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1. Comparison of sporadic and familial behavioral variant frontotemporal dementia (FTD) in a North American cohort

Author

Heuer, Hilary W, Wang, P, Rascovsky, K, Wolf, A, Appleby, B, Bove, J, Bordelon, Y, Brannelly, P, Brushaber, DE, Caso, C, Coppola, G, Dickerson, B, Dickinson, S, Domoto‐Reilly, K, Faber, K, Ferrall, J, Fields, J, Fishman, A, Fong, J, Foroud, T, Forsberg, LK, Gearhart, D, Ghazanfari, B, Ghoshal, N, Goldman, J, Graff‐Radford, J, Graff‐Radford, N, Grant, I, Grossman, M, Haley, D, Hsiung, G‐Y, Huey, E, Irwin, D, Jones, D, Kantarci, K, Karydas, A, Kaufer, D, Kerwin, D, Knopman, D, Kornak, J, Kramer, JH, Kraft, R, Kremers, WK, Kukull, W, Litvan, I, Ljubenkov, P, Mackenzie, IR, Maldonado, M, Manoochehri, M, McGinnis, S, McKinley, E, Mendez, MF, Miller, BL, Onyike, C, Pantelyat, A, Pearlman, R, Petrucelli, L, Potter, M, Rademakers, R, Ramos, EM, Rankin, KP, Roberson, ED, Rogalski, E, Sengdy, P, Shaw, L, Syrjanen, J, Tartaglia, MC, Tatton, N, Taylor, J, Toga, A, Trojanowski, J, Weintraub, S, Wong, B, Wszolek, Z, Boeve, BF, Rosen, HJ, Boxer, AL, and consortia, on behalf of the ARTFL and LEFFTDS

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Acquired Cognitive Impairment, Frontotemporal Dementia (FTD), Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, Alzheimer's Disease Related Dementias (ADRD), Behavioral and Social Science, Clinical Research, Rare Diseases, Dementia, Brain Disorders, Aging, Genetics, Neurological, Age Factors, Aged, Brain, C9orf72 Protein, Female, Frontotemporal Dementia, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Mutation, Neuropsychological Tests, North America, Progranulins, tau Proteins, bvFTD, C9orf72, clinical trials, frontotemporal dementia, genetics, GRN, MAPT, ARTFL and LEFFTDS consortia, Geriatrics, Clinical sciences, Biological psychology
Abstract

IntroductionBehavioral variant frontotemporal dementia (bvFTD) may present sporadically or due to an autosomal dominant mutation. Characterization of both forms will improve understanding of the generalizability of assessments and treatments.MethodsA total of 135 sporadic (s-bvFTD; mean age 63.3 years; 34% female) and 99 familial (f-bvFTD; mean age 59.9; 48% female) bvFTD participants were identified. f-bvFTD cases included 43 with known or presumed chromosome 9 open reading frame 72 (C9orf72) gene expansions, 28 with known or presumed microtubule-associated protein tau (MAPT) mutations, 14 with known progranulin (GRN) mutations, and 14 with a strong family history of FTD but no identified mutation.ResultsParticipants with f-bvFTD were younger and had earlier age at onset. s-bvFTD had higher total Neuropsychiatric Inventory Questionnaire (NPI-Q) scores due to more frequent endorsement of depression and irritability.Discussionf-bvFTD and s-bvFTD cases are clinically similar, suggesting the generalizability of novel biomarkers, therapies, and clinical tools developed in either form to the other.

Published
2020

2. Active lifestyles moderate clinical outcomes in autosomal dominant frontotemporal degeneration

Author

Casaletto, KB, Staffaroni, AM, Wolf, A, Appleby, B, Brushaber, D, Coppola, G, Dickerson, B, Domoto‐Reilly, K, Elahi, FM, Fields, J, Fong, JC, Forsberg, L, Ghoshal, N, Graff‐Radford, N, Grossman, M, Heuer, HW, Hsiung, G‐Y, Huey, ED, Irwin, D, Kantarci, K, Kaufer, D, Kerwin, D, Knopman, D, Kornak, J, Kramer, JH, Litvan, I, Mackenzie, IR, Mendez, M, Miller, B, Rademakers, R, Ramos, EM, Rascovsky, K, Roberson, ED, Syrjanen, JA, Tartaglia, MC, Weintraub, S, Boeve, B, Boxer, AL, Rosen, H, Yaffe, K, and Study, the ARTFL LEFFTDS

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Psychology, Basic Behavioral and Social Science, Rare Diseases, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aging, Neurodegenerative, Clinical Research, Brain Disorders, Prevention, Frontotemporal Dementia (FTD), Behavioral and Social Science, Biomedical Imaging, Alzheimer's Disease Related Dementias (ADRD), Alzheimer's Disease, Neurosciences, Acquired Cognitive Impairment, Dementia, Neurological, Aged, Atrophy, Cognition, Exercise, Female, Frontotemporal Lobar Degeneration, Humans, Leisure Activities, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, cognitive activity, cognitive reserve, exercise, frontotemporal dementia, physical activity, ARTFL/LEFFTDS Study, Clinical Sciences, Geriatrics, Clinical sciences, Biological psychology
Abstract

IntroductionLeisure activities impact brain aging and may be prevention targets. We characterized how physical and cognitive activities relate to brain health for the first time in autosomal dominant frontotemporal lobar degeneration (FTLD).MethodsA total of 105 mutation carriers (C9orf72/MAPT/GRN) and 69 non-carriers reported current physical and cognitive activities at baseline, and completed longitudinal neurobehavioral assessments and brain magnetic resonance imaging (MRI) scans.ResultsGreater physical and cognitive activities were each associated with an estimated >55% slower clinical decline per year among dominant gene carriers. There was also an interaction between leisure activities and frontotemporal atrophy on cognition in mutation carriers. High-activity carriers with frontotemporal atrophy (-1 standard deviation/year) demonstrated >two-fold better cognitive performances per year compared to their less active peers with comparable atrophy rates.DiscussionActive lifestyles were associated with less functional decline and moderated brain-to-behavior relationships longitudinally. More active carriers "outperformed" brain volume, commensurate with a cognitive reserve hypothesis. Lifestyle may confer clinical resilience, even in autosomal dominant FTLD.

Published
2020

3. Active lifestyles moderate clinical outcomes in autosomal dominant frontotemporal degeneration.

Author

Casaletto, KB, Staffaroni, AM, Wolf, A, Appleby, B, Brushaber, D, Coppola, G, Dickerson, B, Domoto-Reilly, K, Elahi, FM, Fields, J, Fong, JC, Forsberg, L, Ghoshal, N, Graff-Radford, N, Grossman, M, Heuer, HW, Hsiung, G-Y, Huey, ED, Irwin, D, Kantarci, K, Kaufer, D, Kerwin, D, Knopman, D, Kornak, J, Kramer, JH, Litvan, I, Mackenzie, IR, Mendez, M, Miller, B, Rademakers, R, Ramos, EM, Rascovsky, K, Roberson, ED, Syrjanen, JA, Tartaglia, MC, Weintraub, S, Boeve, B, Boxer, AL, Rosen, H, Yaffe, K, and ARTFL/LEFFTDS Study

Subjects
ARTFL/LEFFTDS Study, Humans, Atrophy, Magnetic Resonance Imaging, Exercise, Longitudinal Studies, Cognition, Neuropsychological Tests, Leisure Activities, Aged, Middle Aged, Female, Male, Frontotemporal Lobar Degeneration, cognitive activity, cognitive reserve, exercise, frontotemporal dementia, physical activity, Acquired Cognitive Impairment, Neurodegenerative, Brain Disorders, Alzheimer's Disease Related Dementias (ADRD), Prevention, Aging, Biomedical Imaging, Rare Diseases, Clinical Research, Dementia, Frontotemporal Dementia (FTD), Behavioral and Social Science, Neurosciences, Alzheimer's Disease, Basic Behavioral and Social Science, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurological, Geriatrics, Clinical Sciences
Abstract

IntroductionLeisure activities impact brain aging and may be prevention targets. We characterized how physical and cognitive activities relate to brain health for the first time in autosomal dominant frontotemporal lobar degeneration (FTLD).MethodsA total of 105 mutation carriers (C9orf72/MAPT/GRN) and 69 non-carriers reported current physical and cognitive activities at baseline, and completed longitudinal neurobehavioral assessments and brain magnetic resonance imaging (MRI) scans.ResultsGreater physical and cognitive activities were each associated with an estimated >55% slower clinical decline per year among dominant gene carriers. There was also an interaction between leisure activities and frontotemporal atrophy on cognition in mutation carriers. High-activity carriers with frontotemporal atrophy (-1 standard deviation/year) demonstrated >two-fold better cognitive performances per year compared to their less active peers with comparable atrophy rates.DiscussionActive lifestyles were associated with less functional decline and moderated brain-to-behavior relationships longitudinally. More active carriers "outperformed" brain volume, commensurate with a cognitive reserve hypothesis. Lifestyle may confer clinical resilience, even in autosomal dominant FTLD.

Published
2020

4. Comparison of sporadic and familial behavioral variant frontotemporal dementia (FTD) in a North American cohort.

Author

Heuer, Hilary W, Wang, P, Rascovsky, K, Wolf, A, Appleby, B, Bove, J, Bordelon, Y, Brannelly, P, Brushaber, DE, Caso, C, Coppola, G, Dickerson, B, Dickinson, S, Domoto-Reilly, K, Faber, K, Ferrall, J, Fields, J, Fishman, A, Fong, J, Foroud, T, Forsberg, LK, Gearhart, D, Ghazanfari, B, Ghoshal, N, Goldman, J, Graff-Radford, J, Graff-Radford, N, Grant, I, Grossman, M, Haley, D, Hsiung, G-Y, Huey, E, Irwin, D, Jones, D, Kantarci, K, Karydas, A, Kaufer, D, Kerwin, D, Knopman, D, Kornak, J, Kramer, JH, Kraft, R, Kremers, WK, Kukull, W, Litvan, I, Ljubenkov, P, Mackenzie, IR, Maldonado, M, Manoochehri, M, McGinnis, S, McKinley, E, Mendez, MF, Miller, BL, Onyike, C, Pantelyat, A, Pearlman, R, Petrucelli, L, Potter, M, Rademakers, R, Ramos, EM, Rankin, KP, Roberson, ED, Rogalski, E, Sengdy, P, Shaw, L, Syrjanen, J, Tartaglia, MC, Tatton, N, Taylor, J, Toga, A, Trojanowski, J, Weintraub, S, Wong, B, Wszolek, Z, Boeve, BF, Rosen, HJ, Boxer, AL, and ARTFL and LEFFTDS consortia

Subjects
ARTFL and LEFFTDS consortia, Brain, Humans, Genetic Predisposition to Disease, tau Proteins, Neuropsychological Tests, Age Factors, Mutation, Aged, Middle Aged, North America, Female, Male, Frontotemporal Dementia, C9orf72 Protein, Progranulins, C9orf72, GRN, MAPT, bvFTD, clinical trials, frontotemporal dementia, genetics, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Acquired Cognitive Impairment, Genetics, Neurosciences, Alzheimer's Disease Related Dementias (ADRD), Frontotemporal Dementia (FTD), Brain Disorders, Aging, Rare Diseases, Clinical Research, Neurodegenerative, Behavioral and Social Science, Neurological, Geriatrics, Clinical Sciences
Abstract

IntroductionBehavioral variant frontotemporal dementia (bvFTD) may present sporadically or due to an autosomal dominant mutation. Characterization of both forms will improve understanding of the generalizability of assessments and treatments.MethodsA total of 135 sporadic (s-bvFTD; mean age 63.3 years; 34% female) and 99 familial (f-bvFTD; mean age 59.9; 48% female) bvFTD participants were identified. f-bvFTD cases included 43 with known or presumed chromosome 9 open reading frame 72 (C9orf72) gene expansions, 28 with known or presumed microtubule-associated protein tau (MAPT) mutations, 14 with known progranulin (GRN) mutations, and 14 with a strong family history of FTD but no identified mutation.ResultsParticipants with f-bvFTD were younger and had earlier age at onset. s-bvFTD had higher total Neuropsychiatric Inventory Questionnaire (NPI-Q) scores due to more frequent endorsement of depression and irritability.Discussionf-bvFTD and s-bvFTD cases are clinically similar, suggesting the generalizability of novel biomarkers, therapies, and clinical tools developed in either form to the other.

Published
2020

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