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Longitudinal evaluation of familial frontotemporal dementia subjects (LEFFTDS): Subject characteristics, aims, and methodology
Source: Alzheimer's & Dementia 2015 Jul;11(7):318-319.
Author: Bradley Boeve, Bradley Boeve, Howard J. Rosen, Adam L. Boxer, Brad Dickerson, Howard Feldman, Nupur Ghoshal, Jill Goldman, Neill Graff-Radford, Murray Grossman, Ging-Yuek Robin Hsiung, Edward D. Huey, David J. Irwin, Clifford R. Jack Jr., Kejal Kantarci, David S. Knopman, John Kornak, Ian Mackenzie, Bruce L. Miller, Leonard Petrucelli, Rosa Rademakers, Leslie M. Shaw, Arthur W. Toga, John Q. Trojanowski, Zbigniew Wszolek
Abstract:
Background Future clinical trials involving putative disease-modifying therapies in familial frontotemporal lobar degeneration (f-FTLD) will require natural history data on the clinical, neuropsychological, neuroimaging and biofluid findings in presymptomatic (presym) and symptomatic (symp) mutation carriers. Methods As part of the Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) protocol (U01 AG045390), investigators at 8 centers in North America pooled data and developed strategies for evaluating subjects in kindreds with mutations in microtubule associated protein tau (MAPT), progranulin (GRN), or chromosome 9 open reading frame 72 (C9orf72) genes. Results There are 306 known kindreds with 835 total subjects (including >295 mutation carriers) already identified, and the median (±SD) age of onset across all genetic groups is 55±11 years. Characteristics for each genetic group are as follows: MAPT – 45 kindreds, 223 subjects (including 50 symp and >36 asymp mutation carriers), median age 49±10 years; GRN – 81 kindreds, 335 subjects (including 55 symp and >27 asymp mutation carriers), median age 61±12 years; and C9orf72– 180 kindreds, 277 subjects (including 99 symp and >28 asymp mutation carriers), median age 55±11 years. The protocol involves periodic comprehensive clinical and neuropsychological assessments from 2015 to 2019 in 300 subjects, as well as brain MRI and biofluid sampling (eg, DNA, plasma, mRNA and CSF), to address several key aims: 1) to model the rates of decline in traditional measures of clinical (neuropsychological and behavioral composites) function and cortical volume on structural MRI in the symptomatic phase, 2) to model the rates of decline is the same measures in the asymptomatic phase, 3) to assess the value of novel imaging and clinical measures for characterizing asymptomatic f-FTLD subjects, and identify factors predicting clinical rates of progression in each group, and 4) to identify genetic and biofluid factors that modify rates of clinical and neuroimaging decline in the asymptomatic and symptomatic phases of f-FTLD. Conclusions The clinical, neuropsychological and biomarker data, which will be available to interested investigators worldwide, should facilitate planning for upcoming disease-modifying therapeutic trials in f-FTLD.
Source: Alzheimer's & Dementia 2015 Jul;11(7):318-319.
Author: Bradley Boeve, Bradley Boeve, Howard J. Rosen, Adam L. Boxer, Brad Dickerson, Howard Feldman, Nupur Ghoshal, Jill Goldman, Neill Graff-Radford, Murray Grossman, Ging-Yuek Robin Hsiung, Edward D. Huey, David J. Irwin, Clifford R. Jack Jr., Kejal Kantarci, David S. Knopman, John Kornak, Ian Mackenzie, Bruce L. Miller, Leonard Petrucelli, Rosa Rademakers, Leslie M. Shaw, Arthur W. Toga, John Q. Trojanowski, Zbigniew Wszolek
Abstract:
Background Future clinical trials involving putative disease-modifying therapies in familial frontotemporal lobar degeneration (f-FTLD) will require natural history data on the clinical, neuropsychological, neuroimaging and biofluid findings in presymptomatic (presym) and symptomatic (symp) mutation carriers. Methods As part of the Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) protocol (U01 AG045390), investigators at 8 centers in North America pooled data and developed strategies for evaluating subjects in kindreds with mutations in microtubule associated protein tau (MAPT), progranulin (GRN), or chromosome 9 open reading frame 72 (C9orf72) genes. Results There are 306 known kindreds with 835 total subjects (including >295 mutation carriers) already identified, and the median (±SD) age of onset across all genetic groups is 55±11 years. Characteristics for each genetic group are as follows: MAPT – 45 kindreds, 223 subjects (including 50 symp and >36 asymp mutation carriers), median age 49±10 years; GRN – 81 kindreds, 335 subjects (including 55 symp and >27 asymp mutation carriers), median age 61±12 years; and C9orf72– 180 kindreds, 277 subjects (including 99 symp and >28 asymp mutation carriers), median age 55±11 years. The protocol involves periodic comprehensive clinical and neuropsychological assessments from 2015 to 2019 in 300 subjects, as well as brain MRI and biofluid sampling (eg, DNA, plasma, mRNA and CSF), to address several key aims: 1) to model the rates of decline in traditional measures of clinical (neuropsychological and behavioral composites) function and cortical volume on structural MRI in the symptomatic phase, 2) to model the rates of decline is the same measures in the asymptomatic phase, 3) to assess the value of novel imaging and clinical measures for characterizing asymptomatic f-FTLD subjects, and identify factors predicting clinical rates of progression in each group, and 4) to identify genetic and biofluid factors that modify rates of clinical and neuroimaging decline in the asymptomatic and symptomatic phases of f-FTLD. Conclusions The clinical, neuropsychological and biomarker data, which will be available to interested investigators worldwide, should facilitate planning for upcoming disease-modifying therapeutic trials in f-FTLD.