Early diagnosis: Neuropsychology and biomarkers
Discovery and validation of disease markers for AD and other neurodegenerative disorders are key research areas in DDRC, which include new biofluid markers, brain imaging and neuropsychology. The biomarker research aims to discover and validate new biofluid markers for the early diagnosis of AD and for the prediction of disease progression using proteomics and genomics technologies. DDRC conducts and participates in several brain imaging studies on early diagnosis of dementia that include both structural and functional brain imaging, including studies with amyloid-specific PET tracers.
Many biomarker studies are carried out in collaboration with other Danish centres, as well as a wide range of European centres. Neuropsychological research mainly focuses on characterisation of cognitive deficits in the early phase of dementia diseases and MCI. In recent years several studies on cognitive processes in aging have been published, with changes in personality traits and social cognition in manifest and premanifest Huntington gene-expansion carriers gathering a great deal of attention.
Familial neurodegenerative disorders
Neurogenetic research focuses on clinical characteristics, ancillary investigations and basic research into gene function and therapy. Many neurodegenerative disorders, including AD, FTD and ataxias manifest with progressive loss of specific subsets of neurons in the brain. In some diseases genetic mechanisms are involved. Different diseases have different genetic backgrounds, but evidence shows that common mechanisms of neurodegeneration may exist. Some of our research focuses on the identification of common molecular mechanisms in neurodegeneration, e.g. in FTD linked to chromosome 3 (FTD3) and spinocerebellar ataxia type 2 (SCA2).
We are also exploring the cellular environment in patient-derived cell cultures to pinpoint therapeutic targets. The FReJA Consortium investigates FTD linked to FTD3, which occurs in a large FTD family in western Jutland. Research in this disease focuses on the molecular disease mechanism, with neuronal cell lines now derived using stem cell technology to further explore the potential of gene therapy. The Copenhagen Memory Clinic’s neurogenetics section is a significant international contributor to research in HD, and our large cohorts of patients are assessed with detailed clinical and neuropsychological evaluations, genetic markers and CSF profiles.
Medication and health services
Using nationwide registry data we investigate the quality of diagnostic evaluation, access to health services and the use of medication in patients with dementia as compared to the general Danish population. Using nationwide registry data allows us to study time trends concerning the use of medication among patients with dementia in Denmark. The research is carried out in cooperation with the National Centre for Register-based Research at Aarhus University. Recently, projects investigating patterns of use of opioids, other analgetics, psychotropics and anti-dementia medication were conducted. One important recent result is that, despite a decrease in prevalence of antipsychotic drug use over the past decade, there is a pronounced geographical variation in use. The results of ongoing studies aimed at identifying and defining the consequences and background for the high level of use are incorporated into the national dementia plan, where reduction of antipsychotic use is one of several goals. Our research will help provide evidence for creating new guidelines and for DDRC teaching materials.
Rehabilitation and psychosocial support
We have extensive experience in carrying out large-scale multi-centre intervention studies investigating non-pharmacological treatment in neurodegenerative diseases, some of which examine the effects of psychosocial education programmes or cognitive stimulation. The recently completed ADEX study demonstrated a positive effect of physical exercise on neuropsychiatric symptoms in early AD. This project was initiated to establish a platform for future collaboration on dementia research in Danish memory clinics. In parallel with the physical exercise study, a platform was established creating a research alliance between Danish memory clinics with benchmarking to Swedish and Dutch networks.
The ongoing ReACT project develops a software programme that meets some of the cognitive support needs of people with dementia. An iterative user-driven innovation process was used to design and develop the software, resulting in an innovative adaptive application devised to support memory, structuring and communication. ReACT validated the tool, which is one of the first of its kind in the development of personalised systems for cognitive rehabilitation.
Global health and cross-cultural aspects of dementia
DDRC is conducting various studies on cross-cultural aspects of dementia. For some years the centre has studied cognitive functions in different ethnic groups in Denmark and in other European countries in an effort to improve diagnostic evaluation and care of European ethnic minorities with dementia. A special interest is the development and validation of cross-cultural cognitive tests and screening instruments for use in low and middle-income populations. Population-based studies have been conducted in Lebanon and a new research project in the Philippines focuses on the attributable risk of vascular risk factors for dementia. Greater knowledge about these factors will aid in designing public health programmes with the ultimate goal of reducing the incidence and prevalence of dementia.
Pharmacological treatments: From first in man to proof-of-concept and large scale clinical trials
DDRC has extensive experience in the conduction of phase 1-3 clinical pharmacological trials in patients with AD, MCI and HD and as advisors for trial design and safety monitoring. The collaboration between Danish memory clinics (ADEX network) represents a platform for Denmark’s contribution to international trials. On average, DDRC’s track record shows that the inclusion of patients is more than 30% above the intended number. The clinical trials are conducted with state-of-the-art imaging techniques in collaboration with the Danish Research Centre for Magnetic Resonance, Hvidovre Hospital and the PET and Cyclotron Unit, Rigshospitalet.