The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Accuracy of Brain Amyloid Detection in Clinical Practice Using Cerebrospinal Fluid β-Amyloid 42: A Cross-Validation Study Against Amyloid Positron Emission Tomography
Abstract
IMPORTANCE: Before adding cerebrospinal fluid (CSF) biomarkers to the diagnostic workup of Alzheimer disease, it needs to be determined whether CSF biomarkers analyzed in routine clinical practice can reliably predict cortical β-amyloid (Aβ) deposition. OBJECTIVES: To study whether CSF biomarkers, analyzed consecutively in routine clinical practice during 2 years, can predict cortical Aβ deposition and to establish a threshold for Aβ42 abnormality. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study (The Swedish BioFINDER [Biomarkers For Identifying Neurodegenerative Disorders Early and Reliably] Study) was conducted at 3 memory clinics. It involved consecutively referred, nondemented patients with mild cognitive symptoms (original cohort, n = 118; validation cohort, n = 38). EXPOSURES: Amyloid positron emission tomography imaging with 18F-flutemetamol. MAIN OUTCOMES AND MEASURES: Analyses of CSF Aβ42, total tau, and phosphorylated tau using an enzyme-linked immunosorbent assay (INNOTEST) in clinical samples. RESULTS: The agreement between Aβ classification with CSF Aβ42 and 18F-flutemetamol positron emission tomography was very high (κ = 0.85). Of all the cases, 92% were classified identically using an Aβ42 cutoff of 647 pg/mL or less. Cerebrospinal fluid Aβ42 predicted abnormal cortical Aβ deposition accurately (odds ratio, 165; 95% CI, 39-693; area under the receiver operating characteristic curve, 0.94; 95% CI, 0.88-0.97). The association was independent of age, sex, APOE (apolipoprotein E) genotype, hippocampal volume, memory, and global cognition (adjusted odds ratio, 169; 95% CI, 25-1143). Using ratios of CSF Aβ42:tau or Aβ42:phosphorylated tau did not improve the prediction of Aβ deposition. Cerebrospinal fluid Aβ42 correlated significantly with Aβ deposition in all cortical regions. The highest correlations were in regions with high 18F-flutemetamol retention (eg, posterior cingulum and precuneus, r = -0.72). 18F-flutemetamol retention, but not CSF Aβ42, correlated significantly with global cognition (r = -0.32), memory function (r = -0.28), and hippocampal volume (r = -0.36) among those with abnormal Aβ deposition. Finally, the CSF Aβ42 cutoff derived from the original cohort (≤647 pg/mL) had an equally high agreement (95%; κ = 0.89) with 18F-flutemetamol positron emission tomography in the validation cohort. CONCLUSIONS AND RELEVANCE: Cerebrospinal fluid Aβ42 analyzed consecutively in routine clinical practice at an accredited laboratory can be used with high accuracy to determine whether a patient has normal or increased cortical Aβ deposition and so can be valuable for the early diagnosis of Alzheimer disease. Abnormal 18F-flutemetamol retention levels correlate with disease stage in patients with mild cognitive symptoms, but this is not the case for CSF Aβ42 measurements.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Mixture modeling statistics provide an unbiased threshold for abnormality (i.e., the diagnosis or status is not used in analysis) and it is a well-established method for defining Aβ PET cut-offs12, 17, 60, 61.”
From Earliest accumulation of β-amyloid occurs within the default-mode network and concurrently affects brain connectivity (2017) · cites this paper as [60]
Citations
Cites
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282
Practical Statistics for Medical Research.
Walter, S., & Altman, D. G. (1992) · Biometrics · doi:10.2307/2532320 · Cited by 11,666
Practical Statistics for Medical Research
Altman, D. G. (1990) · doi:10.1201/9780429258589 · Cited by 10,668
Measuring agreement in method comparison studies
Bland, J. M., & Altman, D. G. (1999) · Statistical Methods in Medical Research · doi:10.1177/096228029900800204 · Cited by 9,619
Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade
Jack, C. R., Knopman, D. S., Jagust, W. J., Shaw, L. M., Aisen, P. S., Weiner, M. W., Petersen, R. C., & Trojanowski, J. Q. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70299-6 · Cited by 4,806
Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound‐B
Klunk, W. E., Engler, H., Nordberg, A., Wang, Y., Blomqvist, G., Holt, D. P., Bergström, M., Savitcheva, I., Huang, G., Estrada, S., et al. (2004) · Annals of Neurology · doi:10.1002/ana.20009 · Cited by 4,496
Villemagne, V. L., Burnham, S., Bourgeat, P., Brown, B., Ellis, K. A., Salvado, O., Szoeke, C., Macaulay, S. L., Martins, R., Maruff, P., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70044-9 · Cited by 2,279
Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects
Shaw, L. M., Vanderstichele, H., Knapik‐Czajka, M., Clark, C. M., Aisen, P. S., Petersen, R. C., Blennow, K., Soares, H., Simon, A., Lewczuk, P., et al. (2009) · Annals of Neurology · doi:10.1002/ana.21610 · Cited by 2,065
Self-citationCerebrospinal fluid and plasma biomarkers in Alzheimer disease
Blennow, K., Hampel, H., Weiner, M., & Zetterberg, H. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2010.4 · Cited by 1,863
Self-citationPassing, H., & Bablok, W. (1983) · cclm · doi:10.1515/cclm.1983.21.11.709 · Cited by 1,513
Cited by
Sorted by citations
Scheltens, P., Blennow, K., Breteler, M. M. B., de Strooper, B., Frisoni, G. B., Salloway, S., & Van der Flier, W. M. (2016) · The Lancet · doi:10.1016/s0140-6736(15)01124-1 · Cited by 3,125
Self-citationPreclinical Alzheimer’s Disease: Definition, Natural History, and Diagnostic Criteria
Dubois, B., Hampel, H., Feldman, H. H., Scheltens, P., Aisen, P., Andrieu, S., Bakardjian, H., Benali, H., Bertram, L., Blennow, K., et al. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.02.002 · Cited by 1,925
Self-citationMasters, C. L., Bateman, R., Blennow, K., Rowe, C. C., Sperling, R. A., & Cummings, J. L. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.56 · Cited by 1,853
Self-citationPrevalence of Cerebral Amyloid Pathology in Persons Without Dementia: A Meta-analysis
Jansen, W. J., Ossenkoppele, R., Knol, D. L., Tijms, B. M., Scheltens, P., Verhey, F. R. J., Visser, P. J., Aalten, P., Aarsland, D., Alcolea, D., et al. (2015) · JAMA · doi:10.1001/jama.2015.4668 · Cited by 1,610
Self-citationJanelidze, S., Mattsson, N., Palmqvist, S., Smith, R., Beach, T. G., Serrano, G. E., Chai, X., Proctor, N. K., Eichenlaub, U., Zetterberg, H., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0755-1 · Cited by 1,247
Self-citation
Metadata
- Authors
- Palmqvist, S., Zetterberg, H., Blennow, K., Vestberg, S., Andreasson, U., Brooks, D. J., Owenius, R., Hägerström, D., Wollmer, P., Minthon, L., & Hansson, O.
- Affiliations
- Lund University (SE)
- University of Gothenburg (SE)
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg and Mölndal, Sweden
- Aarhus University (DK)
- GE Healthcare, Life Sciences, Uppsala, Sweden
- Skåne University Hospital (SE)
- Corresponding author
- Hansson, Oskar
- ORCID
- Venue
- JAMA Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2014-10-01
- Volume
- 71
- Issue
- 10
- Pages
- 1282
- ISSN
- 2168-6149 (ISSN-L)
- OpenAlex
- W1992165389
- Cited by
- 368
- References
- 48
- Citations by year
- 2026: 5 · 2025: 25 · 2024: 21 · 2023: 16 · 2022: 27 · 2021: 38 · 2020: 48 · 2019: 46 · 2018: 31 · 2017: 34 · 2016: 33 · 2015: 39 · 2014: 3
- FWCI
- 27.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA Neurology (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (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 › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
- Keywords
- Alzheimer's disease, cerebrospinal fluid biomarkers, amyloid-beta 42, cortical amyloid deposition, 18F-flutemetamol PET, total tau, phosphorylated tau, diagnostic accuracy, mild cognitive impairment, APOE genotype, hippocampal volume, memory clinics, early detection of neurodegeneration
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Aniline Compounds, Brain, Cerebral Cortex, Cross-Sectional Studies, Female, Gyrus Cinguli, Humans, Male, Middle Aged, Peptide Fragments, Reproducibility of Results, Cohort Studies, Amyloid beta-Peptides, Radiopharmaceuticals, Early Diagnosis, Positron-Emission Tomography, Benzothiazoles, Cognitive Dysfunction
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
