المؤلفون: Bradford C. Dickerson, David J. Irwin, Eliana Marisa Ramos, Joel H. Kramer, Adam L. Boxer, Gink-Yuek Hsiung, Kamalini G. Ranasinghe, David S. Knopman, Yann Cobigo, John Kornak, Leah Forsberg, Julie Fields, Diana R. Kerwin, Brian S. Appleby, Murray Grossman, Jamie Fong, Daniel I. Kaufer, Jeremy Syrjanen, Rosa Rademakers, Ian R. A. Mackenzie, Brad F. Boeve, Kejal Kantarci, Bruce L. Miller, Neill R. Graff-Radford, Gianina Toller, Nupur Ghoshal, Katya Rascovsky, Sandra Weintraub, Katherine P. Rankin, Howard J. Rosen, Erik D. Roberson, Adam M. Staffaroni, Irene Litvan, Kimiko Domoto-Reilly, Edward D. Huey, Carmela Tartaglia, Mario F. Mendez, Hilary Heuer, Danielle Brushaber, Giovanni Coppola

المساهمون: ARTFL/LEFFTDS Consortium

المصدر: Neurology

مصطلحات موضوعية: 0301 basic medicine, Oncology, Adult, Male, medicine.medical_specialty, Asymptomatic, Article, 03 medical and health sciences, 0302 clinical medicine, Atrophy, Internal medicine, Surveys and Questionnaires, medicine, Clinical endpoint, Humans, Longitudinal Studies, Biology, Aged, Clinical Trials as Topic, Socioemotional selectivity theory, business.industry, Self-Management, Reproducibility of Results, Caregiver burden, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Clinical trial, Facial Expression, Expressed Emotion, 030104 developmental biology, Caregivers, Frontotemporal Dementia, Self-monitoring, Female, Neurology (clinical), Human medicine, medicine.symptom, business, 030217 neurology & neurosurgery, Frontotemporal dementia

الوصف: ObjectiveTo investigate whether the Revised Self-Monitoring Scale (RSMS), an informant measure of socioemotional sensitivity, is a potential clinical endpoint for treatment trials for patients with behavioral variant frontotemporal dementia (bvFTD).MethodsWe investigated whether RSMS informant ratings reflected disease severity in 475 participants (71 bvFTD mutation+, 154 bvFTD mutation−, 12 behavioral mild cognitive impairment [MCI] mutation+, 98 asymptomatic mutation+, 140 asymptomatic mutation−). In a subset of 62 patients (20 bvFTD mutation+, 35 bvFTD mutation−, 7 MCI mutation+) who had at least 2 time points of T1-weighted images available on the same 3T scanner, we examined longitudinal changes in RSMS score over time and its correspondence to progressive gray matter atrophy.ResultsRSMS score showed a similar pattern in mutation carriers and noncarriers, with significant drops at each stage of progression from asymptomatic to very mild, mild, moderate, and severe disease (F4,48 = 140.10, p < 0.001) and a significant slope of decline over time in patients with bvFTD (p = 0.004, 95% confidence interval [CI] −1.90 to −0.23). More rapid declines on the RSMS corresponded to faster gray matter atrophy predominantly in the salience network (SN), and RSMS score progression best predicted thalamic volume in very mild and mild disease stages of bvFTD. Higher RSMS score predicted more caregiver burden (p < 0.001, 95% CI −0.30 to −0.11).ConclusionsThe RSMS is sensitive to progression of both socioemotional symptoms and SN atrophy in patients with bvFTD and corresponds directly to caregiver burden. The RSMS may be useful in both neurologic practice and clinical trials aiming to treat behavioral symptoms of patients with bvFTD.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6dcc7449f55e5eb9eecf15c04fdd63a5Test
https://pubmed.ncbi.nlm.nih.gov/32371446Test

المؤلفون: Andrea G. Alioto, Christie C. Mead, Alicia B. Vanden Bussche Jantz, Adam M. Staffaroni, Joel H. Kramer

مصطلحات موضوعية: mental disorders, nutritional and metabolic diseases, nervous system diseases

الوصف: Frontotemporal dementia (FTD) is a progressive neurological syndrome with diverse clinical presentations and underlying pathologies. FTD is a common cause of dementia, particularly among individuals younger than age 65 years. The three core FTD syndromes are behavioral variant FTD, semantic variant primary progressive aphasia, and nonfluent variant primary progressive aphasia. Neuropsychiatric symptoms and language difficulties are common in FTD, but the heterogeneity of clinical presentations poses significant challenges that can impact accurate diagnosis and patient care. A comprehensive clinical assessment involving the evaluation of cognition, socioemotional functioning, neuroimaging, and other in vivo biomarkers assists with early diagnosis and treatment planning. As the understanding of genetic risk factors and the molecular basis for FTD improves, promising pharmacological therapies are being developed. This chapter summarizes the clinically relevant findings typically seen in each of the three FTD subtypes. It reviews the spectrum of underlying pathological and genetic substrates, addresses common diagnostic challenges, and summarize best practices associated with management of FTD.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::b7d68e7fedb0b316ff9ce28b10dff441Test
https://doi.org/10.1093/oxfordhb/9780190664121.013.31Test

المؤلفون: Joel H. Kramer, Samantha M Walters, Kaitlin B. Casaletto, Dena B. Dubal, Fanny M. Elahi, Kristine Yaffe, Bruce L. Miller, Adam M. Staffaroni, Amy Wolf, Wilfredo Rivera Contreras

المصدر: Neurobiol Aging

مصطلحات موضوعية: 0301 basic medicine, Cognitive aging, Male, Aging, Time Factors, Audiology, Neuropsychological Tests, Healthy Aging, 0302 clinical medicine, Mood, 80 and over, Medicine, Cognitive decline, Gray Matter, Episodic memory, Aged, 80 and over, General Neuroscience, Cognition, Middle Aged, Alzheimer's disease, Magnetic Resonance Imaging, White Matter, Cytokines, Female, Mental health, Episodic, Processing speed, medicine.medical_specialty, Memory, Episodic, Clinical Sciences, Neuroimaging, Article, 03 medical and health sciences, Sex Factors, Memory, Clinical Research, Behavioral and Social Science, Humans, Depressive symptoms, Aged, Neurology & Neurosurgery, business.industry, Tumor Necrosis Factor-alpha, Neurosciences, Hyperintensity, 030104 developmental biology, Cognitive Aging, Neurology (clinical), Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Developmental Biology

الوصف: Age-related cognitive decline is a public health problem but highly diverse and difficult to predict. We captured nonoverlapping cognitive phenotypes in high-functioning adults and identified baseline factors differentiating trajectories. Three hundred fourteen functionally normal adults (M= 69 y) completed 2+ visits. Participants with sample-based longitudinal slopes in memory or processing speed less than-1 SD were classified as "declining" on that measure; 29 and 50 individuals had slopes less than-1 SD on processing speed or memory, respectively; 2.5% met criteria for both, who were excluded. At baseline, speed decliners demonstrated greater age, inflammation, and cognitive complaints compared with speed-stable adults; memory decliners were more likely to be male and had lower depressive symptoms, gray matter volumes, and white matter hyperintensities compared with memory-stable adults. Baseline speed, TNFα, and cognitive complaints accurately classified 96.3% of future speed decliners; baseline memory, sex, precuneal volume, and white matter hyperintensities accurately classified 88.5% of future memory decliners. There are discrete cognitive aging phenotypes reflecting nonoverlapping vulnerabilities in high-functioning adults. Early markers can predict cognition even within the "normal" spectrum and underscore therapeutic targets.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5ecadae50595498da369d0d5ed303be3Test
https://escholarship.org/uc/item/3kn4j9fvTest

المؤلفون: Marilu Gorno-Tempini, Bradford C. Dickerson, John Kornak, David S. Knopman, Howard J. Rosen, Alexandre Bejanin, Gil D. Rabinovici, Gabe Marx, Yann Cobigo, Leonardo Iaccarino, William J. Jagust, Bruce L. Miller, Gautam Tammewar, Adam L. Boxer, Adam M. Staffaroni, Bradley F. Boeve

المصدر: Neurology
Neurology, vol 95, iss 2

مصطلحات موضوعية: 0301 basic medicine, Male, Aging, Neurodegenerative, Audiology, Neuropsychological Tests, Alzheimer's Disease, Primary progressive aphasia, 0302 clinical medicine, 2.1 Biological and endogenous factors, Longitudinal Studies, Aetiology, Prefrontal cortex, Cerebral Cortex, Parietal lobe, Frontotemporal lobar degeneration, Middle Aged, Magnetic Resonance Imaging, Frontotemporal Dementia (FTD), medicine.anatomical_structure, Frontotemporal Dementia, Neurological, Disease Progression, Biomedical Imaging, Cognitive Sciences, Female, Motor cortex, Frontotemporal dementia, medicine.medical_specialty, Clinical Sciences, Posterior parietal cortex, Neuroimaging, Article, 03 medical and health sciences, Rare Diseases, Atrophy, Clinical Research, Fluorodeoxyglucose F18, Aphasia, Acquired Cognitive Impairment, medicine, Humans, Aged, Neurology & Neurosurgery, business.industry, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), medicine.disease, Brain Disorders, 030104 developmental biology, Positron-Emission Tomography, Dementia, Neurology (clinical), Radiopharmaceuticals, business, 030217 neurology & neurosurgery

الوصف: ObjectiveTo compare the sensitivity of structural MRI and 18F-fludeoxyglucose PET (18FDG-PET) to detect longitudinal changes in frontotemporal dementia (FTD).MethodsThirty patients with behavioral variant FTD (bvFTD), 7 with nonfluent/agrammatic variant primary progressive aphasia (nfvPPA), 16 with semantic variant primary progressive aphasia (svPPA), and 43 cognitively normal controls underwent 2–4 MRI and 18FDG-PET scans (total scans/visit = 270) as part of the Frontotemporal Lobar Degeneration Neuroimaging Initiative study. Linear mixed-effects models were carried out voxel-wise and in regions of interest to identify areas showing decreased volume or metabolism over time in patients as compared to controls.ResultsAt baseline, patients with bvFTD showed bilateral temporal, dorsolateral, and medial prefrontal atrophy/hypometabolism that extended with time into adjacent structures and parietal lobe. In nfvPPA, baseline atrophy/hypometabolism in supplementary motor cortex extended with time into left greater than right precentral, dorsolateral, and dorsomedial prefrontal cortex. In svPPA, baseline atrophy/hypometabolism encompassed the anterior temporal and medial prefrontal cortex and longitudinal changes were found in temporal, orbitofrontal, and lateral parietal cortex. Across syndromes, there was substantial overlap in the brain regions showing volume and metabolism loss. Even though the pattern of metabolic decline was more extensive, metabolic changes were also more variable and sample size estimates were similar or higher for 18FDG-PET compared to MRI.ConclusionOur findings demonstrated the sensitivity of 18FDG-PET and structural MRI for tracking disease progression in FTD. Both modalities showed highly overlapping patterns of longitudinal change and comparable sample size estimates to detect longitudinal changes in future clinical trials.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f286c728049723523d9c87ec75f230b9Test
https://pubmed.ncbi.nlm.nih.gov/32591470Test

المؤلفون: Cutter A. Lindbergh, Samantha M Walters, Yann Cobigo, Joel H. Kramer, Amy Wolf, Adam M. Staffaroni, Fanny M. Elahi, Kaitlin B. Casaletto, Howard J. Rosen

المصدر: Hum Brain Mapp
Human brain mapping, vol 40, iss 12

مصطلحات موضوعية: Male, Aging, cerebral blood flow, Perfusion scanning, 0302 clinical medicine, Cognition, 80 and over, processing speed, Aging brain, older adults, Research Articles, Aged, 80 and over, dorsolateral prefrontal cortex, neuroimaging, Radiological and Ultrasound Technology, 05 social sciences, Brain, Experimental Psychology, Middle Aged, diffusion tensor imaging, executive functions, Magnetic Resonance Imaging, Mental Health, medicine.anatomical_structure, Diffusion Tensor Imaging, Neurology, Cerebral blood flow, Neurological, Cardiology, Biomedical Imaging, Cognitive Sciences, Female, Anatomy, medicine.medical_specialty, 1.1 Normal biological development and functioning, Perfusion Imaging, Basic Behavioral and Social Science, 050105 experimental psychology, 03 medical and health sciences, Neuroimaging, Clinical Research, Underpinning research, thalamus, Internal medicine, Behavioral and Social Science, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Cerebral perfusion pressure, Aged, business.industry, Neurosciences, arterial spin labeling, Hyperintensity, Dorsolateral prefrontal cortex, Cross-Sectional Studies, Neurology (clinical), business, 030217 neurology & neurosurgery, Diffusion MRI

الوصف: Cerebral perfusion declines across the lifespan and is altered in the early stages of several age-related neuropathologies. Little is known, however, about the longitudinal evolution of perfusion in healthy older adults, particularly when perfusion is quantified using magnetic resonance imaging with arterial spin labeling (ASL). The objective was to characterize longitudinal perfusion in typically aging adults and elucidate associations with cognition and brain structure. Adults who were functionally intact at baseline (n = 161, ages 47-89) underwent ASL imaging to quantify whole-brain gray matter perfusion; a subset (n = 136) had repeated imaging (average follow-up: 2.3 years). Neuropsychological testing at each visit was summarized into executive function, memory, and processing speed composites. Global gray matter volume, white matter microstructure (mean diffusivity), and white matter hyperintensities were also quantified. We assessed baseline associations among perfusion, cognition, and brain structure using linear regression, and longitudinal relationships using linear mixed effects models. Greater baseline perfusion, particularly in the left dorsolateral prefrontal cortex and right thalamus, was associated with better executive functions. Greater whole-brain perfusion loss was associated with worsening brain structure and declining processing speed. This study helps validate noninvasive MRI-based perfusion imaging and underscores the importance of cerebral blood flow in cognitive aging.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1a1b9be7caffcbe92bb9b72a4b3bc943Test
https://pubmed.ncbi.nlm.nih.gov/31062904Test

المؤلفون: Edward D. Huey, Bradford C. Dickerson, Murray Grossman, Hiroko H. Dodge, Chiadi U. Onyike, Diane Lucente, David J. Irwin, Neill R. Graff-Radford, Jessica Ferrall, Dana Haley, Leah K. Forsberg, Eliana Marisa Ramos, Jill Goldman, Behnaz Ghazanfari, Ian R. A. Mackenzie, Brad F. Boeve, John Kornak, Kimiko Domoto-Reilly, Madeline Potter, Susan Dickinson, Emily Rogalski-Miller, Sara A. Farmer, Adam L. Boxer, David T.W. Jones, Diana R. Kerwin, Tatiana Foroud, Pheth Sengdy, Len Petrucelli, Jamie Fong, Rosa Rademakers, Julie A. Fields, Bruce L. Miller, Joel H. Kramer, Sandra Weintraub, Bonnie Wong, Christina Dheel, Carmela Tartaglia, Christina Caso, Joanne Taylor, Codrin Lungu, John Q. Trojanowski, Zbigniew K. Wszolek, Jeremy Syrjanen, Giovanni Coppola, Peter A. Ljubenkov, Walter A. Kukull, Miranda Maldonado, Masood Manoochehri, Reilly Dever, Alexander Pantelyat, Jonathan Graff-Radford, Ruth Kraft, Katherine P. Rankin, Daniel I. Kaufer, Amy Rindels, Adam M. Staffaroni, Sophia Dominguez, Arthur W. Toga, Kejal Kantarci, Howard J. Rosen, Margaret Sutherland, Maria I. Lapid, Ian Grant, Katya Rascovsky, Jessica Bove, Ann Fishman, Artfl, Irene Litvan, Brian S. Appleby, Les Shaw, Hilary W. Heuer, Nadine Tatton, Patrick Brannelly, Mario F. Mendez, Emily C. McKinley, Erik D. Roberson, Nupur Ghoshal, John K. Hsiao, Scott M. McGinnis, Rodney Pearlman, Danielle Brushaber, Yvette Bordelon, Ralitza H. Gavrilova, Anna Karydas, Deb Gearhart, David S. Knopman, Namita Multani, Jaya Padmanabhan, Walter K. Kremers, Lynne Jones, Kelley Faber, Ping Wang, Lilah M. Besser, Robin Hsiung

المساهمون: ARTFL/LEFFTDS Consortium

المصدر: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring
Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, Vol 11, Iss 1, Pp 797-808 (2019)

مصطلحات موضوعية: lcsh:Geriatrics, Standard score, Generalized additive models, lcsh:RC346-429, Standard deviation, Shape constrained additive models, 03 medical and health sciences, 0302 clinical medicine, Nonlinear Z‐score correction, Statistics, Effects of sleep deprivation on cognitive performance, 10. No inequality, Additive model, Biology, lcsh:Neurology. Diseases of the nervous system, 030304 developmental biology, Mathematics, 0303 health sciences, Neuropsychological testing scores, Generalized additive model, Cognition, Variance (accounting), lcsh:RC952-954.6, Psychiatry and Mental health, Nonlinear system, Cognitive & Behavioral Assessment, Neurology (clinical), Human medicine, 030217 neurology & neurosurgery, Heterogenous variance modeling, Nonlinear Z-score correction

الوصف: Introduction Conventional Z-scores are generated by subtracting the mean and dividing by the standard deviation. More recent methods linearly correct for age, sex, and education, so that these “adjusted” Z-scores better represent whether an individual's cognitive performance is abnormal. Extreme negative Z-scores for individuals relative to this normative distribution are considered indicative of cognitive deficiency. Methods In this article, we consider nonlinear shape constrained additive models accounting for age, sex, and education (correcting for nonlinearity). Additional shape constrained additive models account for varying standard deviation of the cognitive scores with age (correcting for heterogeneity of variance). Results Corrected Z-scores based on nonlinear shape constrained additive models provide improved adjustment for age, sex, and education, as indicated by higher adjusted-R2. Discussion Nonlinearly corrected Z-scores with respect to age, sex, and education with age-varying residual standard deviation allow for improved detection of non-normative extreme cognitive scores.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1bc9110d60a83219bf362edb9a1526cfTest
https://repository.uantwerpen.be/docstore/d:irua:5307Test

المؤلفون: Karoline Carvalho Carmona, Maira Tonidandel Barbosa, Viviane Amaral Carvalho, Leonardo Cruz de Souza, Lea T. Grinberg, Kevin Chiang, Howard J. Rosen, Isabel E. Allen, Paulo Caramelli, Henrique Cerqueira Guimarães, Adam M. Staffaroni, Elisa de Paula França Resende

المصدر: Frontiers in Aging Neuroscience, Vol 10 (2018)
Frontiers in Aging Neuroscience

مصطلحات موضوعية: Aging, medicine.medical_specialty, hippocampus, Cognitive Neuroscience, Hippocampus, Mnemonic, Neurodegenerative, Hippocampal formation, Audiology, Alzheimer's Disease, 050105 experimental psychology, lcsh:RC321-571, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, Clinical Research, Behavioral and Social Science, Acquired Cognitive Impairment, medicine, 2.1 Biological and endogenous factors, Dementia, Alzheimer's Disease including Alzheimer's Disease Related Dementias, 0501 psychology and cognitive sciences, Aetiology, Episodic memory, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Cognitive reserve, education, neuroimaging, business.industry, Prevention, 05 social sciences, aging, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Cognition, episodic memory, Brief Research Report, medicine.disease, cognitive reserve, Brain Disorders, Mental Health, Neurological, Cognitive Sciences, Biochemistry and Cell Biology, business, 030217 neurology & neurosurgery, Neuroscience

الوصف: According to the cognitive reserve theory, intellectual stimuli acquired during life can prevent against developing cognitive impairment. The underlying cognitive reserve mechanisms were underexplored in low-educated individuals. Because episodic memory impairment due to hippocampal dysfunction is a key feature of Alzheimer’s dementia (AD), we sought to look at a possible cognitive reserve mechanism by determining whether few years of education moderated the relationship between the hippocampal volumes and the episodic-memory scores. The sample was composed by 183 older adults, 40.1% male, with the median age of 78[76,82] years and the median years of education of 4[2,10] who had undergone an episodic-memory test and a 3-Tesla MRI scan to access the hippocampal volumes. Overall, 112 were cognitively healthy, 26 had cognitive impairment-no dementia (CIND) and 45 had dementia. We used multiple linear regression to assess whether the interaction between years of education and each hippocampal volume significantly predicted the episodic-memory scores’ variance, controlling for cognitive diagnosis and nuisance variables. The interaction term with the left hippocampus (ß = 0.2, p = 0.043, CI = 1.0, 1.4), but not with the right (ß = 0.1, p = 0.218, CI = 0.9, 1.2) significantly predicted the variation on memory scores. The mechanism by which the left hippocampus seems to play a more important role on memory processing in more educated individuals needs to be further investigated and might be associated with a better use of mnemonic strategies or higher hippocampal connectivity. Because the sample’s median years of education was four, which corresponds to primary school, we may infer that this level might be sufficient to contribute for building cognitive reserve.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d75641da0d97f40c2815039892d3f0d8Test
https://www.frontiersin.org/article/10.3389/fnagi.2018.00381/fullTest

المؤلفون: Joel H. Kramer, Kaitlin B. Casaletto, Adam L. Boxer, Samantha M Walters, Julio C. Rojas, Anna Karydas, Fanny M. Elahi, Henrik Zetterberg, Ryan Fitch, Adam M. Staffaroni, Brianne M. Bettcher, Emily P. Fox

مصطلحات موضوعية: 0301 basic medicine, Male, Analyte, Aging, medicine.medical_treatment, Coefficient of variation, Interleukin-1beta, Immunology, Biology, Biochemistry, Article, Typical aging, Meso scale, 03 medical and health sciences, Quanterix, 0302 clinical medicine, Plasma markers, medicine, Brain mri, 80 and over, Genetics, Immunology and Allergy, Humans, Meso Scale Discovery, Molecular Biology, Brain aging, Aged, Aged, 80 and over, Immunoassay, Immune activation, Plasma samples, Tumor Necrosis Factor-alpha, Interleukin-6, Neurosciences, Reproducibility of Results, Hematology, Middle Aged, Interleukin-10, Brain Disorders, Blood draw, 030104 developmental biology, Cytokine, Good Health and Well Being, Cytokines, Female, Biochemistry and Cell Biology, 030217 neurology & neurosurgery, Biomarkers

الوصف: BACKGROUND:Quantification of biofluid cytokines is a rapidly growing area of translational research. However, comparability across the expanding number of available assay platforms for detection of the same proteins remains to be determined. We aimed to directly compare a panel of commonly measured cytokines in plasma of typically aging adults across two high sensitivity quantification platforms, Meso Scale Discovery high performance electrochemiluminiscence (HPE) and single-molecule immunosorbent assays (Simoa) by Quanterix. METHODS:57 community-dwelling older adults completed a blood draw, neuropsychological assessment, and brain MRI as part of a healthy brain aging study. Plasma samples from the same draw dates were analyzed for IL-10, IP-10, IL-6, TNFα, and IL-1β on HPE and Simoa, separately. Reliable detectability (coefficient of variance (CV) 0.32), with the exception of IL-1β which was only reliably measured using Simoa (68.4%). On average, CVs were acceptable at

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9ed540e31aa38da12d20f18f9a3f6361Test
https://escholarship.org/uc/item/3w02j8s6Test

المؤلفون: Gina Jerome, David S. Knopman, Anne M. Fagan, Brad F. Boeve, Adam L. Boxer, Peter A. Ljubenkov, Anna Karydas, Yann Cobigo, Adam M. Staffaroni, Salvatore Spina, Ping Wang, Hilary W. Heuer, Bradford C. Dickerson, William W. Seeley, Julio C. Rojas, John Kornak, Bruce L. Miller, Lea T. Grinberg, Joel H. Kramer, Isabel E. Allen, Howard J. Rosen

المصدر: Annals of clinical and translational neurology, vol 5, iss 10
Annals of Clinical and Translational Neurology

مصطلحات موضوعية: Oncology, medicine.medical_specialty, Aging, Neurofilament light, Clinical Sciences, Neurodegenerative, Alzheimer's Disease, Primary progressive aphasia, Primary progressive, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Clinical Research, Internal medicine, Fractional anisotropy, mental disorders, medicine, Acquired Cognitive Impairment, Aphasia, 2.1 Biological and endogenous factors, Clinical severity, 030212 general & internal medicine, Aetiology, Alzheimer's Disease Related Dementias (ADRD), Research Articles, business.industry, General Neuroscience, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), medicine.disease, 3. Good health, Brain Disorders, Frontotemporal Dementia (FTD), Neurological, Mixed effects, Dementia, Neurology (clinical), business, 030217 neurology & neurosurgery, Research Article, Frontotemporal dementia

الوصف: Author(s): Ljubenkov, Peter A; Staffaroni, Adam M; Rojas, Julio C; Allen, Isabel E; Wang, Ping; Heuer, Hilary; Karydas, Anna; Kornak, John; Cobigo, Yann; Seeley, William W; Grinberg, Lea T; Spina, Salvatore; Fagan, Anne M; Jerome, Gina; Knopman, David; Boeve, Brad F; Dickerson, Bradford C; Kramer, Joel; Miller, Bruce; Boxer, Adam L; Rosen, Howard J | Abstract: ObjectiveThe prognostic value of cerebrospinal fluid neurofilament light chain, total tau, phosphorylated tau181, and amyloid beta1-42 was examined in frontotemporal dementia subtypes.MethodsWe compared baseline biomarkers between 49 controls, 40 patients with behavioral variant frontotemporal dementia, 24 with semantic variant primary progressive aphasia, and 26 with nonfluent variant primary progressive aphasia. Linear mixed effect models were used to assess the value of baseline biomarkers in predicting clinical and radiographic change in patient cohorts over multiple yearly follow up visits.ResultsNeurofilament light chain concentrations were lowest in controls. Elevated baseline neurofilament light chain predicted faster worsening in clinical severity, frontotemporal volume and frontotemporal fractional anisotropy in patients with behavioral variant frontotemporal dementia and nonfluent variant primary progressive aphasia. High total tau similarly predicted faster progression in nonfluent variant primary progressive aphasia. In behavioral variant frontotemporal dementia, higher phosphorylated tau181 predicted faster clinical progression whereas lower amyloid beta1-42 predicted faster volumetric and fractional anisotropy reduction. Neurofilament light chain and phosphorylated tau181 were of greater predictive value in patients with tau pathology as compared to TDP-43 pathology. Baseline neurofilament light chain correlated with baseline clinical severity and frontotemporal volume in behavioral variant frontotemporal dementia. Baseline total tau correlated with baseline clinical severity in semantic variant primary progressive aphasia.InterpretationHigh cerebrospinal fluid neurofilament light chain predicts more aggressive disease in behavioral variant frontotemporal dementia and nonfluent variant primary progressive aphasia. Total tau, phosphorylated tau181, and amyloid beta1-42 also predict some measures of disease aggressiveness in frontotemporal dementia.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5e1df706d7d7330520bde4a6b3ebdcadTest
https://escholarship.org/uc/item/74t3v9p8Test

المؤلفون: Adam L. Boxer, Murray Grossman, M. Carmela Tartaglia, Adam M. Staffaroni, Hilary W. Heuer, Ging-Yuek Robin Hsiung, Kaitlin B. Casaletto, Howard J. Rosen, David S. Knopman, Nupur Ghoshal, Zbigniew K. Wszolek, Suzee E. Lee, Leah K. Forsberg, Neill R. Graff-Radford, Kejal Kantarci, Bradley F. Boeve, Walter K. Kremers, Bruce L. Miller, Sheng-Yang M. Goh, Amy Wolf, Elise Ong, Joel H. Kramer, Katya Rascovsky, Otto Pedraza, John Kornak, Yann Cobigo, Ian R. A. Mackenzie

المصدر: JAMA Network Open

مصطلحات موضوعية: Adult, Male, Oncology, medicine.medical_specialty, Clinical Dementia Rating, Neuroimaging, tau Proteins, Progranulins, Atrophy, C9orf72, Internal medicine, mental disorders, Severity of illness, Humans, Medicine, Dementia, Genetic Testing, Original Investigation, Aged, Cerebral atrophy, C9orf72 Protein, business.industry, Research, General Medicine, Frontotemporal lobar degeneration, Middle Aged, medicine.disease, Online Only, Frontotemporal Dementia, Female, business, Frontotemporal dementia

الوصف: This observation study characterizes regions and rates of atrophy in the 3 primary familial frontotemporal lobar degeneration genes (MAPT, GRN, and C9orf72) across all disease stages from asymptomatic to dementia.
Key Points Question How does the trajectory of atrophy differ between the 3 primary genetic groups (MAPT, GRN, and C9orf72) associated with familial frontotemporal lobar degeneration? Findings Among 160 members of families affected by familial frontotemporal lobar degeneration in this case-control study, MAPT and GRN pathogenic variants were associated with increases in the rate of volume loss as a function of disease stage, whereas C9orf72 expansion carriers showed minimal increases in the rate of volume loss with disease progression. Meaning This study advances the knowledge of between-gene differences in atrophy rates as a function of disease severity; treatment studies enrolling familial frontotemporal dementia cases should consider the heterogeneity conferred by both the altered gene and the disease stage.
Importance Several clinical trials are planned for familial forms of frontotemporal lobar degeneration (f-FTLD). Precise modeling of brain atrophy in f-FTLD could improve the power to detect a treatment effect. Objective To characterize regions and rates of atrophy in the 3 primary f-FTLD genetic groups (MAPT, GRN, and C9orf72) across all disease stages from asymptomatic to dementia. Design, Setting, and Participants This investigation was a case-control study of participants enrolled in the Advancing Research and Treatment for Frontotemporal Lobar Degeneration or Longitudinal Evaluation of Familial Frontotemporal Dementia studies. The study took place at 18 North American academic medical centers between January 2009 and September 2018. Participants with f-FTLD (n = 100) with a known pathogenic variant (MAPT [n = 28], GRN [n = 33], or C9orf72 [n = 39]) were grouped according to disease stage (ie, Clinical Dementia Rating [CDR] plus National Alzheimer’s Coordinating Center [NACC] FTLD module). Included were participants with at least 2 structural magnetic resonance images at presymptomatic (CDR + NACC FTLD = 0 [n = 57]), mild or questionable (CDR + NACC FTLD = 0.5 [n = 15]), or symptomatic (CDR + NACC FTLD = ≥1 [n = 28]) disease stages. The control group included family members of known pathogenic variant carriers who did not carry the pathogenic variant (n = 60). Main Outcomes and Measures This study fitted bayesian linear mixed-effects models in each voxel of the brain to quantify the rate of atrophy in each of the 3 genes, at each of the 3 disease stages, compared with controls. The study also analyzed rates of clinical decline in each of these groups, as measured by the CDR + NACC FTLD box score. Results The sample included 100 participants with f-FTLD with a known pathogenic variant (mean [SD] age, 50.48 [13.78] years; 53 [53%] female) and 60 family members of known pathogenic variant carriers who did not carry the pathogenic variant (mean [SD] age, 47.51 [12.43] years; 36 [60%] female). MAPT and GRN pathogenic variants were associated with increased rates of volume loss compared with controls at all stages of disease. In MAPT pathogenic variant carriers, statistically significant regions of accelerated volume loss compared with controls were identified in temporal regions bilaterally in the presymptomatic stage, with global spread in the symptomatic stage. For example, mean [SD] rates of atrophy in the left temporal were −231 [47] mm3 per year during the presymptomatic stage, −381 [208] mm3 per year during the mild stage, and −1485 [1025] mm3 per year during the symptomatic stage (P < .05). GRN pathogenic variant carriers generally had minimal increases in atrophy rates between the presymptomatic and mild stages, with rapid increases in atrophy rates in the symptomatic stages. For example, in the right frontal lobes, annualized volume loss was −267 [81] mm3 per year in the presymptomatic stage and −182 [90] mm3 per year in the mild stage, but −1169 [555] mm3 per year in the symptomatic stage. Compared with the other groups, C9orf72 expansion carriers showed minimal increases in rate of volume loss with disease progression. For example, the mean (SD) annualized rates of atrophy in the right frontal lobe in C9orf72 expansion carriers was −272 (118) mm3 per year in presymptomatic stages, −310 (189) mm3 per year in mildly symptomatic stages, and −251 (145) mm3 per year in symptomatic stages. Conclusions and Relevance These findings are relevant to clinical trial planning and suggest that the mechanism by which C9orf72 pathogenic variants lead to symptoms may be fundamentally different from the mechanisms associated with other pathogenic variants.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::61f59187ac78622f5e1e4e4ef2ffcbdfTest
https://doi.org/10.1001/jamanetworkopen.2020.22847Test