Head of research
Dementia
About Dementia
Alzheimer’s disease causes 50-70% of all dementias and is a leading cause of mortality. The prevalence of Alzheimer’s disease is about one percent at age 65 and increases dramatically to between 20-50% in those older than 85 years. The pathological hallmarks of Alzheimer’s disease are extracellular accumulation of amloid β (Aβ) peptide in the brain (“senile plaque” SP) and by intraneuronal accumulation of hyper-phosphorylated tau protein in neurofibrillary tangles (NFT). This is accompanied by synaptic and neuronal losses. Neuropathological criteria of Alzheimer’s disease are based on density and distribution of SP and NFT in the brain. Thus, the pathological diagnosis is Alzheimer type pathology, while the diagnosis of dementia relies on clinical information. Lewy body disease are other common dementias, which present themselves clinically as Dementia with Lewy bodies or Parkinson disease dementia (PDD). There is commonly a large degree of overlapping Alzheimer’s disease and Lewy body pathology in demented individuals.
Aims
Key knowledge gaps both nationally and internationally are our limited understanding of the etiology and molecular pathogenesis of dementia. These mechanisms need to be elucidated in order to identify novel therapeutic targets that can prevent disease progression. Furthermore, better biomarkers for dementia diagnosis and progression need to be identified. Biomarkers would be of particularly high value in dementa as neurodegeneration is already advanced at the time of clinical diagnosis. Furthermore, biomarkers are necessary to provide surrogate endpoints to evaluate the clinical efficacy of new neuroprotective therapies. Hence, biomarkers are pivotal to identify patients with prodromal dementia that may be ideal candidates for neuroprotective therapies.
Research
We will be a partner in the planned ANeED Study, headed by Associate Professor Arvid Rongve at Helse Fonna. This is a phase IIa multicentre randomized controlled double blind clinical trial to demonstrate clinical efficacy on cognitive, neuropsychiatric and functional outcomes of Ambroxol in New and Early patients with prodromal and mild Dementia with Lewy bodies.
The dementia cohort study will start during 2020 and aims at identifying molecular processes that are relevant across sub-groups of dementia and processes that can help stratify dementia into sub-groups that reflect underlying biology. The central hypothesis in this project is that converging molecular pathways exist across subtypes of dementia, but also that there are underlying subtypes that may not be fully reflected in the current classification system of dementia. We will identify biological overlap and disease subtypes, based on a transdisciplinary approach integrating cognitive testing, clinical investigations, neuroimaging and molecular biomarkers. Thus, this approach will enable us to reclassify and stratify Dementia according to underlying biological patterns. Our overarching objective is to establish a cohort with multidimensional data that can be integrated in order to the complex clinical and biological spectrum of in Dementia and stratify it into subclasses with homogeneous biology and prognosis. This knowledge will then be used to develop diagnostic and prognostic biomarkers and identify novel therapeutic targets. Secondary objectives include:
1) Establish and characterize the Dementia cohort, a population-based dementia cohort focusing on AD and DLB
2) Elucidate genome-wide epigenetic and transcriptomic signatures associated with Dementia
3) Establish an objective molecular classification system for Dementia
4) Develop precision biomarkers for accurate molecular diagnosis and patient stratification in clinical practice
Professor Dag Arsland is a collaborator in this study.