Abstract
Around one-third of frontotemporal dementia (FTD) is autosomal dominant with the major genetic causes being mutations in MAPT, GRN and C9orf72. Studying familial forms of FTD can provide a window into the earliest stages of the illness, many years before symptoms start. Large cohort studies have been set up in recent years to better understand this presymptomatic phase, including the Genetic FTD Initiative (GENFI) and the Advancing Research and Treatment for Frontotemporal Lobar Degeneration and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (ARTFL/LEFFTDS) studies. Whilst these studies have focused on the investigation of a variety of aspects of genetic FTD, from understanding the molecular pathogenesis to developing biomarkers, they also have a common goal: finding a way to prevent FTD. Researchers from these cohort studies have therefore come together to form the FTD Prevention Initiative (FPI), which has the overarching aim of promoting clinical trials of new therapies to prevent FTD through creating an international database of participants eligible for trials and uniform standards for conducting such trials. This chapter outlines the work of the FPI so far and its future goals over the next few years.
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References
Bateman RJ, Benzinger TL, Berry S, Clifford DB, Duggan C, Fagan AM et al (2017) DIAN-TU pharma consortium for the dominantly inherited Alzheimer network. The DIAN-TU Next Generation Alzheimer’s prevention trial: Adaptive design and disease progression model. Alzheimers Dement 13(1):8–19
Boxer AL, Gold M, Feldman H, Boeve BF, Dickinson SL, Fillit H et al (2020) New directions in clinical trials for frontotemporal lobar degeneration: methods and outcome measures. Alzheimers Dement 16(1):131–143
Chen Q, Boeve BF, Senjem M, Tosakulwong N, Lesnick T, Brushaber D et al (2020) Trajectory of lobar atrophy in asymptomatic and symptomatic GRN mutation carriers: a longitudinal MRI study Neurobiol Aging 88:42–50
Chen Q, Boeve BF, Senjem M, Tosakulwong N, Lesnick TG, Brushaber D et al (2019) Rates of lobar atrophy in asymptomatic MAPT mutation carriers. Alzheimers Dement (N Y) 5:338–346
Coyle-Gilchrist IT, Dick KM, Patterson K, Vázquez RodrÃquez P, Wehmann E, Wilcox A et al (2016) Prevalence, characteristics, and survival of frontotemporal lobar degeneration syndromes. Neurology 86(18):1736–1743
Galimberti D, Fumagalli GG, Fenoglio C, Cioffi SMG, Arighi A, Serpente M et al (2018) Genetic FTD Initiative (GENFI) Progranulin plasma levels predict the presence of GRN mutations in asymptomatic subjects and do not correlate with brain atrophy: results from the GENFI study. Neurobiol Aging 62:245.e9–245.e12
Greaves CV, Rohrer JD (2019) An update on genetic frontotemporal dementia. J Neurol 266(8):2075–2086
Heller C, Foiani MS, Moore K, Convery R, Bocchetta M, Neason M et al (2020 Mar) Plasma glial fibrillary acidic protein is raised in progranulin-associated frontotemporal dementia. J Neurol Neurosurg Psychiatry 91(3):263–270
Jiskoot LC, Bocchetta M, Nicholas JM, Cash DM, Thomas D, Modat M et al (2018) Presymptomatic white matter integrity loss in familial frontotemporal dementia in the GENFI cohort: a cross-sectional diffusion tensor imaging study. Ann Clin Transl Neurol 5(9):1025–1036
Meeter LH, Dopper EG, Jiskoot LC, Sanchez-Valle R, Graff C, Benussi L et al (2016) Neurofilament light chain: a biomarker for genetic frontotemporal dementia. Ann Clin Transl Neurol 3(8):623–636
Meeter LHH, Gendron TF, Sias AC, Jiskoot LC, Russo SP, Donker Kaat L et al (2018) Poly(GP), neurofilament and grey matter deficits in C9orf72 expansion carriers. Ann Clin Transl Neurol 5(5):583–597
Miyagawa T, Brushaber D, Syrjanen J, Kremers W, Fields J, Forsberg LK et al (2020) Use of the CDR® plus NACC FTLD in mild FTLD: data from the ARTFL/LEFFTDS consortium. Alzheimers Dement 16(1):79–90
Moore KM, Nicholas J, Grossman M, McMillan CT, Irwin DJ, Massimo L et al (2020) Age at symptom onset and death and disease duration in genetic frontotemporal dementia: an international retrospective cohort study. Lancet Neurol 19(2):145–156
Olney NT, Ong E, Goh SM, Bajorek L, Dever R, Staffaroni AM et al (2020) Clinical and volumetric changes with increasing functional impairment in familial frontotemporal lobar degeneration. Alzheimers Dement 16(1):49–59
Onyike CU, Diehl-Schmid J (2013) The epidemiology of frontotemporal dementia. Int Rev Psychiatry 25(2):130–137
Quintana M, Shrader J, Slota C, Joe G, McKew JC, Fitzgerald M et al (2019) Bayesian model of disease progression in GNE myopathy. Stat Med 38(8):1459–1474
Rohrer JD, Nicholas JM, Cash DM, van Swieten J, Dopper E, Jiskoot L et al (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(3):253–262
Rohrer JD, Warren JD, Fox NC, Rossor MN (2013) Presymptomatic studies in genetic frontotemporal dementia. Rev Neurol (Paris) 169(10):820–824
Rosen HJ, Boeve BF, Boxer AL (2020) Tracking disease progression in familial and sporadic frontotemporal lobar degeneration: recent findings from ARTFL and LEFFTDS. Alzheimers Dement 16(1):71–78
Staffaroni AM, Bajorek L, Casaletto KB, Cobigo Y, Goh SM, Wolf A et al (2020 Jan) Assessment of executive function declines in presymptomatic and mildly symptomatic familial frontotemporal dementia: NIH-EXAMINER as a potential clinical trial endpoint. Alzheimers Dement 16(1):11–21
Sudre CH, Bocchetta M, Heller C, Convery R, Neason M, Moore KM et al (2019) White matter hyperintensities in progranulin-associated frontotemporal dementia: a longitudinal GENFI study. Neuroimage Clin 24:102077
Tsai RM, Bejanin A, Lesman-Segev O, LaJoie R, Visani A, Bourakova V et al (2019) 18F-flortaucipir (AV-1451) tau PET in frontotemporal dementia syndromes. Alzheimers Res Ther 11(1):13
van der Ende EL, Meeter LH, Poos JM, Panman JL, Jiskoot LC, Dopper EGP et al (2019 Dec) Serum neurofilament light chain in genetic frontotemporal dementia: a longitudinal, multicentre cohort study. Lancet Neurol 18(12):1103–1111
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Rohrer, J.D., Boxer, A.L. (2021). The Frontotemporal Dementia Prevention Initiative: Linking Together Genetic Frontotemporal Dementia Cohort Studies. In: Ghetti, B., Buratti, E., Boeve, B., Rademakers, R. (eds) Frontotemporal Dementias . Advances in Experimental Medicine and Biology, vol 1281. Springer, Cham. https://doi.org/10.1007/978-3-030-51140-1_8
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