Advanced

Long-term treatment response, predictors and biochemical markers in Alzheimer’s disease.

Wallin, Åsa LU (2008) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2008:73.
Abstract
Alzheimer’s disease (AD) is clinically characterised by an insidious onset with progressive symptoms of memory impairment, dysphasia, dyspraxia, dygnosia and visuospatial difficulties. Degeneration of neurons in specific regions of the brain, formation of senile plaques and neurofibrillary changes are some of the neuropathological features of the disease. As a result of the degenerating process a deficiency in cholinergic function occurs in AD. This has been a target for therapy since the cholinesterase inhibitors (ChEIs) (tacrine, donepezil, rivastigmine, galantamine) were introduced as treatments for AD. Multiple short-term randomised clinical trials of ChEI treatment show beneficial effects on cognition, global functioning and... (More)
Alzheimer’s disease (AD) is clinically characterised by an insidious onset with progressive symptoms of memory impairment, dysphasia, dyspraxia, dygnosia and visuospatial difficulties. Degeneration of neurons in specific regions of the brain, formation of senile plaques and neurofibrillary changes are some of the neuropathological features of the disease. As a result of the degenerating process a deficiency in cholinergic function occurs in AD. This has been a target for therapy since the cholinesterase inhibitors (ChEIs) (tacrine, donepezil, rivastigmine, galantamine) were introduced as treatments for AD. Multiple short-term randomised clinical trials of ChEI treatment show beneficial effects on cognition, global functioning and activities of daily living in AD. Whether the effects of long-term ChEI treatment in a routine clinical setting are equally positive remains to be investigated. In the present study patients from naturalistic settings were investigated in long-term treatment studies (tacrine-study and The Swedish Alzheimer Treatment Study, SATS). Patients were repeatedly assessed with cognitive scales and global ratings over 3-5 years. A positive response to treatment was described in different response models. At 6 months 3/4 of the patients and at 3 years 1/3 were better or unchanged. Treatment for more than a year and positive response to tacrine treatment delayed nursing-home placement but did not influence survival. CSF T-tau and P-tau were possible markers for disease severity and P-tau for the abundance of symptoms in AD. A fast pre-treatment progression rate was a positive predictor for response to ChEI treatment even after adjusting for disease severity, another positive predictor of response. Baseline factors such as age, gender, CSF biomarkers and APOE genotype did not predict response to treatment. Dropout in these naturalistic settings was lower than expected. ChEI treatment changed the progression of the disease for more than 6 months and stabilised groups of patients for even longer (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Engedal, Knut, Ullevål University Hospital, Oslo, Norge
organization
publishing date
type
Thesis
publication status
published
subject
keywords
treatment response, cholinesterase inhibitor, CSF-biomarkers, pre-treatment progression, predictors, Alzheimer’s disease
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2008:73
pages
157 pages
publisher
Department of Clinical Sciences, Lund University
defense location
Clinical Research Centre (CRC, Malmö University Hospital, Entrance 72, Malmö
defense date
2008-06-05 13:00
ISSN
1652-8220
ISBN
978-91-86059-26-2
language
English
LU publication?
yes
id
9ee48eb1-c21e-49ae-995a-27807113361f (old id 1150245)
date added to LUP
2008-05-19 11:25:29
date last changed
2016-09-19 08:44:46
@phdthesis{9ee48eb1-c21e-49ae-995a-27807113361f,
  abstract     = {Alzheimer’s disease (AD) is clinically characterised by an insidious onset with progressive symptoms of memory impairment, dysphasia, dyspraxia, dygnosia and visuospatial difficulties. Degeneration of neurons in specific regions of the brain, formation of senile plaques and neurofibrillary changes are some of the neuropathological features of the disease. As a result of the degenerating process a deficiency in cholinergic function occurs in AD. This has been a target for therapy since the cholinesterase inhibitors (ChEIs) (tacrine, donepezil, rivastigmine, galantamine) were introduced as treatments for AD. Multiple short-term randomised clinical trials of ChEI treatment show beneficial effects on cognition, global functioning and activities of daily living in AD. Whether the effects of long-term ChEI treatment in a routine clinical setting are equally positive remains to be investigated. In the present study patients from naturalistic settings were investigated in long-term treatment studies (tacrine-study and The Swedish Alzheimer Treatment Study, SATS). Patients were repeatedly assessed with cognitive scales and global ratings over 3-5 years. A positive response to treatment was described in different response models. At 6 months 3/4 of the patients and at 3 years 1/3 were better or unchanged. Treatment for more than a year and positive response to tacrine treatment delayed nursing-home placement but did not influence survival. CSF T-tau and P-tau were possible markers for disease severity and P-tau for the abundance of symptoms in AD. A fast pre-treatment progression rate was a positive predictor for response to ChEI treatment even after adjusting for disease severity, another positive predictor of response. Baseline factors such as age, gender, CSF biomarkers and APOE genotype did not predict response to treatment. Dropout in these naturalistic settings was lower than expected. ChEI treatment changed the progression of the disease for more than 6 months and stabilised groups of patients for even longer},
  author       = {Wallin, Åsa},
  isbn         = {978-91-86059-26-2},
  issn         = {1652-8220},
  keyword      = {treatment response,cholinesterase inhibitor,CSF-biomarkers,pre-treatment progression,predictors,Alzheimer’s disease},
  language     = {eng},
  pages        = {157},
  publisher    = {Department of Clinical Sciences, Lund University},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Long-term treatment response, predictors and biochemical markers in Alzheimer’s disease.},
  volume       = {2008:73},
  year         = {2008},
}