Journal
NEUROLOGY
Volume 74, Issue 19, Pages 1531-1537Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0b013e3181dd4dd8
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Funding
- Swedish Research Council [14002, 2006-6227]
- Alzheimer's Association [NIRG-08-90356]
- Royal Swedish Academy of Sciences
- Stiftelsen for Gamla Tjanarinnor
- Swedish Foundations of the National Board of Health and Welfare
- Swedish Alzheimer Foundation
- Swedish Society of Medicine
- Swedish Brain Power
- Trolle-Wachtmeister Foundation
- Skane County Council
- Lund University
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Objective: To investigate if patterns of CSF biomarkers (T-tau, P-tau, and A beta 42) can predict cognitive progression, outcome of cholinesterase inhibitor (ChEI) treatment, and mortality in Alzheimer disease (AD). Methods: We included outpatients with AD (n = 151) from a prospective treatment study with ChEI. At baseline, patients underwent cognitive assessments and lumbar puncture. The patients were assessed longitudinally. The 5-year survival rate was evaluated. CSF-A beta 42, T-tau, and P-tau were analyzed at baseline. K-means cluster analysis including the 3 CSF biomarkers was carried out. Results: Cluster 1 contained 87 patients with low levels of A beta 42 and relatively low levels of T-tau and P-tau. Cluster 2 contained 52 patients with low levels of A beta 42 and intermediate levels of T-tau and P-tau. Cluster 3 contained 12 patients with low levels of A beta 42 and very high levels of CSF T-tau and P-tau. There were no differences between the clusters regarding age, gender, years of education, baseline instrumental activities of daily living, or APOE genotype. Even though there was no difference between cluster 3 and the other clusters in disease duration or global rating, the patients in cluster 3 performed worse on cognitive tests already at baseline. Patients in cluster 3 exhibited a very poor outcome of ChEI treatment. Finally, cognition deteriorated faster over time and the mortality rate was substantially increased in cluster 3. Conclusion: A subgroup of patients with Alzheimer disease with extreme levels of CSF biomarkers exhibits worse clinical outcomes over time, including faster progression of cognitive deficits, no response to ChEI treatment, and a higher mortality. Neurology (R) 2010;74:1531-1537
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