• Startsida - ki.se
• Utbildning
• Forskning
• Biblioteket
• Om Karolinska Institutet
• Sök
• Sök personal

Sök och bläddra bland Karolinska Institutets avhandlingar

1995   1996   1997   1998   1999   2000   2001   2002   2003   2004   2005   2006   2007   2008   2009   2010    Info

Doktorsavhandling vid Karolinska Institutet
Westman, Eric Magnetic resonance studies in Alzheimer´s disease Fredagen den 16 oktober 2009, kl. 09.30. Seminariesalen 4U Solen, Alfred Nobels Allé 8, Huddinge.	Thesis Frame Original [PDF] Beställ dok- torsavhandling   Acrobat Reader

ISBN: 978-91-7409-624-8

Diss: 09:291

Abstract:

Alzheimer’s disease (AD) is one of the most common forms of neurodegenerative disorders connected with gradual loss of cognitive functions such as episodic memory. The disease is related to pathological amyloid depositions and hyper phosphorilation of structural proteins in the brain which lead to progressive loss of function, metabolic alterations and structural changes in the brain. In vivo biomarkers need to be established to be able to set an early diagnosis, monitor disease progression and finally to observe pharmaceutical treatment effects. The aim of this thesis is to investigate the potential use of combining multivariate analysis with magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to monitor disease and treatment in AD. Due to the complexity of Alzheimer’s disease, we hypothesized, that considering patterns of disease markers is more useful for the evaluation of patients or a study outcome, than making decisions based on single biomarkers alone.
Studies I and II combine multivariate analysis with MRS to monitor disease and treatment effects in two different mouse models. Study III utilizes multivariate analysis in combination with different MRI measures (regional and global volumetric and cortical thickness measures) to discriminate between three groups, AD patients, MCI patients and healthy controls. Study IV investigates the added value of MRS in the early diagnosis of AD. In this study the multivariate models were built combining both MRI and MRS variables.
The methods could successfully be applied in both animals and humans. Metabolic fingerprints of disease and treatment could be identified as well as patterns of atrophy. The combination of multivariate data analysis with different magnetic resonance measures is a powerful tool for identifying treatment effects and distinguishing between different subject groups. The multivariate combination of different measures was clearly more powerful and predictive than focusing only on single measures using traditional analysis.

---

List of papers

	Carbamazepine treatment recovered low N-acetylaspartate+N-acetylaspartylglutamate (tNAA) levels in the megencephaly mouse BALB/cByJ-Kv1.1(mceph/mceph). Westman E, Spenger C, Wahlund LO, Lavebratt C. Neurobiol Dis, 2006; 26(1): 221-8
	In vivo 1H-magnetic resonance spectroscopy can detect metabolic changes in APP/PS1 mice after donepezil treatment. Westman E, Spenger C, Oberg J, Reyer H, Pahnke J, Wahlund LO. BMC Neurosci, 2009; 10: 33
	Multivariate analysis of MRI data for Alzheimer´s disease, mild cognitive impairment and healthy controls. Westman E, Simmons A, Zhang Y, Muehlboeck J-S, Tunnard C, Liu Y, Collins L, Evans A, Mecocci P, Vellas B, Tsolaki M, Kłoszewska I, Soininen H, Lovestone S, Spenger C, Wahlund L-O Submitted
	Combining MRI and MRS to distinguish between Alzheimer´s disease and healthy controls Westman E, Wahlund L-O, Foy C, Poppe M, Cooper A, Murphy D, Spenger C, Lovestone S, Simmons A Submitted