title: Can CSF biomarkers or pre-treatment progression rate predict response to cholinesterase inhibitor treatment in Alzheimer's disease?
abstract: OBJECTIVE
  The main objective of this study was to investigate possible predictors of response to cholinesterase inhibitor (ChEI) treatment, including pre-treatment progression rates and levels of the cerebrospinal fluid (CSF) biomarkers. A secondary objective was to evaluate whether treatment with ChEI changed progression.
  
  
  METHODS
  Out-patient individuals (n = 191) with the clinical diagnosis of Alzheimer's disease received ChEI treatment and were part of the Swedish Alzheimer Treatment Study (SATS), a prospective, longitudinal, non-randomised study in a routine clinical setting. Patients were assessed with MMSE, ADAS-cog and a global rating (CIBIC) at baseline, 2 months and every 6 months for a total period of 3 years. The following potential predictors of treatment response were investigated: age, gender, APOE epsilon 4 carrier, education, duration of disease, cognitive level, pre-treatment progression rate (in MMSE) and the levels of the CSF biomarkers A beta 42, T-tau and P-tau.
  
  
  RESULTS
  Fast pre-treatment progression rate was a predictor of treatment response even after adjusting for baseline severity, another positive predictor of response. Patients in the fastest quartile of pre-treatment progression rates were significantly more prone to be responders at 2 months (adjusted OR 6.6, p = 0.001) and 6 months (adjusted OR 10.4, p < 0.001) than those in the slowest progressing quartile. Moreover, the linearity of progression was significantly changed by ChEI treatment at 6 months compared to the pre-treatment period.
  
  
  CONCLUSIONS
  The rate of pre-treatment progression was the most consistent positive predictor of ChEI treatment response in the routine clinical setting. The progression rate was significantly changed by ChEI treatment.
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden. asa.k.wallin@skane.se
authors.forename: A K
authors.initials: AK
authors.lastname: Wallin
authors.forename: O
authors.initials: O
authors.lastname: Hansson
authors.forename: K
authors.initials: K
authors.lastname: Blennow
authors.forename: E
authors.initials: E
authors.lastname: Londos
authors.forename: L
authors.initials: L
authors.lastname: Minthon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D005838:Genotype; D015577:Geriatric Assessment; D006801:Humans; D008297:Male; D015233:Models, Statistical; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011581:Psychological Tests; D012720:Severity of Illness Index; D013548:Sweden; D016896:Treatment Outcome; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; D002800:Cholinesterase Inhibitors; D010446:Peptide Fragments; C538897:amyloid beta-protein (40-42); D016875:tau Proteins