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Published in: Alzheimer's Research & Therapy 1/2018

Open Access 01-12-2018 | Research

The EMIF-AD PreclinAD study: study design and baseline cohort overview

Authors: Elles Konijnenberg, Stephen F. Carter, Mara ten Kate, Anouk den Braber, Jori Tomassen, Chinenye Amadi, Linda Wesselman, Hoang-Ton Nguyen, Jacoba A. van de Kreeke, Maqsood Yaqub, Matteo Demuru, Sandra D. Mulder, Arjan Hillebrand, Femke H. Bouwman, Charlotte E. Teunissen, Erik H. Serné, Annette C. Moll, Frank D. Verbraak, Rainer Hinz, Neil Pendleton, Adriaan A. Lammertsma, Bart N. M. van Berckel, Frederik Barkhof, Dorret I. Boomsma, Philip Scheltens, Karl Herholz, Pieter Jelle Visser

Published in: Alzheimer's Research & Therapy | Issue 1/2018

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Abstract

Background

Amyloid pathology is the pathological hallmark in Alzheimer’s disease (AD) and can precede clinical dementia by decades. So far it remains unclear how amyloid pathology leads to cognitive impairment and dementia. To design AD prevention trials it is key to include cognitively normal subjects at high risk for amyloid pathology and to find predictors of cognitive decline in these subjects. These goals can be accomplished by targeting twins, with additional benefits to identify genetic and environmental pathways for amyloid pathology, other AD biomarkers, and cognitive decline.

Methods

From December 2014 to October 2017 we enrolled cognitively normal participants aged 60 years and older from the ongoing Manchester and Newcastle Age and Cognitive Performance Research Cohort and the Netherlands Twins Register. In Manchester we included single individuals, and in Amsterdam monozygotic twin pairs. At baseline, participants completed neuropsychological tests and questionnaires, and underwent physical examination, blood sampling, ultrasound of the carotid arteries, structural and resting state functional brain magnetic resonance imaging, and dynamic amyloid positron emission tomography (PET) scanning with [18F]flutemetamol. In addition, the twin cohort underwent lumbar puncture for cerebrospinal fluid collection, buccal cell collection, magnetoencephalography, optical coherence tomography, and retinal imaging.

Results

We included 285 participants, who were on average 74.8 ± 9.7 years old, 64% female. Fifty-eight participants (22%) had an abnormal amyloid PET scan.

Conclusions

A rich baseline dataset of cognitively normal elderly individuals has been established to estimate risk factors and biomarkers for amyloid pathology and future cognitive decline.
Appendix
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Literature
1.
go back to reference Braak H, Braak E. Diagnostic criteria for neuropathologic assessment of Alzheimer's disease. Neurobiol Aging. 1997;18(4 Suppl):S85–8.CrossRefPubMed Braak H, Braak E. Diagnostic criteria for neuropathologic assessment of Alzheimer's disease. Neurobiol Aging. 1997;18(4 Suppl):S85–8.CrossRefPubMed
2.
go back to reference Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, Marcus DS, Cairns NJ, Xie X, Blazey TM, et al. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med. 2012;367(9):795–804.CrossRefPubMedPubMedCentral Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, Marcus DS, Cairns NJ, Xie X, Blazey TM, et al. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med. 2012;367(9):795–804.CrossRefPubMedPubMedCentral
3.
go back to reference Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, Szoeke C, Macaulay SL, Martins R, Maruff P, et al. Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol. 2013;12:357–67.CrossRefPubMed Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, Szoeke C, Macaulay SL, Martins R, Maruff P, et al. Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol. 2013;12:357–67.CrossRefPubMed
4.
go back to reference Jansen WJ, Ossenkoppele R, Knol DL, Tijms BM, Scheltens P, Verhey FR, Visser PJ, Amyloid Biomarker Study G, Aalten P, Aarsland D, et al. Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis. JAMA. 2015;313:1924–38.CrossRefPubMedPubMedCentral Jansen WJ, Ossenkoppele R, Knol DL, Tijms BM, Scheltens P, Verhey FR, Visser PJ, Amyloid Biomarker Study G, Aalten P, Aarsland D, et al. Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis. JAMA. 2015;313:1924–38.CrossRefPubMedPubMedCentral
5.
go back to reference Price JL, Morris JC. Tangles and plaques in nondemented aging and “preclinical” Alzheimer’s disease. Ann Neurol. 1999;45:358–68.CrossRefPubMed Price JL, Morris JC. Tangles and plaques in nondemented aging and “preclinical” Alzheimer’s disease. Ann Neurol. 1999;45:358–68.CrossRefPubMed
6.
go back to reference Mintun MA, Larossa GN, Sheline YI, Dence CS, Lee SY, Mach RH, Klunk WE, Mathis CA, DeKosky ST, Morris JC. [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurol. 2006;67:446–52.CrossRef Mintun MA, Larossa GN, Sheline YI, Dence CS, Lee SY, Mach RH, Klunk WE, Mathis CA, DeKosky ST, Morris JC. [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurol. 2006;67:446–52.CrossRef
7.
go back to reference Aizenstein HJ, Nebes RD, Saxton JA, Price JC, Mathis CA, Tsopelas ND, Ziolko SK, James JA, Snitz BE, Houck PR, et al. Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch Neurol. 2008;65:1509–17.CrossRefPubMedPubMedCentral Aizenstein HJ, Nebes RD, Saxton JA, Price JC, Mathis CA, Tsopelas ND, Ziolko SK, James JA, Snitz BE, Houck PR, et al. Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch Neurol. 2008;65:1509–17.CrossRefPubMedPubMedCentral
8.
go back to reference Rowe CC, Ellis KA, Rimajova M, Bourgeat P, Pike KE, Jones G, Fripp J, Tochon-Danguy H, Morandeau L, O’Keefe G, et al. Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiol Aging. 2010;31:1275–83.CrossRefPubMed Rowe CC, Ellis KA, Rimajova M, Bourgeat P, Pike KE, Jones G, Fripp J, Tochon-Danguy H, Morandeau L, O’Keefe G, et al. Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiol Aging. 2010;31:1275–83.CrossRefPubMed
9.
go back to reference Chételat G, La Joie R, Villain N, Perrotin A, de La Sayette V, Eustache F, Vandenberghe R. Amyloid imaging in cognitively normal individuals, at-risk populations and preclinical Alzheimer’s disease. NeuroImage. 2013;2:356–65.CrossRefPubMed Chételat G, La Joie R, Villain N, Perrotin A, de La Sayette V, Eustache F, Vandenberghe R. Amyloid imaging in cognitively normal individuals, at-risk populations and preclinical Alzheimer’s disease. NeuroImage. 2013;2:356–65.CrossRefPubMed
10.
go back to reference Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, DeKosky ST, Gauthier S, Selkoe D, Bateman R, et al. Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol. 2014;13:614–29.CrossRefPubMed Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, DeKosky ST, Gauthier S, Selkoe D, Bateman R, et al. Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol. 2014;13:614–29.CrossRefPubMed
11.
go back to reference McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CRJ, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:263–9.CrossRefPubMedPubMedCentral McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CRJ, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:263–9.CrossRefPubMedPubMedCentral
12.
go back to reference Dickerson BC, Wolk DA. MRI cortical thickness biomarker predicts AD-like CSF and cognitive decline in normal adults. Neurology. 2011;78:84–90.CrossRefPubMed Dickerson BC, Wolk DA. MRI cortical thickness biomarker predicts AD-like CSF and cognitive decline in normal adults. Neurology. 2011;78:84–90.CrossRefPubMed
13.
go back to reference Lunnon K, Sattlecker M, Furney SJ, Coppola G, Simmons A, Proitsi P, Lupton MK, Lourdusamy A, Johnston C, Soininen H, et al. A blood gene expression marker of early Alzheimer’s disease. J Alzheimers Dis. 2013;33:737–53.CrossRefPubMed Lunnon K, Sattlecker M, Furney SJ, Coppola G, Simmons A, Proitsi P, Lupton MK, Lourdusamy A, Johnston C, Soininen H, et al. A blood gene expression marker of early Alzheimer’s disease. J Alzheimers Dis. 2013;33:737–53.CrossRefPubMed
14.
go back to reference Hye A, Riddoch-Contreras J, Baird AL, Ashton NJ, Bazenet C, Leung R, Westman E, Simmons A, Dobson R, Sattlecker M, et al. Plasma proteins predict conversion to dementia from prodromal disease. Alzheimers Dement. 2014;10(6):799–807. e792CrossRefPubMedPubMedCentral Hye A, Riddoch-Contreras J, Baird AL, Ashton NJ, Bazenet C, Leung R, Westman E, Simmons A, Dobson R, Sattlecker M, et al. Plasma proteins predict conversion to dementia from prodromal disease. Alzheimers Dement. 2014;10(6):799–807. e792CrossRefPubMedPubMedCentral
15.
go back to reference Fjell AM, Walhovd KB, Fennema-Notestine C, McEvoy LK, Hagler DJ, Holland D, Blennow K, Brewer JB, Dale AM. Brain atrophy in healthy aging is related to CSF levels of Abeta1–42. Cereb Cortex. 2010;20:2069–79.CrossRefPubMedPubMedCentral Fjell AM, Walhovd KB, Fennema-Notestine C, McEvoy LK, Hagler DJ, Holland D, Blennow K, Brewer JB, Dale AM. Brain atrophy in healthy aging is related to CSF levels of Abeta1–42. Cereb Cortex. 2010;20:2069–79.CrossRefPubMedPubMedCentral
16.
go back to reference Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science. 1993;261(5123):921–3.CrossRefPubMed Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science. 1993;261(5123):921–3.CrossRefPubMed
17.
go back to reference Jack CRJ, Wiste HJ, Weigand SD, Knopman DS, Vemuri P, Mielke MM, Lowe V, Senjem ML, Gunter JL, Machulda MM, et al. Age, sex, and APOE epsilon4 effects on memory, brain structure, and beta-amyloid across the adult life span. JAMA Neurol. 2015;72:511–9.CrossRefPubMedPubMedCentral Jack CRJ, Wiste HJ, Weigand SD, Knopman DS, Vemuri P, Mielke MM, Lowe V, Senjem ML, Gunter JL, Machulda MM, et al. Age, sex, and APOE epsilon4 effects on memory, brain structure, and beta-amyloid across the adult life span. JAMA Neurol. 2015;72:511–9.CrossRefPubMedPubMedCentral
18.
go back to reference Wirth M, Villeneuve S, La Joie R, Marks SM, Jagust WJ. Gene-environment interactions: lifetime cognitive activity, APOE genotype, and beta-amyloid burden. J Neurosci. 2014;34(25):8612–7.CrossRefPubMedPubMedCentral Wirth M, Villeneuve S, La Joie R, Marks SM, Jagust WJ. Gene-environment interactions: lifetime cognitive activity, APOE genotype, and beta-amyloid burden. J Neurosci. 2014;34(25):8612–7.CrossRefPubMedPubMedCentral
19.
go back to reference Vos SJ, Xiong C, Visser PJ, Jasielec MS, Hassenstab J, Grant EA, Cairns NJ, Morris JC, Holtzman DM, Fagan AM. Preclinical Alzheimer’s disease and its outcome: a longitudinal cohort study. Lancet Neurol. 2013;12:957–65.CrossRefPubMedPubMedCentral Vos SJ, Xiong C, Visser PJ, Jasielec MS, Hassenstab J, Grant EA, Cairns NJ, Morris JC, Holtzman DM, Fagan AM. Preclinical Alzheimer’s disease and its outcome: a longitudinal cohort study. Lancet Neurol. 2013;12:957–65.CrossRefPubMedPubMedCentral
20.
go back to reference Buckley RF, Hanseeuw B, Schultz AP, Vannini P, Aghjayan SL, Properzi MJ, Jackson JD, Mormino EC, Rentz DM, Sperling RA, et al. Region-specific association of subjective cognitive decline with tauopathy independent of global β-amyloid burden. JAMA Neurol. 2017;74(12):1455–63.CrossRefPubMedPubMedCentral Buckley RF, Hanseeuw B, Schultz AP, Vannini P, Aghjayan SL, Properzi MJ, Jackson JD, Mormino EC, Rentz DM, Sperling RA, et al. Region-specific association of subjective cognitive decline with tauopathy independent of global β-amyloid burden. JAMA Neurol. 2017;74(12):1455–63.CrossRefPubMedPubMedCentral
21.
go back to reference Lim YY, Maruff P, Pietrzak RH, Ellis KA, Darby D, Ames D, Harrington K, Martins RN, Masters CL, Szoeke C, et al. Aβ and cognitive change: examining the preclinical and prodromal stages of Alzheimer's disease. Alzheimers Dement. 2014;10(6):743–51. e741CrossRefPubMed Lim YY, Maruff P, Pietrzak RH, Ellis KA, Darby D, Ames D, Harrington K, Martins RN, Masters CL, Szoeke C, et al. Aβ and cognitive change: examining the preclinical and prodromal stages of Alzheimer's disease. Alzheimers Dement. 2014;10(6):743–51. e741CrossRefPubMed
22.
go back to reference Landau SM, Lu M, Joshi AD, Pontecorvo M, Mintun MA, Trojanowski JQ, Shaw LM, Jagust WJ. Alzheimer’s Disease Neuroimaging Initiative. Comparing PET imaging and CSF measurements of Aβ. Ann Neurol. 2013;74(6):826–36. Landau SM, Lu M, Joshi AD, Pontecorvo M, Mintun MA, Trojanowski JQ, Shaw LM, Jagust WJ. Alzheimer’s Disease Neuroimaging Initiative. Comparing PET imaging and CSF measurements of Aβ. Ann Neurol. 2013;74(6):826–36.
23.
go back to reference Zwan M, van Harten A, Ossenkoppele R, Bouwman F, Teunissen C, Adriaanse S, Lammertsma A, Scheltens P, van Berckel B, van der Flier W. Concordance between cerebrospinal fluid biomarkers and [11C]PIB PET in a memory clinic cohort. J Alzheimers Dis. 2014;41:801–7.CrossRefPubMed Zwan M, van Harten A, Ossenkoppele R, Bouwman F, Teunissen C, Adriaanse S, Lammertsma A, Scheltens P, van Berckel B, van der Flier W. Concordance between cerebrospinal fluid biomarkers and [11C]PIB PET in a memory clinic cohort. J Alzheimers Dis. 2014;41:801–7.CrossRefPubMed
24.
go back to reference Mattsson N, Insel PS, Donohue M, Landau S, Jagust WJ, Shaw LM, Trojanowski JQ, Zetterberg H, Blennow K, Weiner MW, et al. Independent information from cerebrospinal fluid amyloid-beta and florbetapir imaging in Alzheimer's disease. Brain. 2015;138(Pt 3):772–83.CrossRefPubMed Mattsson N, Insel PS, Donohue M, Landau S, Jagust WJ, Shaw LM, Trojanowski JQ, Zetterberg H, Blennow K, Weiner MW, et al. Independent information from cerebrospinal fluid amyloid-beta and florbetapir imaging in Alzheimer's disease. Brain. 2015;138(Pt 3):772–83.CrossRefPubMed
25.
go back to reference Palmqvist S, Mattsson N, Hansson O, Alzheimer’s Disease Neuroimaging Initiative. Cerebrospinal fluid analysis detects cerebral amyloid-beta accumulation earlier than positron emission tomography. Brain. 2016;139(Pt 4):1226–36.CrossRefPubMedPubMedCentral Palmqvist S, Mattsson N, Hansson O, Alzheimer’s Disease Neuroimaging Initiative. Cerebrospinal fluid analysis detects cerebral amyloid-beta accumulation earlier than positron emission tomography. Brain. 2016;139(Pt 4):1226–36.CrossRefPubMedPubMedCentral
26.
go back to reference PMA R, et al. The University of Manchester longitudinal study of cognition in normal healthy old age, 1983 through 2003. Aging Neuropsychol C. 2004;11:245–79.CrossRef PMA R, et al. The University of Manchester longitudinal study of cognition in normal healthy old age, 1983 through 2003. Aging Neuropsychol C. 2004;11:245–79.CrossRef
27.
go back to reference Willemsen G, Vink JM, Abdellaoui A, den Braber A, van Beek JH, Draisma HH, van Dongen J, van ‘t Ent D, Geels LM, van Lien R, et al. The adult Netherlands twin register: twenty-five years of survey and biological data collection. Twin Res Hum Genet. 2013;16(1):271–81.CrossRefPubMedPubMedCentral Willemsen G, Vink JM, Abdellaoui A, den Braber A, van Beek JH, Draisma HH, van Dongen J, van ‘t Ent D, Geels LM, van Lien R, et al. The adult Netherlands twin register: twenty-five years of survey and biological data collection. Twin Res Hum Genet. 2013;16(1):271–81.CrossRefPubMedPubMedCentral
28.
go back to reference Gatz M, Reynolds CA, Fratiglioni L, Johansson B, Mortimer JA, Berg S, Fiske A, Pedersen NL. Role of genes and environments for explaining Alzheimer disease. Arch Gen Psychiatry. 2006;63(2):168–74.CrossRefPubMed Gatz M, Reynolds CA, Fratiglioni L, Johansson B, Mortimer JA, Berg S, Fiske A, Pedersen NL. Role of genes and environments for explaining Alzheimer disease. Arch Gen Psychiatry. 2006;63(2):168–74.CrossRefPubMed
29.
go back to reference Boomsma DI, de Geus EJ, Vink JM, Stubbe JH, Distel MA, Hottenga JJ, Posthuma D, van Beijsterveldt TC, Hudziak JJ, Bartels M, et al. Netherlands Twin Register: from twins to twin families. Twin Res Hum Genet. 2006;9(6):849–57.CrossRefPubMed Boomsma DI, de Geus EJ, Vink JM, Stubbe JH, Distel MA, Hottenga JJ, Posthuma D, van Beijsterveldt TC, Hudziak JJ, Bartels M, et al. Netherlands Twin Register: from twins to twin families. Twin Res Hum Genet. 2006;9(6):849–57.CrossRefPubMed
30.
go back to reference Willemsen G, de Geus EJ, Bartels M, van Beijsterveldt CE, Brooks AI, Estourgie-van Burk GF, Fugman DA, Hoekstra C, Hottenga JJ, Kluft K, et al. The Netherlands Twin Register biobank: a resource for genetic epidemiological studies. Twin Res Hum Genet. 2010;13(3):231–45.CrossRefPubMed Willemsen G, de Geus EJ, Bartels M, van Beijsterveldt CE, Brooks AI, Estourgie-van Burk GF, Fugman DA, Hoekstra C, Hottenga JJ, Kluft K, et al. The Netherlands Twin Register biobank: a resource for genetic epidemiological studies. Twin Res Hum Genet. 2010;13(3):231–45.CrossRefPubMed
31.
go back to reference van Beijsterveldt CE, van Baal GC, Molenaar PC, Boomsma DI, de Geus EJ. Stability of genetic and environmental influences on P300 amplitude: a longitudinal study in adolescent twins. Behav Genet. 2001;31(6):533–43.CrossRefPubMed van Beijsterveldt CE, van Baal GC, Molenaar PC, Boomsma DI, de Geus EJ. Stability of genetic and environmental influences on P300 amplitude: a longitudinal study in adolescent twins. Behav Genet. 2001;31(6):533–43.CrossRefPubMed
32.
go back to reference Posthuma D, Meulenbelt I, de Craen AJ, de Geus EJ, Slagboom PE, Boomsma DI, Westendorp RG. Human cytokine response to ex vivo amyloid-beta stimulation is mediated by genetic factors. Twin Res Hum Genet. 2005;8(2):132–7.CrossRefPubMed Posthuma D, Meulenbelt I, de Craen AJ, de Geus EJ, Slagboom PE, Boomsma DI, Westendorp RG. Human cytokine response to ex vivo amyloid-beta stimulation is mediated by genetic factors. Twin Res Hum Genet. 2005;8(2):132–7.CrossRefPubMed
33.
go back to reference den Braber A, van ‘t Ent D, Cath DC, Veltman DJ, Boomsma DI, de Geus EJ. Brain activation during response interference in twins discordant or concordant for obsessive compulsive symptoms. Twin Res Hum Genet. 2012;15(3):372–83.CrossRefPubMed den Braber A, van ‘t Ent D, Cath DC, Veltman DJ, Boomsma DI, de Geus EJ. Brain activation during response interference in twins discordant or concordant for obsessive compulsive symptoms. Twin Res Hum Genet. 2012;15(3):372–83.CrossRefPubMed
34.
go back to reference Morris JC, Heyman A, Mohs RC, Hughes JP, van Belle G, Fillenbaum G, Mellits ED, Clark C. The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part I Clinical and neuropsychological assessment of Alzheimer’s disease. Neurol. 1989;39:1159–65.CrossRef Morris JC, Heyman A, Mohs RC, Hughes JP, van Belle G, Fillenbaum G, Mellits ED, Clark C. The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part I Clinical and neuropsychological assessment of Alzheimer’s disease. Neurol. 1989;39:1159–65.CrossRef
35.
go back to reference Aebi C. Validierung der neuropsychologischen Testbatterie CERAD-NP: eine Multi-Center Studie [Validation of the CERAD neuropsychological assessment battery: a multi-centre study]. Basel: University of Basel; 2002. Aebi C. Validierung der neuropsychologischen Testbatterie CERAD-NP: eine Multi-Center Studie [Validation of the CERAD neuropsychological assessment battery: a multi-centre study]. Basel: University of Basel; 2002.
36.
go back to reference de Jager CA, Budge MM, Clarke R. Utility of TICS-M for the assessment of cognitive function in older adults. Int J Geriatr Psychiatry. 2003;18:318–24.CrossRefPubMed de Jager CA, Budge MM, Clarke R. Utility of TICS-M for the assessment of cognitive function in older adults. Int J Geriatr Psychiatry. 2003;18:318–24.CrossRefPubMed
37.
go back to reference Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, Leirer VO. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res. 1982;17:37–49.CrossRefPubMed Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, Leirer VO. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res. 1982;17:37–49.CrossRefPubMed
38.
go back to reference Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurol. 1993;43:2412–4.CrossRef Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurol. 1993;43:2412–4.CrossRef
39.
go back to reference Rey A. L’examen clinique en psychologie. Paris: Presses Universitaires de France; 1964. Rey A. L’examen clinique en psychologie. Paris: Presses Universitaires de France; 1964.
40.
go back to reference Lindeboom J, Schmand B, Tulner L, Walstra G, Jonker C. Visual association test to detect early dementia of the Alzheimer type. J Neurol Neurosurg Psychiatry. 2002;73:126–33.CrossRefPubMedPubMedCentral Lindeboom J, Schmand B, Tulner L, Walstra G, Jonker C. Visual association test to detect early dementia of the Alzheimer type. J Neurol Neurosurg Psychiatry. 2002;73:126–33.CrossRefPubMedPubMedCentral
41.
go back to reference Rentz DM, Amariglio RE, Becker JA, Frey M, Olson LE, Frishe K, Carmasin J, Maye JE, Johnson KA, Sperling RA. Face-name associative memory performance is related to amyloid burden in normal elderly. Neuropsychologia. 2011;49:2776–83.CrossRefPubMedPubMedCentral Rentz DM, Amariglio RE, Becker JA, Frey M, Olson LE, Frishe K, Carmasin J, Maye JE, Johnson KA, Sperling RA. Face-name associative memory performance is related to amyloid burden in normal elderly. Neuropsychologia. 2011;49:2776–83.CrossRefPubMedPubMedCentral
42.
go back to reference Meyers JE, Bayless JD, Meyers KR. Rey complex figure: memory error patterns and functional abilities. Appl Neuropsychol. 1996;3:89–92.CrossRefPubMed Meyers JE, Bayless JD, Meyers KR. Rey complex figure: memory error patterns and functional abilities. Appl Neuropsychol. 1996;3:89–92.CrossRefPubMed
43.
go back to reference Robbins TW, James M, Owen AM, Sahakian BJ, McInnes L, Rabbitt P. Cambridge Neuropsychological Test Automated Battery (CANTAB): a factor analytic study of a large sample of normal elderly volunteers. Dementia. 1994;5:266–81.PubMed Robbins TW, James M, Owen AM, Sahakian BJ, McInnes L, Rabbitt P. Cambridge Neuropsychological Test Automated Battery (CANTAB): a factor analytic study of a large sample of normal elderly volunteers. Dementia. 1994;5:266–81.PubMed
44.
go back to reference Wechsler D. Manual for the Wechsler adult intelligence scale. San Antonio: The Psychological Corporation; 1997. Wechsler D. Manual for the Wechsler adult intelligence scale. San Antonio: The Psychological Corporation; 1997.
46.
go back to reference Tombaugh TN. Trail Making Test A and B: normative data stratified by age and education. Arch Clin Neuropsychol. 2004;19:203–14.CrossRefPubMed Tombaugh TN. Trail Making Test A and B: normative data stratified by age and education. Arch Clin Neuropsychol. 2004;19:203–14.CrossRefPubMed
47.
go back to reference Wechsler D. Wechsler adult intelligence scale—revised manual. New York: Psychological Corporation; 1981. Wechsler D. Wechsler adult intelligence scale—revised manual. New York: Psychological Corporation; 1981.
48.
go back to reference Jakobsson U. Using the 12-item short form health survey (SF-12) to measure quality of life among older people. Aging Clin Ex Res. 2007;19:457–64.CrossRef Jakobsson U. Using the 12-item short form health survey (SF-12) to measure quality of life among older people. Aging Clin Ex Res. 2007;19:457–64.CrossRef
49.
go back to reference Landau SM, Marks SM, Mormino EC, Rabinovici GD, Oh H, O’Neil JP, Wilson RS, Jagust WJ. Association of lifetime cognitive engagement and low beta-amyloid deposition. Arch Neurol. 2012;69:623–9.CrossRefPubMedPubMedCentral Landau SM, Marks SM, Mormino EC, Rabinovici GD, Oh H, O’Neil JP, Wilson RS, Jagust WJ. Association of lifetime cognitive engagement and low beta-amyloid deposition. Arch Neurol. 2012;69:623–9.CrossRefPubMedPubMedCentral
50.
go back to reference Washburn RA, Smith KW, Jette AM, Janney CA. The Physical Activity Scale for the Elderly (PASE): development and evaluation. J Clin Epidemiol. 1993;46:153–62.CrossRefPubMed Washburn RA, Smith KW, Jette AM, Janney CA. The Physical Activity Scale for the Elderly (PASE): development and evaluation. J Clin Epidemiol. 1993;46:153–62.CrossRefPubMed
51.
go back to reference Boeve BF, Molano JR, Ferman TJ, Smith GE, Lin SC, Bieniek K, Haidar W, Tippmann-Peikert M, Knopman DS, Graff-Radford NR, et al. Validation of the Mayo Sleep Questionnaire to screen for REM sleep behavior disorder in an aging and dementia cohort. Sleep Med. 2011;12:445–53.CrossRefPubMedPubMedCentral Boeve BF, Molano JR, Ferman TJ, Smith GE, Lin SC, Bieniek K, Haidar W, Tippmann-Peikert M, Knopman DS, Graff-Radford NR, et al. Validation of the Mayo Sleep Questionnaire to screen for REM sleep behavior disorder in an aging and dementia cohort. Sleep Med. 2011;12:445–53.CrossRefPubMedPubMedCentral
52.
go back to reference Netzer NC, Stoohs RA, Netzer CM, Clark K, Strohl KP. Using the Berlin Questionnaire to identify patients at risk for the sleep apnea syndrome. Ann Intern Med. 1999;131:485–91.CrossRefPubMed Netzer NC, Stoohs RA, Netzer CM, Clark K, Strohl KP. Using the Berlin Questionnaire to identify patients at risk for the sleep apnea syndrome. Ann Intern Med. 1999;131:485–91.CrossRefPubMed
53.
go back to reference Sikkes SA, Knol DL, Pijnenburg YA, de Lange-de Klerk ES, Uitdehaag BM, Scheltens P. Validation of the Amsterdam IADL Questionnaire©, a new tool to measure instrumental activities of daily living in dementia. Neuroepidemiol. 2013;41:35–41.CrossRef Sikkes SA, Knol DL, Pijnenburg YA, de Lange-de Klerk ES, Uitdehaag BM, Scheltens P. Validation of the Amsterdam IADL Questionnaire©, a new tool to measure instrumental activities of daily living in dementia. Neuroepidemiol. 2013;41:35–41.CrossRef
54.
go back to reference Pfeffer RI, Kurosaki TT, Harrah CHJ, Chance JM, Filos S. Measurement of functional activities in older adults in the community. J Gerontol. 1982;37:323–9.CrossRefPubMed Pfeffer RI, Kurosaki TT, Harrah CHJ, Chance JM, Filos S. Measurement of functional activities in older adults in the community. J Gerontol. 1982;37:323–9.CrossRefPubMed
55.
go back to reference Saykin AJ, Wishart HA, Rabin LA, Santulli RB, Flashman LA, West JD, McHugh TL, Mamourian AC. Older adults with cognitive complaints show brain atrophy similar to that of amnestic MCI. Neurology. 2006;67:834–42.CrossRefPubMedPubMedCentral Saykin AJ, Wishart HA, Rabin LA, Santulli RB, Flashman LA, West JD, McHugh TL, Mamourian AC. Older adults with cognitive complaints show brain atrophy similar to that of amnestic MCI. Neurology. 2006;67:834–42.CrossRefPubMedPubMedCentral
56.
go back to reference Kaufer DI, Cummings JL, Ketchel P, Smith V, MacMillan A, Shelley T, Lopez OL, DeKosky ST. Validation of the NPI-Q, a brief clinical form of the neuropsychiatric inventory. J Neuropsychiatry Clin Neurosci. 2000;12:233–9.CrossRefPubMed Kaufer DI, Cummings JL, Ketchel P, Smith V, MacMillan A, Shelley T, Lopez OL, DeKosky ST. Validation of the NPI-Q, a brief clinical form of the neuropsychiatric inventory. J Neuropsychiatry Clin Neurosci. 2000;12:233–9.CrossRefPubMed
57.
go back to reference Kaasenbrood F, Hollander M, Rutten FH, Gerhards LJ, Hoes AW, Tieleman RG. Yield of screening for atrial fibrillation in primary care with a hand-held, single-lead electrocardiogram device during influenza vaccination. Europace. 2016;18(10):1514–20. Kaasenbrood F, Hollander M, Rutten FH, Gerhards LJ, Hoes AW, Tieleman RG. Yield of screening for atrial fibrillation in primary care with a hand-held, single-lead electrocardiogram device during influenza vaccination. Europace. 2016;18(10):1514–20.
58.
go back to reference Teunissen CE, Tumani H, Engelborghs S, Mollenhauer B. Biobanking of CSF: international standardization to optimize biomarker development. Clin Biochem. 2014;47(4–5):288–92.CrossRefPubMed Teunissen CE, Tumani H, Engelborghs S, Mollenhauer B. Biobanking of CSF: international standardization to optimize biomarker development. Clin Biochem. 2014;47(4–5):288–92.CrossRefPubMed
59.
go back to reference Meulenbelt I, Droog S, Trommelen GJ, Boomsma DI, Slagboom PE. High-yield noninvasive human genomic DNA isolation method for genetic studies in geographically dispersed families and populations. Am J Hum Genet. 1995;57(5):1252–4.PubMedPubMedCentral Meulenbelt I, Droog S, Trommelen GJ, Boomsma DI, Slagboom PE. High-yield noninvasive human genomic DNA isolation method for genetic studies in geographically dispersed families and populations. Am J Hum Genet. 1995;57(5):1252–4.PubMedPubMedCentral
60.
go back to reference Ehli EA, Abdellaoui A, Fedko IO, Grieser C, Nohzadeh-Malakshah S, Willemsen G, de Geus EJ, Boomsma DI, Davies GE, Hottenga JJ. A method to customize population-specific arrays for genome-wide association testing. Eur J Hum Genet. 2017;25(2):267–70.CrossRefPubMed Ehli EA, Abdellaoui A, Fedko IO, Grieser C, Nohzadeh-Malakshah S, Willemsen G, de Geus EJ, Boomsma DI, Davies GE, Hottenga JJ. A method to customize population-specific arrays for genome-wide association testing. Eur J Hum Genet. 2017;25(2):267–70.CrossRefPubMed
61.
go back to reference Fedko IO, Hottenga JJ, Medina-Gomez C, Pappa I, van Beijsterveldt CE, Ehli EA, Davies GE, Rivadeneira F, Tiemeier H, Swertz MA, et al. Estimation of genetic relationships between individuals across cohorts and platforms: application to childhood height. Behav Genet. 2015;45(5):514–28.CrossRefPubMedPubMedCentral Fedko IO, Hottenga JJ, Medina-Gomez C, Pappa I, van Beijsterveldt CE, Ehli EA, Davies GE, Rivadeneira F, Tiemeier H, Swertz MA, et al. Estimation of genetic relationships between individuals across cohorts and platforms: application to childhood height. Behav Genet. 2015;45(5):514–28.CrossRefPubMedPubMedCentral
62.
go back to reference Das S, Forer L, Schonherr S, Sidore C, Locke AE, Kwong A, Vrieze SI, Chew EY, Levy S, McGue M, et al. Next-generation genotype imputation service and methods. Nat Genet. 2016;48(10):1284–7.CrossRefPubMedPubMedCentral Das S, Forer L, Schonherr S, Sidore C, Locke AE, Kwong A, Vrieze SI, Chew EY, Levy S, McGue M, et al. Next-generation genotype imputation service and methods. Nat Genet. 2016;48(10):1284–7.CrossRefPubMedPubMedCentral
63.
go back to reference Ghebranious N, Ivacic L, Mallum J, Dokken C. Detection of ApoE E2, E3 and E4 alleles using MALDI-TOF mass spectrometry and the homogeneous mass-extend technology. Nucleic Acids Res. 2005;33(17):e149.CrossRefPubMedPubMedCentral Ghebranious N, Ivacic L, Mallum J, Dokken C. Detection of ApoE E2, E3 and E4 alleles using MALDI-TOF mass spectrometry and the homogeneous mass-extend technology. Nucleic Acids Res. 2005;33(17):e149.CrossRefPubMedPubMedCentral
64.
go back to reference van der Lee SJ, Wolters FJ, Ikram MK, Hofman A, Ikram MA, Amin N, van Duijn CM. The effect of APOE and other common genetic variants on the onset of Alzheimer's disease and dementia: a community-based cohort study. Lancet Neurol. 2018;17(5):434–44.CrossRefPubMed van der Lee SJ, Wolters FJ, Ikram MK, Hofman A, Ikram MA, Amin N, van Duijn CM. The effect of APOE and other common genetic variants on the onset of Alzheimer's disease and dementia: a community-based cohort study. Lancet Neurol. 2018;17(5):434–44.CrossRefPubMed
65.
go back to reference Moneta GL, Edwards JM, Chitwood RW, Taylor LMJ, Lee RW, Cummings CA, Porter JM. Correlation of North American Symptomatic Carotid Endarterectomy Trial (NASCET) angiographic definition of 70% to 99% internal carotid artery stenosis with duplex scanning. J Vasc Surg. 1993;17:152–7. discussion 157–159CrossRefPubMed Moneta GL, Edwards JM, Chitwood RW, Taylor LMJ, Lee RW, Cummings CA, Porter JM. Correlation of North American Symptomatic Carotid Endarterectomy Trial (NASCET) angiographic definition of 70% to 99% internal carotid artery stenosis with duplex scanning. J Vasc Surg. 1993;17:152–7. discussion 157–159CrossRefPubMed
66.
go back to reference Cardenas VA, Reed B, Chao LL, Chui H, Sanossian N, Decarli CC, Mack W, Kramer J, Hodis HN, Yan M, et al. Associations among vascular risk factors, carotid atherosclerosis, and cortical volume and thickness in older adults. Stroke. 2012;43:2865–70.CrossRefPubMedPubMedCentral Cardenas VA, Reed B, Chao LL, Chui H, Sanossian N, Decarli CC, Mack W, Kramer J, Hodis HN, Yan M, et al. Associations among vascular risk factors, carotid atherosclerosis, and cortical volume and thickness in older adults. Stroke. 2012;43:2865–70.CrossRefPubMedPubMedCentral
67.
go back to reference Wendell CR, Waldstein SR, Ferrucci L, O’Brien RJ, Strait JB, Zonderman AB. Carotid atherosclerosis and prospective risk of dementia. Stroke. 2012;43:3319–24.CrossRefPubMedPubMedCentral Wendell CR, Waldstein SR, Ferrucci L, O’Brien RJ, Strait JB, Zonderman AB. Carotid atherosclerosis and prospective risk of dementia. Stroke. 2012;43:3319–24.CrossRefPubMedPubMedCentral
68.
go back to reference van Sloten TT, Schram MT, van den Hurk K, Dekker JM, Nijpels G, Henry RM, Stehouwer CD. Local stiffness of the carotid and femoral artery is associated with incident cardiovascular events and all-cause mortality. J Am College Cardiol. 2014;63:1739–47.CrossRef van Sloten TT, Schram MT, van den Hurk K, Dekker JM, Nijpels G, Henry RM, Stehouwer CD. Local stiffness of the carotid and femoral artery is associated with incident cardiovascular events and all-cause mortality. J Am College Cardiol. 2014;63:1739–47.CrossRef
69.
go back to reference Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA. MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. AJR. 1987;149:351–6.CrossRefPubMed Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA. MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. AJR. 1987;149:351–6.CrossRefPubMed
70.
go back to reference Scheltens P, Launer LJ, Barkhof F, Weinstein HC, van Gool WA. Visual assessment of medial temporal lobe atrophy on magnetic resonance imaging: interobserver reliability. J Neurol. 1995;242:557–60.CrossRefPubMed Scheltens P, Launer LJ, Barkhof F, Weinstein HC, van Gool WA. Visual assessment of medial temporal lobe atrophy on magnetic resonance imaging: interobserver reliability. J Neurol. 1995;242:557–60.CrossRefPubMed
71.
go back to reference Pasquier F, Leys D, Weerts JG, Mounier-Vehier F, Barkhof F, Scheltens P. Inter- and intraobserver reproducibility of cerebral atrophy assessment on MRI scans with hemispheric infarcts. Eur Neurol. 1996;36:268–72.CrossRefPubMed Pasquier F, Leys D, Weerts JG, Mounier-Vehier F, Barkhof F, Scheltens P. Inter- and intraobserver reproducibility of cerebral atrophy assessment on MRI scans with hemispheric infarcts. Eur Neurol. 1996;36:268–72.CrossRefPubMed
72.
go back to reference Koedam ELGE, Lehmann M, van der Flier WM, Scheltens P, Pijnenburg YAL, Fox N, Barkhof F, Wattjes MP. Visual assessment of posterior atrophy development of a MRI rating scale. Eur Radiol. 2011;21:2618–25.CrossRefPubMedPubMedCentral Koedam ELGE, Lehmann M, van der Flier WM, Scheltens P, Pijnenburg YAL, Fox N, Barkhof F, Wattjes MP. Visual assessment of posterior atrophy development of a MRI rating scale. Eur Radiol. 2011;21:2618–25.CrossRefPubMedPubMedCentral
73.
go back to reference Curtis C, Gamez JE, Singh U, Sadowsky CH, Villena T, Sabbagh MN, Beach TG, Duara R, Fleisher AS, Frey KA, et al. Phase 3 trial of flutemetamol labeled with radioactive fluorine 18 imaging and neuritic plaque density. JAMA Neurol. 2015;72(3):287–94.CrossRefPubMed Curtis C, Gamez JE, Singh U, Sadowsky CH, Villena T, Sabbagh MN, Beach TG, Duara R, Fleisher AS, Frey KA, et al. Phase 3 trial of flutemetamol labeled with radioactive fluorine 18 imaging and neuritic plaque density. JAMA Neurol. 2015;72(3):287–94.CrossRefPubMed
76.
go back to reference Hu ZON, Renisch S, et al. MR-based attenuation correction for a whole-body sequential PET/MR system. In: IEEE Nucl Sci Symp Conference; 2009. p. 3508–12. Hu ZON, Renisch S, et al. MR-based attenuation correction for a whole-body sequential PET/MR system. In: IEEE Nucl Sci Symp Conference; 2009. p. 3508–12.
77.
go back to reference Healthcare G. EPAR product information—summary of product characteristics. 2014. Healthcare G. EPAR product information—summary of product characteristics. 2014.
78.
go back to reference del Campo M, Mollenhauer B, Bertolotto A, Engelborghs S, Hampel H, Simonsen AH, Kapaki E, Kruse N, Le Bastard N, Lehmann S, et al. Recommendations to standardize preanalytical confounding factors in Alzheimer's and Parkinson's disease cerebrospinal fluid biomarkers: an update. Biomark Med. 2012;6(4):419–30.CrossRefPubMed del Campo M, Mollenhauer B, Bertolotto A, Engelborghs S, Hampel H, Simonsen AH, Kapaki E, Kruse N, Le Bastard N, Lehmann S, et al. Recommendations to standardize preanalytical confounding factors in Alzheimer's and Parkinson's disease cerebrospinal fluid biomarkers: an update. Biomark Med. 2012;6(4):419–30.CrossRefPubMed
79.
go back to reference Stam CJ. Use of magnetoencephalography (MEG) to study functional brain networks in neurodegenerative disorders. J Neurol Sci. 2010;289:128–34.CrossRefPubMed Stam CJ. Use of magnetoencephalography (MEG) to study functional brain networks in neurodegenerative disorders. J Neurol Sci. 2010;289:128–34.CrossRefPubMed
80.
go back to reference de Haan W, van der Flier WM, Koene T, Smits LL, Scheltens P, Stam CJ. Disrupted modular brain dynamics reflect cognitive dysfunction in Alzheimer’s disease. NeuroImage. 2012;59:3085–93.CrossRefPubMed de Haan W, van der Flier WM, Koene T, Smits LL, Scheltens P, Stam CJ. Disrupted modular brain dynamics reflect cognitive dysfunction in Alzheimer’s disease. NeuroImage. 2012;59:3085–93.CrossRefPubMed
81.
go back to reference Demuru M, Gouw AA, Hillebrand A, Stam CJ, van Dijk BW, Scheltens P, Tijms BM, Konijnenberg E, Ten Kate M, den Braber A, et al. Functional and effective whole brain connectivity using magnetoencephalography to identify monozygotic twin pairs. Sci Rep. 2017;7(1):9685.CrossRefPubMedPubMedCentral Demuru M, Gouw AA, Hillebrand A, Stam CJ, van Dijk BW, Scheltens P, Tijms BM, Konijnenberg E, Ten Kate M, den Braber A, et al. Functional and effective whole brain connectivity using magnetoencephalography to identify monozygotic twin pairs. Sci Rep. 2017;7(1):9685.CrossRefPubMedPubMedCentral
82.
go back to reference Mayer MA, Hornegger J, Mardin CY, Tornow RP. Retinal nerve fiber layer segmentation on FD-OCT scans of normal subjects and glaucoma patients. Biomed Opt Express. 2010;1:1358–83.CrossRefPubMedPubMedCentral Mayer MA, Hornegger J, Mardin CY, Tornow RP. Retinal nerve fiber layer segmentation on FD-OCT scans of normal subjects and glaucoma patients. Biomed Opt Express. 2010;1:1358–83.CrossRefPubMedPubMedCentral
83.
go back to reference Koronyo Y, Salumbides BC, Black KL, Koronyo-Hamaoui M. Alzheimer’s disease in the retina: imaging retinal abeta plaques for early diagnosis and therapy assessment. Neurodegener Dis. 2012;10:285–93.CrossRefPubMed Koronyo Y, Salumbides BC, Black KL, Koronyo-Hamaoui M. Alzheimer’s disease in the retina: imaging retinal abeta plaques for early diagnosis and therapy assessment. Neurodegener Dis. 2012;10:285–93.CrossRefPubMed
84.
go back to reference Nandakumar N, Buzney S, Weiter JJ. Lipofuscin and the principles of fundus autofluorescence: a review. Semin Ophthalmol. 2012;27:197–201.CrossRefPubMed Nandakumar N, Buzney S, Weiter JJ. Lipofuscin and the principles of fundus autofluorescence: a review. Semin Ophthalmol. 2012;27:197–201.CrossRefPubMed
85.
go back to reference Frost S, Kanagasingam Y, Sohrabi H, Vignarajan J, Bourgeat P, Salvado O, Villemagne V, Rowe CC, Macaulay SL, Szoeke C, et al. Retinal vascular biomarkers for early detection and monitoring of Alzheimer’s disease. Transl Psychiatry. 2013;3:e233.CrossRefPubMedPubMedCentral Frost S, Kanagasingam Y, Sohrabi H, Vignarajan J, Bourgeat P, Salvado O, Villemagne V, Rowe CC, Macaulay SL, Szoeke C, et al. Retinal vascular biomarkers for early detection and monitoring of Alzheimer’s disease. Transl Psychiatry. 2013;3:e233.CrossRefPubMedPubMedCentral
86.
go back to reference Minica CC, Dolan CV, Kampert MM, Boomsma DI, Vink JM. Sandwich corrected standard errors in family-based genome-wide association studies. Eur J Hum Genet. 2015;23(3):388–94. Minica CC, Dolan CV, Kampert MM, Boomsma DI, Vink JM. Sandwich corrected standard errors in family-based genome-wide association studies. Eur J Hum Genet. 2015;23(3):388–94.
87.
go back to reference Vitaro FBM, Arseneault L. The discordant MZ-twin method: one step closer to the holy grail of causality. Int J Behav Dev. 2009;33(4):376–82.CrossRef Vitaro FBM, Arseneault L. The discordant MZ-twin method: one step closer to the holy grail of causality. Int J Behav Dev. 2009;33(4):376–82.CrossRef
88.
go back to reference Blokland GA, de Zubicaray GI, McMahon KL, Wright MJ. Genetic and environmental influences on neuroimaging phenotypes: a meta-analytical perspective on twin imaging studies. Twin Res Hum Genet. 2012;15(3):351–71.CrossRefPubMedPubMedCentral Blokland GA, de Zubicaray GI, McMahon KL, Wright MJ. Genetic and environmental influences on neuroimaging phenotypes: a meta-analytical perspective on twin imaging studies. Twin Res Hum Genet. 2012;15(3):351–71.CrossRefPubMedPubMedCentral
89.
go back to reference Fennema-Notestine C, McEvoy LK, Notestine R, Panizzon MS, Yau WW, Franz CE, Lyons MJ, Eyler LT, Neale MC, Xian H, et al. White matter disease in midlife is heritable, related to hypertension, and shares some genetic influence with systolic blood pressure. Neuroimage Clin. 2016;12:737–45.CrossRefPubMedPubMedCentral Fennema-Notestine C, McEvoy LK, Notestine R, Panizzon MS, Yau WW, Franz CE, Lyons MJ, Eyler LT, Neale MC, Xian H, et al. White matter disease in midlife is heritable, related to hypertension, and shares some genetic influence with systolic blood pressure. Neuroimage Clin. 2016;12:737–45.CrossRefPubMedPubMedCentral
Metadata
Title
The EMIF-AD PreclinAD study: study design and baseline cohort overview
Authors
Elles Konijnenberg
Stephen F. Carter
Mara ten Kate
Anouk den Braber
Jori Tomassen
Chinenye Amadi
Linda Wesselman
Hoang-Ton Nguyen
Jacoba A. van de Kreeke
Maqsood Yaqub
Matteo Demuru
Sandra D. Mulder
Arjan Hillebrand
Femke H. Bouwman
Charlotte E. Teunissen
Erik H. Serné
Annette C. Moll
Frank D. Verbraak
Rainer Hinz
Neil Pendleton
Adriaan A. Lammertsma
Bart N. M. van Berckel
Frederik Barkhof
Dorret I. Boomsma
Philip Scheltens
Karl Herholz
Pieter Jelle Visser
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2018
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-018-0406-7

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