PT  - JOURNAL ARTICLE
AU  - Wallin, Å.K.
AU  - Blennow, K.
AU  - Zetterberg, H.
AU  - Londos, E.
AU  - Minthon, L.
AU  - Hansson, O.
TI  - CSF biomarkers predict a more malignant outcome in Alzheimer disease
AID  - 10.1212/WNL.0b013e3181dd4dd8
DP  - 2010 May 11
TA  - Neurology
PG  - 1531--1537
VI  - 74
IP  - 19
4099  - http://n.neurology.org/content/74/19/1531.short
4100  - http://n.neurology.org/content/74/19/1531.full
SO  - Neurology2010 May 11; 74
AB  - Objective: To investigate if patterns of CSF biomarkers (T-tau, P-tau, and Aβ42) 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-Aβ42, 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 Aβ42 and relatively low levels of T-tau and P-tau. Cluster 2 contained 52 patients with low levels of Aβ42 and intermediate levels of T-tau and P-tau. Cluster 3 contained 12 patients with low levels of Aβ42 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. Aβ42=β-amyloid 1-42; AD=Alzheimer disease; ADAS-cog=Alzheimer's Disease Assessment Scale–Cognitive Subscale; ChEI=cholinesterase inhibitor; CI=confidence interval; DSM-IV=Diagnostic and Statistical Manual of Mental Disorders, 4th edition; IADL=Instrumental Activities Of Daily Living scale; MMSE=Mini-Mental State Examination; P-tau=phosphorylated tau; SATS=Swedish Alzheimer Treatment Study; T-tau=total tau.