المؤلفون: Barker, Megan S, Gottesman, Reena T, Manoochehri, Masood, Chapman, Silvia, Appleby, Brian S, Brushaber, Danielle, Devick, Katrina L, Dickerson, Bradford C, Domoto-Reilly, Kimiko, Fields, Julie A, Forsberg, Leah K, Galasko, Douglas R, Ghoshal, Nupur, Goldman, Jill, Graff-Radford, Neill R, Grossman, Murray, Heuer, Hilary W, Hsiung, Ging-Yuek, Knopman, David S, Kornak, John, Litvan, Irene, Mackenzie, Ian R, Masdeu, Joseph C, Mendez, Mario F, Pascual, Belen, Staffaroni, Adam M, Tartaglia, Maria Carmela, Boeve, Bradley F, Boxer, Adam L, Rosen, Howard J, Rankin, Katherine P, Cosentino, Stephanie, Rascovsky, Katya, Huey, Edward D, Foroud, Tatiana, Kaufer, Daniel, Kremers, Walter, Leger, Gabriel, Onyike, Chiadi, Ritter, Aaron, Roberson, Erik D, Weintraub, Sandra

المصدر: Brain. 145(3)

مصطلحات موضوعية: Clinical and Health Psychology, Psychology, Behavioral and Social Science, Dementia, Neurosciences, Alzheimer's Disease, Rare Diseases, Frontotemporal Dementia (FTD), Acquired Cognitive Impairment, Aging, Brain Disorders, Prevention, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Clinical Research, Alzheimer's Disease Related Dementias (ADRD), Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Alzheimer Disease, Biomarkers, Frontotemporal Dementia, Frontotemporal Lobar Degeneration, Humans, Neuropsychological Tests, behavioural variant frontotemporal dementia, prodromal, mild behavioural impairment, mild cognitive impairment, criteria, ALLFTD Consortium, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences

الوصف: At present, no research criteria exist for the diagnosis of prodromal behavioural variant frontotemporal dementia (bvFTD), though early detection is of high research importance. Thus, we sought to develop and validate a proposed set of research criteria for prodromal bvFTD, termed 'mild behavioural and/or cognitive impairment in bvFTD' (MBCI-FTD). Participants included 72 participants deemed to have prodromal bvFTD; this comprised 55 carriers of a pathogenic mutation known to cause frontotemporal lobar degeneration, and 17 individuals with autopsy-confirmed frontotemporal lobar degeneration. All had mild behavioural and/or cognitive changes, as judged by an evaluating clinician. Based on extensive clinical workup, the prodromal bvFTD group was divided into a Development Group (n = 22) and a Validation Group (n = 50). The Development Group was selected to be the subset of the prodromal bvFTD group for whom we had the strongest longitudinal evidence of conversion to bvFTD, and was used to develop the MBCI-FTD criteria. The Validation Group was the remainder of the prodromal bvFTD group and was used as a separate sample on which to validate the criteria. Familial non-carriers were included as healthy controls (n = 165). The frequencies of behavioural and neuropsychiatric features, neuropsychological deficits, and social cognitive dysfunction in the prodromal bvFTD Development Group and healthy controls were assessed. Based on sensitivity and specificity analyses, seven core features were identified: apathy without moderate-severe dysphoria, behavioural disinhibition, irritability/agitation, reduced empathy/sympathy, repetitive behaviours (simple and/or complex), joviality/gregariousness, and appetite changes/hyperorality. Supportive features include a neuropsychological profile of impaired executive function or naming with intact orientation and visuospatial skills, reduced insight for cognitive or behavioural changes, and poor social cognition. Three core features or two core features plus one supportive feature are required for the diagnosis of possible MBCI-FTD; probable MBCI-FTD requires imaging or biomarker evidence, or a pathogenic genetic mutation. The proposed MBCI-FTD criteria correctly classified 95% of the prodromal bvFTD Development Group, and 74% of the prodromal bvFTD Validation Group, with a false positive rate of

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/4238f45wTest
https://escholarship.org/content/qt4238f45w/qt4238f45w.pdfTest

المؤلفون: Barker, Megan S, Manoochehri, Masood, Rizer, Sandra J, Appleby, Brian S, Brushaber, Danielle, Dev, Sheena I, Devick, Katrina L, Dickerson, Bradford C, Fields, Julie A, Foroud, Tatiana M, Forsberg, Leah K, Galasko, Douglas R, Ghoshal, Nupur, Graff-Radford, Neill R, Grossman, Murray, Heuer, Hilary W, Hsiung, Ging-Yuek, Kornak, John, Litvan, Irene, Mackenzie, Ian R, Mendez, Mario F, Pascual, Belen, Rankin, Katherine P, Rascovsky, Katya, Staffaroni, Adam M, Tartaglia, Maria Carmela, Weintraub, Sandra, Wong, Bonnie, Boeve, Bradley F, Boxer, Adam L, Rosen, Howard J, Goldman, Jill, Huey, Edward D, Cosentino, Stephanie, ALLFTD consortium

مصطلحات موضوعية: ALLFTD consortium, Humans, Pick Disease of the Brain, Cognition, Neuropsychological Tests, Heterozygote, Mutation, Frontotemporal Dementia, Progranulins, Behavioral variant frontotemporal dementia, Episodic memory, Genetic frontotemporal dementia, Neuropsychology, Prodromal disease, Behavioral variant frontotemporal, dementia, Frontotemporal Dementia (FTD), Alzheimer's Disease, Rare Diseases, Alzheimer's Disease Related Dementias (ADRD), Behavioral and Social Science, Dementia, Neurosciences, Genetics, Aging, Acquired Cognitive Impairment, Brain Disorders, Clinical Research, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, Genetic Testing, Basic Behavioral and Social Science, 2.1 Biological and endogenous factors, Neurological, Mental health, Experimental Psychology, Psychology, Cognitive Sciences

الوصف: Although executive dysfunction is the characteristic cognitive marker of behavioral variant frontotemporal dementia (bvFTD), episodic memory deficits are relatively common, and may be present even during the prodromal disease phase. In a cohort of mutation carriers with mild behavioral and/or cognitive symptoms consistent with prodromal bvFTD, we aimed to investigate patterns of performance on an abbreviated list learning task, with a particular focus on recognition memory. We further aimed to characterize the cognitive prodromes associated with the three major genetic causes of frontotemporal dementia, as emerging evidence suggests there may be subtle differences in cognitive profiles among carriers of different genetic mutations. Participants included 57 carriers of a pathogenic mutation in microtubule-associated protein tau (MAPT, N = 23), or progranulin (GRN, N = 15), or a or a hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9orf72, N = 19), with mild cognitive and/or behavioral symptoms consistent with prodromal bvFTD. Familial non-carriers were included as controls (N = 143). All participants completed a comprehensive neuropsychological examination, including an abbreviated list learning test assessing episodic memory recall and recognition. MAPT mutation carriers performed worse than non-carriers in terms of list recall, and had difficulty discriminating targets from distractors on the recognition memory task, primarily due to the endorsement of distractors as targets. MAPT mutation carriers also showed nonverbal episodic memory and semantic memory dysfunction (object naming). GRN mutation carriers were variable in performance and overall the most dysexecutive. Slowed psychomotor speed was evident in C9orf72 repeat expansion carriers. Identifying the earliest cognitive indicators of bvFTD is of critical clinical and research importance. List learning may be a sensitive cognitive marker for incipient dementia in MAPT and potentially a subset of GRN carriers. Our results highlight that distinct cognitive profiles may be evident in carriers of the three disease-causing genes during the prodromal disease stage.

الوصول الحر: https://escholarship.org/uc/item/9kc5t2hmTest

المؤلفون: Boeve, Bradley F, Boxer, Adam L, Rosen, Howard J, Forsberg, Leah K, Heuer, Hilary W, Brushaber, Danielle, Appleby, Brian, Biernacka, Joanna M, Bordelon, Yvette M, Botha, Hugo, Brannelly, Patrick, Dickerson, Brad C, Dickson, Dennis W, Kimiko, Domoto‐Reilly, Faber, Kelley, Fagan, Anne, Fields, Julie A, Fishman, Ann, Foroud, Tatiana M, Galasko, Doug R, Gavrilova, Ralitza H, Gendron, Tania F, Geschwind, Daniel H, Ghoshal, Nupur, Goldman, Jill, Graff‐Radford, Jonathan, Graff‐Radford, Neill R, Grant, Ian, Grossman, Murray, Hsiung, Ging‐Yuek Robin, Huang, Eric J, Huey, Edward, Irwin, David J, Jones, David T, Kantarci, Kejal, Karydas, Anna M, Kaufer, Daniel, Knopman, David S, Kramer, Joel H, Kremers, Walter K, Kornak, John, Kukull, Walter A, Lagone, Emma, Leger, Gabriel C, Litvan, Irene, Ljubenkov, Peter A, Lucente, Diane E, Mackenzie, Ian R, Manoochehri, Masood, Masdeu, Joseph C, McGinnis, Scott, Mendez, Mario F, Miller, Bruce L, Miyagawa, Toji, Nelson, Kevin M, Onyike, Chiadi U, Pantelyat, Alex, Pascual, Belen, Pearlman, Rodney, Petrucelli, Leonard, Rademakers, Rosa, Ramos, Eliana Marisa, Rankin, Katherine, Rascovsky, Katya, Rexach, Jessica E, Ritter, Aaron, Roberson, Erik D, Rojas, Julio C, Sabbagh, Marwan N, Salmon, David P, Savica, Rodolfo, Seeley, William W, Staffaroni, Adam M, Syrjanen, Jeremy, Tartaglia, Carmela, Tatton, Nadine, Taylor, Joanne, Toga, Arthur W, Weintraub, Sandra, Wheaton, Diana, Wong, Bonnie, Wszolek, Zbigniew

المصدر: Alzheimer's & Dementia. 16(S6)

مصطلحات موضوعية: Brain Disorders, Rare Diseases, Acquired Cognitive Impairment, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Clinical Trials and Supportive Activities, Clinical Research, Frontotemporal Dementia (FTD), Alzheimer's Disease Related Dementias (ADRD), Genetics, Neurosciences, Dementia, 2.1 Biological and endogenous factors, Geriatrics, Clinical Sciences

الوصول الحر: https://escholarship.org/uc/item/7qb391hmTest

المؤلفون: Moore, Katrina M, Nicholas, Jennifer, Grossman, Murray, McMillan, Corey T, Irwin, David J, Massimo, Lauren, Van Deerlin, Vivianna M, Warren, Jason D, Fox, Nick C, Rossor, Martin N, Mead, Simon, Bocchetta, Martina, Boeve, Bradley F, Knopman, David S, Graff-Radford, Neill R, Forsberg, Leah K, Rademakers, Rosa, Wszolek, Zbigniew K, van Swieten, John C, Jiskoot, Lize C, Meeter, Lieke H, Dopper, Elise Gp, Papma, Janne M, Snowden, Julie S, Saxon, Jennifer, Jones, Matthew, Pickering-Brown, Stuart, Le Ber, Isabelle, Camuzat, Agnès, Brice, Alexis, Caroppo, Paola, Ghidoni, Roberta, Pievani, Michela, Benussi, Luisa, Binetti, Giuliano, Dickerson, Bradford C, Lucente, Diane, Krivensky, Samantha, Graff, Caroline, Öijerstedt, Linn, Fallström, Marie, Thonberg, Håkan, Ghoshal, Nupur, Morris, John C, Borroni, Barbara, Benussi, Alberto, Padovani, Alessandro, Galimberti, Daniela, Scarpini, Elio, Fumagalli, Giorgio G, Mackenzie, Ian R, Hsiung, Ging-Yuek R, Sengdy, Pheth, Boxer, Adam L, Rosen, Howie, Taylor, Joanne B, Synofzik, Matthis, Wilke, Carlo, Sulzer, Patricia, Hodges, John R, Halliday, Glenda, Kwok, John, Sanchez-Valle, Raquel, Lladó, Albert, Borrego-Ecija, Sergi, Santana, Isabel, Almeida, Maria Rosário, Tábuas-Pereira, Miguel, Moreno, Fermin, Barandiaran, Myriam, Indakoetxea, Begoña, Levin, Johannes, Danek, Adrian, Rowe, James B, Cope, Thomas E, Otto, Markus, Anderl-Straub, Sarah, de Mendonça, Alexandre, Maruta, Carolina, Masellis, Mario, Black, Sandra E, Couratier, Philippe, Lautrette, Geraldine, Huey, Edward D, Sorbi, Sandro, Nacmias, Benedetta, Laforce, Robert, Tremblay, Marie-Pier L, Vandenberghe, Rik, Damme, Philip Van, Rogalski, Emily J, Weintraub, Sandra, Gerhard, Alexander, Onyike, Chiadi U, Ducharme, Simon, Papageorgiou, Sokratis G, Ng, Adeline Su Lyn, Brodtmann, Amy, Finger, Elizabeth, Guerreiro, Rita

المصدر: The Lancet. Neurology. 19(2)

مصطلحات موضوعية: FTD Prevention Initiative, Humans, Disease Progression, tau Proteins, Retrospective Studies, Cohort Studies, Family, Age of Onset, Phenotype, Mutation, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Frontotemporal Dementia, C9orf72 Protein, Progranulins, Clinical Research, Rare Diseases, Dementia, Aging, Brain Disorders, Genetic Testing, Neurodegenerative, Neurosciences, Alzheimer's Disease Related Dementias (ADRD), Prevention, Genetics, Acquired Cognitive Impairment, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), 2.1 Biological and endogenous factors, Neurological, Neurology & Neurosurgery, Clinical Sciences

الوصف: BackgroundFrontotemporal dementia is a heterogenous neurodegenerative disorder, with about a third of cases being genetic. Most of this genetic component is accounted for by mutations in GRN, MAPT, and C9orf72. In this study, we aimed to complement previous phenotypic studies by doing an international study of age at symptom onset, age at death, and disease duration in individuals with mutations in GRN, MAPT, and C9orf72.MethodsIn this international, retrospective cohort study, we collected data on age at symptom onset, age at death, and disease duration for patients with pathogenic mutations in the GRN and MAPT genes and pathological expansions in the C9orf72 gene through the Frontotemporal Dementia Prevention Initiative and from published papers. We used mixed effects models to explore differences in age at onset, age at death, and disease duration between genetic groups and individual mutations. We also assessed correlations between the age at onset and at death of each individual and the age at onset and at death of their parents and the mean age at onset and at death of their family members. Lastly, we used mixed effects models to investigate the extent to which variability in age at onset and at death could be accounted for by family membership and the specific mutation carried.FindingsData were available from 3403 individuals from 1492 families: 1433 with C9orf72 expansions (755 families), 1179 with GRN mutations (483 families, 130 different mutations), and 791 with MAPT mutations (254 families, 67 different mutations). Mean age at symptom onset and at death was 49·5 years (SD 10·0; onset) and 58·5 years (11·3; death) in the MAPT group, 58·2 years (9·8; onset) and 65·3 years (10·9; death) in the C9orf72 group, and 61·3 years (8·8; onset) and 68·8 years (9·7; death) in the GRN group. Mean disease duration was 6·4 years (SD 4·9) in the C9orf72 group, 7·1 years (3·9) in the GRN group, and 9·3 years (6·4) in the MAPT group. Individual age at onset and at death was significantly correlated with both parental age at onset and at death and with mean family age at onset and at death in all three groups, with a stronger correlation observed in the MAPT group (r=0·45 between individual and parental age at onset, r=0·63 between individual and mean family age at onset, r=0·58 between individual and parental age at death, and r=0·69 between individual and mean family age at death) than in either the C9orf72 group (r=0·32 individual and parental age at onset, r=0·36 individual and mean family age at onset, r=0·38 individual and parental age at death, and r=0·40 individual and mean family age at death) or the GRN group (r=0·22 individual and parental age at onset, r=0·18 individual and mean family age at onset, r=0·22 individual and parental age at death, and r=0·32 individual and mean family age at death). Modelling showed that the variability in age at onset and at death in the MAPT group was explained partly by the specific mutation (48%, 95% CI 35-62, for age at onset; 61%, 47-73, for age at death), and even more by family membership (66%, 56-75, for age at onset; 74%, 65-82, for age at death). In the GRN group, only 2% (0-10) of the variability of age at onset and 9% (3-21) of that of age of death was explained by the specific mutation, whereas 14% (9-22) of the variability of age at onset and 20% (12-30) of that of age at death was explained by family membership. In the C9orf72 group, family membership explained 17% (11-26) of the variability of age at onset and 19% (12-29) of that of age at death.InterpretationOur study showed that age at symptom onset and at death of people with genetic frontotemporal dementia is influenced by genetic group and, particularly for MAPT mutations, by the specific mutation carried and by family membership. Although estimation of age at onset will be an important factor in future pre-symptomatic therapeutic trials for all three genetic groups, our study suggests that data from other members of the family will be particularly helpful only for individuals with MAPT mutations. Further work in identifying both genetic and environmental factors that modify phenotype in all groups will be important to improve such estimates.FundingUK Medical Research Council, National Institute for Health Research, and Alzheimer's Society.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/8c33n4x6Test

المؤلفون: Miyagawa, Toji, Brushaber, Danielle, Syrjanen, Jeremy, Kremers, Walter, Fields, Julie, Forsberg, Leah K, Heuer, Hilary W, Knopman, David, Kornak, John, Boxer, Adam, Rosen, Howie, Boeve, Bradley, ARTFL/LEFFTDS Consortium

المصدر: Alzheimer's & dementia : the journal of the Alzheimer's Association. 16(1)

مصطلحات موضوعية: ARTFL/LEFFTDS Consortium, Humans, Cross-Sectional Studies, Behavior, Language, Personality, Adult, Aged, Middle Aged, Female, Frontotemporal Lobar Degeneration, Frontotemporal Dementia, Mental Status and Dementia Tests, CDR®, Comportment and personality, Frontotemporal dementia, Frontotemporal lobar degeneration, NACC FTLD Module, Primary progressive aphasia, CDR, Primary progressive aphasia Language, Neurodegenerative, Acquired Cognitive Impairment, Alzheimer's Disease Related Dementias (ADRD), Clinical Research, Frontotemporal Dementia (FTD), Rare Diseases, Dementia, Behavioral and Social Science, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Aging, Geriatrics, Clinical Sciences

الوصف: IntroductionBehavior/Comportment/Personality (BEHAV) and Language (LANG) domains were added to the Clinical Dementia Rating (CDR®) for improving evaluation of patients with frontotemporal lobar degeneration (FTLD) (CDR® plus NACC FTLD).MethodsWe analyzed the CDR® plus NACC FTLD among participants from the baseline visit of the Advancing Research and Treatment for Frontotemporal Lobar Degeneration/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects Consortium.ResultsThe CDR® plus NACC FTLD was able to detect early symptoms in the mildly impaired participants who were rated as CDR® sum of boxes (CDR®-SB) = 0. The CDR®-SB was not sensitive, particularly in participants with mild nonfluent/agrammatic primary progressive aphasia. Participants with familial and sporadic behavioral variant FTD exhibited similar CDR® plus NACC FTLD profiles except that language impairment was more frequent in participants with mild sporadic behavioral variant FTD. Adding the BEHAV and/or LANG domains to the CDR®-SB significantly enhanced discriminatory power in differentiating among the FTLD spectrum disorders.DiscussionThe BEHAV and LANG domains enable the CDR® plus NACC FTLD to capture early symptomatology of FTLD.

الوصول الحر: https://escholarship.org/uc/item/6np868k1Test

المؤلفون: Olney, Nicholas T, Ong, Elise, Goh, Sheng-Yang M, Bajorek, Lynn, Dever, Reilly, Staffaroni, Adam M, Cobigo, Yann, Bock, Meredith, Chiang, Kevin, Ljubenkov, Peter, Kornak, John, Heuer, Hilary W, Wang, Ping, Rascovsky, Katya, Wolf, Amelia, Appleby, Brian, Bove, Jessica, Bordelon, Yvette, Brannelly, Patrick, Brushaber, Danielle, Caso, Christine, Coppola, Giovanni, Dickerson, Bradford C, Dickinson, Susan, Domoto-Reilly, Kimiko, Faber, Kelly, Ferrall, Jessica, Fields, Julie, Fishman, Ann, Fong, Jamie, Foroud, Tatiana, Forsberg, Leah K, Gearhart, Debra J, Ghazanfari, Behnaz, Ghoshal, Nupur, Goldman, Jill, Graff-Radford, Jonathan, Graff-Radford, Neill R, Grant, Ian, Grossman, Murray, Haley, Dana, Hsiung, Gingyuek, Huey, Edward D, Irwin, David J, Jones, David T, Kantarci, Kejal, Karydas, Anna M, Kaufer, Daniel, Kerwin, Diana, Knopman, David S, Kramer, Joel H, Kraft, Ruth, Kremers, Walter, Kukull, Walter, Lapid, Maria I, Litvan, Irene, Mackenzie, Ian R, Maldonado, Miranda, Manoochehri, Masood, McGinnis, Scott M, McKinley, Emily C, Mendez, Mario F, Miller, Bruce L, Onyike, Chiadi, Pantelyat, Alex, Pearlman, Rodney, Petrucelli, Len, Potter, Madeleine, Rademakers, Rosa, Ramos, Eliana M, Rankin, Katherine P, Roberson, Erik D, Rogalski, Emily, Sengdy, Pheth, Shaw, Leslie M, Syrjanen, Jeremy, Tartaglia, M Carmela, Tatton, Nadine, Taylor, Joanne, Toga, Arthur, Trojanowski, John Q, Weintraub, Sandra, Wong, Bonnie, Wszolek, Zbigniew, Boxer, Adam L, Boeve, Brad F, Rosen, Howard J, ARTFL and LEFFTDS consortia

المصدر: Alzheimer's & dementia : the journal of the Alzheimer's Association. 16(1)

مصطلحات موضوعية: ARTFL and LEFFTDS consortia, Temporal Lobe, Humans, Atrophy, Genetic Predisposition to Disease, tau Proteins, Magnetic Resonance Imaging, Longitudinal Studies, Neuropsychological Tests, Image Processing, Computer-Assisted, Middle Aged, Female, Male, Frontotemporal Lobar Degeneration, C9orf72 Protein, Progranulins, C9ORF72, Familial, Frontotemporal lobar degeneration, GRN, Genetic, MAPT, Frontotemporalobar degeneration, Neurodegenerative, Behavioral and Social Science, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease Related Dementias (ADRD), Biomedical Imaging, Aging, Alzheimer's Disease, Clinical Trials and Supportive Activities, Acquired Cognitive Impairment, Dementia, Clinical Research, Brain Disorders, Neurosciences, Rare Diseases, Frontotemporal Dementia (FTD), 2.1 Biological and endogenous factors, Neurological, Geriatrics, Clinical Sciences

الوصف: IntroductionThe 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.MethodsWe 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.ResultsAsymptomatic 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.DiscussionImaging changes appear to precede clinical changes in familial-frontotemporal lobar degeneration, but specific early clinical and imaging changes vary across individuals.

الوصول الحر: https://escholarship.org/uc/item/52q202d2Test

المؤلفون: Ramos, Eliana Marisa, Dokuru, Deepika Reddy, Van Berlo, Victoria, Wojta, Kevin, Wang, Qing, Huang, Alden Y, Deverasetty, Sandeep, Qin, Yue, van Blitterswijk, Marka, Jackson, Jazmyne, Appleby, Brian, Bordelon, Yvette, Brannelly, Patrick, Brushaber, Danielle E, Dickerson, Bradford, Dickinson, Susan, Domoto‐Reilly, Kimiko, Faber, Kelley, Fields, Julie, Fong, Jamie, Foroud, Tatiana, Forsberg, Leah K, Gavrilova, Ralitza, Ghoshal, Nupur, Goldman, Jill, Graff‐Radford, Jonathan, Graff‐Radford, Neill, Grant, Ian, Grossman, Murray, Heuer, Hilary W, Hsiung, Ging‐Yuek R, Huey, Edward, Irwin, David, Kantarci, Kejal, Karydas, Anna, Kaufer, Daniel, Kerwin, Diana, Knopman, David, Kornak, John, Kramer, Joel H, Kremers, Walter, Kukull, Walter, Litvan, Irene, Ljubenkov, Peter, Lungu, Codrin, Mackenzie, Ian, Mendez, Mario F, Miller, Bruce L, Onyike, Chiadi, Pantelyat, Alexander, Pearlman, Rodney, Petrucelli, Len, Potter, Madeline, Rankin, Katherine P, Rascovsky, Katya, Roberson, Erik D, Rogalski, Emily, Shaw, Leslie, Syrjanen, Jeremy, Tartaglia, Maria Carmela, Tatton, Nadine, Taylor, Joanne, Toga, Arthur, Trojanowski, John Q, Weintraub, Sandra, Wong, Bonnie, Wszolek, Zbigniew, Rademakers, Rosa, Boeve, Brad F, Rosen, Howard J, Boxer, Adam L, consortium, on behalf of the ARTFL LEFFTDS, Coppola, Giovanni

المصدر: Alzheimer's & Dementia. 16(1)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Biological Psychology, Clinical Sciences, Neurosciences, Psychology, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Neurodegenerative, Frontotemporal Dementia (FTD), Genetics, Alzheimer's Disease, Human Genome, Prevention, Rare Diseases, Aging, Brain Disorders, Clinical Research, Acquired Cognitive Impairment, Genetic Testing, Alzheimer's Disease Related Dementias (ADRD), Aetiology, 2.1 Biological and endogenous factors, Neurological, C9orf72 Protein, Female, Frontotemporal Dementia, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Progranulins, tau Proteins, C9orf72, familial, frontotemporal dementia, GRN, MAPT, sporadic, ARTFL/LEFFTDS consortium, Geriatrics, Clinical sciences, Biological psychology

الوصف: IntroductionThe Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) consortia are two closely connected studies, involving multiple North American centers that evaluate both sporadic and familial frontotemporal dementia (FTD) participants and study longitudinal changes.MethodsWe screened the major dementia-associated genes in 302 sporadic and 390 familial (symptomatic or at-risk) participants enrolled in these studies.ResultsAmong the sporadic patients, 16 (5.3%) carried chromosome 9 open reading frame 72 (C9orf72), microtubule-associated protein tau (MAPT), and progranulin (GRN) pathogenic variants, whereas in the familial series we identified 207 carriers from 146 families. Of interest, one patient was found to carry a homozygous C9orf72 expansion, while another carried both a C9orf72 expansion and a GRN pathogenic variant. We also identified likely pathogenic variants in the TAR DNA binding protein (TARDBP), presenilin 1 (PSEN1), and valosin containing protein (VCP) genes, and a subset of variants of unknown significance in other rare FTD genes.DiscussionOur study reports the genetic characterization of a large FTD series and supports an unbiased sequencing screen, irrespective of clinical presentation or family history.

الوصول الحر: https://escholarship.org/uc/item/90d8d1rhTest

المؤلفون: Mak, Elijah, Reid, Robert I, Przybelski, Scott A, Lesnick, Timothy G, Schwarz, Christopher G, Senjem, Matthew L, Raghavan, Sheelakumari, Vemuri, Prashanthi, Jack, Clifford R, Min, Hoon Ki, Jain, Manoj K, Miyagawa, Toji, Forsberg, Leah K, Fields, Julie A, Savica, Rodolfo, Graff-Radford, Jonathan, Jones, David T, Botha, Hugo, St Louis, Erik K, Knopman, David S, Ramanan, Vijay K, Dickson, Dennis W, Graff-Radford, Neill R, Ferman, Tanis J, Petersen, Ronald C, Lowe, Val J, Boeve, Bradley F, O'Brien, John T, Kantarci, Kejal

مصطلحات موضوعية: 32 Biomedical and Clinical Sciences, 5202 Biological Psychology, 5204 Cognitive and Computational Psychology, 3209 Neurosciences, 52 Psychology, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Alzheimer's Disease, Neurosciences, Alzheimer's Disease Related Dementias (ADRD), Aging, Dementia, Physical Injury - Accidents and Adverse Effects, Clinical Research, Acquired Cognitive Impairment, Lewy Body Dementia, 2 Aetiology, 2.1 Biological and endogenous factors, Neurological

الوصف: Funder: National Institute of Health, R01 AG40042 ; Dementia with Lewy bodies (DLB) is a neurodegenerative condition often co-occurring with Alzheimer's disease (AD) pathology. Characterizing white matter tissue microstructure using Neurite Orientation Dispersion and Density Imaging (NODDI) may help elucidate the biological underpinnings of white matter injury in individuals with DLB. In this study, diffusion tensor imaging (DTI) and NODDI metrics were compared in 45 patients within the dementia with Lewy bodies spectrum (mild cognitive impairment with Lewy bodies (n = 13) and probable dementia with Lewy bodies (n = 32)) against 45 matched controls using conditional logistic models. We evaluated the associations of tau and amyloid-β with DTI and NODDI parameters and examined the correlations of AD-related white matter injury with Clinical Dementia Rating (CDR). Structural equation models (SEM) explored relationships among age, APOE ε4, amyloid-β, tau, and white matter injury. The DLB spectrum group exhibited widespread white matter abnormalities, including reduced fractional anisotropy, increased mean diffusivity, and decreased neurite density index. Tau was significantly associated with limbic and temporal white matter injury, which was, in turn, associated with worse CDR. SEM revealed that amyloid-β exerted indirect effects on white matter injury through tau. We observed widespread disruptions in white matter tracts in DLB that were not attributed to AD pathologies, likely due to α-synuclein-related injury. However, a fraction of the white matter injury could be attributed to AD pathology. Our findings underscore the impact of AD pathology on white matter integrity in DLB and highlight the utility of NODDI in elucidating the biological basis of white matter injury in DLB.

وصف الملف: application/pdf; text/xml

العلاقة: https://www.repository.cam.ac.uk/handle/1810/366670Test

الإتاحة: https://www.repository.cam.ac.uk/handle/1810/366670Test