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BEDREHELSE-Bedre helse og livskvalitet

Educational attainment, lifestyle factors and gene-environmental interactions in dementia

Awarded: NOK 5.3 mill.

Project Number:

213805

Application Type:

Project Period:

2012 - 2016

Location:

Partner countries:

GENIDEM examines the extent to which social inequalities in health (education and income) and modifiable lifestyle factors like cholesterol, smoking, nutrition, alcohol habits and physical activity, as well as diabetes and mental health affects the incidence of dementia and especially the most common form, Alzheimer's disease. GENIDEM utilizes data from large Norwegian population studies (CONOR and 3 counties) and Norwegian Twin Registry. The project studies the interaction between genes and environment in order to understand more about the role of the genetic material plays in those who develop dementia. Postdoctoral researcher Tor Rosness, Department of Health and Society, coordinates the project together with senior researcher Bjørn Heine Strand and Espen Bjertness who is responsible for the project. GENIDEM project has had a productive year and got accepted 10 international peer-reviewed articles in the report period 01.10.2014-01.10.2015, hence one in the prestigious Lancet Diabetes Endocrinol. In addition, we published an overviwe article in the Norwegian journal Demens & Alderspsykiatri. Per 08.09.2015, we also have two articles under consideration in international peer-reviewed journals and three under construction. GENIDEM has been active in the media and had postings in Dagsavisen, Dagbladet, Dagens Næringsliv, local newspapers, forskning.no, alzforum.org, nrk.no and been interviewed about the research both live and recorded on NRK P1, P2 and Alltid Nyheter (Norgesglasset , Dagsnytt, Her og nå. During the past year, we have studied the importance of blood glucose levels early in life and dementia risk for non-diabetics. We have looked at overweight and underweight midway in life and got published our results in the Lancet Diabetes & Endocrinologi. In a continuation of this we prepare now an article where we look at changes in weight from 40 to 50 years of age and dementia death. Few other studies have the opportunity to study this, so here we are at the very cutting edge of research. Furthermore, we have looked at what height has to say for dementia, we have looked at mental health, alcohol use and physical activity. In GENIDEM we use dementia-related mortality on the death certificate as the endpoint and no clinical diagnosis of dementia. We therefore conducted a validation study of endpoint dementia death. The study was published this year: We genotyped 1,200 people for ApoE gene in a nested case-control study and found similar risk associated with the different allele combinations as studies with clinical diagnosis of dementia. This article will be an important reference article for other GENIDEM articles. GENIDEM possesses both data on the two SNPs defining APOE e2, e3 and e4, and GWAS data. And for GWAS analysis we have used Illumina HumanCoreExome. GENIDEM plans to do a new survey on body weight, hypertension and risk of dementia death during autumn 2015, as well as studies on gene-gene-environment interactions. Cooperation GENIDEM is in the process of establishing cooperation in genetics with deCODE. GENIDEM project reaches out to more and more international groups, which is reflected in the increased number of citations. Our findings have been used in several summaries of risk factors for dementia, and we have also supplied data to a larger mataanalyse under consideration in Diabetes Care. GENIDEM continue collaborating with the University of Oxford, project NUTRI-COG is an innovative double-blind randomized controlled studies aiming to investigate whether treatment with B vitamins (vitamin B12, B6, folic acid) and / or vitamin D and Omega-3 fatty acids (DHA, EPA) can slow the development of dementia and further loss of cognitive function. Subprojects GENIDEM continues a subproject on the prevalence of dementia in Norway, and invited leading researchers in dementia to participate in the cooperation, while we want to expand this project with a validation study of dementia diagnoses on death certificates, in collaboration with the National Centre for Ageing and Health (Geir Selbæk and Knut Engedal),Institute of Public Health (Per Magnus, Heine Strand, Vegard Skirbekk and Kristian Tambs), Nasjonalforeningen for folkehelsen (Knut Engedal and Anne Rita Øksengaard), Department of Clinical Medicine, University of Tromsø (Henrik Schirmer), Institute of Clinical Medicine, University of Bergen (Anette Ranhoff), Aust-Agder (Susanne Hernes), Department of Neuroscience, NTNU (Sigrid Sando, Ingvild Saltvedt and Olav Sletvold), and University of Stavanger (Dag Aarsland). There is promising news that it is circulated to the Dementia Plan, a proposal of a prevalence study in the planning period - during the next few years. GENIDEM has been active in comments to this plan.

We expect a dramatic increase in dementia prevalence, including Alzheimer's disease (AD), the most common form of dementia. There is no efficient way to prevent AD and there is an urgent need to find new clues to the etiology. Norway has the ability to re spond to the challenge through our available cohort studies and registries. Our approach is to focus on socio-economic position and modifiable, environmental factors (cholesterol, hypertension, smoking, alcohol intake, obesity, physical activity and depre ssion) and estimate their effect on dementia/AD in large cohort studies, as well as to perform nested case-control studies to examine whether the effect of these factors are influenced by the presence of candidate genes such as the alleles of the APOE gen e, and possible effects of genetic interaction with APOE. Furthermore, we have the advantages of including sibs and twins in our cohorts, which opens for estimating heritability as well as following subjects who are discordant for modifiable factors. The data sources are: Cohort of Norway (CONOR) includes 173,236 subjects and 10,850 deaths. About 1700 subjects have died with dementia. DNA is extractd from most of participants and EDTA-fullblood stored; The Norwegian Counties Study includes 68,645 persons; Norwegian Twin Registry: approximately 16 000 complete twin pairs with zygosity information, approximately 4000-5000 biological samples; The Norwegian Prescription Database (NorPD): A linkage between CONOR and the NorPD showed that 2,639 subjects have r eceived medication against AD (ATC-code N06D) in the period 2004-2009; The Norwegian Cause of Death Register: the validity of Norwegian death certificates recording dementia-related codes shows a 100% specificity indicating that rate ratio estimates based on death certificate data will be unbiased. The genotyping will be performed at the Norwegian Research Councils technology platform for SNP genotyping (CIGENE).

Funding scheme:

BEDREHELSE-Bedre helse og livskvalitet