cluster Analysis Predicts Alzheimer's Disease in the European Prospective DESCRIPA Study
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Background/Aims: To identify prodromal Alzheimer's disease (AD) subjects using a data-driven approach to determine cognitive profiles in mild cognitive impairment (MCI). Methods: A total of 881 MCI subjects were recruited from 20 memory clinics and followed for up to 5 years. Outcome measures included cognitive variables, conversion to AD, and biomarkers (e.g. CSF, and MRI markers). Two hierarchical cluster analyses (HCA) were performed to identify clusters of subjects with distinct cognitive profiles. The first HCA included all subjects with complete cognitive data, whereas the second one selected subjects with very mild MCI (MMSE ≥28). ANOVAs and ANCOVAs were computed to examine whether the clusters differed with regard to conversion to AD, and to AD-specific biomarkers. Results: The HCAs identified 4-cluster solutions that best reflected the sample structure. One cluster (aMCIsingle) had a significantly higher conversion rate (19%), compared to subjective cognitive impairment (SCI, p < 0.0001), and non-amnestic MCI (naMCI, p = 0.012). This cluster was the only one showing a significantly different biomarker profile (Aβ 42, t-tau, APOE ε4, and medial temporal atrophy), compared to SCI or naMCI. Conclusion: In subjects with mild MCI, the single-domain amnestic MCI profile was associated with the highest risk of conversion, even if memory impairment did not necessarily cross specific cut-off points. A cognitive profile characterized by isolated memory deficits may be sufficient to warrant applying prevention strategies in MCI, whether or not memory performance lies below specific z-scores. This is supported by our preliminary biomarker analyses. However, further analyses with bigger samples are needed to corroborate these findings.
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The similarity of the MCI regional atrophy pattern to that of AD is consistent with the hypothesis that single-domain amnestic MCI is the one most likely to evolve to AD.
“is consistent with the hypothesis that the single-domain amnestic profile of MCI is the one most likely to evolve to AD [42].”
From Atrophy of presubiculum and subiculum is the earliest hippocampal anatomical marker of Alzheimer's disease (2015) · cites this paper as [42]
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- Authors
- Damian, M., Hausner, L., Jekel, K., Richter, M., Froelich, L., Almkvist, O., Boada, M., Bullock, R., De Deyn, P. P., Frisoni, G. B., Hampel, H., Jones, R. W., Kehoe, P., Lenoir, H., Minthon, L., Olde Rikkert, M. G. M., Rodriguez, G., Scheltens, P., Soininen, H., Spiru, L., Touchon, J., Tsolaki, M., Vellas, B., Verhey, F. R. J., Winblad, B., Wahlund, L.-O., Wilcock, G., & Visser, P. J.
- Affiliations
- Heidelberg University (DE)
- Stockholm University (SE)
- Centro San Giovanni di Dio Fatebenefratelli (IT)
- Goethe University Frankfurt (DE)
- The Research Institute for the Care of Older People (GB)
- Inserm (FR)
- Lund University (SE)
- Assistance Publique – Hôpitaux de Paris (FR)
- Maastricht University (NL)
- Carol Davila University of Medicine and Pharmacy (RO)
- Aristotle University of Thessaloniki (GR)
- Radboud University Nijmegen (NL)
- Maastricht University Medical Centre (NL)
- Karolinska Institutet (SE)
- Karolinska University Hospital (SE)
- University of Antwerp (BE)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- ORCID
- Venue
- Dementia and Geriatric Cognitive Disorders
- Publisher
- S. Karger AG
- Published
- 2013
- Volume
- 36
- Issue
- 1-2
- Pages
- 1-19
- ISSN
- 1420-8008 (ISSN-L)
- 1421-9824
- OpenAlex
- W1986522803
- Cited by
- 53
- References
- 45
- Citations by year
- 2025: 6 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 5 · 2020: 5 · 2019: 6 · 2018: 2 · 2017: 3 · 2016: 5 · 2015: 8 · 2014: 3
- FWCI
- 3.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Dementia and Geriatric Cognitive Disorders (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- Pure Amsterdam UMC (publishedVersion)
- Bristol Research (University of Bristol) (publishedVersion)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Explore Bristol Research (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Kuopion Yliopistollinen Sairaala
- Sixth Framework Programme
- 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
- amnestic mild cognitive impairment, conversion to Alzheimer's disease, prodromal Alzheimer's disease, cognitive profile, clustering, memory impairment, amyloid-beta 42, tau protein, APOE ε4, medial temporal lobe atrophy, cerebrospinal fluid biomarkers, MRI biomarkers
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Europe, Female, Genotype, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Mental Recall, Tomography, X-Ray Computed, Reproducibility of Results, Cohort Studies, Biomarkers, Cluster Analysis, Logistic Models, Disease Progression, Cognitive Dysfunction
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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