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BEHANDLING-God og treffsikker diagnostikk, behandling og rehabilitering

Dementia Disease Initiation

Awarded: NOK 2.4 mill.

DDI is a national, cross-regional cooperation project involving leading neuroscience research institutes in South-Eastern, Western, Mid- and Northern Norway. The project focuses on the most common brain organic diseases and include Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies and cerebrovascular disease. Large clinical patient cohorts and corresponding normal controls are made available for the project, and advanced technological approaches are used to better explore and understand the underlying disease mechanisms. We have aimed to develop new, applicable technology within imaging, blood and cerebrospinal fluid investigations as well as serach for more sensitive neuropsychological criteria in early disease. Dementia diseases typically have long initial periods with a paucity of symptoms while, however, brain damage is incurred (preclinical stages), followed by subjective and mild cognitive impairment prior to dementia. These periods may cover for two decades. This project aims to identify early diagnostic markers of pre-dementia stages, as well as improve and harmonize diagnostic pre-dementia procedures at a national level. So far, close to 600 participants have been recruited to the study in total, whereof 300 will have completed 2-year follow-up at year-end. Descriptions of cohorts have been published, as has several cross-sectional studies. Findings from 2-year follow are presently being analyzed and published. Our findings point towards new mechanisms for early brain damage in dementia diseases, partly at connections between nerve cells (synapses, in particular post-synaptic spines), partly immune activation which also may contribute to synapse affection. As a future prospect, these markers and mechanisms could be exploited for monitoring therapy, and may aid choice of treatment. We also hope that our new blood-based techniques may aid patient diagnostics.

For the first time, DDI brings together trans-national advanced neuroscientific communities combining technology (MRI, PIB-PET), know-how (neurochemistry, post-processing) and advanced equipment as well as patient cohorts, to ultimately combat incipient c ognitive impairment and dementia. The project benefits also from texisting NORNI-project, and most importantly from the combined analysis and harmonization of existing large national patient- and control cohorts from Helse Sør-Øst ("MCI-GO"), HelseVest (" DemVest") and HelseMidt ("Trønderbrain"), and starting up a similar cohort in Helse Nord. Major knowledge gains will be made already from cross-cohort analysis of existing data (see proj. plan.). Building on national, EU (JPND) Scandinavian and highly adv anced international networks for collaboration, we will fruitfully integrate Alzheimer (AD) and Parkinson/Diffuse Lewy Body (PD/DLB) research by contrasting major cognitive disease trajectories to normal aging (NA). AD and PD/DLB are major dementia disea ses (60-80% of all cases). Years and decades of pre-clinical and predementia cognitive impairment and utlimatel extremely challenging due to extensive behavioral, emotional and cognitive disturbance and rapidly increasing high costs to society. To prevent dementia, a focus-shift to predementia stages and knowledge of early mechanisms putatively amenable to prevention and intervention are needed. Dementia patients have suffered neuronal degeneration, lost neurons and neural networks can not be replaced. So me pathophysiological processes involved have been described, but major knowledge gaps persist. Incipient disease will be mapped in NA chorts, and putative incipient disease manifestations and predictors will be mapped accross neurochemistry, imaging mod alities and genetics to gain insight in initial disease mechanisms, trajectories. Build on regional established running projects, intnl. networks, trans-regional advanced competence DDI has a high success-likelyhood

Funding scheme:

BEHANDLING-God og treffsikker diagnostikk, behandling og rehabilitering