[935] Memory Dysfunction in Alzheimer's Disease

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Our group has a long standing expertise in the field of Alzheimer's and related diseases. Our main research interest focuses on translational neuroimaging combining basic research with the understanding of pathogenesis of neurodegeneration and contributing to the diagnosis of dementia in clinical settings.

In particular:

  • In vivo neuropathology of Alzheimer's disease and related diseases with nuclear magnetic resonance and PET techniques.
  • Biomarkers imaging and CSF for the early diagnosis and "disease tracking" of Alzheimer's and related diseases.
  • Drugs for the prevention of Alzheimer's disease.
  • Integration of advanced imaging techniques (PET amyloid, tau PET, MR 7T) into clinical practice.
  • The role of microbiota in the pathogenesis of Alzheimer's disease.
  • The computerized and automated analysis of large databases imaging of the brain

Research ProjectS

Personne de contact: Marie Louise MONTANDON

Behavioural and Psychological Symptoms of Dementia (BPSD) continue to raise difficult problems, because they are difficult to manage, both for caregivers and health professionals. The RECAGE project, funded by the European Union's Horizon 2020 research and innovation program, aims to assess the efficacy (alleviating BPSD and improving quality of life of patients and caregivers) and the cost-effectiveness of a quite novel intervention, the Special Care Unit for patients with BPSD. The Geriatric Service, through the participation of the Memory Center and the SOMADEM unit (SOMAtic DEMentia), is one of the centers of the six countries (Italy, France, Germany, Greece, Norway, Switzerland) selected to participate in the study. SOMADEM unit is a specialized geriatric unit for patients with dementia and exacerbated behavioral disorders in the context of an acute somatic episode.

 

Personne de contact: Christian Moro

The AMYPAD project is a new research initiative that will bring together partners from academia and the private sector to improve the understanding of the role of beta-amyloid (β-amyloid) proteins as diagnostic and therapeutic markers for Alzheimer's disease using positron emission tomography. The AMYPAD consortium includes 8 academic centres, 3 pharmaceutical companies, 2 SMEs and 1 patient organisation across Europe.

 

Working directly in the clinical setting, AMYPAD seeks to determine for which types of patients and under which circumstances diagnostic β-amyloid imaging would be particularly relevant. The project also aims to assess how the information gathered can influence the certainty of diagnosis and the management of patients in a way that minimises costs. In this way, the AMYPAD project will provide an in-depth understanding of the evolution of Alzheimer's disease at a pre-symptomatic stage, allowing for better secondary prevention of the disease and more efficient selection of patients for clinical trials. In order to achieve these goals, AMYPAD will work closely with the EPAD project (http://ep-ad.org/).

 

AMYPAD is primarily funded by the European Union's Horizon 2020 Framework Programme for Research and Innovation and by the European pharmaceutical industry (EFPIA), under the auspices of the Innovative Medicines Initiative Joint Undertaking (IMI JU).

 

Personne de contact: Szymon TOMCZYK

Research project in which data concerning clinical and neuropsychological assessments acquired in the course of routine care of patients at the Memory Clinic of the University Hospitals of Geneva are collected and organised in a dedicated database. It is an observational study, cross-sectional in its comparison between different diagnostic groups, as well as longitudinal, in order to analyse the progression of each dementia, with the final aim of developing precise and feasible diagnostic and prognostic biomarkers for neurodegenerative diseases.

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Personne de contact: Federica RIBALDI

In the field of Alzheimer’s disease (AD), realities such as the constant improvement of risk estimation, or of the accuracy of blood tests for a large-scale screening of AD biomarkers, as well as the possibility of earlier detection in cognitively unimpaired individuals might change the individual and public attitude towards predictive medicine and medicine in general. PreTAD aims to clarify people’s needs in relation to the health care system and its services.

 

Personne de contact: Moira MARIZZONI

The aim of the project is to evaluate the interaction between: the intestinal bacteria (gut microbiota or flora), the peripheral inflammatory states, and the presence of bamyloid or Tau proteins in the brain, in patients with mild cognitive impairment or cognitively healthy.

Personne de contact: Claire CHEVALIER

The aim of this pre-clinical study is to evaluate the effect of fecal transplantation (eg, intestinal flora) in the treatment of Alzheimer’s disease (AD). A selection of individuals protected against AD, or with diagnosed AD will be used as donors for microbiota transplantation to a mice model of AD. We wish to identify which microbiota (or which bacteria) can attenuates or treat AD, and if fecal transplantation could be a new therapeutic tool for AD.

Personne de contact: Daniel ALTOMARE

CLAMP aims to assess whether an intervention consisting of 40 Hz multi-sensory (auditory and visual) stimulation is able to reduce the amyloid load in non-demented amyloid-positive individuals. As secondary endpoints, we will assess whether such intervention is able to: (i) improve the brain electrical activity, (ii) improve or slow down the worsening of Alzheimer’s blood-based biomarkers, (iii) improve or slow down the worsening of cognition.

 

Personne de contact: Federica RIBALDI

Nowadays, about 25% of memory clinics patients complain of cognitive decline in absence of objective deficits (subjective cognitive decline, SCD). These individuals could be at higher risk of developing dementia, but the majority have psychiatric conditions, physical diseases, polypharmacy, or simply normal brain ageing. Differentiating these potential causes is often a difficult exercise even for expert physicians. This project aims to investigate possible subgroups of SCD and their association with neurological, psychiatric, and physical causes.

 

Personne de contact: Valentina Garibotto

This is a longitudinal study that aim at evaluating the risk of cognitive deterioration in individuals with no or subtle cognitive symptoms who are fully characterized in term of Amyloid, Tau and Neurodegeneration status. This study will have strong impact on our knowledge on the longitudinal interplay of amyloid and tau accumulation on disease progression.

Personne de contact: Blanche Pirotte

This is a phase 3, multi-centre, randomised, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of aducanumab in patients with early Alzheimer's disease. The treatment period is 18 months, during which time individuals who meet all protocol inclusion criteria will be blinded to either the treatment or placebo group. The study will include 1350 patients from approximately 180 sites worldwide. The Memory Centre of the University Hospital of Geneva is among the sites selected to participate in the study. The study leader is Professor Giovanni Frisoni and the coordinator is Mrs Blanche Pirotte.

Contact person : Rahel Park

Normal pressure hydrocephalus (NPH) is the leading cause of reversible dementia in aging. It is caused by altered cerebrospinal fluid (CSF) dynamics bringing about increased CSF in the lateral ventricles, distortion of brain tissue, with ensuing neurological symptoms. The precise etiology and pathophysiology of idiopathic type NPH (iNPH) still largely remains unclear.

Technological advancements during the last decade have allowed understanding the type and quantity of microbes that humans host in their skin, mouth, and guts in health and disease. Gut bacteria have been shown to play a role among others in Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis, but the involvement of gut microbiota in iNPH has never been investigated. The main objective of the project is to investigate potential links between gut microbiome composition and/or its metabolites and the pathophysiology of iNPH.

Contact person : Blanche Pirotte

This is a pilot, monocentric, randomized, prospective study with a radiotherapy group and an observation group (without radiotherapy). Therapies targeting amyloid and tau proteins in the context of Alzheimer's disease have been developed in recent years. However, their results, for the moment, are inconclusive or under evaluation, hence the importance of testing alternative strategies. Radiotherapy in the context of this disease has two main arguments in its favour: 1. radiotherapy would reduce the systemic forms of amyloidosis and 2. it would have an anti-inflammatory effect. This last mode of action is particularly interesting in the context of Alzheimer's disease because recent studies have shown that the development of the amyloid protein in the brain is accelerated by an inflammatory phenomenon. The objective of this promising study is to determine the safety and adverse effects associated with low-dose brain radiation therapy and the reduction of amyloid plaques in patients with Alzheimer's disease. The study will include 20 participants at the single site of the University Hospital of Geneva.

Contact person : Blanche Pirotte

EMBARK is a Phase 3b, open-label, multicenter, longitudinal, single arm clinical trial. It follows the interruptions of previous BIOGEN studies that evaluated the treatment of aducanumab in early-stage Alzheimer's disease. Indeed, the results of futility analyzes of these studies did not show any encouraging effect. However, the additional results on the data set subsequently showed a significant slowing of cognitive and functional decline in people in the high-dose group, hence the need for a new clinical trial: the EMBARK study. This study evaluates the long-term efficacy and safety of aducanumab in patients with early-stage Alzheimer's disease who have participated in previous aducanumab studies. Patients receive treatment by intravenous infusion once a month for a period of 24 months. 1696 subjects are included in this clinical trial spread over 297 sites worldwide. The Memory Center of Geneva University Hospitals selected to participate in the study, is the site with the most active patients in Switzerland. The head of the study is Professor Giovanni Frisoni.

Contact person : Blanche Pirotte

 

EPAD LCS is a prospective, multicentre, pan-European and longitudinal cohort study. This European project for the Prevention of Alzheimer's Dementia (EPAD LCS) has been established to overcome the major hurdles hampering drug development for secondary prevention of dementia due to Alzheimer’s disease. Interventions must start early in the course of Alzheimer’s disease, but accurate disease models covering the entire course of it before dementia onset are lacking. Its objective is therefore to create a cohort of well-phenotyped people by studying multiple risk and protective factors for the disease and, thus, to represent a spectrum of the probability of developing Alzheimer's dementia. Participants are stratified and placed on an overall risk continuum derived from three dimensions: cognition, biomarkers, and traditional risk factors (genetic and environmental). For this they are subjected to blood, saliva and urine samples in addition to MRI, neuropsychological tests, various questionnaires and lumbar punctures repeated over time.

Considering these continuous dimensions allows for greater efficiency and insight into why and where a participant falls in the overall probability continuum spectrum as they may indeed have similar overall risk probability but with very different contributions.

In addition to allowing continuous improvement of models of Alzheimer's disease in people without dementia, this study provides a well-phenotyped population for a clinical trial and thus minimizes trial screening failures

Contact person : Moira Marizzoni

The aim of the project is to apply a non-invasive imaging tool, positron emission tomography (PET), to study the involvement of peripheral organs in Alzheimer’s Disease (AD). 18F-Flutemetamol PET has been extensively applied to identify amyloid pathology in the brain, and here we will explore whether it enables the detection of amyloid-related deposits in the abdomen.

Contact person  : Estefania Vilarino

Alzheimer’s Disease (AD) is associated with staggering costs and suffering, which are particularly related to the social impacts of caring for increasingly disabled individuals. These functional disabilities can be almost undetectable in the early stages of the disease, worsening over time often and at a varying rate of progression in different people. The measurement of such functional disabilities is typically blunt and relies on direct observation or caregiver recall. Digital technologies, particularly those based on the use of smartphones, wearables and/or home-based monitoring devices, here defined as ‘Remote Measurement Technologies’ (RMTs), provide an opportunity to change radically the way in which functional assessment is undertaken in AD,  RMTs have the potential to obtain better measurements of behavioural and biological parameters associated with individual Activities of Daily Living (ADL) when compared to the current subjective scales or questionnaires. Divergence from normative ADL profiles could objectively indicate the presence of specific functional disabilities even at the very early stages of AD. Therefore, the main hypothesis of this project is that RMTs should allow the detection of impairments in functional component of ADLs that occur below the threshold of clinical scale detection or disability questionnaires.