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Abstract
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.
Glossary
- 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.
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