Clinical and volumetric changes with increasing functional impairment in familial frontotemporal lobar degeneration
Nicholas T Olney, Elise Ong, Sheng-Yang M Goh, Lynn Bajorek, Reilly Dever, Adam M Staffaroni, Yann Cobigo, Meredith Bock, Kevin Chiang, Peter Ljubenkov, John Kornak, Hilary W Heuer, Ping Wang, Katya Rascovsky, Amelia Wolf, Brian Appleby, Jessica Bove, Yvette Bordelon, Patrick Brannelly, Danielle Brushaber, Christine Caso, Giovanni Coppola, Bradford C Dickerson, Susan Dickinson, Kimiko Domoto-Reilly, Kelly Faber, Jessica Ferrall, Julie Fields, Ann Fishman, Jamie Fong, Tatiana Foroud, Leah K Forsberg, Debra J Gearhart, Behnaz Ghazanfari, Nupur Ghoshal, Jill Goldman, Jonathan Graff-Radford, Neill R Graff-Radford, Ian Grant, Murray Grossman, Dana Haley, Gingyuek Hsiung, Edward D Huey, David J Irwin, David T Jones, Kejal Kantarci, Anna M Karydas, Daniel Kaufer, Diana Kerwin, David S Knopman, Joel H Kramer, Ruth Kraft, Walter Kremers, Walter Kukull, Maria I Lapid, Irene Litvan, Ian R Mackenzie, Miranda Maldonado, Masood Manoochehri, Scott M McGinnis, Emily C McKinley, Mario F Mendez, Bruce L Miller, Chiadi Onyike, Alex Pantelyat, Rodney Pearlman, Len Petrucelli, Madeleine Potter, Rosa Rademakers, Eliana M Ramos, Katherine P Rankin, Erik D Roberson, Emily Rogalski, Pheth Sengdy, Leslie M Shaw, Jeremy Syrjanen, M Carmela Tartaglia, Nadine Tatton, Joanne Taylor, Arthur Toga, John Q Trojanowski, Sandra Weintraub, Bonnie Wong, Zbigniew Wszolek, Adam L Boxer, Brad F Boeve, Howard J Rosen, ARTFL and LEFFTDS consortia, Nicholas T Olney, Elise Ong, Sheng-Yang M Goh, Lynn Bajorek, Reilly Dever, Adam M Staffaroni, Yann Cobigo, Meredith Bock, Kevin Chiang, Peter Ljubenkov, John Kornak, Hilary W Heuer, Ping Wang, Katya Rascovsky, Amelia Wolf, Brian Appleby, Jessica Bove, Yvette Bordelon, Patrick Brannelly, Danielle Brushaber, Christine Caso, Giovanni Coppola, Bradford C Dickerson, Susan Dickinson, Kimiko Domoto-Reilly, Kelly Faber, Jessica Ferrall, Julie Fields, Ann Fishman, Jamie Fong, Tatiana Foroud, Leah K Forsberg, Debra J Gearhart, Behnaz Ghazanfari, Nupur Ghoshal, Jill Goldman, Jonathan Graff-Radford, Neill R Graff-Radford, Ian Grant, Murray Grossman, Dana Haley, Gingyuek Hsiung, Edward D Huey, David J Irwin, David T Jones, Kejal Kantarci, Anna M Karydas, Daniel Kaufer, Diana Kerwin, David S Knopman, Joel H Kramer, Ruth Kraft, Walter Kremers, Walter Kukull, Maria I Lapid, Irene Litvan, Ian R Mackenzie, Miranda Maldonado, Masood Manoochehri, Scott M McGinnis, Emily C McKinley, Mario F Mendez, Bruce L Miller, Chiadi Onyike, Alex Pantelyat, Rodney Pearlman, Len Petrucelli, Madeleine Potter, Rosa Rademakers, Eliana M Ramos, Katherine P Rankin, Erik D Roberson, Emily Rogalski, Pheth Sengdy, Leslie M Shaw, Jeremy Syrjanen, M Carmela Tartaglia, Nadine Tatton, Joanne Taylor, Arthur Toga, John Q Trojanowski, Sandra Weintraub, Bonnie Wong, Zbigniew Wszolek, Adam L Boxer, Brad F Boeve, Howard J Rosen, ARTFL and LEFFTDS consortia
Abstract
Introduction: The Advancing Research and Treatment in Frontotemporal Lobar Degeneration and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects longitudinal studies were designed to describe the natural history of familial-frontotemporal lobar degeneration due to autosomal dominant mutations.
Methods: We examined cognitive performance, behavioral ratings, and brain volumes from the first time point in 320 MAPT, GRN, and C9orf72 family members, including 102 non-mutation carriers, 103 asymptomatic carriers, 43 mildly/questionably symptomatic carriers, and 72 carriers with dementia.
Results: Asymptomatic carriers showed similar scores on all clinical measures compared with noncarriers but reduced frontal and temporal volumes. Those with mild/questionable impairment showed decreased verbal recall, fluency, and Trail Making Test performance and impaired mood and self-monitoring. Dementia was associated with impairment in all measures. All MAPT carriers with dementia showed temporal atrophy, but otherwise, there was no single cognitive test or brain region that was abnormal in all subjects.
Discussion: Imaging changes appear to precede clinical changes in familial-frontotemporal lobar degeneration, but specific early clinical and imaging changes vary across individuals.
Keywords: C9ORF72; Familial; Frontotemporal lobar degeneration; GRN; Genetic; MAPT.
© 2019 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.
Figures
References
- Deleon J, Miller BL. Frontotemporal dementia. Handb Clin Neurol 2018;148:409–30.
- Tsai RM, Boxer AL. Therapy and clinical trials in frontotemporal dementia: past, present, and future. J Neurochem 2016;138:211–21.
- Rabinovici GD, Miller BL. Frontotemporal lobar degeneration: epidemiology, pathophysiology, diagnosis and management. CNS Drugs 2010;24:375–98.
- Rademakers R, Neumann M, Mackenzie IR. Advances in understanding the molecular basis of frontotemporal dementia. Nat Rev Neurol 2012;8:423–34.
- Weintraub S, Besser L, Dodge HH, Teylan M, Ferris S, Goldstein FC, et al. Version 3 of the Alzheimer Disease Centers’ Neuropsychological Test Battery in the Uniform Data Set (UDS). Alzheimer Dis Assoc Disord 2018;32:10–7.
- Delis DC, Kramer JH, Kaplan E, Ober BA. California Verbal Learning Test. 2nd ed. San Antonio, TX: The Psychological Corporation; 2000.
- Kaufer DI, Cummings JL, Ketchel P, Smith V, MacMillan A, Shelley T, et al. Validation of the NPI-Q, a brief clinical form of the Neuropsychiatric Inventory. J Neuropsychiatry Clin Neurosci 2000; 12:233–9.
- Anderson LR. Test-retest reliability of the revised Self-monitoring scale over a two-year period. Psychol Rep 1991;68:1057–8.
- Carver CS, White TL. Behavioral inhibition, behavioral activation, and affective responses to impending reward and punishment. J Personal Social Psychol 1994;67:319–33.
- Yesavage JA, Brink TL, Rolse TL, Lum O, Huang V, Adey M, et al. Development and validity of a geriatric depression scale: a preliminary report. J Psychiatr Res 1983;17:37–49.
- Movement Disorder Society Task Force on Rating Scales for Parkinson’s Disease. The Unified Parkinson’s Disease Rating Scale (UPDRS): status and recommendations. Mov Disord 2003; 18:738–50.
- Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules [see comments]. Neurology 1993;43:2412–4.
- Knopman DS, Weintraub S, Pankratz VS. Language and behavior domains enhance the value of the clinical dementia rating scale. Alzheimers Dement 2011;7:293–9.
- Golbe LI, Ohman-Strickland PA. A clinical rating scale for progressive supranuclear palsy. Brain 2007;130:1552–65.
- Binney RJ, Pankov A, Marx G, He X, McKenna F, Staffaroni AM, et al. Data-driven regions of interest for longitudinal change in three variants of frontotemporal lobar degeneration. Brain Behav 2017; 7:e00675.
- Ossenkoppele R, Cohn-Sheehy BI, La Joie R, Vogel JW, Moller C, Lehmann M, et al. Atrophy patterns in early clinical stages across distinct phenotypes of Alzheimer’s disease. Hum Brain Mapp 2015; 36:4421–37.
- Staffaroni AM, Ljubenkov PA, Kornak J, Cobigo Y, Datta S, Marx G, et al. Longitudinal multimodal imaging and clinical endpoints for frontotemporal dementia clinical trials. Brain 2019;142:443–59.
- Desikan RS, Segonne F, Fischl B, Quinn BT, Dickerson BC, Blacker D, et al. An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage 2006;31:968–80.
- Fonov V, Evans AC, Botteron K, Almli CR, McKinstry RC, Collins DL, et al. Unbiased average age-appropriate atlases for pediatric studies. Neuroimage 2011;54:313–27.
- Kornak J, Fields J, Kremers W, Farmer S, Heuer HW, Forsberg L, et al. Nonlinear Z-score modeling for improved detection of cognitive abnormality. Alzheimers Dement (Amst) 2019;11 10.1016/j.dadm.2019.08.003..In press.
- Dopper EG, Rombouts SA, Jiskoot LC, den Heijer T, de Graaf JR, de Koning I, et al. Structural and functional brain connectivity in presymptomatic familial frontotemporal dementia. Neurology 2014; 83:e19–26.
- Rohrer JD, Nicholas JM, Cash DM, van Swieten J, Dopper E, Jiskoot L, et al. Presymptomatic cognitive and neuroanatomical changes in genetic frontotemporal dementia in the Genetic Frontotemporal dementia Initiative (GENFI) study: a cross-sectional analysis. Lancet Neurol 2015;14:253–62.
- Meeter LH, Kaat LD, Rohrer JD, van Swieten JC. Imaging and fluid biomarkers in frontotemporal dementia. Nat Rev Neurol 2017; 13:406–19.
- Whitwell JL, Weigand SD, Boeve BF, Senjem ML, Gunter JL, DeJesus-Hernandez M, et al. Neuroimaging signatures of frontotemporal dementia genetics: C9ORF72, tau, progranulin and sporadics. Brain 2012;135:794–806.
- Staffaroni AM, Cobigo Y, Goh SM, Kornak J, Bajorek L, Chiang K, et al. Individualized atrophy scores predict dementia onset in familial frontotemporal lobar degeneration. Alzheimers Dement 2019. 10.1016/j.jalz.2019.04.007.
Source: PubMed