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CSF biomarkers predict rate of cognitive decline in Alzheimer disease.
Neurology 2009; 73(17):1353-8Neur

Abstract

OBJECTIVE

CSF biomarkers amyloid beta 1-42 (Abeta(42)), total tau (tau), and tau phosphorylated at threonine 181 (p-tau-181) are useful diagnostic markers for Alzheimer disease (AD). Less is known about these biomarkers as predictors for further cognitive decline in patients with AD. We hypothesized that high tau, especially in combination with relatively low p-tau-181, is a marker of rapid decline, since it has been associated with fast neuronal degeneration.

METHODS

A total of 151 patients with AD of whom we had baseline CSF were included from our memory clinic. All patients had at least 2 Mini-Mental State Examination (MMSE) scores, obtained no less than 1 year apart. Linear mixed models were used to assess associations between CSF biomarkers and the rate of cognitive decline as measured with the MMSE. CSF biomarkers were used in quintiles, random intercept and random slope with time were assumed, and the analyses were corrected for sex and age.

RESULTS

The patients with AD (45% women, age 66 +/- 9 years, baseline MMSE 22 +/- 4) had a follow-up period of 2.0 (1.0-5.0) years. Linear mixed models revealed no relations between any CSF biomarker and baseline MMSE. However, CSF biomarkers did predict cognitive decline over time. A low p-tau-181/tau ratio was the strongest predictor with a dose-dependent effect (lowest vs highest quintile: 2.9 vs 1.3 MMSE points annual decline, p for trend <0.001). In addition, low Abeta(42), high tau, and high tau/Abeta(42)-ratio were associated with rapid cognitive decline (p < 0.05).

CONCLUSION

At the time of diagnosis, a combination of high CSF tau without proportionally elevated p-tau-181 is associated with a faster rate of cognitive decline.

Authors+Show Affiliations

Alzheimer Center and Department of Neurology, VU University Medical Center, Amsterdam, the Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19858456

Citation

Kester, M I., et al. "CSF Biomarkers Predict Rate of Cognitive Decline in Alzheimer Disease." Neurology, vol. 73, no. 17, 2009, pp. 1353-8.
Kester MI, van der Vlies AE, Blankenstein MA, et al. CSF biomarkers predict rate of cognitive decline in Alzheimer disease. Neurology. 2009;73(17):1353-8.
Kester, M. I., van der Vlies, A. E., Blankenstein, M. A., Pijnenburg, Y. A., van Elk, E. J., Scheltens, P., & van der Flier, W. M. (2009). CSF biomarkers predict rate of cognitive decline in Alzheimer disease. Neurology, 73(17), pp. 1353-8. doi:10.1212/WNL.0b013e3181bd8271.
Kester MI, et al. CSF Biomarkers Predict Rate of Cognitive Decline in Alzheimer Disease. Neurology. 2009 Oct 27;73(17):1353-8. PubMed PMID: 19858456.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CSF biomarkers predict rate of cognitive decline in Alzheimer disease. AU - Kester,M I, AU - van der Vlies,A E, AU - Blankenstein,M A, AU - Pijnenburg,Y A L, AU - van Elk,E J, AU - Scheltens,P, AU - van der Flier,W M, PY - 2009/10/28/entrez PY - 2009/10/28/pubmed PY - 2009/12/16/medline SP - 1353 EP - 8 JF - Neurology JO - Neurology VL - 73 IS - 17 N2 - OBJECTIVE: CSF biomarkers amyloid beta 1-42 (Abeta(42)), total tau (tau), and tau phosphorylated at threonine 181 (p-tau-181) are useful diagnostic markers for Alzheimer disease (AD). Less is known about these biomarkers as predictors for further cognitive decline in patients with AD. We hypothesized that high tau, especially in combination with relatively low p-tau-181, is a marker of rapid decline, since it has been associated with fast neuronal degeneration. METHODS: A total of 151 patients with AD of whom we had baseline CSF were included from our memory clinic. All patients had at least 2 Mini-Mental State Examination (MMSE) scores, obtained no less than 1 year apart. Linear mixed models were used to assess associations between CSF biomarkers and the rate of cognitive decline as measured with the MMSE. CSF biomarkers were used in quintiles, random intercept and random slope with time were assumed, and the analyses were corrected for sex and age. RESULTS: The patients with AD (45% women, age 66 +/- 9 years, baseline MMSE 22 +/- 4) had a follow-up period of 2.0 (1.0-5.0) years. Linear mixed models revealed no relations between any CSF biomarker and baseline MMSE. However, CSF biomarkers did predict cognitive decline over time. A low p-tau-181/tau ratio was the strongest predictor with a dose-dependent effect (lowest vs highest quintile: 2.9 vs 1.3 MMSE points annual decline, p for trend <0.001). In addition, low Abeta(42), high tau, and high tau/Abeta(42)-ratio were associated with rapid cognitive decline (p < 0.05). CONCLUSION: At the time of diagnosis, a combination of high CSF tau without proportionally elevated p-tau-181 is associated with a faster rate of cognitive decline. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/19858456/CSF_biomarkers_predict_rate_of_cognitive_decline_in_Alzheimer_disease_ L2 - http://www.neurology.org/cgi/pmidlookup?view=long&amp;pmid=19858456 DB - PRIME DP - Unbound Medicine ER -