Can CSF biomarkers or pre-treatment progression rate predict response to cholinesterase inhibitor treatment in Alzheimer's disease?

• Published in: International journal of geriatric psychiatry Vol. 24; no. 6; pp. 638 - 647
• Main Authors: Wallin, Å. K., Hansson, O., Blennow, K., Londos, E., Minthon, L.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.06.2009; Psychology Press; Wiley Subscription Services, Inc
• Subjects: Adult and adolescent clinical studies; Aged; Aged, 80 and over; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - drug therapy; Alzheimer Disease - physiopathology; Alzheimer's disease; Amyloid beta-Peptides - cerebrospinal fluid; Apolipoprotein E4 - genetics; Biological and medical sciences; Biomarkers; Biomarkers - cerebrospinal fluid; Body fluids; cholinesterase inhibitor treatment; Cholinesterase Inhibitors - therapeutic use; Clinical Medicine; CSF biomarkers; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Progression; Female; Genotype; Geriatric Assessment; Geriatric psychiatry; Humans; Inhibitor drugs; Klinisk medicin; Male; MEDICAL AND HEALTH SCIENCES; Medical sciences; Medical treatment; MEDICIN OCH HÄLSOVETENSKAP; Models, Statistical; Neurologi; Neurology; Neuropharmacology; Organic mental disorders. Neuropsychology; Peptide Fragments - cerebrospinal fluid; Pharmacology. Drug treatments; pre-treatment progression; Predictive Value of Tests; predictors; Prospective Studies; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychological Tests; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; response; Severity of Illness Index; Studies; Sweden; tau Proteins - cerebrospinal fluid; Treatment Outcome; Sweden; Human; predictors; Nervous system diseases; Prognosis; Alzheimer disease; Rate; Prediction; Biological marker; Cerebrospinal fluid; cholinesterase inhibitor treatment; Cerebral disorder; Response; Treatment; pre-treatment progression; Central nervous system disease; Evolution; Degenerative disease; Anticholinesterase agent; Pretreatment; Predictive factor; CSF biomarkers; Elderly; Alzheimer's disease
• ISSN: 0885-6230; 1099-1166; 1099-1166
• DOI: 10.1002/gps.2195

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 ε4 carrier, education, duration of disease, cognitive level, pre‐treatment progression rate (in MMSE) and the levels of the CSF biomarkers Aβ42, 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. Conclusion 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. Copyright © 2009 John Wiley & Sons, Ltd.