The presymptomatic phase of amyotrophic lateral sclerosis: are we merely scratching the surface?

go back to reference Miller T, Cudkowicz M, Shaw PJ, Andersen PM, Atassi N, Bucelli RC, Genge A, Glass J, Ladha S, Ludolph AL, Maragakis NJ, McDermott CJ, Pestronk A, Ravits J, Salachas F, Trudell R, Van Damme P, Zinman L, Bennett CF, Lane R, Sandrock A, Runz H, Graham D, Houshyar H, McCampbell A, Nestorov I, Chang I, McNeill M, Fanning L, Fradette S, Ferguson TA (2020) Phase 1–2 trial of antisense oligonucleotide tofersen for SOD1 ALS. The N Engl J Med 383:109–119PubMedCrossRef Miller T, Cudkowicz M, Shaw PJ, Andersen PM, Atassi N, Bucelli RC, Genge A, Glass J, Ladha S, Ludolph AL, Maragakis NJ, McDermott CJ, Pestronk A, Ravits J, Salachas F, Trudell R, Van Damme P, Zinman L, Bennett CF, Lane R, Sandrock A, Runz H, Graham D, Houshyar H, McCampbell A, Nestorov I, Chang I, McNeill M, Fanning L, Fradette S, Ferguson TA (2020) Phase 1–2 trial of antisense oligonucleotide tofersen for SOD1 ALS. The N Engl J Med 383:109–119PubMedCrossRef

go back to reference Mueller C, Berry JD, McKenna-Yasek DM, Gernoux G, Owegi MA, Pothier LM, Douthwright CL, Gelevski D, Luppino SD, Blackwood M, Wightman NS, Oakley DH, Frosch MP, Flotte TR, Cudkowicz ME, Brown RH Jr (2020) SOD1 Suppression with adeno-associated virus and microrna in familial ALS. The N Engl J Med 383:151–158PubMedCrossRef Mueller C, Berry JD, McKenna-Yasek DM, Gernoux G, Owegi MA, Pothier LM, Douthwright CL, Gelevski D, Luppino SD, Blackwood M, Wightman NS, Oakley DH, Frosch MP, Flotte TR, Cudkowicz ME, Brown RH Jr (2020) SOD1 Suppression with adeno-associated virus and microrna in familial ALS. The N Engl J Med 383:151–158PubMedCrossRef

go back to reference Omer T, Finegan E, Hutchinson S, Doherty M, Vajda A, McLaughlin RL, Pender N, Hardiman O, Bede P (2017) Neuroimaging patterns along the ALS-FTD spectrum: a multiparametric imaging study. Amyotroph Lateral Scler Front Degener 18:611–623CrossRef Omer T, Finegan E, Hutchinson S, Doherty M, Vajda A, McLaughlin RL, Pender N, Hardiman O, Bede P (2017) Neuroimaging patterns along the ALS-FTD spectrum: a multiparametric imaging study. Amyotroph Lateral Scler Front Degener 18:611–623CrossRef

go back to reference Burke T, Pinto-Grau M, Lonergan K, Bede P, O’Sullivan M, Heverin M, Vajda A, McLaughlin RL, Pender N, Hardiman O (2017) A Cross-sectional population-based investigation into behavioral change in amyotrophic lateral sclerosis: subphenotypes, staging, cognitive predictors, and survival. Ann Clini Transl Neurol 4:305–317CrossRef Burke T, Pinto-Grau M, Lonergan K, Bede P, O’Sullivan M, Heverin M, Vajda A, McLaughlin RL, Pender N, Hardiman O (2017) A Cross-sectional population-based investigation into behavioral change in amyotrophic lateral sclerosis: subphenotypes, staging, cognitive predictors, and survival. Ann Clini Transl Neurol 4:305–317CrossRef

go back to reference Finegan E, Chipika RH, Shing SLH, Hardiman O, Bede P (2019) Primary lateral sclerosis: a distinct entity or part of the ALS spectrum? Amyotroph Lateral Scler Front Degener 20:133–145CrossRef Finegan E, Chipika RH, Shing SLH, Hardiman O, Bede P (2019) Primary lateral sclerosis: a distinct entity or part of the ALS spectrum? Amyotroph Lateral Scler Front Degener 20:133–145CrossRef

go back to reference Kiernan MC, Ziemann U, Eisen A (2019) Amyotrophic lateral sclerosis: origins traced to impaired balance between neural excitation and inhibition in the neonatal period. Muscle Nerve 60:232–235PubMedCrossRef Kiernan MC, Ziemann U, Eisen A (2019) Amyotrophic lateral sclerosis: origins traced to impaired balance between neural excitation and inhibition in the neonatal period. Muscle Nerve 60:232–235PubMedCrossRef

go back to reference Bertrand A, Wen J, Rinaldi D, Houot M, Sayah S, Camuzat A, Fournier C, Fontanella S, Routier A, Couratier P, Pasquier F, Habert MO, Hannequin D, Martinaud O, Caroppo P, Levy R, Dubois B, Brice A, Durrleman S, Colliot O, Le Ber I (2018) Early cognitive, structural, and microstructural changes in presymptomatic C9orf72 carriers younger than 40 years. JAMA Neurol 75:236–245PubMedCrossRef Bertrand A, Wen J, Rinaldi D, Houot M, Sayah S, Camuzat A, Fournier C, Fontanella S, Routier A, Couratier P, Pasquier F, Habert MO, Hannequin D, Martinaud O, Caroppo P, Levy R, Dubois B, Brice A, Durrleman S, Colliot O, Le Ber I (2018) Early cognitive, structural, and microstructural changes in presymptomatic C9orf72 carriers younger than 40 years. JAMA Neurol 75:236–245PubMedCrossRef

go back to reference Querin G, Bede P, El Mendili MM, Li M, Pelegrini-Issac M, Rinaldi D, Catala M, Saracino D, Salachas F, Camuzat A, Marchand-Pauvert V, Cohen-Adad J, Colliot O, Le Ber I, Pradat PF (2019) Presymptomatic spinal cord pathology in c9orf72 mutation carriers: a longitudinal neuroimaging study. Ann Neurol 86:158–167PubMedCrossRef Querin G, Bede P, El Mendili MM, Li M, Pelegrini-Issac M, Rinaldi D, Catala M, Saracino D, Salachas F, Camuzat A, Marchand-Pauvert V, Cohen-Adad J, Colliot O, Le Ber I, Pradat PF (2019) Presymptomatic spinal cord pathology in c9orf72 mutation carriers: a longitudinal neuroimaging study. Ann Neurol 86:158–167PubMedCrossRef

go back to reference Benatar M, Turner MR, Wuu J (2019) Defining pre-symptomatic amyotrophic lateral sclerosis. Amyotroph Lateral Scler Front Degener 20:303–309CrossRef Benatar M, Turner MR, Wuu J (2019) Defining pre-symptomatic amyotrophic lateral sclerosis. Amyotroph Lateral Scler Front Degener 20:303–309CrossRef

go back to reference Carew JD, Nair G, Andersen PM, Wuu J, Gronka S, Hu X, Benatar M (2011) Presymptomatic spinal cord neurometabolic findings in SOD1-positive people at risk for familial ALS. Neurology 77:1370–1375PubMedPubMedCentralCrossRef Carew JD, Nair G, Andersen PM, Wuu J, Gronka S, Hu X, Benatar M (2011) Presymptomatic spinal cord neurometabolic findings in SOD1-positive people at risk for familial ALS. Neurology 77:1370–1375PubMedPubMedCentralCrossRef

go back to reference Cirak S, Arechavala-Gomeza V, Guglieri M, Feng L, Torelli S, Anthony K, Abbs S, Garralda ME, Bourke J, Wells DJ, Dickson G, Wood MJ, Wilton SD, Straub V, Kole R, Shrewsbury SB, Sewry C, Morgan JE, Bushby K, Muntoni F (2011) Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study. Lancet (London, England) 378:595–605CrossRef Cirak S, Arechavala-Gomeza V, Guglieri M, Feng L, Torelli S, Anthony K, Abbs S, Garralda ME, Bourke J, Wells DJ, Dickson G, Wood MJ, Wilton SD, Straub V, Kole R, Shrewsbury SB, Sewry C, Morgan JE, Bushby K, Muntoni F (2011) Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study. Lancet (London, England) 378:595–605CrossRef

go back to reference Mendell JR, Rodino-Klapac LR, Sahenk Z, Roush K, Bird L, Lowes LP, Alfano L, Gomez AM, Lewis S, Kota J, Malik V, Shontz K, Walker CM, Flanigan KM, Corridore M, Kean JR, Allen HD, Shilling C, Melia KR, Sazani P, Saoud JB, Kaye EM (2013) Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann Neurol 74:637–647PubMedCrossRef Mendell JR, Rodino-Klapac LR, Sahenk Z, Roush K, Bird L, Lowes LP, Alfano L, Gomez AM, Lewis S, Kota J, Malik V, Shontz K, Walker CM, Flanigan KM, Corridore M, Kean JR, Allen HD, Shilling C, Melia KR, Sazani P, Saoud JB, Kaye EM (2013) Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann Neurol 74:637–647PubMedCrossRef

go back to reference Mendell JR, Goemans N, Lowes LP, Alfano LN, Berry K, Shao J, Kaye EM, Mercuri E (2016) Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy. Ann Neurol 79:257–271PubMedPubMedCentralCrossRef Mendell JR, Goemans N, Lowes LP, Alfano LN, Berry K, Shao J, Kaye EM, Mercuri E (2016) Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy. Ann Neurol 79:257–271PubMedPubMedCentralCrossRef

go back to reference Kanouchi T, Ohkubo T, Yokota T (2012) Can regional spreading of amyotrophic lateral sclerosis motor symptoms be explained by prion-like propagation? J Neurol Neurosurg Psychiatry 83:739–745PubMedCrossRef Kanouchi T, Ohkubo T, Yokota T (2012) Can regional spreading of amyotrophic lateral sclerosis motor symptoms be explained by prion-like propagation? J Neurol Neurosurg Psychiatry 83:739–745PubMedCrossRef

go back to reference Bede P, Iyer PM, Schuster C, Elamin M, McLaughlin RL, Kenna K, Hardiman O (2016) The selective anatomical vulnerability of ALS: “disease-defining” and “disease-defying” brain regions. Amyotroph Lateral Scler Front Degener 17:561–570CrossRef Bede P, Iyer PM, Schuster C, Elamin M, McLaughlin RL, Kenna K, Hardiman O (2016) The selective anatomical vulnerability of ALS: “disease-defining” and “disease-defying” brain regions. Amyotroph Lateral Scler Front Degener 17:561–570CrossRef

go back to reference Bede P, Querin G, Pradat PF (2018) The changing landscape of motor neuron disease imaging: the transition from descriptive studies to precision clinical tools. Curr Opin Neurol 31:431–438PubMedCrossRef Bede P, Querin G, Pradat PF (2018) The changing landscape of motor neuron disease imaging: the transition from descriptive studies to precision clinical tools. Curr Opin Neurol 31:431–438PubMedCrossRef

go back to reference Eisen A (2011) The real onset of amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 82:593PubMedCrossRef Eisen A (2011) The real onset of amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 82:593PubMedCrossRef

go back to reference Benatar M, Wuu J (2012) Presymptomatic studies in ALS: rationale, challenges, and approach. Neurology 79:1732–1739PubMedPubMedCentralCrossRef Benatar M, Wuu J (2012) Presymptomatic studies in ALS: rationale, challenges, and approach. Neurology 79:1732–1739PubMedPubMedCentralCrossRef

go back to reference Swash M, Ingram D (1988) Preclinical and subclinical events in motor neuron disease. J Neurol Neurosurg Psychiatry 51:165–168PubMedPubMedCentralCrossRef Swash M, Ingram D (1988) Preclinical and subclinical events in motor neuron disease. J Neurol Neurosurg Psychiatry 51:165–168PubMedPubMedCentralCrossRef

go back to reference Eisen A, Kiernan M, Mitsumoto H, Swash M (2014) Amyotrophic lateral sclerosis: a long preclinical period? J Neurol Neurosurg Psychiatry 85:1232–1238PubMedCrossRef Eisen A, Kiernan M, Mitsumoto H, Swash M (2014) Amyotrophic lateral sclerosis: a long preclinical period? J Neurol Neurosurg Psychiatry 85:1232–1238PubMedCrossRef

go back to reference Aggarwal A, Nicholson G (2002) Detection of preclinical motor neurone loss in SOD1 mutation carriers using motor unit number estimation. J Neurol Neurosurg Psychiatry 73:199–201PubMedPubMedCentralCrossRef Aggarwal A, Nicholson G (2002) Detection of preclinical motor neurone loss in SOD1 mutation carriers using motor unit number estimation. J Neurol Neurosurg Psychiatry 73:199–201PubMedPubMedCentralCrossRef

go back to reference Aggarwal A, Nicholson G (2001) Normal complement of motor units in asymptomatic familial (SOD1 mutation) amyotrophic lateral sclerosis carriers. J Neurol Neurosurg Psychiatry 71:478–481PubMedPubMedCentralCrossRef Aggarwal A, Nicholson G (2001) Normal complement of motor units in asymptomatic familial (SOD1 mutation) amyotrophic lateral sclerosis carriers. J Neurol Neurosurg Psychiatry 71:478–481PubMedPubMedCentralCrossRef

go back to reference Walhout R, Schmidt R, Westeneng HJ, Verstraete E, Seelen M, van Rheenen W, de Reus MA, van Es MA, Hendrikse J, Veldink JH, van den Heuvel MP, van den Berg LH (2015) Brain morphologic changes in asymptomatic C9orf72 repeat expansion carriers. Neurology 85:1780–1788PubMedCrossRef Walhout R, Schmidt R, Westeneng HJ, Verstraete E, Seelen M, van Rheenen W, de Reus MA, van Es MA, Hendrikse J, Veldink JH, van den Heuvel MP, van den Berg LH (2015) Brain morphologic changes in asymptomatic C9orf72 repeat expansion carriers. Neurology 85:1780–1788PubMedCrossRef

go back to reference Floeter MK, Bageac D, Danielian LE, Braun LE, Traynor BJ, Kwan JY (2016) Longitudinal imaging in C9orf72 mutation carriers: relationship to phenotype. NeuroImage Clin 12:1035–1043PubMedPubMedCentralCrossRef Floeter MK, Bageac D, Danielian LE, Braun LE, Traynor BJ, Kwan JY (2016) Longitudinal imaging in C9orf72 mutation carriers: relationship to phenotype. NeuroImage Clin 12:1035–1043PubMedPubMedCentralCrossRef

go back to reference Lee SE, Sias AC, Mandelli ML, Brown JA, Brown AB, Khazenzon AM, Vidovszky AA, Zanto TP, Karydas AM, Pribadi M, Dokuru D, Coppola G, Geschwind DH, Rademakers R, Gorno-Tempini ML, Rosen HJ, Miller BL, Seeley WW (2017) Network degeneration and dysfunction in presymptomatic C9ORF72 expansion carriers. NeuroImage Clin 14:286–297PubMedCrossRef Lee SE, Sias AC, Mandelli ML, Brown JA, Brown AB, Khazenzon AM, Vidovszky AA, Zanto TP, Karydas AM, Pribadi M, Dokuru D, Coppola G, Geschwind DH, Rademakers R, Gorno-Tempini ML, Rosen HJ, Miller BL, Seeley WW (2017) Network degeneration and dysfunction in presymptomatic C9ORF72 expansion carriers. NeuroImage Clin 14:286–297PubMedCrossRef

go back to reference Papma JM, Jiskoot LC, Panman JL, Dopper EG, den Heijer T, Donker Kaat L, Pijnenburg YAL, Meeter LH, van Minkelen R, Rombouts S, van Swieten JC (2017) Cognition and gray and white matter characteristics of presymptomatic C9orf72 repeat expansion. Neurology 89:1256–1264PubMedCrossRef Papma JM, Jiskoot LC, Panman JL, Dopper EG, den Heijer T, Donker Kaat L, Pijnenburg YAL, Meeter LH, van Minkelen R, Rombouts S, van Swieten JC (2017) Cognition and gray and white matter characteristics of presymptomatic C9orf72 repeat expansion. Neurology 89:1256–1264PubMedCrossRef

go back to reference Wen J, Zhang H, Alexander DC, Durrleman S, Routier A, Rinaldi D, Houot M, Couratier P, Hannequin D, Pasquier F, Zhang J, Colliot O, Le Ber I, Bertrand A (2019) Neurite density is reduced in the presymptomatic phase of C9orf72 disease. J Neurol Neurosurg Psychiatry 90:387–394PubMedCrossRef Wen J, Zhang H, Alexander DC, Durrleman S, Routier A, Rinaldi D, Houot M, Couratier P, Hannequin D, Pasquier F, Zhang J, Colliot O, Le Ber I, Bertrand A (2019) Neurite density is reduced in the presymptomatic phase of C9orf72 disease. J Neurol Neurosurg Psychiatry 90:387–394PubMedCrossRef

go back to reference Le Blanc G, Jetté Pomerleau V, McCarthy J, Borroni B, van Swieten J, Galimberti D, Sanchez-Valle R, LaForce R Jr, Moreno F, Synofzik M, Graff C, Masellis M, Tartaglia MC, Rowe JB, Vandenberghe R, Finger E, Tagliavini F, de Mendonça A, Santana I, Butler C, Gerhard A, Danek A, Levin J, Otto M, Frisoni G, Sorbi S, Rohrer JD, Ducharme S (2020) Faster Cortical thinning and surface area loss in presymptomatic and symptomatic C9orf72 repeat expansion adult carriers. Ann Neurol 88:113PubMedCrossRef Le Blanc G, Jetté Pomerleau V, McCarthy J, Borroni B, van Swieten J, Galimberti D, Sanchez-Valle R, LaForce R Jr, Moreno F, Synofzik M, Graff C, Masellis M, Tartaglia MC, Rowe JB, Vandenberghe R, Finger E, Tagliavini F, de Mendonça A, Santana I, Butler C, Gerhard A, Danek A, Levin J, Otto M, Frisoni G, Sorbi S, Rohrer JD, Ducharme S (2020) Faster Cortical thinning and surface area loss in presymptomatic and symptomatic C9orf72 repeat expansion adult carriers. Ann Neurol 88:113PubMedCrossRef

go back to reference De Vocht J et al (2020) Use of Multimodal imaging and clinical biomarkers in presymptomatic carriers of C9orf72 repeat expansion. JAMA Neurol 77(8):1008–1017PubMedCrossRef De Vocht J et al (2020) Use of Multimodal imaging and clinical biomarkers in presymptomatic carriers of C9orf72 repeat expansion. JAMA Neurol 77(8):1008–1017PubMedCrossRef

go back to reference Lulé DE et al (2020) Deficits in verbal fluency in presymptomatic C9orf72 mutation gene carriers-a developmental disorder. J Neurol Neurosurg Psychiatry 91(11):1195–1200PubMedCrossRef Lulé DE et al (2020) Deficits in verbal fluency in presymptomatic C9orf72 mutation gene carriers-a developmental disorder. J Neurol Neurosurg Psychiatry 91(11):1195–1200PubMedCrossRef

go back to reference Gorges M, Vercruysse P, Müller HP, Huppertz HJ, Rosenbohm A, Nagel G, Weydt P, Petersén Å, Ludolph AC, Kassubek J, Dupuis L (2017) Hypothalamic atrophy is related to body mass index and age at onset in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 88:1033–1041PubMedCrossRef Gorges M, Vercruysse P, Müller HP, Huppertz HJ, Rosenbohm A, Nagel G, Weydt P, Petersén Å, Ludolph AC, Kassubek J, Dupuis L (2017) Hypothalamic atrophy is related to body mass index and age at onset in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 88:1033–1041PubMedCrossRef

go back to reference Menke RA, Proudfoot M, Wuu J, Andersen PM, Talbot K, Benatar M, Turner MR (2016) Increased functional connectivity common to symptomatic amyotrophic lateral sclerosis and those at genetic risk. J Neurol Neurosurg Psychiatry 87:580–588PubMedCrossRef Menke RA, Proudfoot M, Wuu J, Andersen PM, Talbot K, Benatar M, Turner MR (2016) Increased functional connectivity common to symptomatic amyotrophic lateral sclerosis and those at genetic risk. J Neurol Neurosurg Psychiatry 87:580–588PubMedCrossRef

go back to reference Vucic S, Winhammar JM, Rowe DB, Kiernan MC (2010) Corticomotoneuronal function in asymptomatic SOD-1 mutation carriers. Clin Neurophysiol 121:1781–1785PubMedCrossRef Vucic S, Winhammar JM, Rowe DB, Kiernan MC (2010) Corticomotoneuronal function in asymptomatic SOD-1 mutation carriers. Clin Neurophysiol 121:1781–1785PubMedCrossRef

go back to reference Ng MC, Ho JT, Ho SL, Lee R, Li G, Cheng TS, Song YQ, Ho PW, Fong GC, Mak W, Chan KH, Li LS, Luk KD, Hu Y, Ramsden DB, Leong LL (2008) Abnormal diffusion tensor in nonsymptomatic familial amyotrophic lateral sclerosis with a causative superoxide dismutase 1 mutation. J Magn Reson Imaging 27:8–13PubMedCrossRef Ng MC, Ho JT, Ho SL, Lee R, Li G, Cheng TS, Song YQ, Ho PW, Fong GC, Mak W, Chan KH, Li LS, Luk KD, Hu Y, Ramsden DB, Leong LL (2008) Abnormal diffusion tensor in nonsymptomatic familial amyotrophic lateral sclerosis with a causative superoxide dismutase 1 mutation. J Magn Reson Imaging 27:8–13PubMedCrossRef

go back to reference Turner MR, Hammers A, Al-Chalabi A, Shaw CE, Andersen PM, Brooks DJ, Leigh PN (2005) Distinct cerebral lesions in sporadic and “D90A” SOD1 ALS: studies with [11C]flumazenil PET. Brain J Neurol 128:1323–1329CrossRef Turner MR, Hammers A, Al-Chalabi A, Shaw CE, Andersen PM, Brooks DJ, Leigh PN (2005) Distinct cerebral lesions in sporadic and “D90A” SOD1 ALS: studies with [11C]flumazenil PET. Brain J Neurol 128:1323–1329CrossRef

go back to reference Premi E, Calhoun VD, Diano M, Gazzina S, Cosseddu M, Alberici A, Archetti S, Paternicò D, Gasparotti R, van Swieten J, Galimberti D, Sanchez-Valle R, Laforce R Jr, Moreno F, Synofzik M, Graff C, Masellis M, Tartaglia MC, Rowe J, Vandenberghe R, Finger E, Tagliavini F, de Mendonça A, Santana I, Butler C, Ducharme S, Gerhard A, Danek A, Levin J, Otto M, Frisoni G, Cappa S, Sorbi S, Padovani A, Rohrer JD, Borroni B (2019) The inner fluctuations of the brain in presymptomatic frontotemporal dementia: the chronnectome fingerprint. Neuroimage 189:645–654PubMedCrossRef Premi E, Calhoun VD, Diano M, Gazzina S, Cosseddu M, Alberici A, Archetti S, Paternicò D, Gasparotti R, van Swieten J, Galimberti D, Sanchez-Valle R, Laforce R Jr, Moreno F, Synofzik M, Graff C, Masellis M, Tartaglia MC, Rowe J, Vandenberghe R, Finger E, Tagliavini F, de Mendonça A, Santana I, Butler C, Ducharme S, Gerhard A, Danek A, Levin J, Otto M, Frisoni G, Cappa S, Sorbi S, Padovani A, Rohrer JD, Borroni B (2019) The inner fluctuations of the brain in presymptomatic frontotemporal dementia: the chronnectome fingerprint. Neuroimage 189:645–654PubMedCrossRef

go back to reference Staffaroni AM, Cobigo Y, Goh SM, Kornak J, Bajorek L, Chiang K, Appleby B, Bove J, Bordelon Y, Brannelly P, Brushaber D, Caso C, Coppola G, Dever R, Dheel C, Dickerson BC, Dickinson S, Dominguez S, Domoto-Reilly K, Faber K, Ferrall J, Fields JA, Fishman A, Fong J, Foroud T, Forsberg LK, Gavrilova R, Gearhart D, Ghazanfari B, Ghoshal N, Goldman J, Graff-Radford J, Graff-Radford N, Grant I, Grossman M, Haley D, Heuer HW, Hsiung GY, Huey ED, Irwin DJ, Jones DT, Jones L, Kantarci K, Karydas A, Kaufer DI, Kerwin DR, Knopman DS, Kraft R, Kramer JH, Kremers WK, Kukull WA, Litvan I, Ljubenkov PA, Lucente D, Lungu C, Mackenzie IR, Maldonado M, Manoochehri M, McGinnis SM, McKinley E, Mendez MF, Miller BL, Multani N, Onyike C, Padmanabhan J, Pantelyat A, Pearlman R, Petrucelli L, Potter M, Rademakers R, Ramos EM, Rankin KP, Rascovsky K, Roberson ED, Rogalski E, Sengdy P, Shaw LM, Syrjanen J, Tartaglia MC, Tatton N, Taylor J, Toga A, Trojanowski JQ, Weintraub S, Wang P, Wong B, Wszolek Z, Boxer AL, Boeve BF, Rosen HJ (2020) Individualized atrophy scores predict dementia onset in familial frontotemporal lobar degeneration. Alzheimer’s Dement J Alzheimer’s Assoc 16:37–48CrossRef Staffaroni AM, Cobigo Y, Goh SM, Kornak J, Bajorek L, Chiang K, Appleby B, Bove J, Bordelon Y, Brannelly P, Brushaber D, Caso C, Coppola G, Dever R, Dheel C, Dickerson BC, Dickinson S, Dominguez S, Domoto-Reilly K, Faber K, Ferrall J, Fields JA, Fishman A, Fong J, Foroud T, Forsberg LK, Gavrilova R, Gearhart D, Ghazanfari B, Ghoshal N, Goldman J, Graff-Radford J, Graff-Radford N, Grant I, Grossman M, Haley D, Heuer HW, Hsiung GY, Huey ED, Irwin DJ, Jones DT, Jones L, Kantarci K, Karydas A, Kaufer DI, Kerwin DR, Knopman DS, Kraft R, Kramer JH, Kremers WK, Kukull WA, Litvan I, Ljubenkov PA, Lucente D, Lungu C, Mackenzie IR, Maldonado M, Manoochehri M, McGinnis SM, McKinley E, Mendez MF, Miller BL, Multani N, Onyike C, Padmanabhan J, Pantelyat A, Pearlman R, Petrucelli L, Potter M, Rademakers R, Ramos EM, Rankin KP, Rascovsky K, Roberson ED, Rogalski E, Sengdy P, Shaw LM, Syrjanen J, Tartaglia MC, Tatton N, Taylor J, Toga A, Trojanowski JQ, Weintraub S, Wang P, Wong B, Wszolek Z, Boxer AL, Boeve BF, Rosen HJ (2020) Individualized atrophy scores predict dementia onset in familial frontotemporal lobar degeneration. Alzheimer’s Dement J Alzheimer’s Assoc 16:37–48CrossRef

go back to reference Gazzina S, Grassi M, Premi E, Cosseddu M, Alberici A, Archetti S, Gasparotti R, Van Swieten J, Galimberti D, Sanchez-Valle R, Laforce RJ, Moreno F, Synofzik M, Graff C, Masellis M, Tartaglia MC, Rowe JB, Vandenberghe R, Finger E, Tagliavini F, de Mendonça A, Santana I, Butler CR, Ducharme S, Gerhard A, Danek A, Levin J, Otto M, Frisoni G, Sorbi S, Padovani A, Rohrer JD, Borroni B (2019) Education modulates brain maintenance in presymptomatic frontotemporal dementia. J Neurol Neurosurg Psychiatry 90:1124–1130PubMedCrossRef Gazzina S, Grassi M, Premi E, Cosseddu M, Alberici A, Archetti S, Gasparotti R, Van Swieten J, Galimberti D, Sanchez-Valle R, Laforce RJ, Moreno F, Synofzik M, Graff C, Masellis M, Tartaglia MC, Rowe JB, Vandenberghe R, Finger E, Tagliavini F, de Mendonça A, Santana I, Butler CR, Ducharme S, Gerhard A, Danek A, Levin J, Otto M, Frisoni G, Sorbi S, Padovani A, Rohrer JD, Borroni B (2019) Education modulates brain maintenance in presymptomatic frontotemporal dementia. J Neurol Neurosurg Psychiatry 90:1124–1130PubMedCrossRef

go back to reference Mutsaerts H, Mirza SS, Petr J, Thomas DL, Cash DM, Bocchetta M, de Vita E, Metcalfe AWS, Shirzadi Z, Robertson AD, Tartaglia MC, Mitchell SB, Black SE, Freedman M, Tang-Wai D, Keren R, Rogaeva E, van Swieten J, Laforce R, Tagliavini F, Borroni B, Galimberti D, Rowe JB, Graff C, Frisoni GB, Finger E, Sorbi S, de Mendonça A, Rohrer JD, MacIntosh BJ, Masellis M (2019) Cerebral perfusion changes in presymptomatic genetic frontotemporal dementia: a GENFI study. Brain 142:1108–1120PubMedPubMedCentralCrossRef Mutsaerts H, Mirza SS, Petr J, Thomas DL, Cash DM, Bocchetta M, de Vita E, Metcalfe AWS, Shirzadi Z, Robertson AD, Tartaglia MC, Mitchell SB, Black SE, Freedman M, Tang-Wai D, Keren R, Rogaeva E, van Swieten J, Laforce R, Tagliavini F, Borroni B, Galimberti D, Rowe JB, Graff C, Frisoni GB, Finger E, Sorbi S, de Mendonça A, Rohrer JD, MacIntosh BJ, Masellis M (2019) Cerebral perfusion changes in presymptomatic genetic frontotemporal dementia: a GENFI study. Brain 142:1108–1120PubMedPubMedCentralCrossRef

go back to reference Fumagalli GG, Basilico P, Arighi A, Bocchetta M, Dick KM, Cash DM, Harding S, Mercurio M, Fenoglio C, Pietroboni AM, Ghezzi L, van Swieten J, Borroni B, de Mendonça A, Masellis M, Tartaglia MC, Rowe JB, Graff C, Tagliavini F, Frisoni GB, Laforce R Jr, Finger E, Sorbi S, Scarpini E, Rohrer JD, Galimberti D (2018) Distinct patterns of brain atrophy in Genetic frontotemporal dementia initiative (GENFI) cohort revealed by visual rating scales. Alzheimer’s Res Ther 10:46CrossRef Fumagalli GG, Basilico P, Arighi A, Bocchetta M, Dick KM, Cash DM, Harding S, Mercurio M, Fenoglio C, Pietroboni AM, Ghezzi L, van Swieten J, Borroni B, de Mendonça A, Masellis M, Tartaglia MC, Rowe JB, Graff C, Tagliavini F, Frisoni GB, Laforce R Jr, Finger E, Sorbi S, Scarpini E, Rohrer JD, Galimberti D (2018) Distinct patterns of brain atrophy in Genetic frontotemporal dementia initiative (GENFI) cohort revealed by visual rating scales. Alzheimer’s Res Ther 10:46CrossRef

go back to reference Cash DM, Bocchetta M, Thomas DL, Dick KM, van Swieten JC, Borroni B, Galimberti D, Masellis M, Tartaglia MC, Rowe JB, Graff C, Tagliavini F, Frisoni GB, Laforce R Jr, Finger E, de Mendonca A, Sorbi S, Rossor MN, Ourselin S, Rohrer JD (2018) Patterns of gray matter atrophy in genetic frontotemporal dementia: results from the GENFI study. Neurobiol Aging 62:191–196PubMedPubMedCentralCrossRef Cash DM, Bocchetta M, Thomas DL, Dick KM, van Swieten JC, Borroni B, Galimberti D, Masellis M, Tartaglia MC, Rowe JB, Graff C, Tagliavini F, Frisoni GB, Laforce R Jr, Finger E, de Mendonca A, Sorbi S, Rossor MN, Ourselin S, Rohrer JD (2018) Patterns of gray matter atrophy in genetic frontotemporal dementia: results from the GENFI study. Neurobiol Aging 62:191–196PubMedPubMedCentralCrossRef

go back to reference Premi E, Grassi M, van Swieten J, Galimberti D, Graff C, Masellis M, Tartaglia C, Tagliavini F, Rowe JB, Laforce R Jr, Finger E, Frisoni GB, de Mendonça A, Sorbi S, Gazzina S, Cosseddu M, Archetti S, Gasparotti R, Manes M, Alberici A, Cardoso MJ, Bocchetta M, Cash DM, Ourselin S, Padovani A, Rohrer JD, Borroni B (2017) Cognitive reserve and TMEM106B genotype modulate brain damage in presymptomatic frontotemporal dementia: a GENFI study. Brain 140:1784–1791PubMedPubMedCentralCrossRef Premi E, Grassi M, van Swieten J, Galimberti D, Graff C, Masellis M, Tartaglia C, Tagliavini F, Rowe JB, Laforce R Jr, Finger E, Frisoni GB, de Mendonça A, Sorbi S, Gazzina S, Cosseddu M, Archetti S, Gasparotti R, Manes M, Alberici A, Cardoso MJ, Bocchetta M, Cash DM, Ourselin S, Padovani A, Rohrer JD, Borroni B (2017) Cognitive reserve and TMEM106B genotype modulate brain damage in presymptomatic frontotemporal dementia: a GENFI study. Brain 140:1784–1791PubMedPubMedCentralCrossRef

go back to reference Tavares TP, Mitchell DGV, Coleman K, Shoesmith C, Bartha R, Cash DM, Moore KM, van Swieten J, Borroni B, Galimberti D, Tartaglia MC, Rowe J, Graff C, Tagliavini F, Frisoni G, Cappa S, Laforce R Jr, de Mendonça A, Sorbi S, Wallstrom G, Masellis M, Rohrer JD, Finger EC (2019) Ventricular volume expansion in presymptomatic genetic frontotemporal dementia. Neurology 93:e1699–e1706PubMedPubMedCentralCrossRef Tavares TP, Mitchell DGV, Coleman K, Shoesmith C, Bartha R, Cash DM, Moore KM, van Swieten J, Borroni B, Galimberti D, Tartaglia MC, Rowe J, Graff C, Tagliavini F, Frisoni G, Cappa S, Laforce R Jr, de Mendonça A, Sorbi S, Wallstrom G, Masellis M, Rohrer JD, Finger EC (2019) Ventricular volume expansion in presymptomatic genetic frontotemporal dementia. Neurology 93:e1699–e1706PubMedPubMedCentralCrossRef

go back to reference Rittman T, Borchert R, Jones S, van Swieten J, Borroni B, Galimberti D, Masellis M, Tartaglia MC, Graff C, Tagliavini F, Frisoni GB, Laforce R Jr, Finger E, Mendonça A, Sorbi S, Rohrer JD, Rowe JB (2019) Functional network resilience to pathology in presymptomatic genetic frontotemporal dementia. Neurobiol Aging 77:169–177PubMedPubMedCentralCrossRef Rittman T, Borchert R, Jones S, van Swieten J, Borroni B, Galimberti D, Masellis M, Tartaglia MC, Graff C, Tagliavini F, Frisoni GB, Laforce R Jr, Finger E, Mendonça A, Sorbi S, Rohrer JD, Rowe JB (2019) Functional network resilience to pathology in presymptomatic genetic frontotemporal dementia. Neurobiol Aging 77:169–177PubMedPubMedCentralCrossRef

go back to reference Cury C, Durrleman S, Cash DM, Lorenzi M, Nicholas JM, Bocchetta M, van Swieten JC, Borroni B, Galimberti D, Masellis M, Tartaglia MC, Rowe JB, Graff C, Tagliavini F, Frisoni GB, Laforce R Jr, Finger E, de Mendonça A, Sorbi S, Ourselin S, Rohrer JD, Modat M (2019) Spatiotemporal analysis for detection of pre-symptomatic shape changes in neurodegenerative diseases: Initial application to the GENFI cohort. Neuroimage 188:282–290PubMedCrossRef Cury C, Durrleman S, Cash DM, Lorenzi M, Nicholas JM, Bocchetta M, van Swieten JC, Borroni B, Galimberti D, Masellis M, Tartaglia MC, Rowe JB, Graff C, Tagliavini F, Frisoni GB, Laforce R Jr, Finger E, de Mendonça A, Sorbi S, Ourselin S, Rohrer JD, Modat M (2019) Spatiotemporal analysis for detection of pre-symptomatic shape changes in neurodegenerative diseases: Initial application to the GENFI cohort. Neuroimage 188:282–290PubMedCrossRef

go back to reference Sudre CH, Bocchetta M, Cash D, Thomas DL, Woollacott I, Dick KM, van Swieten J, Borroni B, Galimberti D, Masellis M, Tartaglia MC, Rowe JB, Graff C, Tagliavini F, Frisoni G, Laforce R Jr, Finger E, de Mendonça A, Sorbi S, Ourselin S, Cardoso MJ, Rohrer JD (2017) White matter hyperintensities are seen only in GRN mutation carriers in the GENFI cohort. Neuroimage Clin 15:171–180PubMedPubMedCentralCrossRef Sudre CH, Bocchetta M, Cash D, Thomas DL, Woollacott I, Dick KM, van Swieten J, Borroni B, Galimberti D, Masellis M, Tartaglia MC, Rowe JB, Graff C, Tagliavini F, Frisoni G, Laforce R Jr, Finger E, de Mendonça A, Sorbi S, Ourselin S, Cardoso MJ, Rohrer JD (2017) White matter hyperintensities are seen only in GRN mutation carriers in the GENFI cohort. Neuroimage Clin 15:171–180PubMedPubMedCentralCrossRef

go back to reference Staffaroni AM, Bajorek L, Casaletto KB, Cobigo Y, Goh SM, Wolf A, Heuer HW, Elahi FM, Ljubenkov PA, Dever R, Kornak J, Appleby B, Bove J, Bordelon Y, Brannelly P, Brushaber D, Caso C, Coppola G, Dheel C, Dickerson BC, Dickinson S, Dominguez S, Domoto-Reilly K, Faber K, Ferrall J, Fields JA, Fishman A, Fong J, Foroud T, Forsberg LK, Gavrilova R, Gearhart D, Ghazanfari B, Ghoshal N, Goldman J, Graff-Radford J, Graff-Radford N, Grant I, Grossman M, Haley D, Hsiung GY, Huey ED, Irwin DJ, Jones DT, Jones L, Kantarci K, Karydas A, Kaufer DI, Kerwin DR, Knopman DS, Kraft R, Kremers WK, Kukull WA, Litvan I, Lucente D, Lungu C, Mackenzie IR, Maldonado M, Manoochehri M, McGinnis SM, McKinley E, Mendez MF, Miller BL, Multani N, Onyike C, Padmanabhan J, Pantelyat A, Pearlman R, Petrucelli L, Potter M, Rademakers R, Ramos EM, Rankin KP, Rascovsky K, Roberson ED, Rogalski E, Sengdy P, Shaw LM, Syrjanen J, Tartaglia MC, Tatton N, Taylor J, Toga A, Trojanowski JQ, Weintraub S, Wang P, Wong B, Wszolek Z, Boxer AL, Boeve BF, Kramer JH, Rosen HJ (2020) Assessment of executive function declines in presymptomatic and mildly symptomatic familial frontotemporal dementia: NIH-EXAMINER as a potential clinical trial endpoint. Alzheimer’s Dement J Alzheimer’s Assoc 16:11–21CrossRef Staffaroni AM, Bajorek L, Casaletto KB, Cobigo Y, Goh SM, Wolf A, Heuer HW, Elahi FM, Ljubenkov PA, Dever R, Kornak J, Appleby B, Bove J, Bordelon Y, Brannelly P, Brushaber D, Caso C, Coppola G, Dheel C, Dickerson BC, Dickinson S, Dominguez S, Domoto-Reilly K, Faber K, Ferrall J, Fields JA, Fishman A, Fong J, Foroud T, Forsberg LK, Gavrilova R, Gearhart D, Ghazanfari B, Ghoshal N, Goldman J, Graff-Radford J, Graff-Radford N, Grant I, Grossman M, Haley D, Hsiung GY, Huey ED, Irwin DJ, Jones DT, Jones L, Kantarci K, Karydas A, Kaufer DI, Kerwin DR, Knopman DS, Kraft R, Kremers WK, Kukull WA, Litvan I, Lucente D, Lungu C, Mackenzie IR, Maldonado M, Manoochehri M, McGinnis SM, McKinley E, Mendez MF, Miller BL, Multani N, Onyike C, Padmanabhan J, Pantelyat A, Pearlman R, Petrucelli L, Potter M, Rademakers R, Ramos EM, Rankin KP, Rascovsky K, Roberson ED, Rogalski E, Sengdy P, Shaw LM, Syrjanen J, Tartaglia MC, Tatton N, Taylor J, Toga A, Trojanowski JQ, Weintraub S, Wang P, Wong B, Wszolek Z, Boxer AL, Boeve BF, Kramer JH, Rosen HJ (2020) Assessment of executive function declines in presymptomatic and mildly symptomatic familial frontotemporal dementia: NIH-EXAMINER as a potential clinical trial endpoint. Alzheimer’s Dement J Alzheimer’s Assoc 16:11–21CrossRef

go back to reference Popuri K, Dowds E, Beg MF, Balachandar R, Bhalla M, Jacova C, Buller A, Slack P, Sengdy P, Rademakers R, Wittenberg D, Feldman HH, Mackenzie IR, Hsiung GR (2018) Gray matter changes in asymptomatic C9orf72 and GRN mutation carriers. NeuroImage Clin 18:591–598PubMedPubMedCentralCrossRef Popuri K, Dowds E, Beg MF, Balachandar R, Bhalla M, Jacova C, Buller A, Slack P, Sengdy P, Rademakers R, Wittenberg D, Feldman HH, Mackenzie IR, Hsiung GR (2018) Gray matter changes in asymptomatic C9orf72 and GRN mutation carriers. NeuroImage Clin 18:591–598PubMedPubMedCentralCrossRef

go back to reference Feis RA, Bouts M, Panman JL, Jiskoot LC, Dopper EGP, Schouten TM, de Vos F, van der Grond J, van Swieten JC, Rombouts S (2019) Single-subject classification of presymptomatic frontotemporal dementia mutation carriers using multimodal MRI. Neuroimage Clin 22:101718PubMedPubMedCentralCrossRef Feis RA, Bouts M, Panman JL, Jiskoot LC, Dopper EGP, Schouten TM, de Vos F, van der Grond J, van Swieten JC, Rombouts S (2019) Single-subject classification of presymptomatic frontotemporal dementia mutation carriers using multimodal MRI. Neuroimage Clin 22:101718PubMedPubMedCentralCrossRef

go back to reference Panman JL, Jiskoot LC, Bouts M, Meeter LHH, van der Ende EL, Poos JM, Feis RA, Kievit AJA, van Minkelen R, Dopper EGP, Rombouts S, van Swieten JC, Papma JM (2019) Gray and white matter changes in presymptomatic genetic frontotemporal dementia: a longitudinal MRI study. Neurobiol Aging 76:115–124PubMedCrossRef Panman JL, Jiskoot LC, Bouts M, Meeter LHH, van der Ende EL, Poos JM, Feis RA, Kievit AJA, van Minkelen R, Dopper EGP, Rombouts S, van Swieten JC, Papma JM (2019) Gray and white matter changes in presymptomatic genetic frontotemporal dementia: a longitudinal MRI study. Neurobiol Aging 76:115–124PubMedCrossRef

go back to reference Feis RA, Bouts M, de Vos F, Schouten TM, Panman JL, Jiskoot LC, Dopper EGP, van der Grond J, van Swieten JC, Rombouts S (2019) A multimodal MRI-based classification signature emerges just prior to symptom onset in frontotemporal dementia mutation carriers. J Neurol Neurosurg Psychiatry 90:1207–1214PubMedCrossRef Feis RA, Bouts M, de Vos F, Schouten TM, Panman JL, Jiskoot LC, Dopper EGP, van der Grond J, van Swieten JC, Rombouts S (2019) A multimodal MRI-based classification signature emerges just prior to symptom onset in frontotemporal dementia mutation carriers. J Neurol Neurosurg Psychiatry 90:1207–1214PubMedCrossRef

go back to reference Rohrer JD, Nicholas JM, Cash DM, van Swieten J, Dopper E, Jiskoot L, van Minkelen R, Rombouts SA, Cardoso MJ, Clegg S, Espak M, Mead S, Thomas DL, De Vita E, Masellis M, Black SE, Freedman M, Keren R, MacIntosh BJ, Rogaeva E, Tang-Wai D, Tartaglia MC, Laforce R Jr, Tagliavini F, Tiraboschi P, Redaelli V, Prioni S, Grisoli M, Borroni B, Padovani A, Galimberti D, Scarpini E, Arighi A, Fumagalli G, Rowe JB, Coyle-Gilchrist I, Graff C, Fallstrom M, Jelic V, Stahlbom AK, Andersson C, Thonberg H, Lilius L, Frisoni GB, Pievani M, Bocchetta M, Benussi L, Ghidoni R, Finger E, Sorbi S, Nacmias B, Lombardi G, Polito C, Warren JD, Ourselin S, Fox NC, Rossor MN, Binetti G (2015) Presymptomatic cognitive and neuroanatomical changes in genetic frontotemporal dementia in the Genetic Frontotemporal dementia Initiative (GENFI) study: a cross-sectional analysis. Lancet Neurol 14:253–262PubMedPubMedCentralCrossRef Rohrer JD, Nicholas JM, Cash DM, van Swieten J, Dopper E, Jiskoot L, van Minkelen R, Rombouts SA, Cardoso MJ, Clegg S, Espak M, Mead S, Thomas DL, De Vita E, Masellis M, Black SE, Freedman M, Keren R, MacIntosh BJ, Rogaeva E, Tang-Wai D, Tartaglia MC, Laforce R Jr, Tagliavini F, Tiraboschi P, Redaelli V, Prioni S, Grisoli M, Borroni B, Padovani A, Galimberti D, Scarpini E, Arighi A, Fumagalli G, Rowe JB, Coyle-Gilchrist I, Graff C, Fallstrom M, Jelic V, Stahlbom AK, Andersson C, Thonberg H, Lilius L, Frisoni GB, Pievani M, Bocchetta M, Benussi L, Ghidoni R, Finger E, Sorbi S, Nacmias B, Lombardi G, Polito C, Warren JD, Ourselin S, Fox NC, Rossor MN, Binetti G (2015) Presymptomatic cognitive and neuroanatomical changes in genetic frontotemporal dementia in the Genetic Frontotemporal dementia Initiative (GENFI) study: a cross-sectional analysis. Lancet Neurol 14:253–262PubMedPubMedCentralCrossRef

go back to reference Burke T, Elamin M, Bede P, Pinto-Grau M, Lonergan K, Hardiman O, Pender N (2016) Discordant performance on the “Reading the Mind in the Eyes” Test, based on disease onset in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Front Degener 17:1–6 Burke T, Elamin M, Bede P, Pinto-Grau M, Lonergan K, Hardiman O, Pender N (2016) Discordant performance on the “Reading the Mind in the Eyes” Test, based on disease onset in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Front Degener 17:1–6

go back to reference Burke T, Pinto-Grau M, Lonergan K, Elamin M, Bede P, Costello E, Hardiman O, Pender N (2016) Measurement of social cognition in amyotrophic lateral sclerosis: a population based study. PLoS ONE 11:e0160850PubMedPubMedCentralCrossRef Burke T, Pinto-Grau M, Lonergan K, Elamin M, Bede P, Costello E, Hardiman O, Pender N (2016) Measurement of social cognition in amyotrophic lateral sclerosis: a population based study. PLoS ONE 11:e0160850PubMedPubMedCentralCrossRef

go back to reference Christidi F, Karavasilis E, Rentzos M, Kelekis N, Evdokimidis I, Bede P (2018) Clinical and radiological markers of extra-motor deficits in amyotrophic lateral sclerosis. Front Neurol 9:1005PubMedPubMedCentralCrossRef Christidi F, Karavasilis E, Rentzos M, Kelekis N, Evdokimidis I, Bede P (2018) Clinical and radiological markers of extra-motor deficits in amyotrophic lateral sclerosis. Front Neurol 9:1005PubMedPubMedCentralCrossRef

go back to reference Elamin M, Pinto-Grau M, Burke T, Bede P, Rooney J, O’Sullivan M, Lonergan K, Kirby E, Quinlan E, Breen N, Vajda A, Heverin M, Pender N, Hardiman O (2017) Identifying behavioural changes in ALS: validation of the Beaumont behavioural inventory (BBI). Amyotroph Lateral Scler Front Degener 18:68–73CrossRef Elamin M, Pinto-Grau M, Burke T, Bede P, Rooney J, O’Sullivan M, Lonergan K, Kirby E, Quinlan E, Breen N, Vajda A, Heverin M, Pender N, Hardiman O (2017) Identifying behavioural changes in ALS: validation of the Beaumont behavioural inventory (BBI). Amyotroph Lateral Scler Front Degener 18:68–73CrossRef

go back to reference Tremolizzo L, Lizio A, Santangelo G, Diamanti S, Lunetta C, Gerardi F, Messina S, La Foresta S, Riva N, Falzone Y, Filippi M, Woolley SC, Sansone VA, Siciliano M, Ferrarese C, Appollonio I (2020) ALS Cognitive behavioral screen (ALS-CBS): normative values for the Italian population and clinical usability. Neurol Sci 41:835–841PubMedCrossRef Tremolizzo L, Lizio A, Santangelo G, Diamanti S, Lunetta C, Gerardi F, Messina S, La Foresta S, Riva N, Falzone Y, Filippi M, Woolley SC, Sansone VA, Siciliano M, Ferrarese C, Appollonio I (2020) ALS Cognitive behavioral screen (ALS-CBS): normative values for the Italian population and clinical usability. Neurol Sci 41:835–841PubMedCrossRef

go back to reference Aggarwal A (2012) Handgrip maximal voluntary isometric contraction does not correlate with thenar motor unit number estimation. Neurol Res Int 2012:187947PubMedPubMedCentralCrossRef Aggarwal A (2012) Handgrip maximal voluntary isometric contraction does not correlate with thenar motor unit number estimation. Neurol Res Int 2012:187947PubMedPubMedCentralCrossRef

go back to reference Proudfoot M, Rohenkohl G, Quinn A, Colclough GL, Wuu J, Talbot K, Woolrich MW, Benatar M, Nobre AC, Turner MR (2017) Altered cortical beta-band oscillations reflect motor system degeneration in amyotrophic lateral sclerosis. Hum Brain Mapp 38:237–254PubMedCrossRef Proudfoot M, Rohenkohl G, Quinn A, Colclough GL, Wuu J, Talbot K, Woolrich MW, Benatar M, Nobre AC, Turner MR (2017) Altered cortical beta-band oscillations reflect motor system degeneration in amyotrophic lateral sclerosis. Hum Brain Mapp 38:237–254PubMedCrossRef

go back to reference Geevasinga N, Menon P, Nicholson GA, Ng K, Howells J, Kril JJ, Yiannikas C, Kiernan MC, Vucic S (2015) Cortical function in asymptomatic carriers and patients with C9orf72 amyotrophic lateral sclerosis. JAMA neurology 72:1268–1274PubMedPubMedCentralCrossRef Geevasinga N, Menon P, Nicholson GA, Ng K, Howells J, Kril JJ, Yiannikas C, Kiernan MC, Vucic S (2015) Cortical function in asymptomatic carriers and patients with C9orf72 amyotrophic lateral sclerosis. JAMA neurology 72:1268–1274PubMedPubMedCentralCrossRef

go back to reference Vucic S, Nicholson GA, Kiernan MC (2008) Cortical hyperexcitability may precede the onset of familial amyotrophic lateral sclerosis. Brain J Neurol 131:1540–1550CrossRef Vucic S, Nicholson GA, Kiernan MC (2008) Cortical hyperexcitability may precede the onset of familial amyotrophic lateral sclerosis. Brain J Neurol 131:1540–1550CrossRef

go back to reference Benussi A, Gazzina S, Premi E, Cosseddu M, Archetti S, Dell’Era V, Cantoni V, Cotelli MS, Alberici A, Micheli A, Benussi L, Ghidoni R, Padovani A, Borroni B (2019) Clinical and biomarker changes in presymptomatic genetic frontotemporal dementia. Neurobiol Aging 76:133–140PubMedCrossRef Benussi A, Gazzina S, Premi E, Cosseddu M, Archetti S, Dell’Era V, Cantoni V, Cotelli MS, Alberici A, Micheli A, Benussi L, Ghidoni R, Padovani A, Borroni B (2019) Clinical and biomarker changes in presymptomatic genetic frontotemporal dementia. Neurobiol Aging 76:133–140PubMedCrossRef

go back to reference Benatar M, Wuu J, Andersen PM, Lombardi V, Malaspina A (2018) Neurofilament light: a candidate biomarker of presymptomatic amyotrophic lateral sclerosis and phenoconversion. Ann Neurol 84:130–139PubMedCrossRef Benatar M, Wuu J, Andersen PM, Lombardi V, Malaspina A (2018) Neurofilament light: a candidate biomarker of presymptomatic amyotrophic lateral sclerosis and phenoconversion. Ann Neurol 84:130–139PubMedCrossRef

go back to reference Benatar M, Wuu J, Lombardi V, Jeromin A, Bowser R, Andersen PM, Malaspina A (2019) Neurofilaments in pre-symptomatic ALS and the impact of genotype. Amyotroph Lateral Scler Front Degener 20:538–548CrossRef Benatar M, Wuu J, Lombardi V, Jeromin A, Bowser R, Andersen PM, Malaspina A (2019) Neurofilaments in pre-symptomatic ALS and the impact of genotype. Amyotroph Lateral Scler Front Degener 20:538–548CrossRef

go back to reference Weydt P, Oeckl P, Huss A, Müller K, Volk AE, Kuhle J, Knehr A, Andersen PM, Prudlo J, Steinacker P, Weishaupt JH, Ludolph AC, Otto M (2016) Neurofilament levels as biomarkers in asymptomatic and symptomatic familial amyotrophic lateral sclerosis. Ann Neurol 79:152–158PubMedCrossRef Weydt P, Oeckl P, Huss A, Müller K, Volk AE, Kuhle J, Knehr A, Andersen PM, Prudlo J, Steinacker P, Weishaupt JH, Ludolph AC, Otto M (2016) Neurofilament levels as biomarkers in asymptomatic and symptomatic familial amyotrophic lateral sclerosis. Ann Neurol 79:152–158PubMedCrossRef

go back to reference Oeckl P, Weydt P, Thal DR, Weishaupt JH, Ludolph AC, Otto M (2020) Proteomics in cerebrospinal fluid and spinal cord suggests UCHL1, MAP2 and GPNMB as biomarkers and underpins importance of transcriptional pathways in amyotrophic lateral sclerosis. Acta Neuropathol 139:119–134PubMedCrossRef Oeckl P, Weydt P, Thal DR, Weishaupt JH, Ludolph AC, Otto M (2020) Proteomics in cerebrospinal fluid and spinal cord suggests UCHL1, MAP2 and GPNMB as biomarkers and underpins importance of transcriptional pathways in amyotrophic lateral sclerosis. Acta Neuropathol 139:119–134PubMedCrossRef

go back to reference Thompson AG, Gray E, Bampton A, Raciborska D, Talbot K, Turner MR (2019) CSF chitinase proteins in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 90:1215–1220PubMedCrossRef Thompson AG, Gray E, Bampton A, Raciborska D, Talbot K, Turner MR (2019) CSF chitinase proteins in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 90:1215–1220PubMedCrossRef

go back to reference Gendron TF, Chew J, Stankowski JN, Hayes LR, Zhang YJ, Prudencio M, Carlomagno Y, Daughrity LM, Jansen-West K, Perkerson EA, O’Raw A, Cook C, Pregent L, Belzil V, van Blitterswijk M, Tabassian LJ, Lee CW, Yue M, Tong J, Song Y, Castanedes-Casey M, Rousseau L, Phillips V, Dickson DW, Rademakers R, Fryer JD, Rush BK, Pedraza O, Caputo AM, Desaro P, Palmucci C, Robertson A, Heckman MG, Diehl NN, Wiggs E, Tierney M, Braun L, Farren J, Lacomis D, Ladha S, Fournier CN, McCluskey LF, Elman LB, Toledo JB, McBride JD, Tiloca C, Morelli C, Poletti B, Solca F, Prelle A, Wuu J, Jockel-Balsarotti J, Rigo F, Ambrose C, Datta A, Yang W, Raitcheva D, Antognetti G, McCampbell A, Van Swieten JC, Miller BL, Boxer AL, Brown RH, Bowser R, Miller TM, Trojanowski JQ, Grossman M, Berry JD, Hu WT, Ratti A, Traynor BJ, Disney MD, Benatar M, Silani V, Glass JD, Floeter MK, Rothstein JD, Boylan KB, Petrucelli L (2017) Poly(GP) proteins are a useful pharmacodynamic marker for C9ORF72-associated amyotrophic lateral sclerosis. Sci Transl Med 9:eaai866CrossRef Gendron TF, Chew J, Stankowski JN, Hayes LR, Zhang YJ, Prudencio M, Carlomagno Y, Daughrity LM, Jansen-West K, Perkerson EA, O’Raw A, Cook C, Pregent L, Belzil V, van Blitterswijk M, Tabassian LJ, Lee CW, Yue M, Tong J, Song Y, Castanedes-Casey M, Rousseau L, Phillips V, Dickson DW, Rademakers R, Fryer JD, Rush BK, Pedraza O, Caputo AM, Desaro P, Palmucci C, Robertson A, Heckman MG, Diehl NN, Wiggs E, Tierney M, Braun L, Farren J, Lacomis D, Ladha S, Fournier CN, McCluskey LF, Elman LB, Toledo JB, McBride JD, Tiloca C, Morelli C, Poletti B, Solca F, Prelle A, Wuu J, Jockel-Balsarotti J, Rigo F, Ambrose C, Datta A, Yang W, Raitcheva D, Antognetti G, McCampbell A, Van Swieten JC, Miller BL, Boxer AL, Brown RH, Bowser R, Miller TM, Trojanowski JQ, Grossman M, Berry JD, Hu WT, Ratti A, Traynor BJ, Disney MD, Benatar M, Silani V, Glass JD, Floeter MK, Rothstein JD, Boylan KB, Petrucelli L (2017) Poly(GP) proteins are a useful pharmacodynamic marker for C9ORF72-associated amyotrophic lateral sclerosis. Sci Transl Med 9:eaai866CrossRef

go back to reference Lehmer C, Oeckl P, Weishaupt JH, Volk AE, Diehl-Schmid J, Schroeter ML, Lauer M, Kornhuber J, Levin J, Fassbender K, Landwehrmeyer B, Schludi MH, Arzberger T, Kremmer E, Flatley A, Feederle R, Steinacker P, Weydt P, Ludolph AC, Edbauer D, Otto M (2017) Poly-GP in cerebrospinal fluid links C9orf72-associated dipeptide repeat expression to the asymptomatic phase of ALS/FTD. EMBO Mol Med 9:859–868PubMedPubMedCentralCrossRef Lehmer C, Oeckl P, Weishaupt JH, Volk AE, Diehl-Schmid J, Schroeter ML, Lauer M, Kornhuber J, Levin J, Fassbender K, Landwehrmeyer B, Schludi MH, Arzberger T, Kremmer E, Flatley A, Feederle R, Steinacker P, Weydt P, Ludolph AC, Edbauer D, Otto M (2017) Poly-GP in cerebrospinal fluid links C9orf72-associated dipeptide repeat expression to the asymptomatic phase of ALS/FTD. EMBO Mol Med 9:859–868PubMedPubMedCentralCrossRef

go back to reference Barschke P, Oeckl P, Steinacker P, Al Shweiki MR, Weishaupt JH, Landwehrmeyer GB, Anderl-Straub S, Weydt P, Diehl-Schmid J, Danek A, Kornhuber J, Schroeter ML, Prudlo J, Jahn H, Fassbender K, Lauer M, van der Ende EL, van Swieten JC, Volk AE, Ludolph AC, Otto M (2020) Different CSF protein profiles in amyotrophic lateral sclerosis and frontotemporal dementia with C9orf72 hexanucleotide repeat expansion. J Neurol Neurosurg Psychiatry 91:503–511PubMedCrossRef Barschke P, Oeckl P, Steinacker P, Al Shweiki MR, Weishaupt JH, Landwehrmeyer GB, Anderl-Straub S, Weydt P, Diehl-Schmid J, Danek A, Kornhuber J, Schroeter ML, Prudlo J, Jahn H, Fassbender K, Lauer M, van der Ende EL, van Swieten JC, Volk AE, Ludolph AC, Otto M (2020) Different CSF protein profiles in amyotrophic lateral sclerosis and frontotemporal dementia with C9orf72 hexanucleotide repeat expansion. J Neurol Neurosurg Psychiatry 91:503–511PubMedCrossRef

go back to reference Stoccoro A, Mosca L, Carnicelli V, Cavallari U, Lunetta C, Marocchi A, Migliore L, Coppedè F (2018) Mitochondrial DNA copy number and D-loop region methylation in carriers of amyotrophic lateral sclerosis gene mutations. Epigenomics 10:1431–1443PubMedCrossRef Stoccoro A, Mosca L, Carnicelli V, Cavallari U, Lunetta C, Marocchi A, Migliore L, Coppedè F (2018) Mitochondrial DNA copy number and D-loop region methylation in carriers of amyotrophic lateral sclerosis gene mutations. Epigenomics 10:1431–1443PubMedCrossRef

go back to reference Chen Q, Boeve BF, Senjem M, Tosakulwong N, Lesnick T, Brushaber D, Dheel C, Fields J, Forsberg L, Gavrilova R, Gearhart D, Graff-Radford J, Graff-Radford N, Jack CR Jr, Jones D, Knopman D, Kremers WK, Lapid M, Rademakers R, Ramos EM, Syrjanen J, Boxer AL, Rosen H, Wszolek ZK, Kantarci K (2020) Trajectory of lobar atrophy in asymptomatic and symptomatic GRN mutation carriers: a longitudinal MRI study. Neurobiol Aging 88:42–50PubMedCrossRef Chen Q, Boeve BF, Senjem M, Tosakulwong N, Lesnick T, Brushaber D, Dheel C, Fields J, Forsberg L, Gavrilova R, Gearhart D, Graff-Radford J, Graff-Radford N, Jack CR Jr, Jones D, Knopman D, Kremers WK, Lapid M, Rademakers R, Ramos EM, Syrjanen J, Boxer AL, Rosen H, Wszolek ZK, Kantarci K (2020) Trajectory of lobar atrophy in asymptomatic and symptomatic GRN mutation carriers: a longitudinal MRI study. Neurobiol Aging 88:42–50PubMedCrossRef

go back to reference Lee SE, Sias AC, Kosik EL, Flagan TM, Deng J, Chu SA, Brown JA, Vidovszky AA, Ramos EM, Gorno-Tempini ML, Karydas AM, Coppola G, Geschwind DH, Rademakers R, Boeve BF, Boxer AL, Rosen HJ, Miller BL, Seeley WW (2019) Thalamo-cortical network hyperconnectivity in preclinical progranulin mutation carriers. Neuroimage Clin 22:101751PubMedPubMedCentralCrossRef Lee SE, Sias AC, Kosik EL, Flagan TM, Deng J, Chu SA, Brown JA, Vidovszky AA, Ramos EM, Gorno-Tempini ML, Karydas AM, Coppola G, Geschwind DH, Rademakers R, Boeve BF, Boxer AL, Rosen HJ, Miller BL, Seeley WW (2019) Thalamo-cortical network hyperconnectivity in preclinical progranulin mutation carriers. Neuroimage Clin 22:101751PubMedPubMedCentralCrossRef

go back to reference Olm CA, McMillan CT, Irwin DJ, Van Deerlin VM, Cook PA, Gee JC, Grossman M (2018) Longitudinal structural gray matter and white matter MRI changes in presymptomatic progranulin mutation carriers. Neuroimage Clin 19:497–506PubMedPubMedCentralCrossRef Olm CA, McMillan CT, Irwin DJ, Van Deerlin VM, Cook PA, Gee JC, Grossman M (2018) Longitudinal structural gray matter and white matter MRI changes in presymptomatic progranulin mutation carriers. Neuroimage Clin 19:497–506PubMedPubMedCentralCrossRef

go back to reference Dopper EG, Rombouts SA, Jiskoot LC, den Heijer T, de Graaf JR, de Koning I, Hammerschlag AR, Seelaar H, Seeley WW, Veer IM, van Buchem MA, Rizzu P, van Swieten JC (2014) Structural and functional brain connectivity in presymptomatic familial frontotemporal dementia. Neurology 83:e19-26PubMedCrossRef Dopper EG, Rombouts SA, Jiskoot LC, den Heijer T, de Graaf JR, de Koning I, Hammerschlag AR, Seelaar H, Seeley WW, Veer IM, van Buchem MA, Rizzu P, van Swieten JC (2014) Structural and functional brain connectivity in presymptomatic familial frontotemporal dementia. Neurology 83:e19-26PubMedCrossRef

go back to reference Caroppo P, Habert MO, Durrleman S, Funkiewiez A, Perlbarg V, Hahn V, Bertin H, Gaubert M, Routier A, Hannequin D, Deramecourt V, Pasquier F, Rivaud-Pechoux S, Vercelletto M, Edouart G, Valabregue R, Lejeune P, Didic M, Corvol JC, Benali H, Lehericy S, Dubois B, Colliot O, Brice A, Le Ber I (2015) Lateral temporal lobe: an early imaging marker of the presymptomatic GRN disease? J Alzheimer’s Dis JAD 47:751–759CrossRef Caroppo P, Habert MO, Durrleman S, Funkiewiez A, Perlbarg V, Hahn V, Bertin H, Gaubert M, Routier A, Hannequin D, Deramecourt V, Pasquier F, Rivaud-Pechoux S, Vercelletto M, Edouart G, Valabregue R, Lejeune P, Didic M, Corvol JC, Benali H, Lehericy S, Dubois B, Colliot O, Brice A, Le Ber I (2015) Lateral temporal lobe: an early imaging marker of the presymptomatic GRN disease? J Alzheimer’s Dis JAD 47:751–759CrossRef

go back to reference Premi E, Cauda F, Costa T, Diano M, Gazzina S, Gualeni V, Alberici A, Archetti S, Magoni M, Gasparotti R, Padovani A, Borroni B (2016) Looking for neuroimaging markers in frontotemporal lobar degeneration clinical trials: a multi-voxel pattern analysis study in granulin disease. J Alzheimer’s Dis JAD 51:249–262CrossRef Premi E, Cauda F, Costa T, Diano M, Gazzina S, Gualeni V, Alberici A, Archetti S, Magoni M, Gasparotti R, Padovani A, Borroni B (2016) Looking for neuroimaging markers in frontotemporal lobar degeneration clinical trials: a multi-voxel pattern analysis study in granulin disease. J Alzheimer’s Dis JAD 51:249–262CrossRef

go back to reference Jacova C, Hsiung GY, Tawankanjanachot I, Dinelle K, McCormick S, Gonzalez M, Lee H, Sengdy P, Bouchard-Kerr P, Baker M, Rademakers R, Sossi V, Stoessl AJ, Feldman HH, Mackenzie IR (2013) Anterior brain glucose hypometabolism predates dementia in progranulin mutation carriers. Neurology 81:1322–1331PubMedPubMedCentralCrossRef Jacova C, Hsiung GY, Tawankanjanachot I, Dinelle K, McCormick S, Gonzalez M, Lee H, Sengdy P, Bouchard-Kerr P, Baker M, Rademakers R, Sossi V, Stoessl AJ, Feldman HH, Mackenzie IR (2013) Anterior brain glucose hypometabolism predates dementia in progranulin mutation carriers. Neurology 81:1322–1331PubMedPubMedCentralCrossRef

go back to reference Premi E, Gazzina S, Bozzali M, Archetti S, Alberici A, Cercignani M, Bianchetti A, Gasparotti R, Turla M, Caltagirone C, Padovani A, Borroni B (2013) Cognitive reserve in granulin-related frontotemporal dementia: from preclinical to clinical stages. PLoS ONE 8:e74762PubMedPubMedCentralCrossRef Premi E, Gazzina S, Bozzali M, Archetti S, Alberici A, Cercignani M, Bianchetti A, Gasparotti R, Turla M, Caltagirone C, Padovani A, Borroni B (2013) Cognitive reserve in granulin-related frontotemporal dementia: from preclinical to clinical stages. PLoS ONE 8:e74762PubMedPubMedCentralCrossRef

go back to reference Milanesi E, Bonvicini C, Alberici A, Pilotto A, Cattane N, Premi E, Gazzina S, Archetti S, Gasparotti R, Cancelli V, Gennarelli M, Padovani A, Borroni B (2013) Molecular signature of disease onset in granulin mutation carriers: a gene expression analysis study. Neurobiol Aging 34:1837–1845PubMedCrossRef Milanesi E, Bonvicini C, Alberici A, Pilotto A, Cattane N, Premi E, Gazzina S, Archetti S, Gasparotti R, Cancelli V, Gennarelli M, Padovani A, Borroni B (2013) Molecular signature of disease onset in granulin mutation carriers: a gene expression analysis study. Neurobiol Aging 34:1837–1845PubMedCrossRef

go back to reference Premi E, Cauda F, Gasparotti R, Diano M, Archetti S, Padovani A, Borroni B (2014) Multimodal FMRI resting-state functional connectivity in granulin mutations: the case of fronto-parietal dementia. PLoS ONE 9:e106500PubMedPubMedCentralCrossRef Premi E, Cauda F, Gasparotti R, Diano M, Archetti S, Padovani A, Borroni B (2014) Multimodal FMRI resting-state functional connectivity in granulin mutations: the case of fronto-parietal dementia. PLoS ONE 9:e106500PubMedPubMedCentralCrossRef

go back to reference Borroni B, Alberici A, Cercignani M, Premi E, Serra L, Cerini C, Cosseddu M, Pettenati C, Turla M, Archetti S, Gasparotti R, Caltagirone C, Padovani A, Bozzali M (2012) Granulin mutation drives brain damage and reorganization from preclinical to symptomatic FTLD. Neurobiol Aging 33:2506–2520PubMedCrossRef Borroni B, Alberici A, Cercignani M, Premi E, Serra L, Cerini C, Cosseddu M, Pettenati C, Turla M, Archetti S, Gasparotti R, Caltagirone C, Padovani A, Bozzali M (2012) Granulin mutation drives brain damage and reorganization from preclinical to symptomatic FTLD. Neurobiol Aging 33:2506–2520PubMedCrossRef

go back to reference Pietroboni AM, Fumagalli GG, Ghezzi L, Fenoglio C, Cortini F, Serpente M, Cantoni C, Rotondo E, Corti P, Carecchio M, Bassi M, Bresolin N, Galbiati D, Galimberti D, Scarpini E (2011) Phenotypic heterogeneity of the GRN Asp22fs mutation in a large Italian kindred. J Alzheimer’s Dis JAD 24:253–259CrossRef Pietroboni AM, Fumagalli GG, Ghezzi L, Fenoglio C, Cortini F, Serpente M, Cantoni C, Rotondo E, Corti P, Carecchio M, Bassi M, Bresolin N, Galbiati D, Galimberti D, Scarpini E (2011) Phenotypic heterogeneity of the GRN Asp22fs mutation in a large Italian kindred. J Alzheimer’s Dis JAD 24:253–259CrossRef

go back to reference Borroni B, Alberici A, Premi E, Archetti S, Garibotto V, Agosti C, Gasparotti R, Di Luca M, Perani D, Padovani A (2008) Brain magnetic resonance imaging structural changes in a pedigree of asymptomatic progranulin mutation carriers. Rejuvenation Res 11:585–595PubMedCrossRef Borroni B, Alberici A, Premi E, Archetti S, Garibotto V, Agosti C, Gasparotti R, Di Luca M, Perani D, Padovani A (2008) Brain magnetic resonance imaging structural changes in a pedigree of asymptomatic progranulin mutation carriers. Rejuvenation Res 11:585–595PubMedCrossRef

go back to reference Wu L, Liu J, Feng X, Dong J, Qin W, Liu Y, Wang J, Lu J, Chen K, Wang Y, Jia J (2018) 11C-CFT-PET in presymptomatic FTDP-17: a potential biomarker predicting onset. J Alzheimer’s Dis JAD 61:613–618CrossRef Wu L, Liu J, Feng X, Dong J, Qin W, Liu Y, Wang J, Lu J, Chen K, Wang Y, Jia J (2018) 11C-CFT-PET in presymptomatic FTDP-17: a potential biomarker predicting onset. J Alzheimer’s Dis JAD 61:613–618CrossRef

go back to reference Domínguez-Vivero C, Wu L, Lee S, Manoochehri M, Cines S, Brickman AM, Rizvi B, Chesebro A, Gazes Y, Fallon E, Lynch T, Heidebrink JL, Paulson H, Goldman JS, Huey E, Cosentino S (2020) Structural brain changes in pre-clinical FTD MAPT mutation carriers. J Alzheimer’s Dis JAD 75:595–606CrossRef Domínguez-Vivero C, Wu L, Lee S, Manoochehri M, Cines S, Brickman AM, Rizvi B, Chesebro A, Gazes Y, Fallon E, Lynch T, Heidebrink JL, Paulson H, Goldman JS, Huey E, Cosentino S (2020) Structural brain changes in pre-clinical FTD MAPT mutation carriers. J Alzheimer’s Dis JAD 75:595–606CrossRef

go back to reference Dopper EG, Chalos V, Ghariq E, den Heijer T, Hafkemeijer A, Jiskoot LC, de Koning I, Seelaar H, van Minkelen R, van Osch MJ, Rombouts SA, van Swieten JC (2016) Cerebral blood flow in presymptomatic MAPT and GRN mutation carriers: a longitudinal arterial spin labeling study. Neuroimage Clin 12:460–465PubMedPubMedCentralCrossRef Dopper EG, Chalos V, Ghariq E, den Heijer T, Hafkemeijer A, Jiskoot LC, de Koning I, Seelaar H, van Minkelen R, van Osch MJ, Rombouts SA, van Swieten JC (2016) Cerebral blood flow in presymptomatic MAPT and GRN mutation carriers: a longitudinal arterial spin labeling study. Neuroimage Clin 12:460–465PubMedPubMedCentralCrossRef

go back to reference Chen Q, Boeve BF, Senjem M, Tosakulwong N, Lesnick TG, Brushaber D, Dheel C, Fields J, Forsberg L, Gavrilova R, Gearhart D, Graff-Radford J, Graff-Radford NR, Jack CR Jr, Jones DT, Knopman DS, Kremers WK, Lapid M, Rademakers R, Syrjanen J, Boxer AL, Rosen H, Wszolek ZK, Kantarci K (2019) Rates of lobar atrophy in asymptomatic MAPT mutation carriers. Alzheimer’s Dement (New York, N Y) 5:338–346CrossRef Chen Q, Boeve BF, Senjem M, Tosakulwong N, Lesnick TG, Brushaber D, Dheel C, Fields J, Forsberg L, Gavrilova R, Gearhart D, Graff-Radford J, Graff-Radford NR, Jack CR Jr, Jones DT, Knopman DS, Kremers WK, Lapid M, Rademakers R, Syrjanen J, Boxer AL, Rosen H, Wszolek ZK, Kantarci K (2019) Rates of lobar atrophy in asymptomatic MAPT mutation carriers. Alzheimer’s Dement (New York, N Y) 5:338–346CrossRef

go back to reference Eskildsen SF, Østergaard LR, Rodell AB, Østergaard L, Nielsen JE, Isaacs AM, Johannsen P (2009) Cortical volumes and atrophy rates in FTD-3 CHMP2B mutation carriers and related non-carriers. Neuroimage 45:713–721PubMedCrossRef Eskildsen SF, Østergaard LR, Rodell AB, Østergaard L, Nielsen JE, Isaacs AM, Johannsen P (2009) Cortical volumes and atrophy rates in FTD-3 CHMP2B mutation carriers and related non-carriers. Neuroimage 45:713–721PubMedCrossRef

go back to reference Rohrer JD, Ahsan RL, Isaacs AM, Nielsen JE, Ostergaard L, Scahill R, Warren JD, Rossor MN, Fox NC, Johannsen P (2009) Presymptomatic generalized brain atrophy in frontotemporal dementia caused by CHMP2B mutation. Dement Geriatr Cogn Disord 27:182–186PubMedCrossRef Rohrer JD, Ahsan RL, Isaacs AM, Nielsen JE, Ostergaard L, Scahill R, Warren JD, Rossor MN, Fox NC, Johannsen P (2009) Presymptomatic generalized brain atrophy in frontotemporal dementia caused by CHMP2B mutation. Dement Geriatr Cogn Disord 27:182–186PubMedCrossRef

go back to reference Lunau L, Mouridsen K, Rodell A, Ostergaard L, Nielsen JE, Isaacs A, Johannsen P (2012) Presymptomatic cerebral blood flow changes in CHMP2B mutation carriers of familial frontotemporal dementia (FTD-3), measured with MRI. BMJ Open 2:e000368PubMedPubMedCentralCrossRef Lunau L, Mouridsen K, Rodell A, Ostergaard L, Nielsen JE, Isaacs A, Johannsen P (2012) Presymptomatic cerebral blood flow changes in CHMP2B mutation carriers of familial frontotemporal dementia (FTD-3), measured with MRI. BMJ Open 2:e000368PubMedPubMedCentralCrossRef

go back to reference Wijeratne PA, Johnson EB, Eshaghi A, Aksman L, Gregory S, Johnson HJ, Poudel GR, Mohan A, Sampaio C, Georgiou-Karistianis N, Paulsen JS, Tabrizi SJ, Scahill RI, Alexander DC (2020) Robust markers and sample sizes for multicenter trials of huntington disease. Ann Neurol 87:751–762PubMedPubMedCentralCrossRef Wijeratne PA, Johnson EB, Eshaghi A, Aksman L, Gregory S, Johnson HJ, Poudel GR, Mohan A, Sampaio C, Georgiou-Karistianis N, Paulsen JS, Tabrizi SJ, Scahill RI, Alexander DC (2020) Robust markers and sample sizes for multicenter trials of huntington disease. Ann Neurol 87:751–762PubMedPubMedCentralCrossRef

go back to reference Wilkes FA, Abaryan Z, Ching CRK, Gutman BA, Madsen SK, Walterfang M, Velakoulis D, Stout JC, Chua P, Egan GF, Thompson PM, Looi JCL, Georgiou-Karistianis N (2019) Striatal morphology and neurocognitive dysfunction in Huntington disease: The IMAGE-HD study. Psychiatry Res Neuroimaging 291:1–8PubMedCrossRef Wilkes FA, Abaryan Z, Ching CRK, Gutman BA, Madsen SK, Walterfang M, Velakoulis D, Stout JC, Chua P, Egan GF, Thompson PM, Looi JCL, Georgiou-Karistianis N (2019) Striatal morphology and neurocognitive dysfunction in Huntington disease: The IMAGE-HD study. Psychiatry Res Neuroimaging 291:1–8PubMedCrossRef

go back to reference Tang X, Ross CA, Johnson H, Paulsen JS, Younes L, Albin RL, Ratnanather JT, Miller MI (2019) Regional subcortical shape analysis in premanifest Huntington’s disease. Hum Brain Mapp 40:1419–1433PubMedCrossRef Tang X, Ross CA, Johnson H, Paulsen JS, Younes L, Albin RL, Ratnanather JT, Miller MI (2019) Regional subcortical shape analysis in premanifest Huntington’s disease. Hum Brain Mapp 40:1419–1433PubMedCrossRef

go back to reference McColgan P, Gregory S, Seunarine KK, Razi A, Papoutsi M, Johnson E, Durr A, Roos RAC, Leavitt BR, Holmans P, Scahill RI, Clark CA, Rees G, Tabrizi SJ (2018) Brain regions showing white matter loss in huntington’s disease are enriched for synaptic and metabolic genes. Biol Psychiatry 83:456–465PubMedPubMedCentralCrossRef McColgan P, Gregory S, Seunarine KK, Razi A, Papoutsi M, Johnson E, Durr A, Roos RAC, Leavitt BR, Holmans P, Scahill RI, Clark CA, Rees G, Tabrizi SJ (2018) Brain regions showing white matter loss in huntington’s disease are enriched for synaptic and metabolic genes. Biol Psychiatry 83:456–465PubMedPubMedCentralCrossRef

go back to reference Castro E, Polosecki P, Rish I, Pustina D, Warner JH, Wood A, Sampaio C, Cecchi GA (2018) Baseline multimodal information predicts future motor impairment in premanifest Huntington’s disease. Neuroimage Clin 19:443–453PubMedPubMedCentralCrossRef Castro E, Polosecki P, Rish I, Pustina D, Warner JH, Wood A, Sampaio C, Cecchi GA (2018) Baseline multimodal information predicts future motor impairment in premanifest Huntington’s disease. Neuroimage Clin 19:443–453PubMedPubMedCentralCrossRef

go back to reference McColgan P, Gregory S, Razi A, Seunarine KK, Gargouri F, Durr A, Roos RA, Leavitt BR, Scahill RI, Clark CA, Tabrizi SJ, Rees G, Track On HDI, Coleman A, Decolongon J, Fan M, Petkau T, Jauffret C, Justo D, Lehericy S, Nigaud K, Valabregue R, Choonderbeek A, Hart EP, Hensman Moss DJ, Crawford H, Johnson E, Papoutsi M, Berna C, Reilmann R, Weber N, Stout J, Labuschagne I, Landwehrmeyer B, Orth M, Johnson H (2017) White matter predicts functional connectivity in premanifest Huntington’s disease. Ann Clin Transl Neurol 4:106–118PubMedPubMedCentralCrossRef McColgan P, Gregory S, Razi A, Seunarine KK, Gargouri F, Durr A, Roos RA, Leavitt BR, Scahill RI, Clark CA, Tabrizi SJ, Rees G, Track On HDI, Coleman A, Decolongon J, Fan M, Petkau T, Jauffret C, Justo D, Lehericy S, Nigaud K, Valabregue R, Choonderbeek A, Hart EP, Hensman Moss DJ, Crawford H, Johnson E, Papoutsi M, Berna C, Reilmann R, Weber N, Stout J, Labuschagne I, Landwehrmeyer B, Orth M, Johnson H (2017) White matter predicts functional connectivity in premanifest Huntington’s disease. Ann Clin Transl Neurol 4:106–118PubMedPubMedCentralCrossRef

go back to reference Ahveninen LM, Stout JC, Georgiou-Karistianis N, Lorenzetti V, Glikmann-Johnston Y (2018) Reduced amygdala volumes are related to motor and cognitive signs in Huntington’s disease: The IMAGE-HD study. Neuroimage Clin 18:881–887PubMedPubMedCentralCrossRef Ahveninen LM, Stout JC, Georgiou-Karistianis N, Lorenzetti V, Glikmann-Johnston Y (2018) Reduced amygdala volumes are related to motor and cognitive signs in Huntington’s disease: The IMAGE-HD study. Neuroimage Clin 18:881–887PubMedPubMedCentralCrossRef

go back to reference Rosas HD, Wilkens P, Salat DH, Mercaldo ND, Vangel M, Yendiki AY, Hersch SM (2018) Complex spatial and temporally defined myelin and axonal degeneration in Huntington disease. Neuroimage Clin 20:236–242PubMedPubMedCentralCrossRef Rosas HD, Wilkens P, Salat DH, Mercaldo ND, Vangel M, Yendiki AY, Hersch SM (2018) Complex spatial and temporally defined myelin and axonal degeneration in Huntington disease. Neuroimage Clin 20:236–242PubMedPubMedCentralCrossRef

go back to reference Lahr J, Minkova L, Tabrizi SJ, Stout JC, Kloppel S, Scheller E (2018) Working memory-related effective connectivity in Huntington’s disease patients. Front Neurol 9:370PubMedPubMedCentralCrossRef Lahr J, Minkova L, Tabrizi SJ, Stout JC, Kloppel S, Scheller E (2018) Working memory-related effective connectivity in Huntington’s disease patients. Front Neurol 9:370PubMedPubMedCentralCrossRef

go back to reference Gordon BA, Blazey TM, Christensen J, Dincer A, Flores S, Keefe S, Chen C, Su Y, McDade EM, Wang G, Li Y, Hassenstab J, Aschenbrenner A, Hornbeck R, Jack CR, Ances BM, Berman SB, Brosch JR, Galasko D, Gauthier S, Lah JJ, Masellis M, van Dyck CH, Mintun MA, Klein G, Ristic S, Cairns NJ, Marcus DS, Xiong C, Holtzman DM, Raichle ME, Morris JC, Bateman RJ, Benzinger TLS (2019) Tau PET in autosomal dominant Alzheimer’s disease: relationship with cognition, dementia and other biomarkers. Brain 142:1063–1076PubMedPubMedCentralCrossRef Gordon BA, Blazey TM, Christensen J, Dincer A, Flores S, Keefe S, Chen C, Su Y, McDade EM, Wang G, Li Y, Hassenstab J, Aschenbrenner A, Hornbeck R, Jack CR, Ances BM, Berman SB, Brosch JR, Galasko D, Gauthier S, Lah JJ, Masellis M, van Dyck CH, Mintun MA, Klein G, Ristic S, Cairns NJ, Marcus DS, Xiong C, Holtzman DM, Raichle ME, Morris JC, Bateman RJ, Benzinger TLS (2019) Tau PET in autosomal dominant Alzheimer’s disease: relationship with cognition, dementia and other biomarkers. Brain 142:1063–1076PubMedPubMedCentralCrossRef

go back to reference Preische O, Schultz SA, Apel A, Kuhle J, Kaeser SA, Barro C, Gräber S, Kuder-Buletta E, LaFougere C, Laske C, Vöglein J, Levin J, Masters CL, Martins R, Schofield PR, Rossor MN, Graff-Radford NR, Salloway S, Ghetti B, Ringman JM, Noble JM, Chhatwal J, Goate AM, Benzinger TLS, Morris JC, Bateman RJ, Wang G, Fagan AM, McDade EM, Gordon BA, Jucker M (2019) Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease. Nat Med 25:277–283PubMedPubMedCentralCrossRef Preische O, Schultz SA, Apel A, Kuhle J, Kaeser SA, Barro C, Gräber S, Kuder-Buletta E, LaFougere C, Laske C, Vöglein J, Levin J, Masters CL, Martins R, Schofield PR, Rossor MN, Graff-Radford NR, Salloway S, Ghetti B, Ringman JM, Noble JM, Chhatwal J, Goate AM, Benzinger TLS, Morris JC, Bateman RJ, Wang G, Fagan AM, McDade EM, Gordon BA, Jucker M (2019) Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease. Nat Med 25:277–283PubMedPubMedCentralCrossRef

go back to reference Gordon BA, Blazey TM, Su Y, Hari-Raj A, Dincer A, Flores S, Christensen J, McDade E, Wang G, Xiong C, Cairns NJ, Hassenstab J, Marcus DS, Fagan AM, Jack CR Jr, Hornbeck RC, Paumier KL, Ances BM, Berman SB, Brickman AM, Cash DM, Chhatwal JP, Correia S, Förster S, Fox NC, Graff-Radford NR, la Fougère C, Levin J, Masters CL, Rossor MN, Salloway S, Saykin AJ, Schofield PR, Thompson PM, Weiner MM, Holtzman DM, Raichle ME, Morris JC, Bateman RJ, Benzinger TLS (2018) Spatial patterns of neuroimaging biomarker change in individuals from families with autosomal dominant Alzheimer’s disease: a longitudinal study. Lancet Neurol 17:241–250PubMedPubMedCentralCrossRef Gordon BA, Blazey TM, Su Y, Hari-Raj A, Dincer A, Flores S, Christensen J, McDade E, Wang G, Xiong C, Cairns NJ, Hassenstab J, Marcus DS, Fagan AM, Jack CR Jr, Hornbeck RC, Paumier KL, Ances BM, Berman SB, Brickman AM, Cash DM, Chhatwal JP, Correia S, Förster S, Fox NC, Graff-Radford NR, la Fougère C, Levin J, Masters CL, Rossor MN, Salloway S, Saykin AJ, Schofield PR, Thompson PM, Weiner MM, Holtzman DM, Raichle ME, Morris JC, Bateman RJ, Benzinger TLS (2018) Spatial patterns of neuroimaging biomarker change in individuals from families with autosomal dominant Alzheimer’s disease: a longitudinal study. Lancet Neurol 17:241–250PubMedPubMedCentralCrossRef

go back to reference Kinnunen KM, Cash DM, Poole T, Frost C, Benzinger TLS, Ahsan RL, Leung KK, Cardoso MJ, Modat M, Malone IB, Morris JC, Bateman RJ, Marcus DS, Goate A, Salloway SP, Correia S, Sperling RA, Chhatwal JP, Mayeux RP, Brickman AM, Martins RN, Farlow MR, Ghetti B, Saykin AJ, Jack CR Jr, Schofield PR, McDade E, Weiner MW, Ringman JM, Thompson PM, Masters CL, Rowe CC, Rossor MN, Ourselin S, Fox NC (2018) Presymptomatic atrophy in autosomal dominant Alzheimer’s disease: a serial magnetic resonance imaging study. Alzheimer’s Dement J Alzheimer’s Assoc 14:43–53CrossRef Kinnunen KM, Cash DM, Poole T, Frost C, Benzinger TLS, Ahsan RL, Leung KK, Cardoso MJ, Modat M, Malone IB, Morris JC, Bateman RJ, Marcus DS, Goate A, Salloway SP, Correia S, Sperling RA, Chhatwal JP, Mayeux RP, Brickman AM, Martins RN, Farlow MR, Ghetti B, Saykin AJ, Jack CR Jr, Schofield PR, McDade E, Weiner MW, Ringman JM, Thompson PM, Masters CL, Rowe CC, Rossor MN, Ourselin S, Fox NC (2018) Presymptomatic atrophy in autosomal dominant Alzheimer’s disease: a serial magnetic resonance imaging study. Alzheimer’s Dement J Alzheimer’s Assoc 14:43–53CrossRef

go back to reference Lee S, Zimmerman ME, Narkhede A, Nasrabady SE, Tosto G, Meier IB, Benzinger TLS, Marcus DS, Fagan AM, Fox NC, Cairns NJ, Holtzman DM, Buckles V, Ghetti B, McDade E, Martins RN, Saykin AJ, Masters CL, Ringman JM, Fӧrster S, Schofield PR, Sperling RA, Johnson KA, Chhatwal JP, Salloway S, Correia S, Jack CR Jr, Weiner M, Bateman RJ, Morris JC, Mayeux R, Brickman AM (2018) White matter hyperintensities and the mediating role of cerebral amyloid angiopathy in dominantly-inherited Alzheimer’s disease. PLoS ONE 13:e0195838PubMedPubMedCentralCrossRef Lee S, Zimmerman ME, Narkhede A, Nasrabady SE, Tosto G, Meier IB, Benzinger TLS, Marcus DS, Fagan AM, Fox NC, Cairns NJ, Holtzman DM, Buckles V, Ghetti B, McDade E, Martins RN, Saykin AJ, Masters CL, Ringman JM, Fӧrster S, Schofield PR, Sperling RA, Johnson KA, Chhatwal JP, Salloway S, Correia S, Jack CR Jr, Weiner M, Bateman RJ, Morris JC, Mayeux R, Brickman AM (2018) White matter hyperintensities and the mediating role of cerebral amyloid angiopathy in dominantly-inherited Alzheimer’s disease. PLoS ONE 13:e0195838PubMedPubMedCentralCrossRef

go back to reference Sala-Llonch R, Falgàs N, Bosch B, Fernández-Villullas G, Balasa M, Antonell A, Perissinotti A, Pavía J, Campos F, Lladó A, Lomeña F, Sánchez-Valle R (2019) Regional patterns of 18F-florbetaben uptake in presenilin 1 mutation carriers. Neurobiol Aging 81:1–8PubMedCrossRef Sala-Llonch R, Falgàs N, Bosch B, Fernández-Villullas G, Balasa M, Antonell A, Perissinotti A, Pavía J, Campos F, Lladó A, Lomeña F, Sánchez-Valle R (2019) Regional patterns of 18F-florbetaben uptake in presenilin 1 mutation carriers. Neurobiol Aging 81:1–8PubMedCrossRef

go back to reference Ryan NS, Keihaninejad S, Shakespeare TJ, Lehmann M, Crutch SJ, Malone IB, Thornton JS, Mancini L, Hyare H, Yousry T, Ridgway GR, Zhang H, Modat M, Alexander DC, Rossor MN, Ourselin S, Fox NC (2013) Magnetic resonance imaging evidence for presymptomatic change in thalamus and caudate in familial Alzheimer’s disease. Brain 136:1399–1414PubMedPubMedCentralCrossRef Ryan NS, Keihaninejad S, Shakespeare TJ, Lehmann M, Crutch SJ, Malone IB, Thornton JS, Mancini L, Hyare H, Yousry T, Ridgway GR, Zhang H, Modat M, Alexander DC, Rossor MN, Ourselin S, Fox NC (2013) Magnetic resonance imaging evidence for presymptomatic change in thalamus and caudate in familial Alzheimer’s disease. Brain 136:1399–1414PubMedPubMedCentralCrossRef

go back to reference Dean DC 3rd, Hurley SA, Kecskemeti SR, O’Grady JP, Canda C, Davenport-Sis NJ, Carlsson CM, Zetterberg H, Blennow K, Asthana S, Sager MA, Johnson SC, Alexander AL, Bendlin BB (2017) Association of amyloid pathology with myelin alteration in preclinical Alzheimer disease. JAMA Neurol 74:41–49PubMedPubMedCentralCrossRef Dean DC 3rd, Hurley SA, Kecskemeti SR, O’Grady JP, Canda C, Davenport-Sis NJ, Carlsson CM, Zetterberg H, Blennow K, Asthana S, Sager MA, Johnson SC, Alexander AL, Bendlin BB (2017) Association of amyloid pathology with myelin alteration in preclinical Alzheimer disease. JAMA Neurol 74:41–49PubMedPubMedCentralCrossRef

go back to reference Donix M, Burggren AC, Suthana NA, Siddarth P, Ekstrom AD, Krupa AK, Jones M, Martin-Harris L, Ercoli LM, Miller KJ, Small GW, Bookheimer SY (2010) Family history of Alzheimer’s disease and hippocampal structure in healthy people. Am J Psychiatry 167:1399–1406PubMedPubMedCentralCrossRef Donix M, Burggren AC, Suthana NA, Siddarth P, Ekstrom AD, Krupa AK, Jones M, Martin-Harris L, Ercoli LM, Miller KJ, Small GW, Bookheimer SY (2010) Family history of Alzheimer’s disease and hippocampal structure in healthy people. Am J Psychiatry 167:1399–1406PubMedPubMedCentralCrossRef

go back to reference Verfaillie SCJ, Pichet Binette A, Vachon-Presseau E, Tabrizi S, Savard M, Bellec P, Ossenkoppele R, Scheltens P, van der Flier WM, Breitner JCS, Villeneuve S (2018) Subjective cognitive decline is associated with altered default mode network connectivity in individuals with a family history of Alzheimer’s disease. Biol Psychiatry Cogn Neurosci Neuroimaging 3:463–472PubMed Verfaillie SCJ, Pichet Binette A, Vachon-Presseau E, Tabrizi S, Savard M, Bellec P, Ossenkoppele R, Scheltens P, van der Flier WM, Breitner JCS, Villeneuve S (2018) Subjective cognitive decline is associated with altered default mode network connectivity in individuals with a family history of Alzheimer’s disease. Biol Psychiatry Cogn Neurosci Neuroimaging 3:463–472PubMed

go back to reference Liu SY, Wile DJ, Fu JF, Valerio J, Shahinfard E, McCormick S, Mabrouk R, Vafai N, McKenzie J, Neilson N, Perez-Soriano A, Arena JE, Cherkasova M, Chan P, Zhang J, Zabetian CP, Aasly JO, Wszolek ZK, McKeown MJ, Adam MJ, Ruth TJ, Schulzer M, Sossi V, Stoessl AJ (2018) The effect of LRRK2 mutations on the cholinergic system in manifest and premanifest stages of Parkinson’s disease: a cross-sectional PET study. Lancet Neurol 17:309–316PubMedPubMedCentralCrossRef Liu SY, Wile DJ, Fu JF, Valerio J, Shahinfard E, McCormick S, Mabrouk R, Vafai N, McKenzie J, Neilson N, Perez-Soriano A, Arena JE, Cherkasova M, Chan P, Zhang J, Zabetian CP, Aasly JO, Wszolek ZK, McKeown MJ, Adam MJ, Ruth TJ, Schulzer M, Sossi V, Stoessl AJ (2018) The effect of LRRK2 mutations on the cholinergic system in manifest and premanifest stages of Parkinson’s disease: a cross-sectional PET study. Lancet Neurol 17:309–316PubMedPubMedCentralCrossRef

go back to reference Vilas D, Segura B, Baggio HC, Pont-Sunyer C, Compta Y, Valldeoriola F, José Martí M, Quintana M, Bayés A, Hernández-Vara J, Calopa M, Aguilar M, Junqué C, Tolosa E (2016) Nigral and striatal connectivity alterations in asymptomatic LRRK2 mutation carriers: a magnetic resonance imaging study. Mov Disord 31:1820–1828PubMedCrossRef Vilas D, Segura B, Baggio HC, Pont-Sunyer C, Compta Y, Valldeoriola F, José Martí M, Quintana M, Bayés A, Hernández-Vara J, Calopa M, Aguilar M, Junqué C, Tolosa E (2016) Nigral and striatal connectivity alterations in asymptomatic LRRK2 mutation carriers: a magnetic resonance imaging study. Mov Disord 31:1820–1828PubMedCrossRef

go back to reference Helmich RC, Thaler A, van Nuenen BF, Gurevich T, Mirelman A, Marder KS, Bressman S, Orr-Urtreger A, Giladi N, Bloem BR, Toni I (2015) Reorganization of corticostriatal circuits in healthy G2019S LRRK2 carriers. Neurology 84:399–406PubMedPubMedCentralCrossRef Helmich RC, Thaler A, van Nuenen BF, Gurevich T, Mirelman A, Marder KS, Bressman S, Orr-Urtreger A, Giladi N, Bloem BR, Toni I (2015) Reorganization of corticostriatal circuits in healthy G2019S LRRK2 carriers. Neurology 84:399–406PubMedPubMedCentralCrossRef

go back to reference Pyatigorskaya N, Sharman M, Corvol JC, Valabregue R, Yahia-Cherif L, Poupon F, Cormier-Dequaire F, Siebner H, Klebe S, Vidailhet M, Brice A, Lehéricy S (2015) High nigral iron deposition in LRRK2 and Parkin mutation carriers using R2* relaxometry. Mov Disord 30:1077–1084PubMedCrossRef Pyatigorskaya N, Sharman M, Corvol JC, Valabregue R, Yahia-Cherif L, Poupon F, Cormier-Dequaire F, Siebner H, Klebe S, Vidailhet M, Brice A, Lehéricy S (2015) High nigral iron deposition in LRRK2 and Parkin mutation carriers using R2* relaxometry. Mov Disord 30:1077–1084PubMedCrossRef

go back to reference Thaler A, Artzi M, Mirelman A, Jacob Y, Helmich RC, van Nuenen BF, Gurevich T, Orr-Urtreger A, Marder K, Bressman S, Bloem BR, Hendler T, Giladi N, Ben Bashat D (2014) A voxel-based morphometry and diffusion tensor imaging analysis of asymptomatic Parkinson’s disease-related G2019S LRRK2 mutation carriers. Mov Disord 29:823–827PubMedCrossRef Thaler A, Artzi M, Mirelman A, Jacob Y, Helmich RC, van Nuenen BF, Gurevich T, Orr-Urtreger A, Marder K, Bressman S, Bloem BR, Hendler T, Giladi N, Ben Bashat D (2014) A voxel-based morphometry and diffusion tensor imaging analysis of asymptomatic Parkinson’s disease-related G2019S LRRK2 mutation carriers. Mov Disord 29:823–827PubMedCrossRef

go back to reference Thaler A, Mirelman A, Helmich RC, van Nuenen BF, Rosenberg-Katz K, Gurevich T, Orr-Urtreger A, Marder K, Bressman S, Bloem BR, Giladi N, Hendler T (2013) Neural correlates of executive functions in healthy G2019S LRRK2 mutation carriers. Cortex 49:2501–2511PubMedCrossRef Thaler A, Mirelman A, Helmich RC, van Nuenen BF, Rosenberg-Katz K, Gurevich T, Orr-Urtreger A, Marder K, Bressman S, Bloem BR, Giladi N, Hendler T (2013) Neural correlates of executive functions in healthy G2019S LRRK2 mutation carriers. Cortex 49:2501–2511PubMedCrossRef

go back to reference Brockmann K, Gröger A, Di Santo A, Liepelt I, Schulte C, Klose U, Maetzler W, Hauser AK, Hilker R, Gomez-Mancilla B, Berg D, Gasser T (2011) Clinical and brain imaging characteristics in leucine-rich repeat kinase 2-associated PD and asymptomatic mutation carriers. Mov Disord 26:2335–2342PubMedCrossRef Brockmann K, Gröger A, Di Santo A, Liepelt I, Schulte C, Klose U, Maetzler W, Hauser AK, Hilker R, Gomez-Mancilla B, Berg D, Gasser T (2011) Clinical and brain imaging characteristics in leucine-rich repeat kinase 2-associated PD and asymptomatic mutation carriers. Mov Disord 26:2335–2342PubMedCrossRef

go back to reference Reetz K, Tadic V, Kasten M, Brüggemann N, Schmidt A, Hagenah J, Pramstaller PP, Ramirez A, Behrens MI, Siebner HR, Klein C, Binkofski F (2010) Structural imaging in the presymptomatic stage of genetically determined parkinsonism. Neurobiol Dis 39:402–408PubMedCrossRef Reetz K, Tadic V, Kasten M, Brüggemann N, Schmidt A, Hagenah J, Pramstaller PP, Ramirez A, Behrens MI, Siebner HR, Klein C, Binkofski F (2010) Structural imaging in the presymptomatic stage of genetically determined parkinsonism. Neurobiol Dis 39:402–408PubMedCrossRef

go back to reference Anders S, Sack B, Pohl A, Münte T, Pramstaller P, Klein C, Binkofski F (2012) Compensatory premotor activity during affective face processing in subclinical carriers of a single mutant Parkin allele. Brain 135:1128–1140PubMedPubMedCentralCrossRef Anders S, Sack B, Pohl A, Münte T, Pramstaller P, Klein C, Binkofski F (2012) Compensatory premotor activity during affective face processing in subclinical carriers of a single mutant Parkin allele. Brain 135:1128–1140PubMedPubMedCentralCrossRef

go back to reference Buhmann C, Binkofski F, Klein C, Büchel C, van Eimeren T, Erdmann C, Hedrich K, Kasten M, Hagenah J, Deuschl G, Pramstaller PP, Siebner HR (2005) Motor reorganization in asymptomatic carriers of a single mutant Parkin allele: a human model for presymptomatic parkinsonism. Brain 128:2281–2290PubMedCrossRef Buhmann C, Binkofski F, Klein C, Büchel C, van Eimeren T, Erdmann C, Hedrich K, Kasten M, Hagenah J, Deuschl G, Pramstaller PP, Siebner HR (2005) Motor reorganization in asymptomatic carriers of a single mutant Parkin allele: a human model for presymptomatic parkinsonism. Brain 128:2281–2290PubMedCrossRef

go back to reference Szamosi A, Nagy H, Kéri S (2013) Delay discounting of reward and caudate nucleus volume in individuals with α-synuclein gene duplication before and after the development of Parkinson’s disease. Neurodegener Dis 11:72–78PubMedCrossRef Szamosi A, Nagy H, Kéri S (2013) Delay discounting of reward and caudate nucleus volume in individuals with α-synuclein gene duplication before and after the development of Parkinson’s disease. Neurodegener Dis 11:72–78PubMedCrossRef

go back to reference Bede P, Siah WF, McKenna MC, Li Hi Shing S (2020) Consideration of C9orf72-associated ALS-FTD as a neurodevelopmental disorder: insights from neuroimaging. J Neurol Neurosurg Psychiatry 91(11):1138PubMedCrossRef Bede P, Siah WF, McKenna MC, Li Hi Shing S (2020) Consideration of C9orf72-associated ALS-FTD as a neurodevelopmental disorder: insights from neuroimaging. J Neurol Neurosurg Psychiatry 91(11):1138PubMedCrossRef

go back to reference Finegan E, Chipika RH, Li Hi Shing S, Doherty MA, Hengeveld JC, Vajda A, Donaghy C, McLaughlin RL, Pender N, Hardiman O, Bede P (2019) The clinical and radiological profile of primary lateral sclerosis: a population-based study. J Neurol 266:2718–2733PubMedCrossRef Finegan E, Chipika RH, Li Hi Shing S, Doherty MA, Hengeveld JC, Vajda A, Donaghy C, McLaughlin RL, Pender N, Hardiman O, Bede P (2019) The clinical and radiological profile of primary lateral sclerosis: a population-based study. J Neurol 266:2718–2733PubMedCrossRef

go back to reference Finegan E, Li Hi Shing S, Siah WF, Chipika RH, Chang KM, McKenna MC, Doherty MA, Hengeveld JC, Vajda A, Donaghy C, Hutchinson S, McLaughlin RL, Hardiman O, Bede P (2020) Evolving diagnostic criteria in primary lateral sclerosis: the clinical and radiological basis of “probable PLS.” J Neurol Sci 417:117052PubMedCrossRef Finegan E, Li Hi Shing S, Siah WF, Chipika RH, Chang KM, McKenna MC, Doherty MA, Hengeveld JC, Vajda A, Donaghy C, Hutchinson S, McLaughlin RL, Hardiman O, Bede P (2020) Evolving diagnostic criteria in primary lateral sclerosis: the clinical and radiological basis of “probable PLS.” J Neurol Sci 417:117052PubMedCrossRef

go back to reference Querin G, El Mendili MM, Lenglet T, Behin A, Stojkovic T, Salachas F, Devos D, Le Forestier N, Del Mar AM, Debs R, Lacomblez L, Meninger V, Bruneteau G, Cohen-Adad J, Lehericy S, Laforet P, Blancho S, Benali H, Catala M, Li M, Marchand-Pauvert V, Hogrel JY, Bede P, Pradat PF (2019) The spinal and cerebral profile of adult spinal-muscular atrophy: a multimodal imaging study. NeuroImage Clinical 21:101618PubMedCrossRef Querin G, El Mendili MM, Lenglet T, Behin A, Stojkovic T, Salachas F, Devos D, Le Forestier N, Del Mar AM, Debs R, Lacomblez L, Meninger V, Bruneteau G, Cohen-Adad J, Lehericy S, Laforet P, Blancho S, Benali H, Catala M, Li M, Marchand-Pauvert V, Hogrel JY, Bede P, Pradat PF (2019) The spinal and cerebral profile of adult spinal-muscular atrophy: a multimodal imaging study. NeuroImage Clinical 21:101618PubMedCrossRef

go back to reference Clark MG, Smallwood Shoukry R, Huang CJ, Danielian LE, Bageac D, Floeter MK (2018) Loss of functional connectivity is an early imaging marker in primary lateral sclerosis. Amyotroph Lateral Scler Front Degener 19:562–569CrossRef Clark MG, Smallwood Shoukry R, Huang CJ, Danielian LE, Bageac D, Floeter MK (2018) Loss of functional connectivity is an early imaging marker in primary lateral sclerosis. Amyotroph Lateral Scler Front Degener 19:562–569CrossRef

go back to reference Schuster C, Elamin M, Hardiman O, Bede P (2015) Presymptomatic and longitudinal neuroimaging in neurodegeneration–from snapshots to motion picture: a systematic review. J Neurol Neurosurg Psychiatry 86:1089–1096PubMedCrossRef Schuster C, Elamin M, Hardiman O, Bede P (2015) Presymptomatic and longitudinal neuroimaging in neurodegeneration–from snapshots to motion picture: a systematic review. J Neurol Neurosurg Psychiatry 86:1089–1096PubMedCrossRef

go back to reference Schuster C, Hardiman O, Bede P (2017) Survival prediction in Amyotrophic lateral sclerosis based on MRI measures and clinical characteristics. BMC Neurol 17:73PubMedPubMedCentralCrossRef Schuster C, Hardiman O, Bede P (2017) Survival prediction in Amyotrophic lateral sclerosis based on MRI measures and clinical characteristics. BMC Neurol 17:73PubMedPubMedCentralCrossRef

go back to reference Westeneng HJ, Debray TPA, Visser AE, van Eijk RPA, Rooney JPK, Calvo A, Martin S, McDermott CJ, Thompson AG, Pinto S, Kobeleva X, Rosenbohm A, Stubendorff B, Sommer H, Middelkoop BM, Dekker AM, van Vugt J, van Rheenen W, Vajda A, Heverin M, Kazoka M, Hollinger H, Gromicho M, Korner S, Ringer TM, Rodiger A, Gunkel A, Shaw CE, Bredenoord AL, van Es MA, Corcia P, Couratier P, Weber M, Grosskreutz J, Ludolph AC, Petri S, de Carvalho M, Van Damme P, Talbot K, Turner MR, Shaw PJ, Al-Chalabi A, Chio A, Hardiman O, Moons KGM, Veldink JH, van den Berg LH (2018) Prognosis for patients with amyotrophic lateral sclerosis: development and validation of a personalised prediction model. Lancet Neurol 17:423PubMedCrossRef Westeneng HJ, Debray TPA, Visser AE, van Eijk RPA, Rooney JPK, Calvo A, Martin S, McDermott CJ, Thompson AG, Pinto S, Kobeleva X, Rosenbohm A, Stubendorff B, Sommer H, Middelkoop BM, Dekker AM, van Vugt J, van Rheenen W, Vajda A, Heverin M, Kazoka M, Hollinger H, Gromicho M, Korner S, Ringer TM, Rodiger A, Gunkel A, Shaw CE, Bredenoord AL, van Es MA, Corcia P, Couratier P, Weber M, Grosskreutz J, Ludolph AC, Petri S, de Carvalho M, Van Damme P, Talbot K, Turner MR, Shaw PJ, Al-Chalabi A, Chio A, Hardiman O, Moons KGM, Veldink JH, van den Berg LH (2018) Prognosis for patients with amyotrophic lateral sclerosis: development and validation of a personalised prediction model. Lancet Neurol 17:423PubMedCrossRef

go back to reference Grollemund V, Chat GL, Secchi-Buhour MS, Delbot F, Pradat-Peyre JF, Bede P, Pradat PF (2020) Development and validation of a 1-year survival prognosis estimation model for Amyotrophic Lateral Sclerosis using manifold learning algorithm UMAP. Sci Rep 10:13378PubMedPubMedCentralCrossRef Grollemund V, Chat GL, Secchi-Buhour MS, Delbot F, Pradat-Peyre JF, Bede P, Pradat PF (2020) Development and validation of a 1-year survival prognosis estimation model for Amyotrophic Lateral Sclerosis using manifold learning algorithm UMAP. Sci Rep 10:13378PubMedPubMedCentralCrossRef

go back to reference Grollemund V, Pradat PF, Querin G, Delbot F, Le Chat G, Pradat-Peyre JF, Bede P (2019) Machine learning in amyotrophic lateral sclerosis: achievements, pitfalls, and future directions. Front Neurosci 13:135PubMedPubMedCentralCrossRef Grollemund V, Pradat PF, Querin G, Delbot F, Le Chat G, Pradat-Peyre JF, Bede P (2019) Machine learning in amyotrophic lateral sclerosis: achievements, pitfalls, and future directions. Front Neurosci 13:135PubMedPubMedCentralCrossRef

go back to reference El Mendili MM, Querin G, Bede P, Pradat PF (2019) Spinal cord imaging in amyotrophic lateral sclerosis: historical concepts-novel techniques. Front Neurol 10:350PubMedPubMedCentralCrossRef El Mendili MM, Querin G, Bede P, Pradat PF (2019) Spinal cord imaging in amyotrophic lateral sclerosis: historical concepts-novel techniques. Front Neurol 10:350PubMedPubMedCentralCrossRef

go back to reference Querin G, El Mendili MM, Bede P, Delphine S, Lenglet T, Marchand-Pauvert V, Pradat PF (2018) Multimodal spinal cord MRI offers accurate diagnostic classification in ALS. J Neurol Neurosurg Psychiatry 89:1220–1221PubMedCrossRef Querin G, El Mendili MM, Bede P, Delphine S, Lenglet T, Marchand-Pauvert V, Pradat PF (2018) Multimodal spinal cord MRI offers accurate diagnostic classification in ALS. J Neurol Neurosurg Psychiatry 89:1220–1221PubMedCrossRef

go back to reference Schuster C, Hardiman O, Bede P (2016) Development of an automated mri-based diagnostic protocol for amyotrophic lateral sclerosis using disease-specific pathognomonic features: a quantitative disease-state classification study. PLoS ONE 11:e0167331PubMedPubMedCentralCrossRef Schuster C, Hardiman O, Bede P (2016) Development of an automated mri-based diagnostic protocol for amyotrophic lateral sclerosis using disease-specific pathognomonic features: a quantitative disease-state classification study. PLoS ONE 11:e0167331PubMedPubMedCentralCrossRef

go back to reference Bede P, Iyer PM, Finegan E, Omer T, Hardiman O (2017) Virtual brain biopsies in amyotrophic lateral sclerosis: diagnostic classification based on in vivo pathological patterns. NeuroImage Clin 15:653–658PubMedPubMedCentralCrossRef Bede P, Iyer PM, Finegan E, Omer T, Hardiman O (2017) Virtual brain biopsies in amyotrophic lateral sclerosis: diagnostic classification based on in vivo pathological patterns. NeuroImage Clin 15:653–658PubMedPubMedCentralCrossRef

go back to reference Chipika RH, Finegan E, Li Hi Shing S, Hardiman O, Bede P (2019) Tracking a fast-moving disease: longitudinal markers, monitoring, and clinical trial endpoints in ALS. Front Neurol 10:229PubMedPubMedCentralCrossRef Chipika RH, Finegan E, Li Hi Shing S, Hardiman O, Bede P (2019) Tracking a fast-moving disease: longitudinal markers, monitoring, and clinical trial endpoints in ALS. Front Neurol 10:229PubMedPubMedCentralCrossRef