Correlation between Cognitive Impairment and CSF Biomarkers in Amnesic MCI, non-Amnesic MCI, and Alzheimer's Disease
Open accessAbstract
Decreased delayed recall, decreased amyloid-β peptides (Aβ1-42), and increased tau protein concentration in cerebrospinal fluid (CSF) are generally regarded to be valid neuropsychological and biological markers for Alzheimer's disease (AD). Previous studies failed to demonstrate clear-cut correlations between neuropsychological impairment and CSF markers. In this study we test recent models of disease progression, that propose that changes in CSF biomarkers already reach a plateau in a preclinical phase, before cognitive decline begins, that is, even before MCI can be diagnosed. We recruited 73 patients with probable AD (n=36) and mild cognitive impairment (MCI) (amnesic MCI=25; non-amnesic MCI=12). We used the CERAD-NP, a widely used neuropsychological battery with norms for different age and education groups, and additional neuropsychological tests for assessing the cognitive profile of these patient groups. We found a significant correlation between Aβ1-42 in the CSF and memory performance for amnesic MCI patients, but not for non-amnesic MCI and AD patients. All other correlations between cognitive tasks and Aβ1-42 were not significant. Tau protein concentration in the CSF was not correlated with any neuropsychological marker in any of the patients groups. We conclude that the decrease of Aβ1-42 in the CSF mirrors disease progression during the early stages up into AD and therefore is not restricted to the preclinical phase. The decrease of Aβ1-42 reaches a plateau only in the full blown demented syndrome and further functional disease progression is then related to neurodegeneration without further reduction of Aβ1-42 in the CSF.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
p-tau in the CSF has been shown to not correlate to any neuropsychological changes and is not associated with AD progression in APOE3-carrying AD patients.
“Furthermore, p-tau in the CSF has been shown to not correlate to any neuropsychological changes [53], and are not associated with AD progression in APOE3-carrying AD patients [77].”
From DNA repair deficiency and senescence in concussed professional athletes involved in contact sports (2019) · cites this paper as [53]
Concentrations of β-amyloid in the CSF of AD patients have been found to not significantly associate with cognitive performance.
“In contrast to these findings, concentrations of β-amyloid in the CSF of AD patients has been found to not significantly associate with cognitive performance [53, 125].”
From DNA repair deficiency and senescence in concussed professional athletes involved in contact sports (2019) · cites this paper as [53]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915 · see citing works
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864 · see citing works
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D. L., & Stadlan, E. (2011) · Neurology · doi:10.1212/01.wnl.0000400650.92875.cf · Cited by 9,882 · see citing works
Mild cognitive impairment as a diagnostic entity
Petersen, R. C. (2004) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2004.01388.x · Cited by 7,864 · see citing works
Winblad, B., Palmer, K., Kivipelto, M., Jelic, V., Fratiglioni, L., Wahlund, L. ‐., Nordberg, A., Bäckman, L., Albert, M., Almkvist, O., et al. (2004) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2004.01380.x · Cited by 4,946 · see citing works
Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS–ADRDA criteria
Dubois, B., Feldman, H. H., Jacova, C., DeKosky, S. T., Barberger-Gateau, P., Cummings, J., Delacourte, A., Galasko, D., Gauthier, S., Jicha, G., et al. (2007) · The Lancet Neurology · doi:10.1016/s1474-4422(07)70178-3 · Cited by 4,411 · see citing works
Moms, J. C., Heyman, A., Mohs, R. C., Hughes, J. P., van Belle, G., Fillenbaum, G., Mellits, E. D., & Clark, C. (1989) · Neurology · doi:10.1212/wnl.39.9.1159 · Cited by 4,130 · see citing works
Correlation Between Elevated Levels of Amyloid β-Peptide in the Brain and Cognitive Decline
Näslund, J. (2000) · JAMA · doi:10.1001/jama.283.12.1571 · Cited by 1,268 · see citing works
Morris, J. C., Mohs, R. C., Rogers, H., Fillenbaum, G. G., & Heyman, A. (1988) · PubMed · Cited by 1,131 · see citing works
Welsh, K. A., Butters, N., Mohs, R. C., Beekly, D., Edland, S., Fillenbaum, G., & Heyman, A. (1994) · Neurology · doi:10.1212/wnl.44.4.609 · Cited by 951 · see citing works
Episodic memory loss is related to hippocampal-mediated -amyloid deposition in elderly subjects
Mormino, E. C., Kluth, J. T., Madison, C. M., Rabinovici, G. D., Baker, S. L., Miller, B. L., Koeppe, R. A., Mathis, C. A., Weiner, M. W., Jagust, W. J., et al. (2009) · Brain · doi:10.1093/brain/awn320 · Cited by 684 · see citing works
Early Aβ accumulation and progressive synaptic loss, gliosis, and tangle formation in AD brain
Ingelsson, M., Fukumoto, H., Newell, K. L., Growdon, J. H., Hedley–Whyte, E. T., Frosch, M. P., Albert, M. S., Hyman, B. T., & Irizarry, M. C. (2004) · Neurology · doi:10.1212/01.wnl.0000115115.98960.37 · Cited by 666 · see citing works
Sunderland, T., Linker, G., Mirza, N., Putnam, K. T., Friedman, D. L., Kimmel, L. H., Bergeson, J., Manetti, G. J., Zimmermann, M., Tang, B., et al. (2003) · JAMA · doi:10.1001/jama.289.16.2094 · Cited by 656 · see citing works
Crystal, H., Dickson, D., Fuld, P., Masur, D., Scott, R., Mehler, M., Masdeu, J., Kawas, C., Aronson, M., & Wolfson, L. (1988) · Neurology · doi:10.1212/wnl.38.11.1682 · Cited by 586 · see citing works
Cerebrospinal fluid protein biomarkers for Alzheimer’s disease
Blennow, K. (2004) · Neurotherapeutics · doi:10.1602/neurorx.1.2.213 · Cited by 487 · see citing works
Morris, J. C., Edland, S., Clark, C., Galasko, D., Koss, E., Mohs, R., van Belle, G., Fillenbaum, G., & Heyman, A. (1993) · Neurology · doi:10.1212/wnl.43.12.2457 · Cited by 441 · see citing works
Genetic dissection of Alzheimer's disease and related dementias: amyloid and its relationship to tau
Hardy, J., Duff, K., Hardy, K. G., Pérez‐Tur, J., & Hutton, M. (1998) · Nature Neuroscience · doi:10.1038/1565 · Cited by 345 · see citing works
Reed, B. R., Mungas, D. M., Kramer, J. H., Ellis, W., Vinters, H. V., Zarow, C., Jagust, W. J., & Chui, H. C. (2007) · Brain · doi:10.1093/brain/awl385 · Cited by 282 · see citing works
DE JAGER, C. A., HOGERVORST, E., COMBRINCK, M., & BUDGE, M. M. (2003) · Psychological Medicine · doi:10.1017/s0033291703008031 · Cited by 259 · see citing works
Longitudinal CSF and MRI biomarkers improve the diagnosis of mild cognitive impairment
de Leon, M. J., DeSanti, S., Zinkowski, R. P., Mehta, P. D., Praticò, D., Segal, S., Rusinek, H., Li, J., Tsui, W., Louis, L. A. S., et al. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.07.003 · Cited by 253 · see citing works
Mild Cognitive Impairment: A Systematic Review
Mariani, E., Monastero, R., & Mecocci, P. (2007) · Journal of Alzheimer s Disease · doi:10.3233/jad-2007-12104 · Cited by 248 · see citing works
Test-retest reliable coefficients and 5-year change scores for the MMSE and 3MS
Tombaugh, T. N. (2005) · Archives of Clinical Neuropsychology · doi:10.1016/j.acn.2004.11.004 · Cited by 224 · see citing works
Mild Cognitive Impairment in the General Population: Occurrence and Progression to Alzheimer Disease
Palmer, K., Bäckman, L., Winblad, B. G., & Fratiglioni, L. (2008) · American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e3181753a64 · Cited by 219 · see citing works
Ralph, M. A. L., Patterson, K. E., Graham, N. L., Dawson, K., & Hodges, J. R. (2003) · Brain · doi:10.1093/brain/awg236 · Cited by 217 · see citing works
Hutchinson, A. D., & Mathias, J. L. (2007) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.2006.100669 · Cited by 187 · see citing works
Verwey, N. A., van der Flier, W. M., Blennow, K., Clark, C. M., Sokolow, S., Deyn, P. P. D., Galasko, D. R., Hampel, H. J., Hartmann, T., Kapaki, E., et al. (2009) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1258/acb.2009.008232 · Cited by 169 · see citing works
Stomrud, E., Hansson, O., Blennow, K., Minthon, L., & Londos, E. (2007) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000105017 · Cited by 164 · see citing works
Subclassifications for mild cognitive impairment: prevalence and predictive validity
BUSSE, A., Bischkopf, J., Riedel-Heller, S. G., et al. (2003) · Psychological Medicine · doi:10.1017/s0033291703007839 · Cited by 151 · see citing works
Neuropsychological testing and assessment for dementia
Jacova, C., Kertesz, A., Blair, M., Fisk, J. D., & Feldman, H. (2007) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2007.07.011 · Cited by 142 · see citing works
Wallin, A., Blennow, K., Andreasen, N. C., & Minthon, L. (2006) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000090631 · Cited by 135 · see citing works
Stomrud, E., Hansson, O., Zetterberg, H., Blennow, K., Minthon, L., & Londos, E. (2010) · Archives of Neurology · doi:10.1001/archneurol.2009.316 · Cited by 116 · see citing works
Forsberg, A., Almkvist, O., Engler, H., Wall, A., Långström, B., & Nordberg, A. K. (2010) · Current Alzheimer Research · doi:10.2174/156720510790274446 · Cited by 104 · see citing works
Preclinical Evidence of Alzheimer Changes
Petrie, E. C., Cross, D. J., Galasko, D. R., Schellenberg, G. D., Raskind, M. A., Peskind, E. R., & Minoshima, S. (2009) · Archives of Neurology · doi:10.1001/archneurol.2009.59 · Cited by 101 · see citing works
Mickes, L., Wixted, J. T., Fennema‐Notestine, C., Galasko, D. R., Bondi, M. W., Thal, L. J., & Salmon, D. P. (2007) · Neuropsychology · doi:10.1037/0894-4105.21.6.696 · Cited by 88 · see citing works
Mollenhauer, B., Bibl, M., Wiltfang, J., Steinacker, P., Ciesielczyk, B., Neubert, K., Trenkwalder, C., & Otto, M. (2006) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2006.035 · Cited by 72 · see citing works
Maccioni, R. B., Manuel Lavados, M., Guillón, M., Mújica, C. L. D., BOSCH, R., FARIAS, G., & FUENTES, P. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.01.011 · Cited by 66 · see citing works
Neuropsychologische Profile in der Demenzdiagnostik: Eine Untersuchung mit der CERAD-NP-Testbatterie
Barth, S., Schönknecht, P., Pantel, J., & Schröder, J. (2005) · Fortschritte der Neurologie · Psychiatrie · doi:10.1055/s-2004-830249 · Cited by 60 · see citing works
Lowndes, G., & Savage, G. R. (2007) · Neuropsychology Review · doi:10.1007/s11065-007-9032-z · Cited by 56 · see citing works
Ivanoiu, A., & Sindic, C. J. M. (2005) · Neurocase · doi:10.1080/13554790490896901 · Cited by 54 · see citing works
Molinuevo, J. L., Gómez‐Ansón, B., Monté, G. C., Bosch, B., Sánchez‐Valle, R., & Rami, L. (2010) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2010.03.016 · Cited by 43 · see citing works
Hildebrandt, H., Haldenwanger, A., & Eling, P. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-0931 · Cited by 32 · see citing works
Self-citationNeuropsychological Differentiation of Late-Onset Schizophrenia and Dementia of the Alzheimer's Type
Zakzanis, K. K., Andrikopoulos, J., Young, D. A., et al. (2003) · Applied Neuropsychology · doi:10.1207/s15324826an1002_06 · Cited by 20 · see citing works
Nordberg, A. K. (2009) · Current Alzheimer Research · doi:10.2174/1567209198607192050 · Cited by 5 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- Beck AT, Hautzinger M, Bailer M, Worall H, Keller F (1985) BDI -Beck-Depressionsinventar. Second edition. Hogrefe, Göttingen.
- World Health Organization (1992) ICD-10: international sta- tistical classification of diseases and related health problems- based on recommendations of the tenth revision conference, 1989 and adopted by the forty-third World Health Assembly, 10th edn. World Health Organization; Geneva.
- Weimer E & Fröhlich L (2005) Labordiagnostik und Liquor- marker bei Alzheimer Krankheit. In: Demenzen. Perspektiven in Praxis und Forschung, H. Förstl (ed.), Elsevier, pp. 59-85.
Cited by
Sorted by citations
Gurevich, P., Stuke, H., Kastrup, A., Stuke, H., & Hildebrandt, H. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00114 · Cited by 53 · see citing works
Self-citationDNA repair deficiency and senescence in concussed professional athletes involved in contact sports
Schwab, N., Grenier, K., & Hazrati, L.-N. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0822-3 · Cited by 47 · see citing works
- Authors
- Haldenwanger, A., Eling, P., Kastrup, A., & Hildebrandt, H.
- Affiliations
- Klinikum Bremen-Mitte (DE)
- Radboud University Nijmegen (NL)
- Carl von Ossietzky Universität Oldenburg (DE)
- Corresponding author
- Hildebrandt, Helmut
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2010-11-25
- Volume
- 22
- Issue
- 3
- Pages
- 971-980
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1600125081
- Cited by
- 54
- References
- 43
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 8 · 2020: 7 · 2019: 3 · 2018: 4 · 2017: 2 · 2016: 6 · 2015: 3 · 2014: 2 · 2013: 4 · 2012: 4
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion)
- 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
- MeSH terms
- Aged, Alzheimer Disease, Amnesia, Cognition Disorders, Humans, Middle Aged, Neuropsychological Tests, Peptide Fragments, Biomarkers, Amyloid beta-Peptides, tau Proteins
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
