Moller HJ

References (8)

Title : Effects of rivastigmine on visual attention in subjects with amnestic mild cognitive impairment: A serial functional MRI activation pilot-study - Bokde_2016_Psychiatry.Res_249_84
Author(s) : Bokde AL , Cavedo E , Lopez-Bayo P , Lista S , Meindl T , Born C , Galluzzi S , Faltraco F , Dubois B , Teipel SJ , Reiser M , Moller HJ , Hampel H
Ref : Psychiatry Res , 249 :84 , 2016
Abstract : A pilot study to investigate the effects of rivastigmine on the brain activation pattern due to visual attention tasks in a group of amnestic Mild Cognitive Impaired patients (aMCI). The design was an initial three-month double blind period with a rivastigmine and placebo arms, followed by a nine-month open-label period. All patients underwent serial functional magnetic resonance imaging (fMRI) at baseline, and after three and six months of follow-up. Primary endpoint was the effect of rivastigmine on functional brain changes during visual attention (face and location matching) tasks. There were five in the rivastigmine arm and two in the placebo arm. The face matching task showed higher activation of visual areas after three months of treatment but no differences compared to baseline at six months. The location matching task showed a higher activation along the dorsal visual pathway at both three and six months follow ups. Treatment with rivastigmine demonstrates a significant effect on brain activation of the dorsal visual pathway during a location matching task in patients with aMCI. Our data support the potential use of task fMRI to map specific treatment effects of cholinergic drugs during prodromal stages of Alzheimer's disease (AD).
ESTHER : Bokde_2016_Psychiatry.Res_249_84
PubMedSearch : Bokde_2016_Psychiatry.Res_249_84
PubMedID: 26851974

Title : Common variants conferring risk of schizophrenia - Stefansson_2009_Nature_460_744
Author(s) : Stefansson H , Ophoff RA , Steinberg S , Andreassen OA , Cichon S , Rujescu D , Werge T , Pietilainen OP , Mors O , Mortensen PB , Sigurdsson E , Gustafsson O , Nyegaard M , Tuulio-Henriksson A , Ingason A , Hansen T , Suvisaari J , Lonnqvist J , Paunio T , Borglum AD , Hartmann A , Fink-Jensen A , Nordentoft M , Hougaard D , Norgaard-Pedersen B , Bottcher Y , Olesen J , Breuer R , Moller HJ , Giegling I , Rasmussen HB , Timm S , Mattheisen M , Bitter I , Rethelyi JM , Magnusdottir BB , Sigmundsson T , Olason P , Masson G , Gulcher JR , Haraldsson M , Fossdal R , Thorgeirsson TE , Thorsteinsdottir U , Ruggeri M , Tosato S , Franke B , Strengman E , Kiemeney LA , Melle I , Djurovic S , Abramova L , Kaleda V , Sanjuan J , de Frutos R , Bramon E , Vassos E , Fraser G , Ettinger U , Picchioni M , Walker N , Toulopoulou T , Need AC , Ge D , Yoon JL , Shianna KV , Freimer NB , Cantor RM , Murray R , Kong A , Golimbet V , Carracedo A , Arango C , Costas J , Jonsson EG , Terenius L , Agartz I , Petursson H , Nothen MM , Rietschel M , Matthews PM , Muglia P , Peltonen L , St Clair D , Goldstein DB , Stefansson K , Collier DA
Ref : Nature , 460 :744 , 2009
Abstract : Schizophrenia is a complex disorder, caused by both genetic and environmental factors and their interactions. Research on pathogenesis has traditionally focused on neurotransmitter systems in the brain, particularly those involving dopamine. Schizophrenia has been considered a separate disease for over a century, but in the absence of clear biological markers, diagnosis has historically been based on signs and symptoms. A fundamental message emerging from genome-wide association studies of copy number variations (CNVs) associated with the disease is that its genetic basis does not necessarily conform to classical nosological disease boundaries. Certain CNVs confer not only high relative risk of schizophrenia but also of other psychiatric disorders. The structural variations associated with schizophrenia can involve several genes and the phenotypic syndromes, or the 'genomic disorders', have not yet been characterized. Single nucleotide polymorphism (SNP)-based genome-wide association studies with the potential to implicate individual genes in complex diseases may reveal underlying biological pathways. Here we combined SNP data from several large genome-wide scans and followed up the most significant association signals. We found significant association with several markers spanning the major histocompatibility complex (MHC) region on chromosome 6p21.3-22.1, a marker located upstream of the neurogranin gene (NRGN) on 11q24.2 and a marker in intron four of transcription factor 4 (TCF4) on 18q21.2. Our findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition.
ESTHER : Stefansson_2009_Nature_460_744
PubMedSearch : Stefansson_2009_Nature_460_744
PubMedID: 19571808

Title : Effects of donepezil on cortical metabolic response to activation during (18)FDG-PET in Alzheimer's disease: a double-blind cross-over trial - Teipel_2006_Psychopharmacology.(Berl)_187_86
Author(s) : Teipel SJ , Drzezga A , Bartenstein P , Moller HJ , Schwaiger M , Hampel H
Ref : Psychopharmacology (Berl) , 187 :86 , 2006
Abstract : RATIONALE: Cholinergic enhancement is among the best established treatments of Alzheimer's disease (AD). The cognitive effects of treatment are thought to be mediated by improvement of neuronal transmission. Positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) by measuring cortical metabolic response to activation assesses integrity of neuronal transmission in vivo. OBJECTIVE: To determine the effects of treatment with donepezil, a centrally selective acetylcholinesterase inhibitor, on cortical metabolism in AD using 18FDG-PET.
METHODS: We enrolled 23 patients, 18 of which completed the study, with mild to moderate probable AD (mini-mental status exam scores of 15-28, inclusive) in a double-blind cross over trial of 8 weeks donepezil compared to 8 weeks placebo with repeated double 18FDG-PET examinations during passive audio-visual stimulation. Effects of treatment on cortical metabolic response to stimulation were determined with a linear model on a voxel level using Statistical Parametric Mapping (SPM 99, Wellcome Department of Imaging Neuroscience, London).
RESULTS: Effects of treatment on cognitive measures were not different between donepezil and placebo. During passive audio-visual stimulation, patients showed activation in posterior visual and auditory areas and decreased activation in frontal cortex and basal ganglia. Resting state metabolism was increased with donepezil in left prefrontal cortex and decreased in right hippocampus. Cortical response to activation was increased in right hippocampus with donepezil compared to placebo. CONCLUSION: Donepezil treatment shows a spatially limited functional effect on right hippocampus and left prefrontal cortical metabolism, independently of clinical response to treatment.
ESTHER : Teipel_2006_Psychopharmacology.(Berl)_187_86
PubMedSearch : Teipel_2006_Psychopharmacology.(Berl)_187_86
PubMedID: 16767418

Title : [Modern therapy for dementia] - Padberg_2005_MMW.Fortschr.Med_147 Spec No 2_71
Author(s) : Padberg F , Moller HJ , Bottlender R , Hampel H
Ref : MMW Fortschr Med , 147 Spec No 2 :71 , 2005
Abstract : The most frequently diagnosed dementia diseases include Alzheimer disease (AD), vascular dementia (VD) and dementia with Lewy bodies. Cholinesterase (ChE) inhibitors and the NMDA receptor antagonist memantine are currently recommended as first line drugs for the treatment of AD. These anti-dementia drugs have not yet been approved for the treatment of VD and DLB although the results of controlled clinical studies support the effectiveness of the ChE inhibitors for both diseases. The treatment of the primary disease and the secondary prevention of cerebrovascular accidents constitute the primary objectives of VD therapy. Although single or multiple domain cognitive deficits are the clinical key symptoms of dementia, noncognitive psychopathological symptoms (so-called behavioral disorders) are particularly common and may even dominate the clinical course in the moderate to severe stages. Therefore, it is important to recognize, diagnose and specifically treat these additional symptoms. During the last decade, the classic neuroleptics and benzodiazepine have been largely replaced by modern antidepressants, atypical antipsychotics and benzodiazepine analogues.
ESTHER : Padberg_2005_MMW.Fortschr.Med_147 Spec No 2_71
PubMedSearch : Padberg_2005_MMW.Fortschr.Med_147 Spec No 2_71
PubMedID: 15968877

Title : [Alzheimer patients. To treat with anti-dementia drugs in spite of unanswered questions] -
Author(s) : Padberg F , Hampel H , Moller HJ
Ref : MMW Fortschr Med , 143 :43 , 2001
PubMedID: 11824167

Title : Double-blind, randomized, placebo-controlled clinical trial on the efficacy and tolerability of a physostigmine patch in patients with senile dementia of the Alzheimer type - Moller_1999_Pharmacopsychiatry_32_99
Author(s) : Moller HJ , Hampel H , Hegerl U , Schmitt W , Walter K
Ref : Pharmacopsychiatry , 32 :99 , 1999
Abstract : Owing to the pharmacokinetic properties of physostigmine when administered by conventional routes, long-term cholinergic treatment of Alzheimer's disease is difficult to manage. In order to overcome the problems associated with the oral and intravenous application of physostigmine, and to improve patients' compliance, a transdermal therapeutic system was developed. The efficacy and tolerability of this system were evaluated in a double-blind, randomized, multicenter study comparing patches containing 30 mg and 60 mg physostigmine with a placebo patch. The clinical trial followed the basic principles of the various guidelines on the evaluation of anti-dementia drugs, and included patients with mild to moderate probable Alzheimer's disease. A total of 204 patients with probable Alzheimer's disease were included in the study. Of these, 136 patients were eligible for the according-to-protocol analysis of efficacy, 167 subjects for the intention-to-treat analysis of efficacy, and 181 patients were included in the safety analysis. In contrast to the hypothesis to be tested, the efficacy of physostigmine was not superior to that of placebo after a treatment period of 24 weeks. On the contrary, there was even a slight, but not statistically significant, trend toward a better outcome in the placebo group. Median physostigmine plasma concentrations of approximately 100 pg/ml were measured, showing a high degree of interindividual variability and no linear dose relationship between the 30 mg and 60 mg dosages. Plasma cholinesterase activity was not significantly affected by physostigmine. The physostigmine patch application in doses of 30 mg and 60 mg apparently did not lead to physostigmine plasma concentrations that were sufficient to compensate for cholinergic deficiencies in affected brain areas and produce clinical benefits. Both the drug and the transdermal system were generally well tolerated under the study conditions. Modifications of the patch system may perhaps make it possible to achieve higher physostigmine plasma concentrations, which seem to be required to induce the expected beneficial effects during long-term treatment of Alzheimer's disease.
ESTHER : Moller_1999_Pharmacopsychiatry_32_99
PubMedSearch : Moller_1999_Pharmacopsychiatry_32_99
PubMedID: 10463377

Title : The effects of donepezil in Alzheimer's disease - results from a multinational trial - Burns_1999_Dement.Geriatr.Cogn.Disord_10_237
Author(s) : Burns A , Rossor M , Hecker J , Gauthier S , Petit H , Moller HJ , Rogers SL , Friedhoff LT
Ref : Dementia & Geriatric Cognitive Disorders , 10 :237 , 1999
Abstract : Donepezil has been shown to be well tolerated and to improve cognition and global function in patients with mild to moderately severe Alzheimer's disease (AD). The current trial was undertaken to investigate further the efficacy and safety of donepezil, in a multinational setting, in patients with mild to moderately severe AD. This 30-week, placebo-controlled, parallel-group study consisted of a 24-week, double-blind treatment phase followed by a 6-week, single-blind, placebo washout. Eight hundred and eighteen patients with mild to moderately severe AD were randomly allocated to treatment with single, daily doses of 5 or 10 mg donepezil, or placebo. The two primary efficacy measures were: a cognitive performance test, the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and a global evaluation, the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC plus). Secondary outcome measures included the Sum of the Boxes of the Clinical Dementia Rating Scale (CDR-SB), a modified Interview for Deterioration in Daily living activities in Dementia (IDDD) and a patient rated quality of life assessment. Statistically significant improvements in cognitive and global function were observed, as evaluated by ADAS-cog and CIBIC plus, respectively, in both the 5 and 10 mg/day donepezil groups, compared with placebo. Treatment-associated changes were also observed in functional skills, as shown by improved scores on the CDR-SB and the complex-tasks component of the IDDD. A dose-response effect was evident, with the 10 mg/day donepezil group demonstrating greater benefits in all outcome measures than the 5 mg/day group. Donepezil was well tolerated by this patient population and did not produce any clinically significant laboratory test abnormalities. The results of this study confirm that donepezil is effective and well tolerated in treating the symptoms of mild to moderately severe AD.
ESTHER : Burns_1999_Dement.Geriatr.Cogn.Disord_10_237
PubMedSearch : Burns_1999_Dement.Geriatr.Cogn.Disord_10_237
PubMedID: 10325453

Title : Reappraising neurotransmitter-based strategies - Moller_1999_Eur.Neuropsychopharmacol_9 Suppl 2_S53
Author(s) : Moller HJ
Ref : European Neuropsychopharmacology , 9 Suppl 2 :S53 , 1999
Abstract : A number of observations support the hypothesis that a central deficit in acetylcholine (ACh) may be responsible for the initiation of Alzheimer's disease (AD). For example, cholinergic innervation in AD is reduced in areas of the brain important for processing information. Further, reduced concentrations of choline acetyltransferase (ChAT), the enzyme responsible for the synthesis of ACh, correlate with the number of beta-amyloid senile plaques and cognitive dysfunction in AD patients. Consequently, several strategies to increase cholinergic neurotransmission have been developed, including ACh precursors, ACh release enhancers, cholinesterase (ChE) inhibitors and receptor agonists. Although ChE inhibitors appear to be the most promising, tacrine, the first ChE inhibitor to be registered and approved for the treatment of AD, has significant tolerability problems. Thus, ChE inhibitors with improved side-effect profiles have been developed and subsequently awarded marketing approval. However, in addition to the cholinergic system that is the most severely affected neurotransmitter system in AD, other neurotransmitter systems may be involved (e.g. serotonergic, noradrenergic and glutamatergic). Therefore, bifunctional compounds or combinations of drugs may provide additional therapeutic value.
ESTHER : Moller_1999_Eur.Neuropsychopharmacol_9 Suppl 2_S53
PubMedSearch : Moller_1999_Eur.Neuropsychopharmacol_9 Suppl 2_S53
PubMedID: 10332935