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Gene-Environment Interaction in Dementia

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 aetiology. Norway has the ability to respond to the challenge through our available cohort studies and registries.

About the project

Our approach is to focus on modifiable, environmental factors (cholesterol, smoking, alcohol intake and physical activity) 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 environmental factors are influenced by the presence of candidate genes. 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.

Objectives

Our overall aim is to give better advice to the population on behaviours that can modify the risk of Alzheimer's disease (AD) and develop new insights that can stimulate further research .

The specific objectives are to:

  1. Estimate the association to death from dementia for modifiable environmental factors (lipid levels, smoking, alcohol intake and physical activity) using the Cohort of Norway (CONOR) and the Norwegian Counties studies linked with the Cause of death registry.
  2. Estimate the association to Alzheimer’s disease for the same variables using the CONOR and the Norwegian Counties studies linked to the Norwegian Prescription Database (NorPD).
  3. Compare the risk of AD or death form dementia for sib pairs and twins who are discordant for environmental risk or protective factors in midlife.
  4. Estimate the interaction between candidate genes and modifiable environmental factors with respect to the risk of dying from dementia (Cause of Death Registry) or using medication for AD (NorPD) using stored DNA samples in CONOR in a nested case-control study.
  5. Estimate the heritability of death from dementia or of using medication for AD, or being diagnosed with AD by linking the Norwegian Twin registry with the Cause of Death Registry and NorPD.

Background

The data sources are:

  • Cohort of Norway (CONOR) study includes 173,236 subjects and 10,850 deaths. About 1,700 subjects have died with dementia. DNA is extracted from most of participants and EDTA-full blood stored;
  • The Norwegian Counties Study (NCS) includes 68,645 persons;
  • Norwegian Twin Registry: approximately 16,000 complete twin pairs with zygosity information, approximately 4,000-5,000 biological samples;
  • The Norwegian Prescription Database (NorPD): A linkage between CONOR and the NorPD showed that 2,639 subjects have received medication against AD (ATC-code N06D) in the period 2004-2009, corresponding to about 1.5 % of the participants. For subjects born in the 1920s, more than 5 % of the participants have received anti-AD medication;
  • 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).

The research group have extensive experience in research on AD and dementia (Kivipelto, Refsum, Schirmer, Bjertness, Bergem, Lannfelt and Engedal), in general epidemiology (Magnus, Tell, Bjertness, Nafstad, Næss, Strand, Holmen), social inequality in health (Næss, Strand), mental health (Tambs), genetics (Djurovic, Knudsen, Lannfelt, Holmen), pharmacoepidemiology (Handal) and statistics (Selmer, Hjellvik), as well as clinical geriatric/pshyciatric medicine (Engedal, Bergem, Schirmer, Lannfelt).

Cooperation

  • The Norwegian Institute of Public Health
  • Oslo University Hospital
  • The Uppsala University, Sweden
  • University of Bergen
  • University of Tromsø
  • Norwegian University of Science and Technology
  • Karolinska Institutet
  • University of Kuopio

Results

Publications:

  1. Strand BH, Tambs K, Engedal K, Bjertness E, Selbæk G, Rosness TA. [How many have dementia in Norway?]. Tidsskr Nor Laegeforen. 2014 Feb 11;134(3):276-7. doi:10.4045/tidsskr.13.1601. Norwegian. PubMed PMID: 24518472.
  2. Strand BH, Langballe EM, Hjellvik V, Handal M, Næss O, Knudsen GP, Refsum H, Tambs K, Nafstad P, Schirmer H, Bergem AL, Selmer R, Engedal K, Magnus P, Bjertness E; GENIDEM-Group. Midlife vascular risk factors and their association with dementia deaths: results from a Norwegian prospective study followed up for 35 years. J Neurol Sci. 2013 Jan 15;324(1-2):124-30. doi: 10.1016/j.jns.2012.10.018. Epub 2012 Nov 10. PubMed PMID: 23146611.
  3. Rosness TA, Strand BH, Engedal K, Bjertness E. Glucose levels and risk of dementia related mortality. J Am Geriatr Soc. 2016 Jan;64(1):156-61. doi: 10.1111/jgs.13870.
  4. Strand BH, Langballe EM, Rosness TA, Engedal K, Bjertness E. Does midlife obesity really lower dementia risk? Lancet Diabetes Endocrinol. 2015 Jul;3(7):498-9. doi: 10.1016/S2213-8587(15)00213-2. PubMed PMID: 26138162.
  5. Strand BH, Rosness TA, Engedal K, Magnus P, Bergem AL, Schirmer H, Bjertness E, Knudsen GP. Interaction of Apolipoprotein E Genotypes, Lifestyle Factors and Future Risk of Dementia-Related Mortality: The Cohort of Norway (CONOR). Dement Geriatr Cogn Disord. 2015;40(3-4):137-47. doi: 10.1159/000431218. Epub 2015 Jun 12. PubMed PMID: 26088392.
  6. Rosness TA, Strand BH, Engedal K, Chemali Z, Bjertness E. What does height tell us about the risk of dementia? Int J Geriatr Psychiatry. 2015 Jul;30(7):776-7. doi:10.1002/gps.4296. PubMed PMID: 26058456.
  7. Rosness TA, Strand BH, Bergem AL, Nafstad P, Langballe EM, Engedal K, Tambs K, Bjertness E. Association of psychological distress late in life and dementia-related mortality. Aging Ment Health. 2015 Apr 14:1-8. [Epub ahead of print] PubMed PMID: 25871314.
  8. Ormstad H, Rosness TA, Bergem AL, Bjertness E, Strand BH. Alcohol consumption in the elderly and risk of dementia related death - a Norwegian prospective study with a 17-year follow-up. Int J Neurosci. 2015 May 22. [Epub ahead of print]PubMed PMID: 25495993.
  9. Rosness TA, Strand BH, Bergem AL, Engedal K, Bjertness E. Associations between Physical Activity in Old Age and Dementia-Related Mortality: A Population-Based Cohort Study. Dement Geriatr Cogn Dis Extra. 2014 Oct 29;4(3):410-8. doi:10.1159/000367938. eCollection 2014 Sep. PubMed PMID: 25493091; PubMed Central PMCID: PMC4255990.
  10. Strand BH, Langballe EM, Rosness TA, Bergem AL, Engedal K, Nafstad P, Tell GS, Ormstad H, Tambs K, Bjertness E; GENIDEM-group. Age, education and dementia related deaths. The Norwegian Counties Study and The Cohort of Norway. J Neurol Sci. 2014 Oct 15;345(1-2):75-82. doi: 10.1016/j.jns.2014.07.009. Epub 2014 Jul10. PubMed PMID: 25034053.
  11. Strand BH, Skirbekk V, Rosness TA, Engedal K, Bjertness E. Income in midlife and dementia related mortality over three decades: A Norwegian prospective study, 2015. Accepted eNeurological Sci.
  12. Chatterjee S, Peters SA, Woodward M, Mejia Arango S, Batty GD, Beckett N, Beiser A, Borenstein AR, Crane PK, Haan M, Hassing LB, Hayden KM, Kiyohara Y, Larson EB, Li CY, Ninomiya T, Ohara T, Peters R, Russ TC, Seshadri S, Strand BH, Walker R, Xu W, Huxley RR. Type 2 Diabetes as a Risk Factor for Dementia in Women Compared With Men: A Pooled Analysis of 2.3 Million People Comprising More Than 100,000 Cases of Dementia. Diabetes Care. 2016 Feb;39(2):300-7. doi: 10.2337/dc15-1588. Epub 2015 Dec 17.
  13. Strand BH, Rosness TA, & Bjertness E. Kan demens forebygges - en oversikt fra Genidem prosjektet. Demens & alderspsykiatri, 2015.
  14. Antidepressants and risk of dementia - a never-ending story? Rosness TA, Strand BH, Bergem AL, Engedal K, Bjertness E. Int J Geriatr Psychiatry. 2016 Jun;31(6):553-4. doi: 10.1002/gps.4367. Epub 2015 Oct 15.

  15. Association Between Random Measured Glucose Levels in Middle and Old Age and Risk of Dementia-Related Death. Rosness TA, Engedal K, Bjertness E, Strand BH. J Am Geriatr Soc. 2016 Jan;64(1):156-61. doi: 10.1111/jgs.13870. 

  16. Response to Cintosun and Colleagues. Rosness TA, Engedal K, Bjertness E, Strand BH. J Am Geriatr Soc. 2016 Jul 18. doi: 10.1111/jgs.14191. [Epub ahead of print]  

  17. Weight Change in Midlife and Risk of Mortality From Dementia up to 35 Years Later. Strand BH, Wills AK, Langballe EM, Rosness TA, Engedal K, Bjertness E. J Gerontol A Biol Sci Med Sci. 2016 Aug 10. pii: glw157.

Abstracts:

  1. 11th European Union Geriatric Medicine Society (EUGMS) congress, 16-18 September 2015, Oslo. Late breaking abstract session:  Strand BH, Langballe EM, Rosness TA, Engedal K, Bjertness E. Does midlife obesity really lower dementia risk?
  2. 68th Annual Scientific Meeting of The Gerontological Society of America. 18-22 November 2015, USA Orlando. Oral presentation: Strand BH, Rosness TA, Engedal K, Magnus P, Bergem AL, Schirmer H, Bjertness E, Knudsen GP. Interaction of Apolipoprotein E Genotypes, Lifestyle Factors and Future Risk of Dementia-Related Mortality: The Cohort of Norway (CONOR).
  3. NordicEpi 2015, Oslo 21-23 September. Oral presentation: Strand BH, Rosness TA, Engedal K, Magnus P, Bergem AL, Schirmer H, Bjertness E, Knudsen GP. Interaction of Apolipoprotein E Genotypes, Lifestyle Factors and Future Risk of Dementia-Related Mortality: The Cohort of Norway (CONOR).
  4. Demensdagene, 1.desember 2015. Risikofaktorer for demens, hva sier litteraturen? Strand BH.
  5. Landskonferansen i alderspsykiatri, Ålesund april 2015. Vant fagjuriens poster-pris. Siafarikas N, Bergem ALM, Nilsen TS, Magnus P, Rosness TA, Strand BH, Schirmer H, Knutsen GP, Engedal K, Bjertness E for GENIDEM-Gruppen. En tvillingundersøkelse om arvelighet ved Alzheimers sykdom og andre demensformer”.

 

Start - Finish

2010 - 2016

Published May 22, 2011 7:56 PM - Last modified Aug. 19, 2016 8:59 AM

Contact

Project leader

Espen Bjertness

Participants

  • Espen Bjertness
  • Per Nafstad
  • Per Magnus
  • Heidi Kristin Ormstad
  • Helga Refsum
  • Knut Arne Engedal
  • Tor Atle Rosness
  • Bjørn Heine Strand
  • Kristian Tambs, FHI
  • Gun Peggy Knudsen, FHI
  • Mina Bergem, AHUS
  • Øyvind Næss, FHI
  • Marte Handal, FHI
  • Vidar Hjellvik, FHI
  • Randi Selmer, FHI
  • Lars Lannfelt, Uppsala University
  • Grete Tell, UiB
  • Henrik Schirmer, UiT
  • Jostein Holmen, NTNU
  • Nikias Siafarikas, AHUS
  • Srdjan Djurovic, OUS
  • Geir Selbæk, Sykehuset Innlandet
  • Miia Kivipelto, Karolinska Institutet
Detailed list of participants