LVR-Klinikum Düsseldorf Hospital of the Heinrich-Heine University ...

LVR-KLINIKUM DÜsseLDORF – hOsPITaL OF The heINRIch-heINe UNIVeRsITY DÜsseLDORF
Alpha
evaluation is being used to address the question of whether
EEG alterations in MCI or beginning AD are associated with
the course of the illness and drug effects (v. Figures 17 and
18).
Study E 2.2: Pharmacological treatment of
patients with mild cognitive impairment
The subject of this 24-month treatment study within
the context of the Competence Network on Dementia
was the preventive effectiveness of early anti-dementia
treatment in patients with mild cognitive impairment (MCI).
In Düsseldorf, 30 patients were included in the study.
They were treated in a double-blind study design with
placebo, the acetylcholinesterase inhibitor galantamine or
with a combination of galantamine and memantine. The
administration of study drugs in this study was terminated
prematurely because two major, international, multicentre
98
FZ (Front zone) CZ (Centrocentral area) PZ (Parietocentral area)
1.0
0.8
0.6
0.4
0.2
0.0
S-MCI P-MCI AD
Figure 18: Investigations into the change of brain-electrical activity using
electroencephalography (EEG) in the progression from MCI (Mild Cognitive
Impairment) to early Alzheimer’s Dementia. Represented is the so-called
alpha frequency band (8-12 Hz) of normal resting activity in the EEG in
three brain areas, FZ (Front central area), CZ (Centrocentral area) and PZ
(Parietocentral area). This showed a statistically significant decrease of the
normal Alpha activity in the parting zone in Alzheimer patients (AD) compared
with a clinically stable MCI (S-MCI), although there was also an Alpha
reduction in clinically progressing MCI syndromes (P-MCI) in comparison with
clinically stable MCI patients. This represents an EEG-based differentiation of
various early forms of cognitive disorders, which will be investigated in later
studies in terms of their predictive value for the development of Alzheimer’s
in cases of MCI. Figure modified after Luckhaus et al.: Quantitative EEG in
progressing vs stable mild cognitive impairment (MCI): results of a 1-year
follow-up study. Int J Geriatr Psychiatry 2008 (11): 1148-55
studies that tested the effectiveness of galantamine in the
aforementioned indication found no improvement in the
primary outcome variable “conversion rate”. The last followup
investigations of the Düsseldorf study participants were
concluded in the spring of 2006.
Study E 3.2: Identification of
genetic markers for dementia disorders
The aim of this study, also performed within the context of the
Competence Network on Dementia, was to elucidate the role
of genetic factors as the cause of dementia disorders. Several
genes may influence the disease risk in sporadic forms. The
aim of this study is the search for dementia risk genes and
the identification of genes which modify the disease course
and the therapeutic response. To this end, a central DNA
bank was established. The LVR-Klinikum participates in the
collection of specimens.
Project Experimental Gerontopsychiatry
Director: C. Lange-Asschenfeldt
Scientific assistants: P. Görtz, U. Henning
Cooperation (internal): C. Luckhaus, General Psychiatry II
Department
Cooperation (external): G. Kojda, Pharmacology Heinrich-
Heine University, M. Siebler, MediClin Essen-Kettwig,
M. Riepe, Gerontopsychiatry, University of Ulm, M. Dihné,
Department of Neurology Heinrich-Heine University,
Düsseldorf, A. Schnitzler, Department of Medical Psychology
and Neurosciences, Heinrich-Heine University, Düsseldorf,
D. Willbold (Jülich Research Centre).
Financing: Departmental research budget
This project deals with experimental methods to study
synaptic plasticity and neuronal network activity.
It also deals with pharmacological effects on such
systems and develops both in vivo and in vitro models of
neurodegenerative disorders. The methods used include
– among others – microelectrode arrays, primary cortical
and hippocampal neuronal cell cultures (mouse and rat),
fluorescence microscopy, extracellular field potential
recordings in acute and organotypic hippocampal slices
(mouse and rat) and immunoblotting. In several research
projects, performed in collaboration of the above mentioned
partner laboratories, the effects of amyloid-ß (1-42)
administration on spontaneous neuronal network activity
and its putative pharmacological manipulation is being
studied in microelectrode arrays (Figure 19).