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CSF biomarkers predict a more malignant outcome in Alzheimer disease.

Artikel i vetenskaplig tidskrift
Författare A K Wallin
Kaj Blennow
Henrik Zetterberg
E Londos
L Minthon
O Hansson
Publicerad i Neurology
Volym 74
Nummer/häfte 19
Sidor 1531-7
ISSN 1526-632X
Publiceringsår 2010
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Sidor 1531-7
Språk en
Länkar dx.doi.org/10.1212/WNL.0b013e3181dd...
Ämnesord Aged, Aged, 80 and over, Alzheimer Disease, diagnosis, drug therapy, mortality, Amyloid beta-Peptides, cerebrospinal fluid, Biological Markers, cerebrospinal fluid, Cholinesterase Inhibitors, therapeutic use, Disease Progression, Female, Humans, Longitudinal Studies, Male, Neuropsychological Tests, Outcome Assessment (Health Care), Peptide Fragments, cerebrospinal fluid, Predictive Value of Tests, Prognosis, Prospective Studies, Sensitivity and Specificity, Severity of Illness Index, Survival Rate, Time Factors, Treatment Outcome, tau Proteins, cerebrospinal fluid
Ämneskategorier Psykiatri

Sammanfattning

OBJECTIVE: To investigate if patterns of CSF biomarkers (T-tau, P-tau, and Abeta42) 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-Abeta42, 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 Abeta42 and relatively low levels of T-tau and P-tau. Cluster 2 contained 52 patients with low levels of Abeta42 and intermediate levels of T-tau and P-tau. Cluster 3 contained 12 patients with low levels of Abeta42 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.

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