109 results on '"Miller, Bruce L."'
Search Results
2. Association of Physical Activity With Neurofilament Light Chain Trajectories in Autosomal Dominant Frontotemporal Lobar Degeneration Variant Carriers.
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Casaletto, Kaitlin B., Kornack, John, Paolillo, Emily W., Rojas, Julio C., VandeBunte, Anna, Staffaroni, Adam S., Lee, Shannon, Heuer, Hilary, Forsberg, Leah, Ramos, Eliana M., Miller, Bruce L., Kramer, Joel H., Yaffe, Kristine, Petrucelli, Leonard, Boxer, Adam, Boeve, Brad, Gendron, Tania F., and Rosen, Howard
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- 2023
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3. Effect of Levetiracetam on Cognition in Patients With Alzheimer Disease With and Without Epileptiform Activity: A Randomized Clinical Trial.
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Vossel, Keith, Ranasinghe, Kamalini G., Beagle, Alexander J., La, Alice, Ah Pook, Kasey, Castro, Madelyn, Mizuiri, Danielle, Honma, Susanne M., Venkateswaran, Nisha, Koestler, Mary, Zhang, Wenbo, Mucke, Lennart, Howell, Michael J., Possin, Katherine L., Kramer, Joel H., Boxer, Adam L., Miller, Bruce L., Nagarajan, Srikantan S., and Kirsch, Heidi E.
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- 2021
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4. Accuracy of Tau Positron Emission Tomography as a Prognostic Marker in Preclinical and Prodromal Alzheimer Disease: A Head-to-Head Comparison Against Amyloid Positron Emission Tomography and Magnetic Resonance Imaging.
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Ossenkoppele, Rik, Smith, Ruben, Mattsson-Carlgren, Niklas, Groot, Colin, Leuzy, Antoine, Strandberg, Olof, Palmqvist, Sebastian, Olsson, Tomas, Jögi, Jonas, Stormrud, Erik, Cho, Hanna, Ryu, Young Hoon, Choi, Jae Yong, Boxer, Adam L., Gorno-Tempini, Maria L., Miller, Bruce L., Soleimani-Meigooni, David, Iaccarino, Leonardo, La Joie, Renaud, and Baker, Suzanne
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- 2021
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5. Assessment of Racial/Ethnic Disparities in Timeliness and Comprehensiveness of Dementia Diagnosis in California.
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Tsoy, Elena, Kiekhofer, Rachel E., Guterman, Elan L., Tee, Boon Lead, Windon, Charles C., Dorsman, Karen A., Lanata, Serggio C., Rabinovici, Gil D., Miller, Bruce L., Kind, Amy J. H., and Possin, Katherine L.
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- 2021
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6. Assessment of Demographic, Genetic, and Imaging Variables Associated With Brain Resilience and Cognitive Resilience to Pathological Tau in Patients With Alzheimer Disease.
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Ossenkoppele, Rik, Lyoo, Chul Hyoung, Jester-Broms, Jonas, Sudre, Carole H., Cho, Hanna, Ryu, Young Hoon, Choi, Jae Yong, Smith, Ruben, Strandberg, Olof, Palmqvist, Sebastian, Kramer, Joel, Boxer, Adam L., Gorno-Tempini, Maria L., Miller, Bruce L., La Joie, Renaud, Rabinovici, Gil D., and Hansson, Oskar
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- 2020
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7. Tau Positron Emission Tomographic Findings in a Former US Football Player With Pathologically Confirmed Chronic Traumatic Encephalopathy.
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Mantyh, William G., Spina, Salvatore, Lee, Alex, Iaccarino, Leonardo, Soleimani-Meigooni, David, Tsoy, Elena, Mellinger, Taylor J., Grant, Harli, Vandevrede, Lawren, La Joie, Renaud, Lesman-Segev, Orit, Gaus, Stephanie, Possin, Katherine L., Grinberg, Lea T., Miller, Bruce L., Seeley, William W., and Rabinovici, Gil D.
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- 2020
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8. Association of Cognitive and Behavioral Features Between Adults With Tuberous Sclerosis and Frontotemporal Dementia.
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Liu, Andy J., Staffaroni, Adam M., Rojas-Martinez, Julio C., Olney, Nicholas T., Alquezar-Burillo, Carolina, Ljubenkov, Peter A., La Joie, Renaud, Fong, Jamie C., Taylor, Joanne, Karydas, Anna, Ramos, Eliana Marisa, Coppola, Giovanni, Boxer, Adam L., Rabinovici, Gil D., Miller, Bruce L., and Kao, Aimee W.
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- 2020
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9. Association Between Caregiver Depression and Emergency Department Use Among Patients With Dementia.
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Guterman, Elan L., Allen, I. Elaine, Josephson, S. Andrew, Merrilees, Jennifer J., Dulaney, Sarah, Chiong, Winston, Lee, Kirby, Bonasera, Stephen J., Miller, Bruce L., and Possin, Katherine L.
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- 2019
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10. Comparison of Visual and Quantitative Florbetapir F 18 Positron Emission Tomography Analysis in Predicting Mild Cognitive Impairment Outcomes
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Schreiber, Stefanie, Landau, Susan M, Gamst, Anthony, Cellar, Janet S, Burns, Jeffrey M, Anderson, Heather S, Laubinger, Mary M, Bartzokis, George, Silverman, Daniel H S, Lu, Po H, Graff-Radford, Neill R, Parfitt, Francine, Johnson, Heather, Soares, Holly, Farlow, Martin, Herring, Scott, Hake, Ann M, van Dyck, Christopher H, MacAvoy, Martha G, Benincasa, Amanda L, Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Green, Robert C, Graham, Simon, Caldwell, Curtis, Hsiung, Ging-Yuek Robin, Feldman, Howard, Assaly, Michele, Kertesz, Andrew, Rogers, John, Trost, Dick, Bernick, Charles, Munic, Donna, Montine, Tom, Wu, Chuang-Kuo, Johnson, Nancy, Mesulam, Marsel, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Scott, Johnson, Kathleen B, Behan, Kelly E, Sperling, Reisa A, Thomas, Ronald G, Rentz, Dorene M, Johnson, Keith A, Rosen, Allyson, Tinklenberg, Jared, Ashford, Wes, Sabbagh, Marwan, Connor, Donald, Jacobson, Sandra, Killiany, Ronald, Norbash, Alexander, Donohue, Michael, Nair, Anil, Obisesan, Thomas O, Jayam-Trouth, Annapurni, Wang, Paul, Lerner, Alan, Hudson, Leon, Ogrocki, Paula, DeCarli, Charles, Fletcher, Evan, Carmichael, Owen, Walter, Sarah, Kittur, Smita, Mirje, Seema, Borrie, Michael, Lee, T-Y, Bartha, Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M, Potkin, Steven G, Preda, Adrian, Dale, Anders, Nguyen, Dana, Tariot, Pierre, Fleisher, Adam, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Hendin, Barry A, Scharre, Douglas W, Kataki, Maria, Bernstein, Matthew, Zimmerman, Earl A, Celmins, Dzintra, Brown, Alice D, Gandy, Sam, Marenberg, Marjorie E, Rovner, Barry W, Pearlson, Godfrey, Blank, Karen, Anderson, Karen, Saykin, Andrew J, Felmlee, Joel, Santulli, Robert B, Englert, Jessica, Williamson, Jeff D, Sink, Kaycee M, Watkins, Franklin, Ott, Brian R, Cohen, Ronald, Salloway, Stephen, Malloy, Paul, Fero, Allison, Fox, Nick, Correia, Stephen, Rosen, Howard J, Miller, Bruce L, Mintzer, Jacobo, Thompson, Paul, Schuff, Norbert, Alexander, Gene, Bandy, Dan, Chen, Kewei, Morris, John, Lee, Virginia M-Y, Korecka, Magdalena, Schreiber, Frank, Crawford, Karen, Neu, Scott, Harvey, Danielle, Kornak, John, Foroud, Tatiana M, Potkin, Steven, Shen, Li, Buckholtz, Neil, Kaye, Jeffrey, Jagust, William J, Dolen, Sara, Quinn, Joseph, Schneider, Lon, Pawluczyk, Sonia, Spann, Bryan M, Brewer, James, Vanderswag, Helen, Heidebrink, Judith L, Lord, Joanne L, Petersen, Ronald, Initiative, Alzheimer's Disease Neuroimaging, Johnson, Kris, Doody, Rachelle S, Villanueva-Meyer, Javier, Chowdhury, Munir, Stern, Yaakov, Honig, Lawrence S, Bell, Karen L, Morris, John C, Mintun, Mark A, Schneider, Stacy, Aisen, Paul, Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, Tang, Cheuk, Marzloff, George, deToledo-Morrell, Leyla, Shah, Raj C, Duara, Ranjan, Varon, Daniel, Jack, Clifford R, Roberts, Peggy, Albert, Marilyn S, Pedroso, Julia, Toroney, Jaimie, Rusinek, Henry, de Leon, Mony J, De Santi, Susan M, Doraiswamy, P Murali, Petrella, Jeffrey R, Aiello, Marilyn, Toga, Arthur W, Clark, Christopher M, Pham, Cassie, Nunez, Jessica, Smith, Charles D, Given, Curtis A, Hardy, Peter, Lopez, Oscar L, Oakley, MaryAnn, Simpson, Donna M, Ismail, M Saleem, Beckett, Laurel, Brand, Connie, BA, Jennifer Richard, Mulnard, Ruth A, Thai, Gaby, Mc-Adams-Ortiz, Catherine, Diaz-Arrastia, Ramon, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I, and Lah, James J
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Male ,medicine.medical_specialty ,diagnostic imaging [Cognitive Dysfunction] ,metabolism [Amyloid beta-Peptides] ,Context (language use) ,Standardized uptake value ,Neuroimaging ,Alzheimer Disease ,Fluorodeoxyglucose F18 ,Predictive Value of Tests ,medicine ,Humans ,Cognitive Dysfunction ,therapy [Cognitive Dysfunction] ,ddc:610 ,Longitudinal Studies ,Psychiatry ,Aged ,Aged, 80 and over ,Amyloid beta-Peptides ,medicine.diagnostic_test ,therapy [Alzheimer Disease] ,business.industry ,methods [Positron-Emission Tomography] ,diagnosis [Alzheimer Disease] ,complications [Alzheimer Disease] ,Middle Aged ,medicine.disease ,Inter-rater reliability ,Treatment Outcome ,Positron emission tomography ,Positron-Emission Tomography ,Predictive value of tests ,Biomarker (medicine) ,Female ,Neurology (clinical) ,Alzheimer's disease ,Psychology ,Nuclear medicine ,business ,analysis [Biomarkers] ,complications [Cognitive Dysfunction] ,Biomarkers - Abstract
Importance The applicability of β-amyloid peptide (Aβ) positron emission tomography (PET) as a biomarker in clinical settings to aid in selection of individuals at preclinical and prodromal Alzheimer disease (AD) will depend on the practicality of PET image analysis. In this context, visual-based Aβ PET assessment seems to be the most feasible approach. Objectives To determine the agreement between visual and quantitative Aβ PET analysis and to assess the ability of both techniques to predict conversion from mild cognitive impairment (MCI) to AD. Design, Setting, and Participants A longitudinal study was conducted among the Alzheimer’s Disease Neuroimaging Initiative (ADNI) sites in the United States and Canada during a 1.6-year mean follow-up period. The study was performed from September 21, 2010, to August 11, 2014; data analysis was conducted from September 21, 2014, to May 26, 2015. Participants included 401 individuals with MCI receiving care at a specialty clinic (219 [54.6%] men; mean [SD] age, 71.6 [7.5] years; 16.2 [2.7] years of education). All participants were studied with florbetapir F 18 [ 18 F] PET. The standardized uptake value ratio (SUVR) positivity threshold was 1.11, and one reader rated all images, with a subset of 125 scans rated by a second reader. Main Outcomes and Measures Sensitivity and specificity of positive and negative [ 18 F] florbetapir PET categorization, which was estimated with cerebrospinal fluid Aβ1-42 as the reference standard. Risk for conversion to AD was assessed using Cox proportional hazards regression models. Results The frequency of Aβ positivity was 48.9% (196 patients; visual analysis), 55.1% (221 patients; SUVR), and 64.8% (166 patients; cerebrospinal fluid), yielding substantial agreement between visual and SUVR data (κ = 0.74) and between all methods (Fleiss κ = 0.71). For approximately 10% of the 401 participants in whom visual and SUVR data disagreed, interrater reliability was moderate (κ = 0.44), but it was very high if visual and quantitative results agreed (κ = 0.92). Visual analysis had a lower sensitivity (79% vs 85%) but higher specificity (96% vs 90%), respectively, compared with SUVR. The conversion rate was 15.2% within a mean of 1.6 years, and a positive [ 18 F] florbetapir baseline scan was associated with a 6.91-fold (SUVR) or 11.38-fold (visual) greater hazard for AD conversion, which changed only modestly after covariate adjustment for apolipoprotein e4, concurrent fludeoxyglucose F 18 PET scan, and baseline cognitive status. Conclusions and Relevance Visual and SUVR Aβ PET analysis may be equivalently used to determine Aβ status for individuals with MCI participating in clinical trials, and both approaches add significant value for clinical course prognostication.
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- 2015
11. Association of Early-Onset Alzheimer Disease With Elevated Low-Density Lipoprotein Cholesterol Levels and Rare Genetic Coding Variants of APOB.
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Wingo, Thomas S., Cutler, David J., Wingo, Aliza P., Le, Ngoc-Anh, Rabinovici, Gil D., Miller, Bruce L., Lah, James J., and Levey, Allan I.
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- 2019
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12. Discriminative Accuracy of [18F]flortaucipir Positron Emission Tomography for Alzheimer Disease vs Other Neurodegenerative Disorders.
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Ossenkoppele, Rik, Rabinovici, Gil D., Smith, Ruben, Cho, Hanna, Schöll, Michael, Strandberg, Olof, Palmqvist, Sebastian, Mattsson, Niklas, Janelidze, Shorena, Santillo, Alexander, Ohlsson, Tomas, Jögi, Jonas, Tsai, Richard, La Joie, Renaud, Kramer, Joel, Boxer, Adam L., Gorno-Tempini, Maria L., Miller, Bruce L., Choi, Jae Y., and Ryu, Young H.
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POSITRON emission tomography ,ALZHEIMER'S disease ,NEURODEGENERATION ,DIAGNOSTIC imaging ,DEMENTIA - Abstract
Importance: The positron emission tomography (PET) tracer [18F]flortaucipir allows in vivo quantification of paired helical filament tau, a core neuropathological feature of Alzheimer disease (AD), but its diagnostic utility is unclear.Objective: To examine the discriminative accuracy of [18F]flortaucipir for AD vs non-AD neurodegenerative disorders.Design, Setting, and Participants: In this cross-sectional study, 719 participants were recruited from 3 dementia centers in South Korea, Sweden, and the United States between June 2014 and November 2017 (160 cognitively normal controls, 126 patients with mild cognitive impairment [MCI], of whom 65.9% were amyloid-β [Aβ] positive [ie, MCI due to AD], 179 patients with AD dementia, and 254 patients with various non-AD neurodegenerative disorders).Exposures: The index test was the [18F]flortaucipir PET standardized uptake value ratio (SUVR) in 5 predefined regions of interest (ROIs). Cut points for tau positivity were determined using the mean +2 SDs observed in controls and Youden Index for the contrast AD dementia vs controls.Main Outcomes and Measures: The reference standard was the clinical diagnosis determined at the specialized memory centers. In the primary analysis, the discriminative accuracy (ie, sensitivity and specificity) of [18F]flortaucipir was examined for AD dementia vs all non-AD neurodegenerative disorders. In secondary analyses, the area under the curve (AUC) of [18F]flortaucipir SUVR was compared with 3 established magnetic resonance imaging measures (hippocampal volumes and AD signature and whole-brain cortical thickness), and sensitivity and specificity of [18F]flortaucipir in MCI due to AD vs non-AD neurodegenerative disorders were determined.Results: Among 719 participants, the overall mean (SD) age was 68.8 (9.2) years and 48.4% were male. The proportions of patients who were amyloid-β positive were 26.3%, 65.9%, 100%, and 23.8% among cognitively normal controls, patients with MCI, patients with AD dementia, and patients with non-AD neurodegenerative disorders, respectively. [18F]flortaucipir uptake in the medial-basal and lateral temporal cortex showed 89.9% (95% CI, 84.6%-93.9%) sensitivity and 90.6% (95% CI, 86.3%-93.9%) specificity using the threshold based on controls (SUVR, 1.34), and 96.8% (95% CI, 92.0%-99.1%) sensitivity and 87.9% (95% CI, 81.9%-92.4%) specificity using the Youden Index-derived cutoff (SUVR, 1.27) for distinguishing AD dementia from all non-AD neurodegenerative disorders. The AUCs for all 5 [18F]flortaucipir ROIs were higher (AUC range, 0.92-0.95) compared with the 3 volumetric MRI measures (AUC range, 0.63-0.75; all ROIs P < .001). Diagnostic performance of the 5 [18F]flortaucipir ROIs were lower in MCI due to AD (AUC range, 0.75-0.84).Conclusions and Relevance: Among patients with established diagnoses at a memory disorder clinic, [18F]flortaucipir PET was able to discriminate AD from other neurodegenerative diseases. The accuracy and potential utility of this test in patient care require further research in clinically more representative populations. [ABSTRACT FROM AUTHOR]- Published
- 2018
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13. Selective Genetic Overlap Between Amyotrophic Lateral Sclerosis and Diseases of the Frontotemporal Dementia Spectrum.
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Karch, Celeste M., Wen, Natalie, Fan, Chun C., Yokoyama, Jennifer S., Kouri, Naomi, Ross, Owen A., Höglinger, Gunter, Müller, Ulrich, Ferrari, Raffaele, Hardy, John, Schellenberg, Gerard D., Sleiman, Patrick M., Momeni, Parastoo, Hess, Christopher P., Miller, Bruce L., Sharma, Manu, Van Deerlin, Vivianna, Smeland, Olav B., Andreassen, Ole A., and Dale, Anders M.
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- 2018
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14. Prevalence of Mathematical and Visuospatial Learning Disabilities in Patients With Posterior Cortical Atrophy.
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Miller, Zachary A., Rosenberg, Lynne, Santos-Santos, Miguel A., Stephens, Melanie, Allen, Isabel E., Hubbard, H. Isabel, Cantwell, Averill, Mandelli, Maria Luisa, Grinberg, Lea T., Seeley, William W., Miller, Bruce L., Rabinovici, Gil D., and Gorno-Tempini, Maria Luisa
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- 2018
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15. Precipitous Deterioration of Motor Function, Cognition, and Behavior.
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Fernández-Fournier, Mireya, Perry, David C., Tartaglia, Maria Carmela, de May, Mary, Boxer, Adam, Coppola, Giovanni, Christine, Chadwick W., Huang, Eric J., Seeley, William W., Miller, Bruce L., De Armond, Steven J., Grinberg, Lea T., and Geschwind, Michael D.
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- 2017
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16. Features of Patients With Nonfluent/Agrammatic Primary Progressive Aphasia With Underlying Progressive Supranuclear Palsy Pathology or Corticobasal Degeneration.
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Santos-Santos, Miguel A., Mandelli, Maria Luisa, Binney, Richard J., Ogar, Jennifer, Wilson, Stephen M., Henry, Maya L., Hubbard, H. Isabel, Meese, Minerva, Attygalle, Suneth, Rosenberg, Lynne, Pakvasa, Mikhail, Trojanowski, John Q., Grinberg, Lea T., Rosen, Howie, Boxer, Adam L., Miller, Bruce L., Seeley, William W., and Gorno-Tempini, Maria Luisa
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- 2016
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17. Artistic Renaissance in Frontotemporal Dementia.
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Erkkinen, Michael G., Zúñiga, Raquel Gutiérrez, Pardo, Cristóbal Carnero, Miller, Bruce L., Miller, Zachary A., Zúñiga, Raquel Gutiérrez, and Pardo, Cristóbal Carnero
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FRONTOTEMPORAL dementia ,CREATIVE ability ,BRAIN function localization ,DISEASES in older people ,NEUROPSYCHOLOGY - Abstract
This Arts and Medicine essay uses case descriptions of 2 patients who experienced a sudden increase in artistic creativity with the onset of frontotemporal dementia to discuss the mechanism of paradoxical functional facilitation, in which loss of activity in one part of the brain leads to release of activity in another. [ABSTRACT FROM AUTHOR]
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- 2018
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18. Prevalence of amyloid PET positivity in dementia syndromes: a meta-analysis.
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Ossenkoppele, Rik, Jansen, Willemijn J, Rabinovici, Gil D, Knol, Dirk L, van der Flier, Wiesje M, van Berckel, Bart N M, Scheltens, Philip, Visser, Pieter Jelle, Verfaillie, Sander C J, Zwan, Marissa D, Adriaanse, Sofie M, Lammertsma, Adriaan A, Barkhof, Frederik, Jagust, William J, Miller, Bruce L, Rosen, Howard J, Landau, Susan M, Villemagne, Victor L, Rowe, Christopher C, and Lee, Dong Y
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Importance: Amyloid-β positron emission tomography (PET) imaging allows in vivo detection of fibrillar plaques, a core neuropathological feature of Alzheimer disease (AD). Its diagnostic utility is still unclear because amyloid plaques also occur in patients with non-AD dementia.Objective: To use individual participant data meta-analysis to estimate the prevalence of amyloid positivity on PET in a wide variety of dementia syndromes.Data Sources: The MEDLINE and Web of Science databases were searched from January 2004 to April 2015 for amyloid PET studies.Study Selection: Case reports and studies on neurological or psychiatric diseases other than dementia were excluded. Corresponding authors of eligible cohorts were invited to provide individual participant data.Data Extraction and Synthesis: Data were provided for 1359 participants with clinically diagnosed AD and 538 participants with non-AD dementia. The reference groups were 1849 healthy control participants (based on amyloid PET) and an independent sample of 1369 AD participants (based on autopsy).Main Outcomes and Measures: Estimated prevalence of positive amyloid PET scans according to diagnosis, age, and apolipoprotein E (APOE) ε4 status, using the generalized estimating equations method.Results: The likelihood of amyloid positivity was associated with age and APOE ε4 status. In AD dementia, the prevalence of amyloid positivity decreased from age 50 to 90 years in APOE ε4 noncarriers (86% [95% CI, 73%-94%] at 50 years to 68% [95% CI, 57%-77%] at 90 years; n = 377) and to a lesser degree in APOE ε4 carriers (97% [95% CI, 92%-99%] at 50 years to 90% [95% CI, 83%-94%] at 90 years; n = 593; P < .01). Similar associations of age and APOE ε4 with amyloid positivity were observed in participants with AD dementia at autopsy. In most non-AD dementias, amyloid positivity increased with both age (from 60 to 80 years) and APOE ε4 carriership (dementia with Lewy bodies: carriers [n = 16], 63% [95% CI, 48%-80%] at 60 years to 83% [95% CI, 67%-92%] at 80 years; noncarriers [n = 18], 29% [95% CI, 15%-50%] at 60 years to 54% [95% CI, 30%-77%] at 80 years; frontotemporal dementia: carriers [n = 48], 19% [95% CI, 12%-28%] at 60 years to 43% [95% CI, 35%-50%] at 80 years; noncarriers [n = 160], 5% [95% CI, 3%-8%] at 60 years to 14% [95% CI, 11%-18%] at 80 years; vascular dementia: carriers [n = 30], 25% [95% CI, 9%-52%] at 60 years to 64% [95% CI, 49%-77%] at 80 years; noncarriers [n = 77], 7% [95% CI, 3%-18%] at 60 years to 29% [95% CI, 17%-43%] at 80 years.Conclusions and Relevance: Among participants with dementia, the prevalence of amyloid positivity was associated with clinical diagnosis, age, and APOE genotype. These findings indicate the potential clinical utility of amyloid imaging for differential diagnosis in early-onset dementia and to support the clinical diagnosis of participants with AD dementia and noncarrier APOE ε4 status who are older than 70 years. [ABSTRACT FROM AUTHOR]- Published
- 2015
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19. Criminal Behavior in Frontotemporal Dementia and Alzheimer Disease.
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Liljegren, Madeleine, Naasan, Georges, Temlett, Julia, Perry, David C., Rankin, Katherine P., Merrilees, Jennifer, Grinberg, Lea T., Seeley, William W., Englund, Elisabet, and Miller, Bruce L.
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- 2015
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20. Effects of the Absence of Apolipoprotein E on Lipoproteins, Neurocognitive Function, and Retinal Function.
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Mak, Angel C. Y., Pullinger, Clive R., Ling Fung Tang, Wong, Jinny S., Deo, Rahul C., Schwarz, Jean-Marc, Gugliucci, Alejandro, Movsesyan, Irina, Ishida, Brian Y., Catherine Chu, Poon, Annie, Kim, Phillip, Stock, Eveline O., Schaefer, Ernst J., Asztalos, Bela F., Castellano, Joseph M., Wyss-Coray, Tony, Duncan, Jacque L., Miller, Bruce L., and Kane, John P.
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- 2014
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21. Emergence of Artistic Talent in Frontotemporal Dementia
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Miller, Bruce L.
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Dementia -- Psychological aspects ,Creative ability -- Physiological aspects - Published
- 1999
22. Science Denial and COVID Conspiracy Theories: Potential Neurological Mechanisms and Possible Responses.
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Miller, Bruce L.
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NEURODEGENERATION , *COVID-19 pandemic , *SCIENTIFIC literacy , *BELIEF & doubt , *LEWY body dementia , *CAPGRAS syndrome , *FRONTOTEMPORAL dementia - Abstract
This Viewpoint discusses possible parallels between the distortion in sensory information and faulty monitoring of ideas characteristic of some patients with neurodegenerative diseases (dementia with Lewy bodies and Capgras syndrome, frontotemporal dementia) and the creation and maintenance of false conspiratorial beliefs about the COVID-19 pandemic in healthy populations that has hobbled an effective national response in the US. [ABSTRACT FROM AUTHOR]
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- 2020
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23. Seizures and Epileptiform Activity in the Early Stages of Alzheimer Disease.
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Vossel, Keith A., Beagle, Alexander J., Rabinovici, Gil D., Huidy Shu, Lee, Suzee E., Naasan, Georges, Hegde, Manu, Cornes, Susannah B., Henry, Maya L., Nelson, Alexandra B., Seeley, William W., Geschwind, Michael D., Gorno-Tempini, Maria L., Shih, Tina, Kirsch, Heidi E., Garcia, Paul A., Miller, Bruce L., and Mucke, Lennart
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- 2013
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24. Progranulin Mutations as Risk Factors for Alzheimer Disease.
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Perry, David C., Lehmann, Manja, Yokoyama, Jennifer S., Karydas, Anna, Lee, Jason JiYong, Coppola, Giovanni, Grinberg, Lea T., Geschwind, Dan, Seeley, William W., Miller, Bruce L., Rosen, Howard, and Rabinovici, Gil
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- 2013
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25. Differential Diagnosis of Jakob-Creutzfeldt Disease.
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Paterson, Ross W., Torres-Chae, Charles C., Kuo, Amy L., Ando, Tim, Nguyen, Elizabeth A., Katherine Wong, DeArmond, Stephen J., Haman, Aissa, Garcia, Paul, Johnson, David Y., Miller, Bruce L., and Geschwind, Michael D.
- Abstract
Objectives: To identify the misdiagnoses of patients with sporadic Jakob-Creutzfeldt disease (sCJD) during the course of their disease and determine which medical specialties saw patients with sCJD prior to the correct diagnosis being made and at what point in the disease course a correct diagnosis was made. Design: Retrospective medical record review. Setting: A specialty referral center of a tertiary academic medical center. Participants: One hundred sixty-three serial patients over a 5.5-year period who ultimately had pathologically proven sCJD. The study used the subset of 97 patients for whom we had adequate medical records. Main Outcome Measures: Other diagnoses considered in the differential diagnosis and types of medical specialties assessing patients with sCJD. Results: Ninety-seven subjects' records were used in the final analysis. The most common disease categories of misdiagnosis were neurodegenerative, autoimmune/ paraneoplastic, infectious, and toxic/metabolic disorders. The most common individual misdiagnoses were viral encephalitis, paraneoplastic disorder, depression, vertigo, Alzheimer disease, stroke, unspecified dementia, central nervous system vasculitis, peripheral neuropathy, and Hashimoto encephalopathy. The physicians who most commonly made these misdiagnoses were primary care physicians and neurologists; in the 18% of patients who were diagnosed correctly at their first assessment, the diagnosis was almost always by a neurologist. The mean time from onset to diagnosis was 7.9 months, an average of two-thirds of the way through their disease course. Conclusions: Diagnosis of sCJD is quite delayed. When evaluating patients with rapidly progressive dementia with suspected neurodegenerative, autoimmune, infectious, or toxic/metabolic etiology, sCJD should also be included in the differential diagnosis, and appropriate diagnostic tests, such as diffusion brain magnetic resonance imaging, should be considered. Primary care physicians and neurologists need improved training in sCJD diagnosis. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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26. Frontotemporal Dementia in a Brazilian Kindred With the C9orf72 Mutation.
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Takada, Leonel T., Pimentel, Maria Lucia V., DeJesus-Hernandez, Mariely, Fong, Jamie C., Yokoyama, Jennifer S., Karydas, Anna, Thibodeau, Marie-Pierre, Rutherford, Nicola J., Baker, Matthew C., Lomen-Hoerth, Catherine, Rademakers, Rosa, and Miller, Bruce L.
- Abstract
Objectives: To describe the clinical features of a Brazilian kindred with C9orf72 frontotemporal dementia-amyotrophic lateral sclerosis and compare them with other described families with C9orf72 and frontotemporal dementia-amyotrophic lateral sclerosis-causing mutations. Design: Report of a kindred. Setting: Dementia center at a university hospital. Patients: One kindred encompassing 3 generations. Results: The presence of a hexanucleotide (GGGGCC) expansion in C9orf72 was confirmed by repeat-primed polymerase chain reaction and Southern blot. The observed phenotypes were behavioral variant frontotemporal dementia and amyotrophic lateral sclerosis with dementia, with significant variability in age at onset and duration of disease. Parkinsonian features with focal dystonia, visual hallucinations, and more posterior atrophy on neuroimaging than is typical for frontotemporal dementia were seen. Conclusions: Behavioral variant frontotemporal dementia due to C9orf72 expansion displays some phenotypic heterogeneity and may be associated with hallucinations, parkinsonism, focal dystonia, and posterior brain atrophy. Personality changes may precede the diagnosis of dementia by many years and may be a distinguishing feature of this mutation. [ABSTRACT FROM AUTHOR]
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- 2012
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27. Saccade Abnormalities in Autopsy-Confirmed Frontotemporal Lobar Degeneration and Alzheimer Disease.
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Boxer, Adam L., Garbutt, Siobhan, Seeley, William W., Jafari, Aria, Heuer, Hilary W., Mirsky, Jacob, Hellmuth, Joanna, Trojanowski, John Q., Huang, Erik, DeArmond, Steven, Neuhaus, John, and Miller, Bruce L.
- Abstract
Background: Deficits in the generation and control of saccades have been described in clinically defined frontotemporal dementia (FTD) and Alzheimer disease (AD). Objective: To determine the saccade abnormalities associated with autopsy-defined cases of frontotemporal lobar degeneration (FTLD) and of AD, because clinical FTD syndromes can correspond to a number of different underlying neuropathologic FTD and non-FTD diagnoses. Design: An infrared eye tracker was used to record visually guided saccades to 10° targets and antisaccades in subjects with autopsy-confirmed FTD and subjects with autopsy-confirmed AD, a mean (SE) of 35.6 (10.0) months prior to death, and age-matched normal controls. Twelve subjects with FTD had an FTLD-TAR DNA-binding protein 43 pathology, 15 had an FTLD-tau pathology, and 1 subject showed an FTLD-fused in sarcoma protein pathology. Receiver operating curve statistics were used to determine the diagnostic value of the oculomotor variables. Neuroanatomical correlates of oculomotor abnormalities were investigated using voxel-based morphometry. Setting: Memory and Aging Center, Department of Neurology, University of California, San Francisco. Participants: A total of 28 subjects with autopsy confirmed FTD, 10 subjects with autopsy-confirmed AD, and 27 age-matched normal controls. Results: All subjects with FTD or AD were impaired relative to normal controls on the antisaccade task. However, only FTLD-tau and AD cases displayed reflexive visually guided saccade abnormalities. The AD cases displayed prominent increases in horizontal saccade latency that differentiated them from the FTD cases. Impairments in velocity and gain were most severe in individuals with progressive supranuclear palsy but were also present in other tauopathies. By using vertical and horizontal saccade velocity and gain as our measures, we were able to differentiate patients with progressive supranuclear palsy from other patients. Vertical saccade velocity was strongly correlated with dorsal midbrain volume. Conclusion: Decreased visually guided saccade velocity and gain are suggestive of underlying tau pathology in FTD, with vertical saccade abnormalities most diagnostic of progressive supranuclear palsy. [ABSTRACT FROM AUTHOR]
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- 2012
28. Apathy Symptom Profile and Behavioral Associations in Frontotemporal Dementia vs Dementia of Alzheimer Type.
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Chow, Tiffany W., Binns, Malcolm A., Cummings, Jeffrey L., Lam, Isabel, Black, Sandra E., Miller, Bruce L., Freedman, Morris, Stuss, Donald T., and van Reekum, Robert
- Abstract
Background: Apathy is a common and significant problem in patients with dementia, regardless of its cause. Observations about frontosubcortical circuit syndromes indicate that apathy may have affective, behavioral, or cognitive manifestations. Objectives: To explore whether the apathy manifested in frontotemporal dementia (FTD), with its predominantly anterior brain neuropathologic features, differs from the apathy in dementia ofAlzheimer type (DAT), with its predominantly hippocampal- and temporoparietal- based neuropathologic features, and to determine whether other behavioral disturbances reported in frontosubcortical circuit syndromes correlate with apathy. Design: Analyses included individual items within Neuropsychiatric Inventory subscale items. Items of the apathy/ indifference subscale were designated by consensus as affective(lacking in emotions), behavioral(inactive, chores abandoned), or cognitive(no interest in the activities of others). Proportions of correlated nonapathy Neuropsychiatric Inventory items were calculated. Setting: Several neurology specialty clinics contributed to our data set. Participants: A total of 92 participants with FTD and 457 with DAT. Main Outcome Measures: The Neuropsychiatric Inventory was analyzed. Results: Apathy was more prevalent in patients with FTD than in those with DAT, but when present, the specific apathy symptoms associated with both types of dementia were rarely restricted to 1 of the 3 domains of apathy. Dysphoria concurrentwith apathy was unique to the DAT group and negatively correlated in the FTD group. Participants with affective apathy more frequently copresented with an orbital frontosubcortical syndrome in FTD (impulsivity and compulsions). Affective apathy also copresented with uncooperative agitation, anger, and physical agitation in both types of dementia. Conclusions: Apathy is common in patients with FTD and DAT, although it is more common in those with FTD. When present, it usually involves changes in affect, behavior, and cognition. It is associated with behaviors that have previously been shown to affect patient safety, independence, and quality of life. [ABSTRACT FROM AUTHOR]
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- 2009
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29. Clinical and Pathological Continuum of Multisystem TDP-43 Proteinopathies.
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Geser, Felix, Martinez-Lage, Maria, Robinson, John, Uryu, Kunihiro, Neumann, Manuela, Brandmeir, Nicholas J., Xie, Sharon X., Kwong, Linda K., Elman, Lauren, McCluskey, Leo, Clark, Chris M., Malunda, Joe, Miller, Bruce L., Zimmerman, Earl A., Jiang Qian, Van Deerlin, Vivianna, Grossman, Murray, Lee, Virginia M.-Y., and Trojanowski, John Q.
- Abstract
Objective: To determine the extent of transactivation response DNA-binding protein with a molecular weight of 43 kDa (TDP-43) pathology in the central nervous system of patients with clinically and autopsy confirmed diagnoses of frontotemporal lobar degeneration with and without motor neuron disease and amyotrophic lateral sclerosis with and without cognitive impairment. Design: Performance of immunohistochemical whole-central nervous system scans for evidence of pathological TDP-43 and retrospective clinical medical record review. Setting: An academic medical center. Participants: We included 64 patients with clinically and pathologically confirmed frontotemporal lobar degeneration with ubiquitinated inclusions with or without motor neuron disease and amyotrophic lateral sclerosis with or without cognitive impairment. Main Outcome Measure: Neuronal and glial TDP-43 pathology. Results: We found evidence of neuronal and glial TDP-43 pathology in all disease groups throughout the neuraxis, albeit with variations in the frequency, morphology, and distribution of TDP-43 lesions. Moreover, the major clinical manifestations (eg, cognitive impairments, motor neuron signs, extrapyramidal symptoms, neuropsychiatric features) were reflected by the predominant distribution and burden of TDP-43 pathology. Conclusion: These findings strongly suggest that amyotrophic lateral sclerosis, frontotemporal lobar degeneration with amyotrophic lateral sclerosis or motor neuron disease, and frontotemporal lobar degenerationwith ubiquitinated inclusions are different manifestations of a multiple-system TDP-43 proteinopathy linked to similar mechanisms of neurodegeneration. [ABSTRACT FROM AUTHOR]
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- 2009
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30. Association of GSK3B With Alzheimer Disease and Frontotemporal Dementia.
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Schaffer, Barbara A. J., Bertram, Lars, Miller, Bruce L., Mullin, Kristina, Weintraub, Sandra, Johnson, Nancy, Bigio, Eileen H., Mesulam, Marsel, Wiedau-Pazos, Martina, Jackson, George R., Cummings, Jeffrey L., Cantor, Rita M., Levey, Allan I., Tanzi, Rudolph E., and Geschwind, Daniel H.
- Abstract
Background: Deposits of abnormally hyperphosphorylated tau are a hallmark of several dementias, including Alzheimer disease (AD), and about 10% of familial frontotemporal dementia (FTD) cases are caused by mutations in the tau gene. As a known tau kinase, GSK3B is a promising candidate gene in the remaining cases of FTD and in AD, for which tau mutations have not been found. Objective: To examine the promoter of GSK3B and all 12 exons, including the surrounding intronic sequence, in patients with FTD, patients with AD, and aged healthy subjects to identify single-nucleotide polymorphisms associated with disease. Design, Setting, and Participants: Singlenucleotide polymorphism frequency was examined in a case-control cohort of 48 patients with probable AD, 102 patients with FTD, 38 patients with primary progressive aphasia, and 85 aged healthy subjects. Results were followed up in 2 independent AD family samples consisting of 437 multiplex families with AD (National Institute of Mental Health Genetics Initiative AD Study) or 150 sibships discordant for AD (Consortium on Alzheimer's Genetics Study). Results: Several rare sequence variants in GSK3B were identified in the case-control study. An intronic polymorphism (IVS2-68G>A) occurred at more than twice the frequency among patients with FTD (10.8%) and patients with AD (14.6%) than in aged healthy subjects (4.1%). The polymorphism showed association with disease in both follow-up samples independently, although only the Consortium on Alzheimer's Genetics sample showed the same direction of association as the case-control sample. Conclusions: To our knowledge, this is the first evidence that a gene known to be involved in tau phosphorylation, GSK3B, is associated with risk for primary neurodegenerative dementias. This supports previous work in animal models suggesting that such genes are therapeutic targets. [ABSTRACT FROM AUTHOR]
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- 2008
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31. Frontal Paralimbic Network Atrophy in Very Mild Behavioral Variant Frontotemporal Dementia.
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Seeley, William W., Crawford, Richard, Rascovsky, Katya, Kramer, Joel H., Weiner, Michael, Miller, Bruce L., and Gorno-Tempini, Maria Luisa
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Background: Behavioral variant frontotemporal dementia (bvFTD) strikes hardest at the frontal lobes, but the sites of earliest injury remain unclear. Objective: To determine atrophy patterns in distinct clinical stages of bvFTD, testing the hypothesis that the mildest stage is restricted to frontal paralimbic cortex. Design: A bvFTD cohort study. Setting: University hospital dementia clinic. Participants: Patients with bvFTD with Clinical Dementia Rating (CDR) scale scores of 0.5 (n=15), 1 (n=15), or 2 to 3 (n=15) age and sex matched to each other and to 45 healthy controls. Main Outcome Measures: Magnetic resonance voxel-based morphometry estimated gray matter and white matter atrophy at each disease stage compared with controls. Results: Patients with a CDR score of 0.5 had gray matter loss in frontal paralimbic cortices, but atrophy also involved a network of anterior cortical and subcortical regions. A CDR score of 1 showed more extensive frontal gray matter atrophy and white matter losses in corpus callosum and brainstem. ACDR score of 2 to 3 showed additional posterior insula, hippocampus, and parietal involvement, with white matter atrophy in presumed frontal projection fibers. Conclusions: Very mild bvFTD targets a specific subset of frontal and insular regions. More advanced disease affects white matter and posterior gray matter structures densely interconnected with the sites of earliest injury. [ABSTRACT FROM AUTHOR]
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- 2008
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32. Patterns of White Matter Atrophy in Frontotemporal Lobar Degeneration.
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Chao, Linda L., Schuff, Norbert, Clevenger, Erin M., Mueller, Susanne G., Rosen, Howard J., Gorno-Tempini, Maria L., Kramer, Joel H., Miller, Bruce L., and Weiner, Michael W.
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Background: Structural magnetic resonance imaging (MRI) has been used to investigate the in vivo pathology of frontotemporal lobar degeneration. However, few neuroimaging studies have focused on white matter(WM) alterations in this disease. Objectives: To use volumetric MRI techniques to identify the patterns of WM atrophy in vivo in 2 clinical variants of frontotemporal lobar degeneration--frontotemporal dementia (FTD) and semantic dementia--and to compare the patterns of WM atrophy with those of gray matter (GM) atrophy in these diseases. Design: Structural MRIs were obtained from patients with FTD (n=12) and semantic dementia (n=13) and in cognitively healthy age-matched controls (n=24). Regional GM and WM were classified automatically from highresolution T1-, T2-, and proton density-weighted MRIs with Expectation-Maximization Segmentation and compared between the groups using a multivariate analysis of covariance model that included age and WM lesion volumes as covariates. Results: Patients with FTD had frontal WM atrophy and frontal, parietal, and temporal GM atrophy compared with controls, who had none. Patients with semantic dementia had temporal WM and GM atrophy and patients with FTD had frontal GM atrophy. Adding temporal WM volume to temporal GM volume significantly improved the discrimination between semantic dementia and FTD. Conclusions: These results show that patients with fron to temporal lobar degeneration who are in relatively early stages of the disease (Clinical Dementia Rating score, 1.0-1.2) have WM atrophy that largely parallels the pattern of GM atrophy typically associated with these disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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33. TDP-43 Pathologic Lesions and Clinical Phenotype in Frontotemporal Lobar Degeneration With Ubiquitin-Positive Inclusions.
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Grossman, Murray, Wood, Elisabeth M., Moore, Peachie, Neumann, Manuela, Kwong, Linda, Forman, Mark S., Clark, Christopher M., McCluskey, Leo F., Miller, Bruce L., Lee, Virginia M.-Y., and Trojanowski, John Q.
- Abstract
Background: TDP-43 is a major ubiquitinated disease protein in the pathologic condition of frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). Objective: To investigate the demographic, clinical, and neuropsychological features associated with subtypes of FTLD-U with TDP-43 inclusions (FTLD-U/TDP-43). Design: Retrospective clinical-pathologic study. Setting: Academic medical center. Patients: Twenty-three patients with histopathologically proven FTLD-U. Main Outcome Measures: Demographic, symptom, neuropsychological, and autopsy characteristics. Results: There are notably different clinical and neuropsychological patterns of impairment in FTLD-U subtypes. Patients with FTLD-U/TDP-43 characterized by numerous neuronal intracytoplasmic inclusions have shorter survival; patients with FTLD-U/TDP-43 featuring numerous neurites have difficulty with object naming; and patients with FTLD-U/TDP-43 in whom neuronal intranuclear inclusions are present have substantial executive deficits. There are also different anatomical distributions of ubiquitin pathologic features in FTLD-U subgroups, consistent with their cognitive deficits. Conclusion: Distinct TDP-43 profiles may affect clinical phenotypes differentially in patients with FTLD-U. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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34. Deformation-Based Morphometry Reveals Brain Atrophy in Frontotemporal Dementia.
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Cardenas, Valerie A., Boxer, Adam L., Chao, Linda L., Gorno-Tempini, Maria L., Miller, Bruce L., Weiner, Michael W., and Studholme, Colin
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Objective: To compare deformation-based maps of local anatomical size between subjects with frontotemporal dementia (FTD) and healthy subjects to identify regions of the brain involved in FTD. Design: Structural magnetic resonance images were obtained from 22 subjects with FTD and 22 cognitively normal, age-matched controls. We applied deformation based morphometry and compared anatomy between groups using an analysis of covariance model that included a categorical variable denoting group membership and covaried for head size. Setting: University of California, San Francisco, Memory and Aging Center, and the San Francisco Veterans Affairs Medical Center. Patients: Twenty-two subjects with FTD and 22 cognitively normal, age-matched controls. Interventions: Neurological, neuropsychological, and functional evaluations and magnetic resonance imaging. Main Outcome Measure: Deformation maps of local anatomical size. Results: Patients with FTD showed extensive, significant atrophy of the frontal lobes, affecting both gray matter and white matter. Atrophy of similar magnitude but less significance was observed in the anterior temporal lobes. The subcortical and midbrain regions, particularly the thalamus, pons, and superior and inferior colliculi, showed strongly significant atrophy of smaller magnitude. Conclusions: We confirmed frontal and anterior temporal gray matter atrophy in FTD. The observed white matter loss, thalamic involvement, and midbrain atrophy are consistent with pathological findings in latestage FTD. Dysfunction of ventral-frontal-brainstem circuitry may underlie some of the unique clinical features of FTD. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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35. Accuracy of the Clinical Evaluation for Frontotemporal Dementia.
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Mendez, Mario F., Shapira, Jill S., McMurtray, Aaron, Licht, Eliot, and Miller, Bruce L.
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Background: Without a definitive clinical test, the early diagnosis of frontotemporal dementia (FTD) can be difficult. Objective: To evaluate the accuracy of the clinical evaluation for FTD. Design: Retrospective assessment of consensus criteria for FTD, neuropsychological measures, magnetic resonance images, and single-photon emission computed tomography/positron emission tomography (SPECT/PET) scans at baseline compared with a standard of subsequent clinical diagnosis after follow-up and reevaluation to year 2. Setting: University hospital. Patients: A total of 134 patients referred for clinical evaluation of suspected FTD. These patients had 1 or more core or supportive features of FTD in the absence of another etiology on initial assessment. Main Outcome Measures: Sensitivities, specificities, and predictive values of consensus criteria for FTD, magnetic resonance images, and SPECT/PET scans at initial assessment. Results: The sensitivities and specificities for the diagnosis of FTD were 36.5% and 100.0% for consensus criteria, 63.5% and 70.4% for magnetic resonance images, and 90.5% and 74.6% for SPECT/PET scans, respectively. With a previous prevalence of nearly 50% for FTD, the positive predictive value was greatest for consensus criteria (100.0%), and the negative predictive value was greatest for SPECT/PET (89.8%). The initial neuropsychological results did not distinguish FTD, but the pattern of progression (worse naming and executive functions and preserved constructional ability) helped establish the diagnosis at year 2. Conclusions: Consensus criteria for FTD and neuropsychological measures lacked sensitivity for FTD; however, neuroimaging, particularly functional brain studies, greatly increased the sensitivity of detecting FTD. The clinical diagnosis of FTD needs to combine neuropsychiatric features with SPECT or PET findings while following the changes on neuropsychological tests. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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36. Continuum of Frontal Lobe Impairment in Amyotrophic Lateral Sclerosis.
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Murphy, Jennifer M., Henry, Roland G., Langmore, Susan, Kramer, Joel H., Miller, Bruce L., and Lomen-Hoerth, Catherine
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Objective: To identify the nature and prevalence of cognitive and behavioral abnormalities in patients with amyotrophic lateral sclerosis (ALS). Design: Survey of clinical characteristics. Setting: Multidisciplinary clinic within a university medical center. Patients: A volunteer sample of 30 new patients with ALS were recruited consecutively. Of those invited, 23 participants (20 with sporadic ALS and 3 with familial ALS) enrolled. Participants ranged in age from 27 to 80 years (mean age, 56.5 years); the education level ranged from 12 to 21 years (mean education level, 3.5 years of college); and 17 participants (74%) were male. Main Outcome Measures: Neuropsychological tests, neurobehavioral interviews, and structured magnetic resonance imaging. Results: Patients were classified into subtypes of frontotemporal lobar degeneration (n = 5), suspected Alzheimer disease (n= 1), and subthreshold variants of cognitive impairment (n = 2), behavioral impairment (n = 4), and cognitively and behaviorally normal (n=11). Five neuropsychological tests, 2 behavioral abnormalities, and right hemisphere gray matter reductions differentiated patients into normal and abnormal groups. Conclusions: In this sample, a sizable proportion of patients with ALS possess a range of behavioral and cognitive changes that lie on a spectrum of frontotemporal impairment. Right hemisphere atrophy may be a biomarker for cognitive impairment in patients with ALS. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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37. Dysphagia in Patients With Frontotemporal Lobar Dementia.
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Langmore, Susan E., Olney, Richard K., Lomen-Hoerth, Catherine, and Miller, Bruce L.
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Background: Hyperorality, compulsive eating and aspiration because of food gorging, has been described in patients with frontotemporal lobar dementia (FTLD), but swallowing function in this population has not been reported. Objective: To identify the swallowing status in a sample of patients with FTLD. Design: Case series. Setting: Referral center, ambulatory care. Patients: A consecutive series of referred patients with 3 variants of FTLD were asked to participate. Twentyone patients were enrolled, including 9 with frontotemporal dementia, 7 with progressive nonfluent aphasia, and 5 with semantic dementia. Intervention: The patients underwent a fiberoptic endoscopic examination of swallowing to assess their ability to swallow liquids and food. Main Outcome Measures: Presence of dysphagia and nature of impaired swallowing. Results: Of the 21 patients, 4 caretakers reported swallowing difficulties. An instrumental examination revealed moderate swallowing abnormalities in 12 of the 21 patients. These abnormalities were not explained by compulsive eating behaviors, but seemed to reflect deficits in cortical and subcortical pathways connecting with the brainstem swallowing center. Conclusions: When assessed via instrumentation, swallowing abnormalities are found in many patients with FTLD. The appearance of dysphagia signals progression of FTLD to brainstem systems. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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38. Patterns of Brain Atrophy That Differentiate Corticobasal Degeneration Syndrome From Progressive Supranuclear Palsy.
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Boxer, Adam L., Geschwind, Michael D., Belfor, Nataliya, Gorno-Tempini, Maria Luisa, Schauer, Guido F., Miller, Bruce L., Weiner, Michael W., and Rosen, Howard J.
- Abstract
Background: Progressive brain atrophy is associated with the corticobasal degeneration syndrome (CBDS) and progressive supranuclear palsy (PSP). Regional differences in brain atrophy may reflect the clinical features of disease. Objective: To quantify the structural neuroanatomical differences between CBDS and PSP. Design: A survey of neurologic deficits was conducted in all patients. Voxel-based morphometry was used to quantify structural neuroanatomical differences on magnetic resonance images in each subject group. Setting: University hospital dementia clinic. Participants: Fourteen patients who met clinical research criteria for CBD and 15 patients who met clinical research criteria for PSP, who were matched for severity of disease, age, and functional status, and 80 age matched control subjects. Main Outcome Measures: Statistically significant differences in regional gray and white matter volume, after multiple comparisons correction, between groups of subjects. Results: The patients with CBDS displayed an asymmetric (left > right) pattern of brain atrophy that involved the bilateral premotor cortex, superior parietal lobules, and striatum. Progressive supranuclear palsy was associated with atrophy of the midbrain, pons, thalamus, and striatum, with minimal involvement of the frontal cortex. Midbrain structures were more atrophied in PSP than in CBD, whereas dorsal frontal and parietal cortices were more atrophied in CBD than in PSP. The degree of atrophy of the midbrain and pontine tegmentum and the left frontal eye field differentiated the 2 patient groups with 93% accuracy. Conclusions: Distinct patterns of brain atrophy exist in CBDS and PSP that can be used to differentiate the 2 diseases. Assessments of brain atrophy in these disorders should be focused on cortical and brainstem ocular motor control areas. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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39. Presenilin 1 Glu318Gly Polymorphism: Interpret With Caution.
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Goldman, Jill S., Johnson, Julene K., McElligott, Karen, Suchowersky, Oksana, Miller, Bruce L., and Van Deerlin, Vivianna M.
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PRESENILINS ,MEMBRANE proteins ,DEMENTIA ,DISEASE relapse ,NEUROBEHAVIORAL disorders ,NEURODEGENERATION ,NEUROLOGY - Abstract
Background The significance of the presenilin 1 (PSEN1) Glu318Gly polymorphism has been described as either a causal mutation with reduced penetrance or a benign polymorphism. When this polymorphism is found in a symptomatic person with a family history of dementia, counseling on recurrence risk becomes very problematic. Objective To demonstrate that the PSEN1 Glu318Gly polymorphism should be interpreted cautiously. Design Case histories of 2 patients with presenile dementia and family histories of dementia are described. The PSEN1 gene was sequenced in the patients and in 11 family members of patient 1. Results Two patients with presenile dementia and personality change were found to carry the PSEN1 Glu318Gly polymorphism. The presence of the polymorphism was confirmed in several family members of patient 1 but was absent in 1 symptomatic relative. Conclusions The Glu318Gly polymorphism may be associated with risk for neurodegenerative disease; however, in the cases described here, it did not appear to be a risk factor. Until there is consensus on whether it is associated with disease, families should be informed that the clinical significance of the polymorphism is uncertain. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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40. Frontotemporal Lobar Degeneration: Demographic Characteristics of 353 Patients.
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Johnson, Julene K., Diehl, Janine, Mendez, Mario F., Neuhaus, John, Shapira, Jill S., Forman, Mark, Chute, Dennis J., Roberson, Erik D., Pace-Savitsky, Catherine, Neumann, Manuela, Chow, Tiffany W., Rosen, Howard J., Forstl, Hans, Kurz, Alexander, and Miller, Bruce L.
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NEURODEGENERATION ,DEMENTIA ,APHASIA ,NEUROBEHAVIORAL disorders ,BRAIN diseases ,NEUROLOGICAL disorders ,NERVOUS system ,NEUROLOGY - Abstract
Background Until recently, frontotemporal lobar degeneration (FTLD) was considered a rare neurodegenerative disorder that was difficult to diagnose. The publication of consensus criteria for FTLD, however, prompted systematic studies. The criteria categorize FTLD into 3 subgroups: frontotemporal dementia, semantic dementia, and progressive nonfluent aphasia. Objective To compare demographic characteristics of patients in the 3 FTLD subgroups. Design We compared diagnostic breakdown, age at onset, sex, Mini-Mental State Examination score at first visit, education, and neuropathological diagnoses in a large sample of FTLD patients from 3 different university dementia clinics, including 2 neurologic clinics in the United States and 1 psychiatric clinic in Germany. Results The frontotemporal dementia subgroup represented approximately half of all FTLD diagnoses. Patients diagnosed as having frontotemporal dementia (mean age, 57.5 years) and semantic dementia (mean age, 59.3 years) had an earlier age at onset than patients diagnosed as having progressive nonfluent aphasia (mean age, 63.0 years). There were significantly more men diagnosed as having frontotemporal dementia (63.5%) and semantic dementia (66.7%) when compared with progressive nonfluent aphasia (39.1%) (P = .005 for frontotemporal dementia vs progressive nonfluent aphasia and P = .002 for semantic dementia vs progressive nonfluent aphasia). Generally, the demographic features and diagnostic categories of the patient populations across the 3 sites were comparable. There were 68 deaths and 37 autopsies. Frontotemporal lobar degeneration with ubiquitin-positive τ-negative inclusions (48.5%), dementia lacking distinctive histopathological features (18.2%), and Pick disease (15.2%) were the most common neuropathological diagnoses. Conclusions These findings show that cohorts of patients can be combined using new research criteria for FTLD and demonstrate striking demographic differences among FTLD subgroups. The sex and age-at-onset differences suggest that there may be biological differences among FTLD subgroups. In this sample, FTLD with ubiquitin-positive inclusions accounted for half of all neuropathological diagnoses. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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41. 17q-Linked Frontotemporal Dementia–Amyotrophic Lateral Sclerosis Without Tau Mutations With Tau and α-Synuclein Inclusions.
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Wilhelmsen, Kirk C., Forman, Mark S., Rosen, Howard J., Alving, Loren I., Goldman, Jill, Feiger, Jennie, Lee, James V., Segall, Samantha K., Kramer, Joel H., Lomen-Hoerth, Catherine, Rankin, Katherine P., Johnson, Julene, Feiler, Heidi S., Weiner, Michael W., Lee, Virginia M. -Y., Trojanowski, John Q., and Miller, Bruce L.
- Subjects
DEMENTIA ,DISEASE risk factors ,EXTRAPYRAMIDAL disorders ,MOTOR neuron diseases ,FAMILIAL diseases ,CHROMOSOME abnormalities ,GENETIC mutation - Abstract
Background: Frontotemporal dementia (FTD) is a clinically heterogeneous condition that can be associated with clinical manifestations of an extrapyramidal disorder or motor neuron disease. A range of histologic patterns has been described in patients with FTD. The most common familial form of this condition is caused by mutations in the microtubule-associated protein tau gene (MAPτ) and is associated with neuronal or glial tau inclusions. Objectives: To determine the clinical, anatomic, and pathological features of San Francisco family A and to map the mutation responsible for disease in this family. Design: A systematic clinical, neuropsychologic, neuroimaging, and chromosome segregation analysis of San Francisco family A was performed. A pathological and biochemical assessment of a family member was made. Setting: Family study. Patients: San Francisco family A, with FTD, variable extrapyramidal symptoms, and prominent motor neuron disease. Afflicted family members donot have a MAPτ coding or splice regulatory sequence mutation, and the MAPτ is genetically excluded. Main Outcome Measures: Comparison of clinical, neuropsychologic, neuroimaging, and linkage findings of San Francisco family A with other familial forms of FTD and amyotrophic lateral sclerosis (ALS). Results: The most probable location for the mutation responsible for this condition is on chromosome arm 17q, distal to the MAPτ. All previously identified susceptibility loci for FTD and ALS are excluded. Autopsy findings from an afflicted family member show distinctive tau and α-synuclein inclusions. Another unique feature is that the insoluble tau protein consists predominantly of the 4R/0N isoform. Conclusion: The condition affecting members of San Francisco family A is clinically, pathologically, and genetically distinct from previous familial forms of FTD and ALS. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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42. When Sporadic Disease Is Not Sporadic.
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Goldman, Jill S., Miller, Bruce L., Safar, Jiri, de Tourreil, Sunita, Martindale, Jennifer L., Prusiner, Stanley B., and Geschwind, Michael D.
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PRION diseases ,ALZHEIMER'S disease ,CREUTZFELDT-Jakob disease ,SLOW virus diseases ,NEUROLOGY - Abstract
Discusses the need for consideration of genetic aetiology of prion disease and early-onset Alzheimer's disease. Discovery of hereditary cause of Creutzfeld-Jakob disease and Alzheimer's disease; Importance of pretest counselling to prepare families in making informed choice about learning genetic results.
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- 2004
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43. Cinguloparietal Atrophy Distinguishes Alzheimer Disease From Semantic Dementia.
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Boxer, Adam L., Rankin, Katherine P., Miller, Bruce L., Schuff, Norbert, Weiner, Michael, Gorno-Tempini, Maria-Luisa, and Rosen, Howard J.
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ALZHEIMER'S disease ,DEMENTIA ,TEMPORAL lobe ,MAGNETIC resonance imaging ,THALAMUS - Abstract
Progressive brain atrophy is associated with Alzheimer disease (AD) and other dementias. Regional differences in brain atrophy may reflect clinical features of disease. To identify regions of cerebral atrophy that are associated with AD vs other dementias. Eleven patients with AD and 11 with semantic dementia (SD), matched for age, sex, education, and degree of overall cognitive impairment and 15 normal controls. Voxel-based morphometry was used to compare patterns of gray matter loss, measured on T1-weighted magnetic resonance images, between patients with AD or SD, a subtype of frontotemporal lobar degeneration, and controls. Statistically significant differences in regional gray matter concentration, after multiple comparisons correction, between groups of subjects were identified. Patients with AD were more impaired than those with SD on tests of visuospatial function and on simple calculations. Consistent with these neuropsychological deficits, the most significant area of atrophy in the AD group was the left parietal cortex vs controls (ζ=5.0; P=.04). Compared with SD, AD was associated with more atrophy in the left parietal lobe (ζ=5.6; P=.04) and bilaterally in the posterior cingulate/precuneus (ζ=5.1; P=.04). A discriminant function analysis demonstrated that the degree of atrophy of right posterior cingulate, left parietal lobe, right amygdala, and right anterior temporal lobe structures correctly classified 96% of the patients. Alzheimer disease is associated with a specific pattern of cortical atrophy compared with SD. [ABSTRACT FROM AUTHOR]
- Published
- 2003
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44. Challenging the Clinical Utility of the 14-3-3 Protein for the Diagnosis of Sporadic Creutzfeldt-Jakob Disease.
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Geschwind, Michael D., Martindale, Jennifer, Miller, Deborah, DeArmond, Stephen J., Uyehara-Lock, Jane, Gaskin, David, Kramer, Joel H., Barbaro, Nicholas M., and Miller, Bruce L.
- Subjects
CREUTZFELDT-Jakob disease ,NEURODEGENERATION ,CEREBROSPINAL fluid ,NEUROLOGICAL research - Abstract
Background: Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and fatal neurodegenerative disorder for which there is no noninvasive and disease-specific test for premortem diagnosis. Previous studies have suggested that, in the proper clinical context, the 14-3-3 protein in cerebrospinal fluid is a reliable marker for sporadic CJD. Objective: To assess the sensitivity of the cerebrospinal fluid 14-3-3 protein test among patients with definite sporadic CJD. Design and Setting: We reviewed cases of sporadic CJD referred to our institution that were ultimately proved by pathological examination and on which cerebrospinal fluid 14-3-3 testing had been performed. Participants: Patients with CJD referred to our institution for clinical and/or pathological evaluation (biopsy- or autopsy-confirmed diagnosis) from January 1, 1998, through July 15, 2002, and on whom 14-3-3 testing had been performed. Thirty-two such patients with definite sporadic CJD were identified. Main Outcome Measure: The 14-3-3 test results, from various laboratories, in these 32 patients. Results: Seventeen of the 32 patients had a positive result for the 14-3-3 test, yielding a sensitivity of only 53%. A positive 14-3-3 result was significantly correlated with a shorter time between disease onset and the lumbar puncture for the 14-3-3 test. Conclusions: Testing for the 14-3-3 protein is only modestly sensitive to sporadic CJD, and we caution against ruling out a diagnosis of the disease on the basis of a negative 14-3-3 result. [ABSTRACT FROM AUTHOR]
- Published
- 2003
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45. Novel Tau Polymorphisms, Tau Haplotypes, and Splicing in Familial and Sporadic Frontotemporal Dementia.
- Author
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Sobrido, Maria-Jesús, Miller, Bruce L., Havlioglu, Necat, Zhukareva, Victoria, Jiang, Zhihong, Nasreddine, Ziad S., Lee, Virginia M.-Y., Chow, Tiffany W., Wilhelmsen, Kirk C., Cummings, Jeffrey L., Wu, Jane Y., and Geschwind, Daniel H.
- Subjects
DEMENTIA ,GENETIC mutation ,GENETICS - Abstract
Background: A subset of familial cases (FTDP-17) of frontotemporal dementia (FTD) are caused by mutations in the tau gene. The role of tau gene mutations and haplotypes in sporadic FTD and the functional consequences of tau polymorphisms are unknown. Objectives: To investigate (1) the frequency of known FTDP-17 mutations in familial and sporadic FTD and compare these results with previous studies; (2) whether the tau H1 haplotype is associated with FTD; and (3) the functional effect of intronic tau sequence variations. Patients and Methods: Patients with familial and sporadic FTD were screened for mutations in the microtubule-binding region of tau. The frequencies of tau haplotypes and genotypes were compared between patients with FTD and control subjects. We analyzed the splicing effect of novel intronic polymorphisms associated with FTD. Results: The P301L mutation was detected in 11% of familial FTD cases. The H1 haplotype was not overrepresented in patients with FTD, but the P301L mutation appeared on the background of the H2 tau haplotype. We identified 4 novel single nucleotide polymorphisms in intron 9 and a 9–base pair deletion in intron 4A. A C-to-T transition 177 base pairs upstream from exon 10 was significantly increased in patients with FTD compared with controls. Direct analysis of brain tissue from a patient with this variant showed an increase in exon 10–containing tau transcripts. Conclusions: Sequence variations in intronic or regulatory regions of tau may have previously unrecognized consequences leading to tau dysfunction and neurodegeneration. [ABSTRACT FROM AUTHOR]
- Published
- 2003
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- View/download PDF
46. Sporadic Creutzfeldt-Jakob Disease Mimicking Variant Creutzfeldt-Jakob Disease.
- Author
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Martindale, Jennifer, Geschwind, Michael D., De Armond, Stephen, Young, Geoffrey, Dillon, W. P., Henry, Roland, Uyehara-Lock, Jane H., Gaskin, David A., and Miller, Bruce L.
- Subjects
CREUTZFELDT-Jakob disease ,PRION diseases - Abstract
Background: The determination of the form of prion disease and early diagnosis are important for prognostic, public health, and epidemiologic reasons. Objective: To describe a patient with sporadic Creutzfeldt-Jakob disease (sCJD) who had a clinical history and initial electroencephalogram and magnetic resonance imaging findings consistent with variant CJD (vCJD). Results: Results of a repeated electroencephalogram were suggestive of sCJD, and a subsequent brain biopsy confirmed this diagnosis. Conclusions: This case cautions against relying solely on T2- and diffusion-weighted pulvinar hyperintensity and clinical features to differentiate between vCJD and sCJD, and further supports established diagnostic criteria for vCJD. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
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47. Cerebrovascular and Brain Morphologic Correlates of Mild Cognitive Impairment in the National Heart, Lung, and Blood Institute Twin Study.
- Author
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DeCarli, Charles, Miller, Bruce L., Swan, Gary E., Reed, Terry, Wolf, Philip A., and Carmelli, Dorit
- Subjects
CEREBROVASCULAR disease risk factors ,PHYSIOLOGICAL aspects of cognition ,BRAIN abnormalities - Abstract
Objective: To evaluate the relative risk (RR) of mild cognitive impairment (MCI) associated with cerebrovascular risk factors and cerebrovascular-related brain changes. Design: Mild cognitive impairment was determined for the subjects of the prospective National Heart, Lung, and Blood Institute Twin Study. Quantitative measures of brain, white matter hyperintensity, cerebral infarction, apolipoprotein E genotype, and psychometric testing were obtained. Results: Subjects with MCI were older (73.5 ± 3.0 vs 72.1 ± 2.8 years), consumed less alcohol (3.7 ± 5.8 vs 7.0 ± 10.7 drinks per week), had greater white matter hyperintensity volumes (0.56% ± 0.82% vs 0.25% ± 0.34% of cranial volume), and had an increased prevalance of apolipoprotein E4 genotype (31.4% vs 19.2%) than normal subjects. White matter hyperintensity and the presence of the apolipoprotein E4 genotype were associated with a significantly increased risk for MCI. When all subjects were included in the analysis, alcohol consumption was associated with a reduced risk for MCI (RR = 0.93, P<.05). When subjects with a history of symptomatic cerebrovascular disease were excluded from the analysis, elevated midlife diastolic blood pressure was associated with an increased risk for MCI (RR = 1.70, P<.05). Conclusions: Elevated midlife blood pressures, and the resulting increased white matter hyperintensities, increase the risk for MCI in a group of community-dwelling older men to at least the same degree as apolipoprotein E4 genotype. Given the common occurrence of elevations in midlife blood pressure, early and effective treatment may be warranted to prevent late-life brain abnormalities and MCI. Moreover, since many individuals with MCI progress to clinical dementia, longitudinal evaluations of this cohort will be important. [ABSTRACT FROM AUTHOR]
- Published
- 2001
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48. Inheritance of Frontotemporal Dementia.
- Author
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Chow, Tiffany W., Miller, Bruce L., Hayashi, Vivian N., and Geschwind, Daniel H.
- Subjects
DEMENTIA ,GENETIC disorders ,NEUROBEHAVIORAL disorders - Abstract
Background: Previous studies of families with frontotemporal dementia (FTD) support an autosomal dominant inheritance pattern, but most studies have described genetic transmission in individual families specifically selected for the presence of multiple affected individuals. Objective: To investigate the familial presentation and inheritance of FTD and related disorders among a large group of FTD index cases unselected for family history of dementia. Design and Setting: We interviewed family members and reviewed medical records and autopsy reports at a university hospital and a university-affiliated hospital to determine the frequency of familial FTD and the most likely mode of inheritance. Characteristic families with the disorder are described, along with the history, clinical findings, and neuroimaging results in affected members of these families. Patients and Participants: The 42 index cases of FTD had a mean age of onset of 56.1 years (range, 40-69 years). Of these patients, 21 (50%) were women. All but one of the patients were white. Participants included male and female spouses and children of the index cases. Results: Of 42 FTD cases, 19 (45%) had at least 1 other family member with an FTD spectrum disorder and were considered familial cases. The majority (17 [89%]) of familial FTD cases showed a pattern consistent with dominant inheritance. If depression is excluded, familial cases decrease from 19 (45%) to 17 (40%), of which 15 (88%) showed a dominant transmission pattern. The initial presentations in the nonindex familial cases varied but most frequently consisted of personality and behavioral changes that preceded cognitive impairment (19 [43%]), followed by psychiatric illness (14 [33%]), dementia without behavioral change (5 [11%]), amyotrophic lateral sclerosis (5 [11%]), and parkinsonism (2 [5%]). Two of the affected nonindex cases had dual presenting diagnoses. The average age of onset was 56.1 years and did not differ significantly betwe... [ABSTRACT FROM AUTHOR]
- Published
- 1999
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49. Differential Genetic Influence for Components of Memory in Aging Adult Twins.
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Swan, Gary E., Reed, Terry, Jack, Lisa M., Miller, Bruce L., Markee, Taryn, Wolf, Philip A., DeCarli, Charles, and Carmelli, Dorit
- Subjects
MEMORY ,OLDER veterans ,TWINS - Abstract
Objective: To investigate the relative proportion of genetic and environmental contributions to verbal memory in community-dwelling World War II veteran twins. Design: The California Verbal Learning Test (CVLT) was administered to 94 monozygotic (MZ) and 89 dizygotic (DZ) elderly male twin pair participants in the fourth examination of the National Heart, Lung, and Blood Institute Twin Study. Setting: Subjects voluntarily participated on an outpatient basis at a research or medical center facility in 1 of 4 sites in the United States. Participants: Subjects had a mean age of 71.8 years (SD, 2.9 years), a mean educational level of 13.6 years (SD, 2.8 years), and no history of stroke and/or a Mini-Mental State Examination score of 23 or greater. Main Outcome Measures: Twin pair similarity in performance on 4 factor analytically derived components of the CVLT measuring verbal learning and memory, response discrimination, learning strategy, and recognition memory. Results: The MZ intraclass correlation was significantly larger than the DZ correlation for verbal learning and memory (I<.001) but not for the other 3 components of memory. Using maximum likelihood methods, the best-fitting genetic model indicated that verbal learning and memory has a substantial genetic component (56% of total variance), whereas response discrimination has a much smaller, although still detectable, genetic component (24% of total variance). There is no evidence of genetic influence on learning strategy or recognition memory. Conclusion: Differential contribution of genetic and environmental influences to specific components of memory suggest that, in this group of elderly male twin pairs, some components may be more amenable to intervention than others. [ABSTRACT FROM AUTHOR]
- Published
- 1999
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50. Dietary Supplements for Brain Health-Reply.
- Author
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Hellmuth, Joanna, Rabinovici, Gil D., and Miller, Bruce L.
- Subjects
DIETARY supplements ,COGNITION disorders ,VITAMIN B complex ,BRAIN ,DEMENTIA - Published
- 2019
- Full Text
- View/download PDF
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