Vantaa 85+ Study. Raimo Sulkava Tuomo Polvikoski

Transcription

1 Vantaa 85+ Study Raimo Sulkava Tuomo Polvikoski

2 Vuoden geriatrinen julkaisu Neuropathol Appl Neurobiol Sep 14 Prevalence and severity of cerebral amyloid angiopathy - a population-based study on very elderly Finns (Vantaa 85+). Tanskanen M, Mäkelä M, Myllykangas L, Notkola IL, Polvikoski T, Sulkava R, Kalimo H, Paetau A.

3 CAA in the 85-year-olds In 69.6%, miehillä enemmän Parietaali-frontaali lohkoissa Ei pelkästään AD:ssa Korreloi apoe e4 -alleeliin

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5 Vantaa 85+ Study

6 The beginning It started first of April, 1991 (All Fools Day) Community nurse Pirkko Ahponen and specialising neurologist Auli Verkkoniemi examined the first patient

7 Raimo Sulkava

8 Leena Niinistö

9 Leena Raimo contacted head physician Leena Niinistö in Vantaa. They were one year at the same school Oriveden yhteiskoulu The public health system, health centres etc were in Vantaa better than in other areas of the capital region Leena understood the importance of Vantaa 85+ Study and organised everything marvellously in the Vantaa Health centre and Katriina Hospital

10 Matti Haltia

11 Tuomo and Matti I heard from prof Matti Haltia that there was one Tuomo, a specialising pathologist, who was interested in neuropathology I contacted Tuomo and the rest is history: in 1991 there were 601 people aged 85+ in Vantaa. Tuomo autopsied 51 per cent of them!

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13 Financing Academy of Finland or private foundations were not interested in people aged 85+ I decided to carry out a drug trial (paroxetine in AD). We could start the study with that money

14 DNA In 1991 almost nobody could imagine that genes and DNA from the old-old people could be important Ethics committee accepted collection of DNA DNA was extracted in 1994 by prof Kimmo Kontula s lab for free

15 Financing pathology and genetics No interest in such a project Tuomo and I thought autopsies might be important Solutions: the city of Vantaa provided room and facilities for autopsies and was able to pay for a minor part of autopsies and Tuomo carried the out them without payment before he went to his work

16 Ghosts in the Katriina Hospital?

17 Follow-up studies The basic study Follow-ups: 1994, 1996, 1999, 2001

18 The genetics of the Vantaa Study Pentti Tienari, Liisa Myllykangas, Terhi Peuralinna, John Hardy, Veli-Matti Isoviita (in future Sonja Sulkava?!) And many others

19 Pathology Matti Haltia, Tuomo Polvikoski, Maarit Tanskanen, Anders Paetau, Minna Oinas, Hannu Kalimo, Liisa Myllykangas, Mira Mäkelä And many others

20 First publication of the Vantaa 85+ Study Original Article Apolipoprotein E, Dementia, and Cortical Deposition of β-amyloid Protein Tuomo Polvikoski, M.D., Raimo Sulkava, M.D., Matti Haltia, M.D., Katariina Kainulainen, M.D., Alpo Vuorio, M.D., Auli Verkkoniemi, M.D., Leena Niinistö, M.D., Pirjo Halonen, Ph.D., and Kimmo Kontula, M.D. N Engl J Med 1995; 333: November 9, 1995

21 Polvikoski et al NEJM 1995;333:1242-7

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23 Prevalence of neuropathological AD in a population aged 85 years and older apoe ε4-20% apoe ε4+ 63% All 33% Polvikoski et al. Neurology 2001

24 ApoE ε4 allele has a strong association with Alzheimer s disease also in very old people. ApoE ε4 allele is associated with accumulation of plaques and tangles. However, other genetic or nongenetic mechanisms must also have a role in the causation because all people with apoe ε4 allele will not become demented even at a very advanced age there is a considerable risk for Alzheimer s disease even without ε4 allele

25 Myllykangas et al. Ann Neurol 1999;46:382-90

26 Friedrich Heinrich Lewy

27 Lewy pathology in people aged 85+ (Oinas et al 2009) Distribution of Lewy-related pathology (LRP) None + Brainstem Limbic Diffuse 207 (68%) 8 (3%) 42 (14%) 47 (15%)

28 Clinical, epidemiology, radiology Auli Verkkoniemi, Anna-Maija Sutela: (depression, the cause of death project), Petteri Viramo: (the cause of death project), Sari Rastas (risk factors for AD), Kati Juva, Terhi Rahkonen, Timo Erkinjuntti, Raimo Sulkava, Lauri Kivikoski, Satu Ahtiluoto, Daniel Davis And many others

29 Kuolleisuus verenpaineen mukaan yli 85-vuotiailla (Rastas ym 2007) 600 Riskisuhde 2,02 ref 0,78 1,78 ref 0,83 kuolleisuus/1000 hv keskim. kuolleisuus 0 SBP DBP matala normaali korkea N

30 Original Publications of Vantaa 85+ Study N=43 Peuralinna T, Tanskanen M, Mäkelä M, Polvikoski T, Paetau A, Kalimo H, Sulkava R, Hardy J, Lai SL, Arepalli S, Hernandez D, Traynor BJ, Singleton A, Tienari PJ, Myllykangas L. APOE and AβPP Gene Variation in Cortical and Cerebrovascular Amyloid-β Pathology and Alzheimer's Disease: A Population-Based Analysis. J Alzheimers Dis Jun 7. [Epub ahead of print] PubMed PMID: Polvikoski TM, van Straaten EC, Barkhof F, Sulkava R, Aronen HJ, Niinistö L, Oinas M, Scheltens P, Erkinjuntti T, Kalaria RN. Frontal lobe white matter hyperintensities and neurofibrillary pathology in the oldest old. Neurology. 2010Dec 7;75(23): Epub 2010 Nov 3. PubMed PMID: ; PubMed Central PMCID: PMC EClipSE Collaborative Members, Brayne C, Ince PG, Keage HA, McKeith IG, Matthews FE, Polvikoski T, Sulkava R. Education, the brain and dementia: neuroprotection or compensation? Brain Aug;133(Pt 8): PubMed PMID: Ahtiluoto S, Polvikoski T, Peltonen M, Solomon A, Tuomilehto J, Winblad B, Sulkava R, Kivipelto M. Diabetes, Alzheimer disease, and vascular dementia: a population-based neuropathologic study. Neurology Sep 28;75(13): Epub 2010 Aug 25. PubMed PMID: Ihara M, Polvikoski TM, Hall R, Slade JY, Perry RH, Oakley AE, Englund E,O'Brien JT, Ince PG, Kalaria RN. Quantification of myelin loss in frontal lobewhite matter in vascular dementia, Alzheimer's disease, and dementia with Lewybodies. Acta Neuropathol May;119(5): Epub 2010 Jan 21. PubMed PMID: ; PubMed Central PMCID: PMC van Munster BC, de Rooij SE, Yazdanpanah M, Tienari PJ, Pitkälä KH, Osse RJ, Adamis D, Smit O, van der Steen MS, van Houten M, Rahkonen T, Sulkava R, Laurila JV, Strandberg TE, Tulen JH, Zwang L, MacDonald AJ, Treloar A, Sijbrands EJ, Zwinderman AH, Korevaar JC. The association of the dopamine transporter gene and the dopamine receptor 2 gene with delirium, a meta-analysis. Am J Med Genet B Neuropsychiatr Genet Mar 5;153B(2): PubMed PMID: EClipSE Collaborative Members. Cohort profile: Epidemiological Clinicopathological studies in Europe (EClipSE). J Alzheimers Dis. 2009;18(3): PubMed PMID: Oinas M, Polvikoski T, Sulkava R, Myllykangas L, Juva K, Notkola IL, Rastas S, Niinistö L, Kalimo H, Paetau A. Neuropathologic findings of dementia with lewy bodies (DLB) in a population-based Vantaa 85+ study. J Alzheimers Dis. 2009;18(3): PubMed PMID:

31 2 Peuralinna T, Oinas M, Polvikoski T, Paetau A, Sulkava R, Niinistö L, Kalimo H, Hernandez D, Hardy J, Singleton A, Tienari PJ, Myllykangas L. Neurofibrillary tau pathology modulated by genetic variation of alpha-synuclein. Ann Neurol. 2008Sep;64(3): PubMed PMID: Myllykangas L, Lammie GA, Notkola IL, Sulkava R, Polvikoski T. Apolipoprotein E (APOE) and lipoprotein lipase (LPL) gene variants and carotid atherosclerotic lesions in the oldest old: a population-based autopsy study. Arch Gerontol Geriatr Jul-Aug;49(1): Epub 2008 Jul 10. PubMed PMID: Tanskanen M, Peuralinna T, Polvikoski T, Notkola IL, Sulkava R, Hardy J, Singleton A, Kiuru-Enari S, Paetau A, Tienari PJ, Myllykangas L. Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation inalpha2-macroglobulin and tau: a population-based autopsy study. Ann Med. 2008;40(3): PubMed PMID: Rastas S, Pirttilä T, Mattila K, Verkkoniemi A, Juva K, Niinistö L, Länsimies E, Sulkava R. Vascular risk factors and dementia in the general population aged >85 years: prospective population-based study. Neurobiol Aging Jan;31(1):1-7. Epub 2008 Apr 1. PubMed PMID: Barkhof F, Polvikoski TM, van Straaten EC, Kalaria RN, Sulkava R, Aronen HJ, Niinistö L, Rastas S, Oinas M, Scheltens P, Erkinjuntti T. The significance of medial temporal lobe atrophy: a postmortem MRI study in the very old. Neurology Oct 9;69(15): PubMed PMID: Oinas M, Sulkava R, Polvikoski T, Kalimo H, Paetau A. Reappraisal of a consecutive autopsy series of patients with primary degenerative dementia: Lewy-related pathology. APMIS Jul;115(7): PubMed PMID: Rastas S, Verkkoniemi A, Polvikoski T, Juva K, Niinistö L, Mattila K, Länsimies E, Pirttilä T, Sulkava R. Atrial fibrillation, stroke, and cognition: alongitudinal population-based study of people aged 85 and older. Stroke May;38(5): Epub 2007 Mar 29. PubMed PMID: Tanskanen M, Kiuru-Enari S, Tienari P, Polvikoski T, Verkkoniemi A, Rastas S, Sulkava R, Paetau A. Senile systemic amyloidosis, cerebral amyloid angiopathy, and dementia in a very old Finnish population. Amyloid Sep;13(3): PubMed PMID:

32 3 Rastas S, Pirttilä T, Viramo P, Verkkoniemi A, Halonen P, Juva K, Niinistö L, Mattila K, Länsimies E, Sulkava R. Association between blood pressure and survival over 9 years in a general population aged 85 and older. J Am Geriatr Soc Jun;54(6): PubMed PMID: Polvikoski T, Sulkava R, Rastas S, Sutela A, Niinistö L, Notkola IL, Verkkoniemi A, Viramo P, Juva K, Haltia M. Incidence of dementia in very elderly individuals: a clinical, neuropathological and molecular genetic study. Neuroepidemiology. 2006;26(2): Epub 2005 Dec 13. PubMed PMID: Tanskanen M, Lindsberg PJ, Tienari PJ, Polvikoski T, Sulkava R, Verkkoniemi A, Rastas S, Paetau A, Kiuru-Enari S. Cerebral amyloid angiopathy in a 95+ cohort: complement activation and apolipoprotein E (ApoE) genotype. Neuropathol Appl Neurobiol Dec;31(6): PubMed PMID: Myllykangas L, Wavrant-De Vrièze F, Polvikoski T, Notkola IL, Sulkava R, Niinistö L, Edland SD, Arepalli S, Adighibe O, Compton D, Hardy J, Haltia M, Tienari PJ. Chromosome 21 BACE2 haplotype associates with Alzheimer's disease: a two-stage study. J Neurol Sci Sep 15;236(1-2): PubMed PMID: Enattah NS, Sulkava R, Halonen P, Kontula K, Järvelä I. Genetic variant of lactase-persistent C/T is associated with bone fractures in very old age. JAm Geriatr Soc Jan;53(1): PubMed PMID: Rastas S, Mattila K, Verkkoniemi A, Niinistö L, Juva K, Sulkava R, Länsimies E. Association of apolipoprotein E genotypes, blood pressure, blood lipids and ECG abnormalities in a general population aged 85+. BMC Geriatr Mar 29;4:1.PubMed PMID: ; PubMed Central PMCID: PMC

33 Lambert JC, Araria-Goumidi L, Myllykangas L, Ellis C, Wang JC, Bullido MJ, Harris JM, Artiga MJ, Hernandez D, Kwon JM, Frigard B, Petersen RC, Cumming AM, Pasquier F, Sastre I, Tienari PJ, Frank A, Sulkava R, Morris JC, St Clair D, MannDM, Wavrant-DeVrièze F, Ezquerra-Trabalon M, Amouyel P, Hardy J, Haltia M, Valdivieso F, Goate AM, Pérez-Tur J, Lendon CL, Chartier-Harlin MC. Contribution of APOE promoter polymorphisms to Alzheimer's disease risk. Neurology Jul 9;59(1): PubMed PMID: Salo A, Ylikoski R, Verkkoniemi A, Polvikoski T, Juva K, Rastas S, Kontula K, Kainulainen K, Niinistö L, Notkola IL, Sulkava R. Does apolipoprotein E influence learning and memory in the nondemented oldest old? Int Psychogeriatr Dec;13(4): PubMed PMID: Myllykangas L, Polvikoski T, Reunanen K, Wavrant-De Vrieze F, Ellis C, Hernandez D, Sulkava R, Kontula K, Verkkoniemi A, Notkola IL, Hardy J, Perez-Tur J, Haltia MJ, Tienari PJ. ApoE epsilon3-haplotype modulates Alzheimer beta-amyloid deposition in the brain. Am J Med Genet Apr 8;114(3): PubMed PMID: Myllykangas L, Polvikoski T, Sulkava R, Notkola IL, Rastas S, Verkkoniemi A, Tienari PJ, Niinistö L, Hardy J, Pérez-Tur J, Kontula K, Haltia M. Association of lipoprotein lipase Ser447Ter polymorphism with brain infarction: a population-based neuropathological study. Ann Med Oct;33(7): PubMed PMID: Oinas M, Polvikoski T, Sulkava R, Paetau A, Haltia M. [Lewy body dementia]. Duodecim. 1998;114(15): Finnish. PubMed PMID: Polvikoski T, Sulkava R, Myllykangas L, Notkola IL, Niinistö L, Verkkoniemi A, Kainulainen K, Kontula K, Pérez-Tur J, Hardy J, Haltia M. Prevalence of Alzheimer's disease in very elderly people: a prospective neuropathological study. Neurology Jun 26;56(12): PubMed PMID: Rahkonen T, Eloniemi-Sulkava U, Halonen P, Verkkoniemi A, Niinistö L, Notkola IL, Sulkava R. Delirium in the non-demented oldest old in the general population: risk factors and prognosis. Int J Geriatr Psychiatry Apr;16(4): PubMed PMID:

34 Välimäki S, Tähtelä R, Kainulainen K, Laitinen K, Löyttyniemi E, Sulkava R, Välimäki M, Kontula K. Relation of collagen type I alpha 1 (COLIA 1) and vitamin D receptor genotypes to bone mass, turnover, and fractures in early postmenopausal women and to hip fractures in elderly people. Eur J Intern Med Feb;12(1): PubMed PMID: Juva K, Verkkoniemi A, Viramo P, Polvikoski T, Kainulainen K, Kontula K, Sulkava R. Apolipoprotein E, cognitive function, and dementia in a general population aged 85 years and over. Int Psychogeriatr Sep;12(3): PubMed PMID: Myllykangas L, Polvikoski T, Sulkava R, Verkkoniemi A, Tienari P, Niinistö L, Kontula K, Hardy J, Haltia M, Pérez-Tur J. Cardiovascular risk factors and Alzheimer's disease: a genetic association study in a population aged 85 or over. Neurosci Lett Oct 13;292(3): PubMed PMID: Baker M, Graff-Radford D, Wavrant DeVrièze F, Graff-Radford N, Petersen RC, Kokmen E, Boeve B, Myllykangas L, Polvikoski T, Sulkava R, Verkoniemi A, Tienari P, Haltia M, Hardy J, Hutton M, Perez-Tur J. No association between TAU haplotype and Alzheimer's disease in population or clinic based series or in familial disease. Neurosci Lett May 12;285(2): PubMed PMID: Juva K, Verkkoniemi A, Viramo P, Polvikoski T, Kainulainen K, Kontula K, Sulkava R. APOE epsilon4 does not predict mortality, cognitive decline, or dementia in the oldest old. Neurology Jan 25;54(2): PubMed PMID: Myllykangas L, Polvikoski T, Sulkava R, Verkkoniemi A, Crook R, Tienari PJ, Pusa AK, Niinistö L, O'Brien P, Kontula K, Hardy J, Haltia M, Pérez-Tur J. Genetic association of alpha2-macroglobulin with Alzheimer's disease in a Finnish elderly population. Ann Neurol Sep;46(3): PubMed PMID:

35 6 Päivärinta A, Verkkoniemi A, Niinistö L, Kivelä SL, Sulkava R. The prevalence and associates of depressive disorders in the oldest-old Finns. Soc Psychiatry Psychiatr Epidemiol Jul;34(7): PubMed PMID: Kiljunen M, Sulkava R, Niinistö L, Polvikoski T, Verkkoniemi A, Halonen P. Depression measured by the Zung Depression Status Inventory is very rare in a Finnish population aged 85 years and over. Int Psychogeriatr Sep;9(3): PubMed PMID: Sulkava R, Kainulainen K, Verkkoniemi A, Niinistö L, Sobel E, Davanipour Z, Polvikoski T, Haltia M, Kontula K. APOE alleles in Alzheimer's disease and vascular dementia in a population aged 85+. Neurobiol Aging May-Jun;17(3): PubMed PMID: Sulkava R, Kontula K, Haltia M. [Recent genetic association in Alzheimer's disease]. Duodecim. 1996;112(8):651, 653, 655. Finnish. PubMed PMID: Polvikoski T, Sulkava R, Haltia M, Kainulainen K, Vuorio A, Verkkoniemi A, Niinistö L, Halonen P, Kontula K. Apolipoprotein E, dementia, and cortical deposition of beta-amyloid protein. N Engl J Med Nov 9;333(19): PubMed PMID:

36 Dissertations of Vantaa 85+ Study (N=6) Tuomo Polvikoski: Alzheimer s disease and apolipoprotein E.A prospective, population-based molecular genetic and neuropathological study of individuals aged 85 years or more. Academic Dissertation, December University of Helsinki, Faculty of Medicine, Haartman Institute, Department of Pathology. Liisa Myllykangas: Genetic modulation of of age-associated brain pathology. University of Helsinki, Faculty of Medicine, Supervisors: Matti Haltia and Pentti Tienari Terhi Rahkonen. Delirium in the non-demented elderly. Causative factors, prognosis and the effects of a support intervention in community care after a delirium episode p. Acad. Diss. Sari Rastas (LL) Vascular Risk Factors in the Very Old with the Emphasis on Mortality and Cognition (Vaskulaariset riskitekijät sekä niiden yhteys kuolleisuuteen ja kognitioon erittäin iäkkäillä) Maarit Tanskanen:Amyloid diseases at old age. A pathological, epidemiological, andgenetic study. Helsingin yliopisto 2008 Minna Oinas.alfa-Synuclein pathology in very elderly Finns A population-based clinico-neuropathologic and molecular genetic study of Dementia with Lewy bodies

37 Tuomo Polvikoski

38 Oikea Tuomo Polvikoski

39 The lesson of the Vantaa Study If you want to do something really new and interesting in science, you are not financed. You will get money only for those things which are already invented or solved. However, if you think that something is really worth doing just do it!

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