Early diagnosis: Neuropsychology and biomarkers
Discovery and validation of disease markers for AD and other neurodegenerative disorders are key DDRC research areas, 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, including the use of proteomics and genomics technologies.
DDRC conducts and participates in several brain imaging studies on early diagnosis of dementia that contain both structural and functional brain imaging, including studies with amyloid-specific PET tracers. In recent years several studies on comorbidity in early diagnosis have been initiated, including multicentre studies on the role of epilepsy in early dementia and MCI, and new studies analysing the use of ear-EEG to examine epilepsy in AD. 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 DDRC have conducted various studies on cognitive processes in aging, as well as longitudinal studies on cognitive deficits and personality traits in gene-expansion carriers.
In 2018 DDRC developed a new Danish cognitive screening instrument for use in general practice.
Rare causes of dementia and inherited neurodegenerative disorders
Neurogenetic research focuses on clinical characteristics, ancillary investigations and basic research on gene function and therapy. Many neurodegenerative disorders, including AD, FTD, Huntington’s disease 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 neurodegeneration mechanisms 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 DDRC neurogenetics section is a significant international contributor to research in HD, and our large cohorts of patients are assessed with detailed clinical evaluations, genetic markers and CSF profiles. DDRC conducts highly specialised diagnostic exami19 nation and treatment of many rare disorders, including normal pressure hydrocephalus (NPH).
The DDRC NPH team is currently studying the effect of treatment and diagnostic procedures.
Public health in dementia
Using nationwide registry data we analyse the quality of diagnostic evaluation, access to health services and the use of medication in patients with dementia compared to the general Danish population. The research is being carried out in collaboration with the National Centre for Register-based Research at Aarhus University and the Section of Social Medicine, University of Copenhagen. Recently, the partnership conducted projects investigating patterns of use of opioids, other analgetics, psychotropics and anti-dementia medication.
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. We also conduct studies on mortality in dementia and on the role of infections in dementia.
Finally, we are taking part in studies on the relationship between stress and dementia. 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 multicentre intervention studies investigating non-pharmacological treatment in neurodegenerative diseases, some of which examine the effects of psychosocial interventions.
In the ongoing ReACT study we examine how assistive technology can be designed to support self-management and rehabilitation of people with dementia. As part of the study an app has been designed and tested that incorporated user-involvement in an innovative process. The study also explores methods for implementation and adoption of assistive technology.
Global health and cross-cultural aspects of dementia
DDRC is conducting several studies on the cross-cultural aspects of dementia. To improve diagnostic evaluation and care of ethnic minorities with dementia, the centre has studied the assessment of dementia in various ethnic groups in Denmark and in other European countries, as well as barriers to accessing dementia care.
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 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-ofconcept 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 requested 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.
In pharmacological trials for dementia DDRC is the national coordinator of the dementia centre in National Experimental Therapy Partnership (NEXT), which is a public-private clinical research partnership involving the regions of Denmark, universities, twelve pharmaceutical companies and one GTS institute, a government-approved, non-profit technological service. NEXT works to optimise clinical trials from start to finish and has established centres in various medical areas. In 2018 NEXT was renamed Trial Nation.