16 results on '"BEHAVIORAL VARIANT"'
Search Results
2. Assessment of executive function declines in presymptomatic and mildly symptomatic familial frontotemporal dementia: NIH-EXAMINER as a potential clinical trial endpoint.
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Staffaroni, Adam M, Bajorek, Lynn, Casaletto, Kaitlin B, Cobigo, Yann, Goh, Sheng-Yang M, Wolf, Amy, Heuer, Hilary W, Elahi, Fanny M, Ljubenkov, Peter A, Dever, Reilly, Kornak, John, Appleby, Brian, Bove, Jessica, Bordelon, Yvette, Brannelly, Patrick, Brushaber, Danielle, Caso, Christina, Coppola, Giovanni, Dheel, Christina, Dickerson, Bradford C, Dickinson, Susan, Dominguez, Sophia, Domoto-Reilly, Kimiko, Faber, Kelly, Ferrall, Jessica, Fields, Julie A, Fishman, Ann, Fong, Jamie, Foroud, Tatiana, Forsberg, Leah K, Gavrilova, Ralitza, Gearhart, Debra, Ghazanfari, Behnaz, Ghoshal, Nupur, Goldman, Jill, Graff-Radford, Jonathan, Graff-Radford, Neill, Grant, Ian, Grossman, Murray, Haley, Dana, Hsiung, Ging-Yuek, Huey, Edward D, Irwin, David J, Jones, David T, Jones, Lynne, Kantarci, Kejal, Karydas, Anna, Kaufer, Daniel I, Kerwin, Diana R, Knopman, David S, Kraft, Ruth, Kremers, Walter K, Kukull, Walter A, Litvan, Irene, Lucente, Diane, Lungu, Codrin, Mackenzie, Ian R, Maldonado, Miranda, Manoochehri, Masood, McGinnis, Scott M, McKinley, Emily, Mendez, Mario F, Miller, Bruce L, Multani, Namita, Onyike, Chiadi, Padmanabhan, Jaya, Pantelyat, Alex, Pearlman, Rodney, Petrucelli, Len, Potter, Madeline, Rademakers, Rosa, Ramos, Eliana Marisa, Rankin, Katherine P, Rascovsky, Katya, 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, Wang, Ping, Wong, Bonnie, Wszolek, Zbigniew, Boxer, Adam L, Boeve, Brad F, Kramer, Joel H, Rosen, Howard J, and ARTFL/LEFFTDS consortium
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ARTFL/LEFFTDS consortium ,Humans ,Disease Progression ,Magnetic Resonance Imaging ,Longitudinal Studies ,Neuropsychological Tests ,Mutation ,Middle Aged ,Female ,Male ,Executive Function ,Frontotemporal Dementia ,Biomarkers ,C9orf72 Protein ,Behavioral variant ,Cognition ,Corticobasal syndrome ,Fluency ,Genetic ,Inhibition ,Neuropsychology ,Nonfluent variant ,Primary progressive aphasia ,Progranulin ,Progressive supranuclear palsy ,Semantic variant ,Set-shifting ,Tau ,Working memory ,Clinical Sciences ,Neurosciences ,Geriatrics - Abstract
IntroductionIdentifying clinical measures that track disease in the earliest stages of frontotemporal lobar degeneration (FTLD) is important for clinical trials. Familial FTLD provides a unique paradigm to study early FTLD. Executive dysfunction is a clinically relevant hallmark of FTLD and may be a marker of disease progression.MethodsNinety-three mutation carriers with no symptoms or minimal/questionable symptoms (MAPT, n = 31; GRN, n = 28; C9orf72, n = 34; Clinical Dementia Rating scale plus NACC FTLD Module < 1) and 78 noncarriers enrolled through Advancing Research and Treatment in Frontotemporal Lobar Degeneration/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects studies completed the Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (NIH-EXAMINER) and the UDS neuropsychological battery. Linear mixed-effects models were used to identify group differences in cognition at baseline and longitudinally. We examined associations between cognition, clinical functioning, and magnetic resonance imaging volumes.ResultsNIH-EXAMINER scores detected baseline and differences in slopes between carriers and noncarriers, even in carriers with a baseline Clinical Dementia Rating scale plus NACC FTLD Module = 0. NIH-EXAMINER declines were associated with worsening clinical symptoms and brain volume loss.DiscussionThe NIH-EXAMINER is sensitive to cognitive changes in presymptomatic familial FTLD and is a promising surrogate endpoint.
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- 2020
3. TREM2 risk variants are associated with atypical Alzheimer's disease.
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Kim, Boram, Suh, EunRan, Nguyen, Aivi T., Prokop, Stefan, Mikytuck, Bailey, Olatunji, Olamide A., Robinson, John L., Grossman, Murray, Phillips, Jeffrey S., Irwin, David J., Mechanic-Hamilton, Dawn, Wolk, David A., Trojanowski, John Q., McMillan, Corey T., Van Deerlin, Vivianna M., and Lee, Edward B.
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ALZHEIMER'S disease , *NEUROFIBRILLARY tangles , *NEURODEGENERATION - Abstract
Alzheimer's disease (AD) has multiple clinically and pathologically defined subtypes where the underlying causes of such heterogeneity are not well established. Rare TREM2 variants confer significantly increased risk for clinical AD in addition to other neurodegenerative disease clinical phenotypes. Whether TREM2 variants are associated with atypical clinical or pathologically defined subtypes of AD is not known. We studied here the clinical and pathological features associated with TREM2 risk variants in an autopsy-confirmed cohort. TREM2 variant cases were more frequently associated with non-amnestic clinical syndromes. Pathologically, TREM2 variant cases were associated with an atypical distribution of neurofibrillary tangle density with significantly lower hippocampal NFT burden relative to neocortical NFT accumulation. In addition, NFT density but not amyloid burden was associated with an increase of dystrophic microglia. TREM2 variant cases were not associated with an increased prevalence, extent, or severity of co-pathologies. These clinicopathological features suggest that TREM2 variants contribute to clinical and pathologic AD heterogeneity by altering the distribution of neurofibrillary degeneration and tau-dependent microglial dystrophy, resulting in hippocampal-sparing and non-amnestic AD phenotypes. [ABSTRACT FROM AUTHOR]
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- 2022
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4. MicroRNA biomarkers in frontotemporal dementia and to distinguish from Alzheimer’s disease and amyotrophic lateral sclerosis
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Bridget Martinez and Philip V Peplow
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alzheimer’s disease ,amyotrophic lateral sclerosis ,behavioral variant ,biomarker ,blood plasma ,blood serum ,brain ,cerebrospinal fluid ,cortical tissue ,frontotemporal dementia ,frontotemporal lobar degeneration ,microrna ,primary progressive aphasia ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Frontotemporal lobar degeneration describes a group of progressive brain disorders that primarily are associated with atrophy of the prefrontal and anterior temporal lobes. Frontotemporal lobar degeneration is considered to be equivalent to frontotemporal dementia. Frontotemporal dementia is characterized by progressive impairments in behavior, executive function, and language. There are two main clinical subtypes: behavioral-variant frontotemporal dementia and primary progressive aphasia. The early diagnosis of frontotemporal dementia is critical for developing management strategies and interventions for these patients. Without validated biomarkers, the clinical diagnosis depends on recognizing all the core or necessary neuropsychiatric features, but misdiagnosis often occurs due to overlap with a range of neurologic and psychiatric disorders. In the studies reviewed a very large number of microRNAs were found to be dysregulated but with limited overlap between individual studies. Measurement of specific miRNAs singly or in combination, or as miRNA pairs (as a ratio) in blood plasma, serum, or cerebrospinal fluid enabled frontotemporal dementia to be discriminated from healthy controls, Alzheimer’s disease, and amyotrophic lateral sclerosis. Furthermore, upregulation of miR-223-3p and downregulation of miR-15a-5p, which occurred both in blood serum and cerebrospinal fluid, distinguished behavioral-variant frontotemporal dementia from healthy controls. Downregulation of miR-132-3p in frontal and temporal cortical tissue distinguished frontotemporal lobar degeneration and frontotemporal dementia, respectively, from healthy controls. Possible strong miRNA biofluid biomarker contenders for behavioral-variant frontotemporal dementia are miR-223-3p, miR-15a-5p, miR-22-3p in blood serum and cerebrospinal fluid, and miR-124 in cerebrospinal fluid. No miRNAs were identified able to distinguish between behavioral-variant frontotemporal dementia and primary progressive aphasia subtypes. Further studies are warranted on investigating miRNA expression in biofluids and frontal/temporal cortical tissue to validate and extend these findings.
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- 2022
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5. Disease Progression in Frontotemporal Dementia and Alzheimer Disease: The Contribution of Staging Scales.
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Lima-Silva, Thaís Bento, Mioshi, Eneida, Bahia, Valéria Santoro, Cecchini, Mário Amore, Cassimiro, Luciana, Guimarães, Henrique Cerqueira, Gambogi, Leandro Boson, Caramelli, Paulo, Balthazar, Márcio, Damasceno, Benito, Brucki, Sônia M. D., de Souza, Leonardo Cruz, Nitrini, Ricardo, and Yassuda, Mônica Sanches
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FRONTOTEMPORAL dementia , *ALZHEIMER'S disease , *FRONTOTEMPORAL lobar degeneration , *DISEASE progression , *MEDICAL personnel , *DIAGNOSIS - Abstract
Introduction: There is a shortage of validated instruments to estimate disease progression in frontotemporal dementia (FTD). Objectives: To evaluate the ability of the FTD Rating Scale (FTD-FRS) to detect functional and behavioral changes in patients diagnosed with the behavioral variant of FTD (bvFTD), primary progressive aphasia (PPA), and Alzheimer disease (AD) after 12 months of the initial evaluation, compared to the Clinical Dementia Rating scale−frontotemporal lobar degeneration (CDR-FTLD) and the original Clinical Dementia Rating scale (CDR). Methods: The sample consisted of 70 individuals, aged 40+ years, with at least 2 years of schooling, 31 with the diagnosis of bvFTD, 12 with PPA (8 with semantic variant and 4 with non-fluent variant), and 27 with AD. The FTD-FRS, the CDR, and the 2 additional CDR-FTLD items were completed by a clinician, based on the information provided by the caregiver with frequent contact with the patient. The Addenbrooke Cognitive Examination-Revised was completed by patients. After 12 months, the same protocol was applied. Results: The FTD-FRS, CDR-FTLD, and CDR detected significant decline after 12 months in the 3 clinical groups (exception: FTD-FRS for PPA). The CDR was less sensitive to severe disease stages. Conclusions: The FTD-FRS and the CDR-FTLD are especially useful tools for dementia staging in AD and in the FTD spectrum. [ABSTRACT FROM AUTHOR]
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- 2021
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6. Major or Mild Frontotemporal Neurocognitive Disorder
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Hategan, Ana, Bourgeois, James A., Hirsch, Calvin H., Hategan, Ana, editor, Bourgeois, James A., editor, Hirsch, Calvin H., editor, and Giroux, Caroline, editor
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- 2018
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7. A Spanish Neuropsychological Battery Discriminates Between the Behavioral Variant of Frontotemporal Dementia and Primary Progressive Aphasia in a Colombian Sample
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Lina Velilla, Jonathan Hernández, Margarita Giraldo-Chica, Edmarie Guzmán-Vélez, Yakeel Quiroz, and Francisco Lopera
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frontotemporal dementia ,primary progressive aphasia ,behavioral variant ,neuropsychological tests ,discriminant analyses ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
The differential diagnosis among the behavioral variant of frontotemporal dementia FTD (bvFTD) and the linguist one primary progressive aphasia (PPA) is challenging. Presentations of dementia type or variants dominated by personality change or aphasia are frequently misinterpreted as psychiatric illness, stroke, or other conditions. Therefore, it is important to identify cognitive tests that can distinguish the distinct FTD variants to reduce misdiagnosis and best tailor interventions. We aim to examine the discriminative capacity of the most frequently used cognitive tests in their Spanish version for the context of dementia evaluation as well as the qualitative aspects of the neuropsychological performance such as the frequency and type of errors, perseverations, and false positives that can best discriminate between bvFTD and PPA. We also described mood and behavioral profiles of participants with mild to moderate probable bvFTD and PPA. A total of 55 subjects were included in this cross-sectional study: 20 with PPA and 35 with bvFTD. All participants underwent standard dementia screening that included a medical history and physical examination, brain MRI, a semistructured caregiver interview, and neuropsychological testing. We found that bvFTD patients had worse performance in executive function tests, and the PPA presented with the lower performance in language tests and the global score of Mini-Mental State Examination (MMSE). After running the linear discriminant model, we found three functions of cognitive test and subtests combination and three functions made by the Montreal Cognitive Assessment (MoCA) language subtest and performance errors that predicted group belonging. Those functions were more capable to classify bvFTD cases rather than PPA. In conclusion, our study supports that the combination of an individual test of executive function and language, MoCA's subtest, and performance errors as well have good accuracy to discriminate between bvFTD and PPA.
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- 2021
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8. A Spanish Neuropsychological Battery Discriminates Between the Behavioral Variant of Frontotemporal Dementia and Primary Progressive Aphasia in a Colombian Sample.
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Velilla, Lina, Hernández, Jonathan, Giraldo-Chica, Margarita, Guzmán-Vélez, Edmarie, Quiroz, Yakeel, and Lopera, Francisco
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FRONTOTEMPORAL dementia ,COGNITIVE testing ,MONTREAL Cognitive Assessment ,APHASIA ,DEMENTIA ,MINI-Mental State Examination - Abstract
The differential diagnosis among the behavioral variant of frontotemporal dementia FTD (bvFTD) and the linguist one primary progressive aphasia (PPA) is challenging. Presentations of dementia type or variants dominated by personality change or aphasia are frequently misinterpreted as psychiatric illness, stroke, or other conditions. Therefore, it is important to identify cognitive tests that can distinguish the distinct FTD variants to reduce misdiagnosis and best tailor interventions. We aim to examine the discriminative capacity of the most frequently used cognitive tests in their Spanish version for the context of dementia evaluation as well as the qualitative aspects of the neuropsychological performance such as the frequency and type of errors, perseverations, and false positives that can best discriminate between bvFTD and PPA. We also described mood and behavioral profiles of participants with mild to moderate probable bvFTD and PPA. A total of 55 subjects were included in this cross-sectional study: 20 with PPA and 35 with bvFTD. All participants underwent standard dementia screening that included a medical history and physical examination, brain MRI, a semistructured caregiver interview, and neuropsychological testing. We found that bvFTD patients had worse performance in executive function tests, and the PPA presented with the lower performance in language tests and the global score of Mini-Mental State Examination (MMSE). After running the linear discriminant model, we found three functions of cognitive test and subtests combination and three functions made by the Montreal Cognitive Assessment (MoCA) language subtest and performance errors that predicted group belonging. Those functions were more capable to classify bvFTD cases rather than PPA. In conclusion, our study supports that the combination of an individual test of executive function and language, MoCA's subtest, and performance errors as well have good accuracy to discriminate between bvFTD and PPA. [ABSTRACT FROM AUTHOR]
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- 2021
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9. Assessment of executive function declines in presymptomatic and mildly symptomatic familial frontotemporal dementia: NIH‐EXAMINER as a potential clinical trial endpoint.
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Staffaroni, Adam M., Bajorek, Lynn, Casaletto, Kaitlin B., Cobigo, Yann, Goh, Sheng‐Yang M., Wolf, Amy, Heuer, Hilary W., Elahi, Fanny M., Ljubenkov, Peter A., Dever, Reilly, Kornak, John, Appleby, Brian, Bove, Jessica, Bordelon, Yvette, Brannelly, Patrick, Brushaber, Danielle, Caso, Christina, Coppola, Giovanni, Dheel, Christina, and Dickerson, Bradford C.
- Abstract
Introduction: Identifying clinical measures that track disease in the earliest stages of frontotemporal lobar degeneration (FTLD) is important for clinical trials. Familial FTLD provides a unique paradigm to study early FTLD. Executive dysfunction is a clinically relevant hallmark of FTLD and may be a marker of disease progression. Methods: Ninety‐three mutation carriers with no symptoms or minimal/questionable symptoms (MAPT, n = 31; GRN, n = 28; C9orf72, n = 34; Clinical Dementia Rating scale plus NACC FTLD Module < 1) and 78 noncarriers enrolled through Advancing Research and Treatment in Frontotemporal Lobar Degeneration/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects studies completed the Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (NIH‐EXAMINER) and the UDS neuropsychological battery. Linear mixed‐effects models were used to identify group differences in cognition at baseline and longitudinally. We examined associations between cognition, clinical functioning, and magnetic resonance imaging volumes. Results: NIH‐EXAMINER scores detected baseline and differences in slopes between carriers and noncarriers, even in carriers with a baseline Clinical Dementia Rating scale plus NACC FTLD Module = 0. NIH‐EXAMINER declines were associated with worsening clinical symptoms and brain volume loss. Discussion: The NIH‐EXAMINER is sensitive to cognitive changes in presymptomatic familial FTLD and is a promising surrogate endpoint. [ABSTRACT FROM AUTHOR]
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- 2020
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10. Neuropsychiatric outcomes and caregiver distress in primary progressive aphasia
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Mustafa Seckin, Elif Yıldırım, İlayda Demir, Ömer Orhun, Ezgi Bülbül, H. Aziz Velioğlu, Öget Öktem, Nilüfer Yeşilot, Oğuzhan Çoban, Hakan Gürvit, Işık Üniversitesi, İktisadi, İdari ve Sosyal Bilimler Fakültesi, Psikoloji Bölümü, Işık University, Faculty of Economics, Administrative and Social Sciences, Department of Psychology, and Yıldırım, Elif
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Behavioral variant ,Inventory ,Neuropsychiatric Inventory ,Caregiver Burden ,Burden ,Disturbances ,Caregiver burden ,Reliability ,Primary Progressive Aphasia ,Validity ,Psychiatry and Mental health ,Apraxia ,Stroke Aphasia ,Neuropsychiatric inventory ,Symptoms ,Alzheimers-disease ,Behaviour ,Geriatrics and Gerontology ,Primary progressive aphasia ,Anatomy ,Stroke aphasia ,Gerontology - Abstract
Mustafa Seckin has been supported by a grant from the EC-FP7 co-funded Brain Circulation Scheme (116C020). Background: In this study, we aimed to outline the neuropsychiatric consequences of primary progressive aphasia (PPA) and to understand how neuropsychiatric symptomatology affects distress in caregivers. Methods: The Neuropsychiatric Inventory (NPI) including the distress index (NPI-Distress) was used. Additional information about the caregiver burden was obtained using Zarit Burden Interview (ZBI). NPI, NPI-Distress, and ZBI data from 17 patients with a clinical diagnosis of PPA were compared with 10 stroke aphasia patients. Neuropsychiatric symptomatology was investigated based on three clusters; Mood, Frontal/Comportmental, and Psychotic/Disruptive. Additionally, the Activities of Daily Living Questionnaire (ADLQ) was used to outline the functional impairment. Twelve healthy controls were included to compare the neurocognitive test scores with PPA and stroke aphasia groups. Results: A greater number of neuropsychiatric symptoms were observed in the PPA group compared to the stroke aphasia group. The number of symptoms in Mood, and Frontal/Comportmental clusters were greater than the number of symptoms in Psychotic/Disruptive clusters in the PPA group, whereas no significant relationship between the number of symptoms and symptom clusters was found in the stroke aphasia group. In the PPA group, a strong correlation was found between the NPI-Frequency × Severity scores and the NPI-Distress scores. Moreover, the NPI-Distress scores in the PPA group strongly correlated with the ZBI scores. Scores for anxiety, irritability/lability, and apathy had a stronger correlation with the NPI-Distress scores compared to the other NPI symptoms. The Communication subscale was the most impaired domain in the PPA group. Travel, and Employment and Recreation subscales showed greater functional impairment in the stroke aphasia group compared to the PPA group. Conclusions: Neuropsychiatric symptoms in PPA in our study were more frequent than previously reported. Furthermore, the distress index of the NPI was not only correlated with the severity of the neuropsychiatric symptoms but also reflected the overall burden on the caregivers in the PPA group. European Commission Brain Circulation Scheme Publisher's Version Q4 WOS:000871422800001 PMID: 36273493
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- 2022
11. Cerebrospinal Fluid Biomarkers in Patients with Frontotemporal Dementia Spectrum: A Single-Center Study.
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Engelborghs, Sebastiaan, Abu-Rumeileh, Samir, Mometto, Nicola, Cortelli, Pietro, Liguori, Rocco, Capellari, Sabina, Bartoletti-Stella, Anna, Polischi, Barbara, Oppi, Federico, Poda, Roberto, Stanzani-Maserati, Michelangelo, and Parchi, Piero
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CEREBROSPINAL fluid , *BIOLOGICAL tags , *FRONTOTEMPORAL dementia , *AMYOTROPHIC lateral sclerosis , *DIAGNOSIS of dementia , *DIAGNOSIS of neurological disorders , *ALZHEIMER'S disease , *LEARNING , *LONGITUDINAL method , *MAGNETIC resonance imaging , *NEUROPSYCHOLOGICAL tests , *NERVE tissue proteins , *PEPTIDES , *EQUIPMENT & supplies , *RECEIVER operating characteristic curves - Abstract
Cerebrospinal fluid (CSF) neurofilament light chain protein (NfL) and Alzheimer's disease (AD) core biomarker levels have been evaluated in cohorts of patients with frontotemporal dementia spectrum (FTD), but the distribution of values across the different clinical syndromes and underlying proteinopathies, and the relative diagnostic accuracy appear discordant among studies. We measured CSF NfL, total (t)-tau, phosphorylated (p)-tau, and amyloid-β (Aβ)42 in healthy controls (n = 38) and subjects with a clinical, genetic, CSF biomarker-based, and/or neuropathological diagnosis of FTD (n = 141) or AD (n = 60). Sub-analyses were conducted in a proportion of subjects with definite and/or probable frontotemporal lobar degeneration with tau (FTLD-TAU) (n = 42) or TDP43 pathology (FTLD-TDP) (n = 36). Both FTD and AD groups showed significantly increased CSF NfL levels in comparison to controls (p < 0.001). CSF NfL levels were significantly higher in FTD patients than in AD (p < 0.001), reaching the highest values in amyotrophic lateral sclerosis associated with FTD. Patients with probable and definite FTLD-TDP had significantly higher NfL levels (p < 0.001) and lower p-tau/t-tau values (p < 0.001) in comparison with probable and definite FTLD-TAU cases. NfL showed good diagnostic accuracy in the distinction between FTD and controls (AUC 0.862±0.027) and yielded an accuracy (AUC 0.861±0.045) comparable to that of the p-tau/t-tau ratio (AUC 0.814±0.050), with 80.0% sensitivity and 81.0% specificity, in the discrimination between probable/definite FTLD-TAU and FTLD-TDP. Our data further validate CSF NfL as a surrogate biomarker of neurodegeneration and disease severity in patients with FTD spectrum. Moreover, they demonstrate a good diagnostic value for NfL and p-tau/t-tau ratio in the discrimination between FTLD-TAU and FTLD-TDP. [ABSTRACT FROM AUTHOR]
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- 2018
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12. Modelling the cascade of biomarker changes in GRN-related frontotemporal dementia
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Panman, J. L., Venkatraghavan, V., Van Der Ende, E. L., Steketee, R. M. E., Jiskoot, L. C., Poos, J. M., Dopper, E. G. P., Meeter, L. H. H., Kaat, L. D., Rombouts, S. A. R. B., Vernooij, M. W., Kievit, A. J. A., Premi, E., Cosseddu, M., Bonomi, E., Olives, J., Rohrer, J. D., Sanchez-Valle, R., Borroni, B., Bron, E. E., Van Swieten, J. C., Papma, J. M., Klein, S., Afonso, S., Almeida, M. R., Anderl-Straub, S., Andersson, C., Antonell, A., Archetti, S., Arighi, A., Balasa, M., Barandiaran, M., Bargallo, N., Bartha, R., Bender, B., Black, S., Butler, C., Bocchetta, M., Borrego-Ecija, S., Bras, J., Bruffaerts, R., Caroppo, P., Cash, D., Castelo-Branco, M., Convery, R., Cope, T., Danek, A., De Arriba, M., De Mendonca, A., Di Fede, G., Diaz, Z., Ducharme, S., Duro, D., Fenoglio, C., Ferreira, C. B., Finger, E., Flanagan, T., Fox, N., Freedman, M., Fumagalli, G., Gabilondo, A., Galimberti, D., Gasparotti, R., Gauthier, S., Gazzina, S., Gerhard, A., Giaccone, G., Gorostidi, A., Graff, C., Greaves, C., Guerreiro, R., Heller, C., Hoegen, T., Indakoetxea, B., Jelic, V., Karnath, H. -O., Keren, R., Laforce, R., Leitao, M. J., Levin, J., Llado, A., Loosli, S., Maruta, C., Masellis, M., Mead, S., Miltenberger, G., Van Minkelenm Sara Mitchell, R., Moore, K., Moreno, F., Nicholas, J., Oijerstedt, L., Otto, M., Ourselin, S., Padovani, A., Peakman, G., Pijnenburg, Y., Polito, C., Prioni, S., Prix, C., Rademakers, R., Redaelli, V., Rittman, T., Rogaeva, E., Rosa-Neto, P., Rossi, G., Rosser, M., Rowe, J., Santana, I., Santiago, B., Scarpini, E., Schonecker, S., Shafei, E. S. R., Shoesmith, C., Synofzik, M., Tabuas-Pereira, M., Tagliavini, F., Tartaglia, C., Tainta, M., Taipa, R., Tang-Wai, D., Thomas, D. L., Thonberg, H., Timberlake, C., Tiraboschi, P., Todd, E., Vandamme, P., Vandenberghe, R., Vandenbulcke, M., Veldsman, M., Verdelho, A., Villanua, J., Warren, J., Wilkeione, C., Elisabeth, W., Henrik, W., Zulaica, Z. M., Neurology, Physics and medical technology, Radiology & Nuclear Medicine, Clinical Genetics, and Medical Research Council
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Male ,Oncology ,Disease ,Neuropsychological Tests ,GENFI consortium investigators ,Primary progressive aphasia ,Cognition ,Progranulins ,0302 clinical medicine ,Neurofilament Proteins ,BEHAVIORAL VARIANT ,HETEROGENEITY ,Gray Matter ,11 Medical and Health Sciences ,Language ,Psychiatry ,0303 health sciences ,Brain ,Middle Aged ,Magnetic Resonance Imaging ,White Matter ,17 Psychology and Cognitive Sciences ,ALZHEIMERS-DISEASE ,Psychiatry and Mental health ,Phenotype ,medicine.anatomical_structure ,Frontotemporal Dementia ,Disease Progression ,Biomarker (medicine) ,Female ,Life Sciences & Biomedicine ,Frontotemporal dementia ,medicine.medical_specialty ,Clinical Neurology ,EVENT-BASED MODEL ,Grey matter ,Lateralization of brain function ,White matter ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Internal medicine ,NEUROFILAMENT LIGHT-CHAIN ,medicine ,Humans ,LOBAR DEGENERATION ,PROGRANULIN ,Aged ,030304 developmental biology ,Science & Technology ,Neurology & Neurosurgery ,business.industry ,DISEASE PROGRESSION ,medicine.disease ,Mutation ,WHITE-MATTER INTEGRITY ,Surgery ,Neurosciences & Neurology ,Neurology (clinical) ,business ,GENFI ,Biomarkers ,030217 neurology & neurosurgery ,Progressive disease - Abstract
ObjectiveProgranulin-related frontotemporal dementia (FTD-GRN) is a fast progressive disease. Modelling the cascade of multimodal biomarker changes aids in understanding the aetiology of this disease and enables monitoring of individual mutation carriers. In this cross-sectional study, we estimated the temporal cascade of biomarker changes for FTD-GRN, in a data-driven way.MethodsWe included 56 presymptomatic and 35 symptomatic GRN mutation carriers, and 35 healthy non-carriers. Selected biomarkers were neurofilament light chain (NfL), grey matter volume, white matter microstructure and cognitive domains. We used discriminative event-based modelling to infer the cascade of biomarker changes in FTD-GRN and estimated individual disease severity through cross-validation. We derived the biomarker cascades in non-fluent variant primary progressive aphasia (nfvPPA) and behavioural variant FTD (bvFTD) to understand the differences between these phenotypes.ResultsLanguage functioning and NfL were the earliest abnormal biomarkers in FTD-GRN. White matter tracts were affected before grey matter volume, and the left hemisphere degenerated before the right. Based on individual disease severities, presymptomatic carriers could be delineated from symptomatic carriers with a sensitivity of 100% and specificity of 96.1%. The estimated disease severity strongly correlated with functional severity in nfvPPA, but not in bvFTD. In addition, the biomarker cascade in bvFTD showed more uncertainty than nfvPPA.ConclusionDegeneration of axons and language deficits are indicated to be the earliest biomarkers in FTD-GRN, with bvFTD being more heterogeneous in disease progression than nfvPPA. Our data-driven model could help identify presymptomatic GRN mutation carriers at risk of conversion to the clinical stage.
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- 2021
13. Assessment of executive function declines in presymptomatic and mildly symptomatic familial frontotemporal dementia: NIH-EXAMINER as a potential clinical trial endpoint
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Diane Lucente, Sophia Dominguez, Arthur W. Toga, Ann Fishman, Yvette Bordelon, David J. Irwin, Danielle Brushaber, Debra Gearhart, Katya Rascovsky, Mario F. Mendez, Bradford C. Dickerson, John Kornak, Len Petrucelli, Leah K. Forsberg, Kejal Kantarci, Ping Wang, Zbigniew Wszolek, Anna Karydas, Murray Grossman, Fanny M. Elahi, Ian R. Mackenzie, Patrick Brannelly, Walter A. Kukull, Eliana Marisa Ramos, Edward D. Huey, Kelly Faber, John Q. Trojanowski, Kimiko Domoto-Reilly, Behnaz Ghazanfari, Jill Goldman, David S. Knopman, Emily C. McKinley, Nupur Ghoshal, Ging-Yuek Robin Hsiung, Rosa Rademakers, Masood Manoochehri, Hilary W. Heuer, Walter K. Kremers, Erik D. Roberson, Peter A. Ljubenkov, Adam L. Boxer, David T.W. Jones, Tatiana Foroud, Ian Grant, Brad F. Boeve, Bruce L. Miller, Jonathan Graff-Radford, Miranda Maldonado, Nadine Tatton, Ruth Kraft, Adam M. Staffaroni, Neill Graff-Radford, Joel H. Kramer, Joanne Taylor, Reilly Dever, Irene Litvan, Lynn Bajorek, Giovanni Coppola, Jeremy Syrjanen, Kaitlin B. Casaletto, Yann Cobigo, Codrin Lungu, Namita Multani, Howard J. Rosen, Lynne Jones, Katherine P. Rankin, Julie A. Fields, Alexander Pantelyat, Jaya Padmanabhan, Amy Wolf, Leslie M. Shaw, Brian S. Appleby, Chiadi U. Onyike, Jessica Ferrall, Daniel I. Kaufer, Dana Haley, Diana R. Kerwin, Jessica Bove, M. Carmela Tartaglia, Ralitza H. Gavrilova, Christina Dheel, Christina Caso, Emily Rogalski, Sheng-Yang M. Goh, Madeline Potter, Jamie Fong, Susan Dickinson, Pheth Sengdy, Sandra Weintraub, Bonnie Wong, Scott M. McGinnis, Rodney Pearlman, and ARTFL/LEFFTDS consortium
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Oncology ,Male ,Epidemiology ,Behavioral variant ,Neuropsychological Tests ,Primary progressive aphasia ,Executive Function ,0302 clinical medicine ,Cognition ,C9orf72 ,030212 general & internal medicine ,Longitudinal Studies ,Nonfluent variant ,Inhibition ,Health Policy ,Frontotemporal lobar degeneration ,Middle Aged ,Corticobasal syndrome ,Magnetic Resonance Imaging ,3. Good health ,Psychiatry and Mental health ,Frontotemporal Dementia ,Disease Progression ,Female ,Frontotemporal dementia ,medicine.medical_specialty ,Progranulin ,Semantic variant ,Clinical Dementia Rating ,Article ,Progressive supranuclear palsy ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Genetic ,Neuropsychology ,Internal medicine ,mental disorders ,medicine ,Humans ,C9orf72 Protein ,business.industry ,Surrogate endpoint ,Working memory ,nutritional and metabolic diseases ,medicine.disease ,nervous system diseases ,Set-shifting ,Mutation ,Fluency ,Human medicine ,Neurology (clinical) ,Geriatrics and Gerontology ,Tau ,business ,030217 neurology & neurosurgery ,Biomarkers ,Executive dysfunction - Abstract
Introduction Identifying clinical measures that track disease in the earliest stages of frontotemporal lobar degeneration (FTLD) is important for clinical trials. Familial FTLD provides a unique paradigm to study early FTLD. Executive dysfunction is a clinically relevant hallmark of FTLD and may be a marker of disease progression. Methods Ninety-three mutation carriers with no symptoms or minimal/questionable symptoms (MAPT, n = 31; GRN, n = 28; C9orf72, n = 34; Clinical Dementia Rating scale plus NACC FTLD Module < 1) and 78 noncarriers enrolled through Advancing Research and Treatment in Frontotemporal Lobar Degeneration/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects studies completed the Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (NIH-EXAMINER) and the UDS neuropsychological battery. Linear mixed-effects models were used to identify group differences in cognition at baseline and longitudinally. We examined associations between cognition, clinical functioning, and magnetic resonance imaging volumes. Results NIH-EXAMINER scores detected baseline and differences in slopes between carriers and noncarriers, even in carriers with a baseline Clinical Dementia Rating scale plus NACC FTLD Module = 0. NIH-EXAMINER declines were associated with worsening clinical symptoms and brain volume loss. Discussion The NIH-EXAMINER is sensitive to cognitive changes in presymptomatic familial FTLD and is a promising surrogate endpoint.
- Published
- 2020
14. A Spanish Neuropsychological Battery Discriminates Between the Behavioral Variant of Frontotemporal Dementia and Primary Progressive Aphasia in a Colombian Sample
- Author
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Yakeel T. Quiroz, Edmarie Guzmán-Vélez, Lina Velilla, Francisco Lopera, Margarita Giraldo-Chica, and Jonathan Hernández
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neuropsychological tests ,Context (language use) ,frontotemporal dementia ,Primary progressive aphasia ,03 medical and health sciences ,0302 clinical medicine ,Aphasia ,mental disorders ,medicine ,Dementia ,030212 general & internal medicine ,RC346-429 ,Original Research ,behavioral variant ,Neuropsychology ,Montreal Cognitive Assessment ,discriminant analyses ,medicine.disease ,Cognitive test ,Neurology ,primary progressive aphasia ,Neurology. Diseases of the nervous system ,Neurology (clinical) ,medicine.symptom ,Psychology ,030217 neurology & neurosurgery ,Frontotemporal dementia ,Clinical psychology - Abstract
The differential diagnosis among the behavioral variant of frontotemporal dementia FTD (bvFTD) and the linguist one primary progressive aphasia (PPA) is challenging. Presentations of dementia type or variants dominated by personality change or aphasia are frequently misinterpreted as psychiatric illness, stroke, or other conditions. Therefore, it is important to identify cognitive tests that can distinguish the distinct FTD variants to reduce misdiagnosis and best tailor interventions. We aim to examine the discriminative capacity of the most frequently used cognitive tests in their Spanish version for the context of dementia evaluation as well as the qualitative aspects of the neuropsychological performance such as the frequency and type of errors, perseverations, and false positives that can best discriminate between bvFTD and PPA. We also described mood and behavioral profiles of participants with mild to moderate probable bvFTD and PPA. A total of 55 subjects were included in this cross-sectional study: 20 with PPA and 35 with bvFTD. All participants underwent standard dementia screening that included a medical history and physical examination, brain MRI, a semistructured caregiver interview, and neuropsychological testing. We found that bvFTD patients had worse performance in executive function tests, and the PPA presented with the lower performance in language tests and the global score of Mini-Mental State Examination (MMSE). After running the linear discriminant model, we found three functions of cognitive test and subtests combination and three functions made by the Montreal Cognitive Assessment (MoCA) language subtest and performance errors that predicted group belonging. Those functions were more capable to classify bvFTD cases rather than PPA. In conclusion, our study supports that the combination of an individual test of executive function and language, MoCA's subtest, and performance errors as well have good accuracy to discriminate between bvFTD and PPA.
- Published
- 2021
15. Cerebrospinal Fluid Biomarkers in Patients with Frontotemporal Dementia Spectrum: A Single-Center Study
- Author
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Pietro Cortelli, Nicola Mometto, Piero Parchi, Roberto Poda, Federico Oppi, Barbara Polischi, Michelangelo Stanzani-Maserati, Samir Abu-Rumeileh, Rocco Liguori, Anna Bartoletti-Stella, Sabina Capellari, Abu-Rumeileh, Samir, Mometto, Nicola, Bartoletti-Stella, Anna, Polischi, Barbara, Oppi, Federico, Poda, Roberto, Stanzani-Maserati, Michelangelo, Cortelli, Pietro, Liguori, Rocco, Capellari, Sabina, and Parchi, Piero
- Subjects
0301 basic medicine ,Male ,TDP-43 ,Neuropsychological Tests ,Gastroenterology ,Primary progressive aphasia ,Cohort Studies ,0302 clinical medicine ,Cerebrospinal fluid ,Neurofilament Proteins ,neurofilament light ,amyotrophic lateral sclerosi ,tau ,Amyotrophic lateral sclerosis ,parkinsonism ,General Neuroscience ,Parkinsonism ,General Medicine ,Frontotemporal lobar degeneration ,Alzheimer's disease ,Middle Aged ,Verbal Learning ,Magnetic Resonance Imaging ,Psychiatry and Mental health ,Clinical Psychology ,Frontotemporal Dementia ,Biomarker (medicine) ,Female ,Frontotemporal dementia ,medicine.medical_specialty ,Tomography Scanners, X-Ray Computed ,tau Proteins ,Progressive supranuclear palsy ,03 medical and health sciences ,Alzheimer Disease ,Internal medicine ,mental disorders ,medicine ,Humans ,Aged ,behavioral variant ,Neuroscience (all) ,Amyloid beta-Peptides ,business.industry ,nutritional and metabolic diseases ,corticobasal syndrome ,progressive supranuclear palsy ,medicine.disease ,nervous system diseases ,030104 developmental biology ,ROC Curve ,primary progressive aphasia ,Geriatrics and Gerontology ,business ,030217 neurology & neurosurgery ,Biomarkers - Abstract
Cerebrospinal fluid (CSF) neurofilament light chain protein (NfL) and Alzheimer's disease (AD) core biomarker levels have been evaluated in cohorts of patients with frontotemporal dementia spectrum (FTD), but the distribution of values across the different clinical syndromes and underlying proteinopathies, and the relative diagnostic accuracy appear discordant among studies. We measured CSF NfL, total (t)-tau, phosphorylated (p)-tau, and amyloid-β (Aβ) 42 in healthy controls (n = 38) and subjects with a clinical, genetic, CSF biomarker-based, and/or neuropathological diagnosis of FTD (n = 141) or AD (n = 60). Sub-analyses were conducted in a proportion of subjects with definite and/or probable frontotemporal lobar degeneration with tau (FTLD-TAU) (n = 42) or TDP43 pathology (FTLD-TDP) (n = 36). Both FTD and AD groups showed significantly increased CSF NfL levels in comparison to controls (p < 0.001). CSF NfL levels were significantly higher in FTD patients than in AD (p < 0.001), reaching the highest values in amyotrophic lateral sclerosis associated with FTD. Patients with probable and definite FTLD-TDP had significantly higher NfL levels (p < 0.001) and lower p-tau/t-tau values (p < 0.001) in comparison with probable and definite FTLD-TAU cases. NfL showed good diagnostic accuracy in the distinction between FTD and controls (AUC 0.862±0.027) and yielded an accuracy (AUC 0.861±0.045) comparable to that of the p-tau/t-tau ratio (AUC 0.814±0.050), with 80.0% sensitivity and 81.0% specificity, in the discrimination between probable/definite FTLD-TAU and FTLD-TDP. Our data further validate CSF NfL as a surrogate biomarker of neurodegeneration and disease severity in patients with FTD spectrum. Moreover, they demonstrate a good diagnostic value for NfL and p-tau/t-tau ratio in the discrimination between FTLD-TAU and FTLD-TDP.
- Published
- 2018
16. The mini-Addenbrooke's cognitive examination: a new assessment tool for dementia
- Author
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Hsieh, Sharpley, McGrory, Sarah, Leslie, Felicity, Dawson, Kate, Ahmed, Samrah, Butler, Chris R, Rowe, James B, Mioshi, Eneida, Hodges, John R, Rowe, James [0000-0001-7216-8679], and Apollo - University of Cambridge Repository
- Subjects
Male ,Geriatrics & Gerontology ,DIAGNOSTIC-CRITERIA ,1702 Cognitive Sciences ,education ,Clinical Neurology ,Neuropsychological Tests ,PRIMARY PROGRESSIVE APHASIA ,Sensitivity and Specificity ,VALIDATION ,mental disorders ,BEHAVIORAL VARIANT ,Humans ,Original Research Article ,Cognitive screening test ,Aged ,Psychiatry ,Science & Technology ,Corticobasal degeneration ,MEMORY ,1103 Clinical Sciences ,Alzheimer's disease ,Middle Aged ,ALZHEIMERS-DISEASE ,Geriatrics ,Dementia ,Female ,Neurosciences & Neurology ,1109 Neurosciences ,Life Sciences & Biomedicine ,Frontotemporal dementia - Abstract
Background/Aims: We developed and validated the Mini-Addenbrooke's Cognitive Examination (M-ACE) in dementia patients. Comparisons were also made with the Mini Mental State Examination (MMSE). Method: The M-ACE was developed using Mokken scaling analysis in 117 dementia patients [behavioural variant frontotemporal dementia (bvFTD), n = 25; primary progressive aphasia (PPA), n = 49; Alzheimer's disease (AD), n = 34; corticobasal syndrome (CBS), n = 9] and validated in an independent sample of 164 dementia patients (bvFTD, n = 23; PPA, n = 82; AD, n = 38; CBS, n = 21) and 78 controls, who also completed the MMSE. Results: The M-ACE consists of 5 items with a maximum score of 30. Two cut-offs were identified: (1) ≤25/30 has both high sensitivity and specificity, and (2) ≤21/30 is almost certainly a score to have come from a dementia patient regardless of the clinical setting. The M-ACE is more sensitive than the MMSE and is less likely to have ceiling effects. Conclusion: The M-ACE is a brief and sensitive cognitive screening tool for dementia. Two cut-offs (25 or 21) are recommended. © 2014 S. Karger AG, Basel
- Published
- 2014
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