LOUIS PASTEUR UNIVERSITY STRASBOURG I

Emilie Ritter

Description

Niveau: Supérieur, Doctorat, Bac+8

• dissertation

1 LOUIS PASTEUR UNIVERSITY - STRASBOURG I Ecole Doctorale des Sciences de la Vie et de la Santé And BASEL UNIVERSITY Discipline : Medical sciences Field : Neuropsychology DOCTORAL DISSERTATION Prepared by Emilie RITTER Submitted for the degree of Doctor of Philosophy in the University Louis Pasteur of Strasbourg and the University of Basel Presented in the university Louis Pasteur of Strasbourg on Monday 7th May 2007 Examining Committee: Pr Lilianne Manning (Supervisor) in collaboration with Dr Olivier Despres Pr Andreas U. Monsch (Co-supervisor) Dr Christian Kelche (Louis Pasteur University Reporter) Pr Klaus Opwis (External Reporter) Pr Adrien Ivanoiu (External Reporter) Topographical recognition memory and autobiographical memory in amnestic mild cognitive impairment: a longitudinal study

• his passion


• amnestic mild cognitive


• ecole doctorale des sciences de la vie et de la santé


• neuropsychology

Sujets

• Dissertation
• Dufour
• Despres
• Pasteur
• Louis Pasteur University
• Ritter
• Mönch
• Andreas

Informations

• Publié par: profil-feym-2012
• Nombre de lectures: 52
• Langue: English

Extrait

LOUIS PASTEUR UNIVERSITY - STRASBOURG I

Ecole Doctorale des Sciences de la Vie et de la Santé

And BASEL UNIVERSITY

Discipline : Medical sciences

Field : Neuropsychology

DOCTORAL DISSERTATION

Prepared by Emilie RITTER

Submitted for the degree of Doctor of Philosophy in the University Louis Pasteur of

Strasbourg and the University of Basel




Topographical recognition memory

and autobiographical memory in


amnestic mild cognitive impairment:

a longitudinal study



thPresented in the university Louis Pasteur of Strasbourg on Monday 7 May 2007











Examining Committee:
Pr Lilianne Manning (Supervisor) in collaboration with Dr Olivier Despres
Pr Andreas U. Monsch (Co-supervisor)
Dr Christian Kelche (Louis Pasteur University Reporter)
Pr Klaus Opwis (External Reporter)
Pr Adrien Ivanoiu (External Reporter)
1
LOUIS PASTEUR UNIVERSITY - STRASBOURG I

Ecole Doctorale des Sciences de la Vie et de la Santé

And BASEL UNIVERSITY

Discipline : Medical sciences

Field : Neuropsychology

DOCTORAL DISSERTATION

Prepared by Emilie RITTER

Submitted for the degree of Doctor of Philosophy in the University Louis Pasteur of

Strasbourg and the University of Basel




Topographical recognition memory

and autobiographical memory in


amnestic mild cognitive impairment:

a longitudinal study



thPresented in the university Louis Pasteur of Strasbourg on Monday 7 May 2007










Examining Committee:
Pr Lilianne Manning (Supervisor) in collaboration with Dr Olivier Despres
Pr Andreas U. Monsch (Co-supervisor)
Dr Christian Kelche (Louis Pasteur University Reporter)
Pr Klaus Opwis (External Reporter)
Pr Adrien Ivanoiu (External Reporter)
2











































“All those moments will be lost in time
Like tears in rain”

“Tous les souvenirs se perdront dans l’oubli
Comme les larmes dans la pluie“

Blade runner
A movie from Ridley Scott,1982
3








To all the participants who generously accepted to be assessed for this study
4Acknowledgements
First of all, I am grateful to the members of the committee, Pr Ivanioiu, Pr Opwis and Dr
Kelche for their constructive comments, suggestions and questions.
I would like to thank Pr Monsch for supervising my thesis and receiving me in his Memory
Clinic in Basel.
More especially, thank you very much to Pr. L. Manning for accepting me as her PhD student
and teaching me cognitive neuropsychology. I could begin to fulfil a wish: to try to bind
behaviour and pharmacology.
I wish to express my deepest gratitude to Dr Olivier Després for a lot of things in addition of
supervising my thesis, more especially: his passion for research, his very great generosity and
his open-mindedness. It was a pleasure to work with him.
Thank you to the members of the Cognitive Neuropsychology team: Virginie, Ekaterina,
Anne and Christine for answering to all the questions I had about neuropsychology!
I would like to thank very much the participants of this study.
Moreover, I am very thankful to the persons who helped me in recruiting participants for this
study:
-The associations of retired people (Université du Temps Libre de Strasbourg, La
Maison du Temps Libre, ARCAL, MSA and ARES).
-In addition of her participation, I am very grateful to Mireille Gouget for her help in
persuading people to participate to this study and for her encouraging E-mails she sent
me during my thesis, it was a great confort to me.
-Michèle and Marcel, my parents-in-law, who were very attentive to my work, it was
also a great confort to me.
Thanks to the students of Master 1 of cognitive neuropsychology, for helping me in assessing
the participants: Lena, Luisa, Houssamie, Juliette and Damien. More particularly, I
appreciated Lena’s and Luisa’s involvements for the real interest they expressed in the current
study, thank you.
I thank the directors of LN2C and the Centre of Applied Physiology, Pr Bruno Will and Dr
Alain Muzet, respectively, for receiving me in their laboratories during my thesis. Thanks also
to the members of these laboratories, specifically, Dr André Dufour for his advices in
statistics and Hélène and Sarah for their moral support.
5I am thankful to Lesley King for English revision of this manuscript.
I am deeply grateful to my parents, Martine and Philippe, for enabling me to pursue so far my
studies and to do a fascinating work.
I want to give my best thanks to my friends from Paris: Mathieu who left France to Hong-
Kong, Jacob, Nadia, Sophie and Sidonie, for their sincere and very strong relation, in spite of
the distance.
Finally, I wish to thank warmly Lucas, my boyfriend, for his endless love and for accepting to
leave Paris, his family and friends, to rejoin me to Strasbourg.
This work was supported by ELTEM and France Alzheimer (ER’s grant).
6Abstract
Mild cognitive impairment (MCI) is defined as one or more cognitive deficit(s) of not
sufficient severity to constitute a dementia but of greater severity than that of healthy
individuals of the same age and education level (Petersen et al., 2001). When the cognitive
deficit concerns memory, it is called amnestic MCI (aMCI). It has been shown that
individuals with aMCI are at a high risk of developing dementia of Alzheimer type (Petersen
et al., 1999). Moreover, the finding of medication for slowing cognitive decline of
Alzheimer’s disease (AD) and waiting for new more efficient ones (Roberson & Mucke,
2006) renders research on aMCI, and thereby preclinical markers, of crucial interest.
However, the aMCI syndrome may have causes other than neurodegenerative diseases, such
as depression, and no standardized method exists to distinguish incipient demented aMCI
patients from those who will not develop dementia. The main purpose of this study is to
detect specific markers of preclinical dementia to discriminate aMCI patients who will
develop dementia from those who will not. To this end, we performed a two-year longitudinal
study aiming to examine cognitive evolution of aMCI patients in order to discriminate
declining from non-declining aMCI patients. At the end of the study, we compared declining
aMCI’s cognitive performances at baseline with those of the non-declining to detect markers
of preclinical dementia. Based on their neural substrates, we theorized that deficits in
topographical recognition memory and autobiographical memory (AbM) could be
neuropsychological markers of incipient dementia. The aMCI patients who declined
cognitively were considered as evolving aMCI. Results showed that aMCI was an
heterogeneous syndrome leading to evolving aMCI in a limited proportion whereas additional
depression strongly increased the risk of becoming evolving aMCI. With regard to
topographical recognition memory, aMCI patients were impaired and this memory was not
sensitive to depression. Nevertheless, longitudinal results indicated that deficits in emory were not specific to the evolving aMCI condition. In the
case of AbM, no specific deficit was found. These preliminary results may be useful for very
large scale studies targeting neuropsychological markers of AD. Only a very accurate
diagnosis of evolving aMCI will allow efficient early medical treatment.

7Résumé détaillé en français

Depuis quelques années, le concept amnestic Mild Cognitive Impairment (aMCI)
définit un état transitoire entre le vieillissement normal et la démence de type Alzheimer
(DAT). Les patients aMCI présentent des troubles isolés de la mémoire qui ne sont pas
suffisamment sévères pour constituer une démence (Gauthier et al., 2006 ; Petersen et al.,
2001). Cependant, une proportion importante de ces patients estimée entre 11 et 33% évolue
vers une DAT en deux ans (Ritchie, 2004), alors que la prévalence dans la population
générale n’est que de 2% (Petersen et al., 1999). En 2006, Gauthier et al. ont adopté l’idée que
le MCI pouvait être dû à d’autres causes que la neurodégénérescence, telles que la dépression.
Néanmoins, malgré la découverte de certains traitements de la maladie d’Alzheimer (MA)
stabilisant temporairement la détérioration cognitive (Kurz et al., 2004 ; Potkin, 2002, pour
revue), il n’existe pas, à notre connaissance, de protocole diagnostique standardisé permettant
de disting