125 results on '"Clifford, Jack"'
Search Results
2. Generation of a gene-corrected human isogenic iPSC line from an Alzheimer’s disease iPSC line carrying the PSEN1 H163R mutation
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Damián Hernández, Stephanie Morgan Schlicht, Jordan Elli Clarke, Maciej Daniszewski, Celeste M. Karch, Alison M. Goate, Alice Pébay, Sarah Adams, Ricardo Allegri, Aki Araki, Nicolas Barthelemy, Randall Bateman, Jacob Bechara, Tammie Benzinger, Sarah Berman, Courtney Bodge, Sus Brandon, William (Bill) Brooks, Jared Brosch, Jill Buck, Virginia Buckles, Kathleen Carter, Lisa Cash, Charlie Chen, Jasmeer Chhatwal, Patricio Chrem Mendez, Jasmin Chua, Helena Chui, Laura Courtney, Carlos Cruchaga, Gregory S Day, Chrismary DeLaCruz, Darcy Denner, Anna Diffenbacher, Aylin Dincer, Tamara Donahue, Jane Douglas, Duc Duong, Noelia Egido, Bianca Esposito, Anne Fagan, Marty Farlow, Becca Feldman, Colleen Fitzpatrick, Shaney Flores, Nick Fox, Erin Franklin, Nelly Joseph-Mathurin, Hisako Fujii, Samantha Gardener, Bernardino Ghetti, Alison Goate, Sarah Goldberg, Jill Goldman, Alyssa Gonzalez, Brian Gordon, Susanne Gr¨aber-Sultan, Neill Graff-Radford, Morgan Graham, Julia Gray, Emily Gremminger, Miguel Grilo, Alex Groves, Christian Haass, Lisa H¨asler, Jason Hassenstab, Cortaiga Hellm, Elizabeth Herries, Laura Hoechst-Swisher, Anna Hofmann, David Holtzman, Russ Hornbeck, Yakushev Igor, Ryoko Ihara, Takeshi Ikeuchi, Snezana Ikonomovic, Kenji Ishii, Clifford Jack, Gina Jerome, Erik Johnson, Mathias Jucker, Celeste Karch, Stephan K¨aser, Kensaku Kasuga, Sarah Keefe, William Klunk, Robert Koeppe, Deb Koudelis, Elke Kuder-Buletta, Christoph Laske, Allan Levey, Johannes Levin, Yan Li, Oscar Lopez, Jacob Marsh, Ralph Martins, Neal Scott Mason, Colin Masters, Kwasi Mawuenyega, Austin McCullough, Eric McDade, Arlene Mejia, Estrella Morenas-Rodriguez, John Morris, James Mountz, Cath Mummery, Neelesh Nadkarni, Akemi Nagamatsu, Katie Neimeyer, Yoshiki Niimi, James Noble, Joanne Norton, Brigitte Nuscher, Ulricke Obermüller, Antoinette O’Connor, Riddhi Patira, Richard Perrin, Lingyan Ping, Oliver Preische, Alan Renton, John Ringman, Stephen Salloway, Peter Schofield, Michio Senda, Nicholas T Seyfried, Kristine Shady, Hiroyuki Shimada, Wendy Sigurdson, Jennifer Smith, Lori Smith, Beth Snitz, Hamid Sohrabi, Sochenda Stephens, Kevin Taddei, Sarah Thompson, Jonathan V¨oglein, Peter Wang, Qing Wang, Elise Weamer, Chengjie Xiong, Jinbin Xu, and Xiong Xu
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Biology (General) ,QH301-705.5 - Abstract
We report the generation of a gene-edited human induced pluripotent stem cell (iPSC) line from an Alzheimer’s disease patient-derived iPSC line harbouring the PSEN1 H163R mutation. This line demonstrates pluripotent stem cell morphology, expression of pluripotency markers, and maintains a normal karyotype.
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- 2024
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3. The neurophysiological brain-fingerprint of Parkinson’s diseaseResearch in context
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Jason da Silva Castanheira, Alex I. Wiesman, Justine Y. Hansen, Bratislav Misic, Sylvain Baillet, John Breitner, Judes Poirier, Pierre Bellec, Véronique Bohbot, Mallar Chakravarty, Louis Collins, Pierre Etienne, Alan Evans, Serge Gauthier, Rick Hoge, Yasser Ituria-Medina, Gerhard Multhaup, Lisa-Marie Münter, Natasha Rajah, Pedro Rosa-Neto, Jean-Paul Soucy, Etienne Vachon-Presseau, Sylvia Villeneuve, Philippe Amouyel, Melissa Appleby, Nicholas Ashton, Daniel Auld, Gülebru Ayranci, Christophe Bedetti, Marie-Lise Beland, Kaj Blennow, Ann Brinkmalm Westman, Claudio Cuello, Mahsa Dadar, Leslie-Ann Daoust, Samir Das, Marina Dauar-Tedeschi, Louis De Beaumont, Doris Dea, Maxime Descoteaux, Marianne Dufour, Sarah Farzin, Fabiola Ferdinand, Vladimir Fonov, Julie Gonneaud, Justin Kat, Christina Kazazian, Anne Labonté, Marie-Elyse Lafaille-Magnan, Marc Lalancette, Jean-Charles Lambert, Jeannie-Marie Leoutsakos, Laura Mahar, Axel Mathieu, Melissa McSweeney, Pierre-François Meyer, Justin Miron, Jamie Near, Holly NewboldFox, Nathalie Nilsson, Pierre Orban, Cynthia Picard, Alexa Pichet Binette, Jean-Baptiste Poline, Sheida Rabipour, Alyssa Salaciak, Matthew Settimi, Sivaniya Subramaniapillai, Angela Tam, Christine Tardif, Louise Théroux, Jennifer Tremblay-Mercier, Stephanie Tullo, Irem Ulku, Isabelle Vallée, Henrik Zetterberg, Vasavan Nair, Jens Pruessner, Paul Aisen, Elena Anthal, Alan Barkun, Thomas Beaudry, Fatiha Benbouhoud, Jason Brandt, Leopoldina Carmo, Charles Edouard Carrier, Laksanun Cheewakriengkrai, Blandine Courcot, Doris Couture, Suzanne Craft, Christian Dansereau, Clément Debacker, René Desautels, Sylvie Dubuc, Guerda Duclair, Mark Eisenberg, Rana El-Khoury, Anne-Marie Faubert, David Fontaine, Josée Frappier, Joanne Frenette, Guylaine Gagné, Valérie Gervais, Renuka Giles, Renee Gordon, Clifford Jack, Benoit Jutras, Zaven Khachaturian, David Knopman, Penelope Kostopoulos, Félix Lapalme, Tanya Lee, Claude Lepage, Illana Leppert, Cécile Madjar, David Maillet, Jean-Robert Maltais, Sulantha Mathotaarachchi, Ginette Mayrand, Diane Michaud, Thomas Montine, John Morris, Véronique Pagé, Tharick Pascoal, Sandra Peillieux, Mirela Petkova, Galina Pogossova, Pierre Rioux, Mark Sager, Eunice Farah Saint-Fort, Mélissa Savard, Reisa Sperling, Shirin Tabrizi, Pierre Tariot, Eduard Teigner, Ronald Thomas, Paule-Joanne Toussaint, Miranda Tuwaig, Vinod Venugopalan, Sander Verfaillie, Jacob Vogel, Karen Wan, Seqian Wang, Elsa Yu, Isabelle Beaulieu-Boire, Pierre Blanchet, Sarah Bogard, Manon Bouchard, Sylvain Chouinard, Francesca Cicchetti, Martin Cloutier, Alain Dagher, Clotilde Degroot, Alex Desautels, Marie Hélène Dion, Janelle Drouin-Ouellet, Anne-Marie Dufresne, Nicolas Dupré, Antoine Duquette, Thomas Durcan, Lesley K. Fellows, Edward Fon, Jean-François Gagnon, Ziv Gan-Or, Angela Genge, Nicolas Jodoin, Jason Karamchandani, Anne-Louise Lafontaine, Mélanie Langlois, Etienne Leveille, Martin Lévesque, Calvin Melmed, Oury Monchi, Jacques Montplaisir, Michel Panisset, Martin Parent, Minh-Thy Pham-An, Ronald Postuma, Emmanuelle Pourcher, Trisha Rao, Jean Rivest, Guy Rouleau, Madeleine Sharp, Valérie Soland, Michael Sidel, Sonia Lai Wing Sun, Alexander Thiel, and Paolo Vitali
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Movement disorders ,Parkinson’s disease ,Neural dynamics ,Oscillations ,Arrhythmic brain activity ,Magnetoencephalography ,Medicine ,Medicine (General) ,R5-920 - Abstract
Summary: Background: Research in healthy young adults shows that characteristic patterns of brain activity define individual “brain-fingerprints” that are unique to each person. However, variability in these brain-fingerprints increases in individuals with neurological conditions, challenging the clinical relevance and potential impact of the approach. Our study shows that brain-fingerprints derived from neurophysiological brain activity are associated with pathophysiological and clinical traits of individual patients with Parkinson’s disease (PD). Methods: We created brain-fingerprints from task-free brain activity recorded through magnetoencephalography in 79 PD patients and compared them with those from two independent samples of age-matched healthy controls (N = 424 total). We decomposed brain activity into arrhythmic and rhythmic components, defining distinct brain-fingerprints for each type from recording durations of up to 4 min and as short as 30 s. Findings: The arrhythmic spectral components of cortical activity in patients with Parkinson’s disease are more variable over short periods, challenging the definition of a reliable brain-fingerprint. However, by isolating the rhythmic components of cortical activity, we derived brain-fingerprints that distinguished between patients and healthy controls with about 90% accuracy. The most prominent cortical features of the resulting Parkinson’s brain-fingerprint are mapped to polyrhythmic activity in unimodal sensorimotor regions. Leveraging these features, we also demonstrate that Parkinson’s symptom laterality can be decoded directly from cortical neurophysiological activity. Furthermore, our study reveals that the cortical topography of the Parkinson’s brain-fingerprint aligns with that of neurotransmitter systems affected by the disease’s pathophysiology. Interpretation: The increased moment-to-moment variability of arrhythmic brain-fingerprints challenges patient differentiation and explains previously published results. We outline patient-specific rhythmic brain signaling features that provide insights into both the neurophysiological signature and symptom laterality of Parkinson’s disease. Thus, the proposed definition of a rhythmic brain-fingerprint of Parkinson’s disease may contribute to novel, refined approaches to patient stratification. Symmetrically, we discuss how rhythmic brain-fingerprints may contribute to the improved identification and testing of therapeutic neurostimulation targets. Funding: Data collection and sharing for this project was provided by the Quebec Parkinson Network (QPN), the Pre-symptomatic Evaluation of Novel or Experimental Treatments for Alzheimer’s Disease (PREVENT-AD; release 6.0) program, the Cambridge Centre for Aging Neuroscience (Cam-CAN), and the Open MEG Archives (OMEGA). The QPN is funded by a grant from Fonds de Recherche du Québec - Santé (FRQS). PREVENT-AD was launched in 2011 as a $13.5 million, 7-year public-private partnership using funds provided by McGill University, the FRQS, an unrestricted research grant from Pfizer Canada, the Levesque Foundation, the Douglas Hospital Research Centre and Foundation, the Government of Canada, and the Canada Fund for Innovation. The Brainstorm project is supported by funding to SB from the NIH (R01-EB026299-05). Further funding to SB for this study included a Discovery grant from the Natural Sciences and Engineering Research Council of Canada of Canada (436355-13), and the CIHR Canada research Chair in Neural Dynamics of Brain Systems (CRC-2017-00311).
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- 2024
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4. Predicting brain age from functional connectivity in symptomatic and preclinical Alzheimer disease
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Peter R. Millar, Patrick H. Luckett, Brian A. Gordon, Tammie L.S. Benzinger, Suzanne E. Schindler, Anne M. Fagan, Carlos Cruchaga, Randall J. Bateman, Ricardo Allegri, Mathias Jucker, Jae-Hong Lee, Hiroshi Mori, Stephen P Salloway, Igor Yakushev, John C. Morris, Beau M. Ances, Sarah Adams, MS, Ricardo Allegri, PhD, Aki Araki, Nicolas Barthelemy, PhD, Randall Bateman, MD, Jacob Bechara, BS, Tammie Benzinger, MD, PhD, Sarah Berman, MD, PhD, Courtney Bodge, PhD, Susan Brandon, BS, William (Bill) Brooks, MBBS,MPH, Jared Brosch, MD, PhD, Jill Buck, BSN, Virginia Buckles, PhD, Kathleen Carter, PhD, Lisa Cash, BFA, Charlie Chen, BA, Jasmeer Chhatwal, MD,PhD, Patricio Chrem Mendez, MD, Jasmin Chua, BS, Helena Chui, MD, Laura Courtney, BS, Carlos Cruchaga, PhD, Gregory S Day, MD, Chrismary DeLaCruz, BA, Darcy Denner, PhD, Anna Diffenbacher, MS, Aylin Dincer, BS, Tamara Donahue, MS, Jane Douglas, MPh, Duc Duong, BS, Noelia Egido, BS, Bianca Esposito, BS, Anne Fagan, PhD, Marty Farlow, MD, Becca Feldman, BS,BA, Colleen Fitzpatrick, MS, Shaney Flores, BS, Nick Fox, MD, Erin Franklin, MS, Nelly Joseph-Mathurin, PhD, Hisako Fujii, PhD, Samantha Gardener, PhD, Bernardino Ghetti, MD, Alison Goate, PhD, Sarah Goldberg, MS,LPC,NCC, Jill Goldman, MS,MPhil,CGC, Alyssa Gonzalez, BS, Brian Gordon, PhD, Susanne Gräber-Sultan, PhD, Neill Graff-Radford, MD, Morgan Graham, BA, Julia Gray, MS, Emily Gremminger, BA, Miguel Grilo, MD, Alex Groves, Christian Haass, PhD, Lisa Häsler, MSc, Jason Hassenstab, PhD, Cortaiga Hellm, BA, Elizabeth Herries, BA, Laura Hoechst-Swisher, MS, Anna Hofmann, MD, Anna Hofmann, David Holtzman, MD, Russ Hornbeck, MSCS, MPM, Yakushev Igor, MD, Ryoko Ihara, MD, Takeshi Ikeuchi, MD, Snezana Ikonomovic, MD, Kenji Ishii, MD, Clifford Jack, MD, Gina Jerome, MS, Erik Johnson, MD, PHD, Mathias Jucker, PhD, Celeste Karch, PhD, Stephan Käser, PHD, Kensaku Kasuga, MD, Sarah Keefe, BS, William Klunk, MD, PHD, Robert Koeppe, PHD, Deb Koudelis, MHS,RN, Elke Kuder-Buletta, RN, Christoph Laske, PhD, Allan Levey, MD, PHD, Johannes Levin, MD, Yan Li, PHD, Oscar Lopez, MD, MD, Jacob Marsh, BA, Ralph Martins, PhD, Neal Scott Mason, PhD, Colin Masters, MD, Kwasi Mawuenyega, PhD, Austin McCullough, PhD Candidate, Eric McDade, DO, Arlene Mejia, MD, Estrella Morenas-Rodriguez, MD, PhD, John Morris, MD, James Mountz, MD, Cath Mummery, PhD, N eelesh Nadkarni, MD, PhD, Akemi Nagamatsu, RN, Katie Neimeyer, MS, Yoshiki Niimi, MD, James Noble, MD, Joanne Norton, MSN, RN, PMHCNS-BC, Brigitte Nuscher, Ulricke Obermüller, Antoinette O'Connor, MRCPI, Riddhi Patira, MD, Richard Perrin, MD, PhD, Lingyan Ping, PhD, Oliver Preische, MD, Alan Renton, PhD, John Ringman, MD, Stephen Salloway, MD, Peter Schofield, PhD, Michio Senda, MD, PhD, Nicholas T Seyfried, D.Phil, Kristine Shady, BA, BS, Hiroyuki Shimada, MD, PhD, Wendy Sigurdson, RN, Jennifer Smith, PhD, Lori Smith, PA-C, Beth Snitz, PhD, Hamid Sohrabi, PhD, Sochenda Stephens, BS, CCRP, Kevin Taddei, BS, Sarah Thompson, PA-C, Jonathan Vöglein, MD, Peter Wang, PhD, Qing Wang, PhD, Elise Weamer, MPH, Chengjie Xiong, PhD, Jinbin Xu, PhD, and Xiong Xu, BS, MS
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Brain aging ,Alzheimer disease ,Resting-state functional connectivity ,fMRI ,Machine learning ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
“Brain-predicted age” quantifies apparent brain age compared to normative neuroimaging trajectories. Advanced brain-predicted age has been well established in symptomatic Alzheimer disease (AD), but is underexplored in preclinical AD. Prior brain-predicted age studies have typically used structural MRI, but resting-state functional connectivity (FC) remains underexplored. Our model predicted age from FC in 391 cognitively normal, amyloid-negative controls (ages 18–89). We applied the trained model to 145 amyloid-negative, 151 preclinical AD, and 156 symptomatic AD participants to test group differences. The model accurately predicted age in the training set. FC-predicted brain age gaps (FC-BAG) were significantly older in symptomatic AD and significantly younger in preclinical AD compared to controls. There was minimal correspondence between networks predictive of age and AD. Elevated FC-BAG may reflect network disruption during symptomatic AD. Reduced FC-BAG in preclinical AD was opposite to the expected direction, and may reflect a biphasic response to preclinical AD pathology or may be driven by inconsistency between age-related vs. AD-related networks. Overall, FC-predicted brain age may be a sensitive AD biomarker.
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- 2022
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5. Mechanistic Effects of Aerobic Exercise in Alzheimer's Disease: Imaging Findings From the Pilot FIT-AD Trial
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Fang Yu, Michelle A. Mathiason, SeungYong Han, Jeffrey L. Gunter, David Jones, Hugo Botha, and Clifford Jack
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exercise ,Alzheimer's disease ,dementia ,imaging ,MRI ,hippocampal volume ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Despite strong evidence from animal models of Alzheimer's disease (AD) supporting aerobic exercise as a disease-modifying treatment for AD, human mechanistic studies are limited with mixed findings. The objective of this pilot randomized controlled trial was to examine the effects of 6-month aerobic exercise on hippocampal volume, temporal meta-regions of interest (ROI) cortical thickness, white matter hyperintensity (WMH) volume, and network failure quotient (NFQ), measured with MRI, in community-dwelling older adults with AD dementia. Additionally, the relationships between 6- and 12-month changes in MRI biomarkers and the AD Assessment Scale-Cognition (ADAS-Cog) were examined. Sixty participants were randomized, but one was excluded because baseline MRI failed quality control: 38 randomized to cycling and 21 to stretching. The intervention was moderate-intensity cycling for 20–50 mins, three times a week for 6 months. Control was low-intensity stretching. The study outcomes include hippocampal volume, temporal meta-ROI cortical thickness, WMH volume, and NFQ. Outcomes were measured at baseline, 6 months, and 12 months. The sample averaged 77.3 ± 6.3 years old with 15.6 ± 2.9 years of education and 53% men. Both groups experienced significant declines over 6 months in hippocampal volume (2.64% in cycling vs. 2.89% in stretching) and temporal meta-ROI cortical thickness (0.94 vs. 1.54%), and over 12 months in hippocampal volume (4.47 vs. 3.84%) and temporal meta-ROI cortical thickness (2.27 vs. 1.79%). These declines did not differ between groups. WMH volume increased significantly with the cycling group increasing less (10.9%) than stretching (24.5%) over 6 months (f = 4.47, p = 0.04) and over 12 months (12.1 vs. 27.6%, f = 5.88, p = 0.02). NFQ did not change significantly over time. Pairwise correlational analyses showed a significant negative correlation between 6-month changes in hippocampal volume and ADAS-Cog (r = −0.34, p < 0.05). To conclude, aerobic exercise may reduce the decline in hippocampal volume and temporal meta-ROI cortical thickness during the intervention period, but the effect sizes are likely to be very small and dose-dependent and reverse once the intervention stops. Aerobic exercise is effective on slowing down WMH progression but has no effect on NFQ. Hippocampal atrophy was associated with cognitive decline during the intervention period.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT01954550.
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- 2021
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6. In vivo Analysis of Normal Optic Nerve in an Elderly Population Using Diffusion Magnetic Resonance Imaging Tractography
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Yeji Moon, Jin-Ju Yang, Won June Lee, Ji Young Lee, Yu Jeong Kim, Han Woong Lim, The Alzheimer's Disease Neuroimaging Initiative (ADNI), Michael W Weiner, Paul Aisen, Ronald Petersen, Clifford Jack, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, and Laurel Beckett
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diffusion magnetic resonance imaging ,tractography ,fractional anisotropy ,mean diffusivity ,optic nerve ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Purpose: To quantitatively investigate the microstructural properties of the optic nerve (ON) in vivo using diffusion magnetic resonance imaging (dMRI) tractography in an elderly population and to determine the differences between the ON diffusion properties stratified by basic demographics.Methods: We measured fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) of the intraorbital ON in cognitively normal controls selected from the Alzheimer's Disease Neuroimaging Initiative 3 database (n =104; mean age = 73. 8 ± 8.1 years) using dMRI probabilistic tractography and evaluated the correlation between diffusion parameters and demographic factors. Diffusion parameters were measured in 20 equidistant nodes along the tract, and the data from proximal 70% (14 nodes) of the intraorbital ON were averaged.Results: The mean FA of the intraorbital ON was 0.392 ± 0.063, and the mean MD was 1.163 ± 0.165 μm2/s. The mean RD was 0.882 ± 0.152 μm2/s, and the mean AD was 1.693 ± 0.183 μm2/s. The multiple linear regression model showed a negative correlation between FA and age. FA in females was significantly higher than males, whereas RD in female was significantly lower.Conclusions: We measured the diffusion properties of the intraorbital ON using dMRI tractography in an elderly cognitively normal population. The diffusion properties detected by dMRI tractography may substantially reflect the microstructure of the ON.
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- 2021
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7. Efficacy and mechanisms of combined aerobic exercise and cognitive training in mild cognitive impairment: study protocol of the ACT trial
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Fang Yu, Feng Vankee Lin, Dereck L. Salisbury, Krupa N. Shah, Lisa Chow, David Vock, Nathaniel W. Nelson, Anton P. Porsteinsson, and Clifford Jack
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Aerobic exercise ,Alzheimer’s disease ,Cognitive training ,Neuroimaging ,Executive function ,Memory ,Medicine (General) ,R5-920 - Abstract
Abstract Background Developing non-pharmacological interventions with strong potential to prevent or delay the onset of Alzheimer’s disease (AD) in high-risk populations is critical. Aerobic exercise and cognitive training are two promising interventions. Aerobic exercise increases aerobic fitness, which in turn improves brain structure and function, while cognitive training improves selective brain function intensively. Hence, combined aerobic exercise and cognitive training may have a synergistic effect on cognition by complementary strengthening of different neural functions. Few studies have tested the effects of such a combined intervention, and the findings have been discrepant, largely due to varying doses and formats of the interventions. Methods/design The purpose of this single-blinded, 2 × 2 factorial phase II randomized controlled trial is to test the efficacy and synergistic effects of a 6-month combined cycling and speed of processing training intervention on cognition and relevant mechanisms (aerobic fitness, cortical thickness, and functional connectivity in the default mode network) in older adults with amnestic mild cognitive impairment. This trial will randomize 128 participants equally to four arms: cycling and speed of processing, cycling only, speed of processing only, or attention control for 6 months, and then follow them for another 12 months. Cognition and aerobic fitness will be assessed at baseline and at 3, 6, 12, and 18 months; cortical thickness and functional connectivity at baseline and at 6, 12, and 18 months; Alzheimer’s disease (AD) conversion at 6, 12, and 18 months. The specific aims are to (1) determine the efficacy and synergistic effects of the combined intervention on cognition over 6 months, (2) examine the underlying mechanisms of the combined intervention, and (3) calculate the long-term effect sizes of the combined intervention on cognition and AD conversion. The analysis will use intention-to-treat and linear mixed-effects modeling. Discussion This trial will be among the first to test the synergistic effects on cognition and mechanisms (relevant to Alzheimer’s-associated neurodegeneration) of a uniquely conceptualized and rigorously designed aerobic exercise and cognitive training intervention in older adults with mild cognitive impairment. It will advance Alzheimer’s prevention research by providing precise effect-size estimates of the combined intervention. Trial registration ClinicalTrials.gov, NCT03313895. Registered on 18 October 2017.
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- 2018
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8. Serum neurofilament light chain levels are associated with white matter integrity in autosomal dominant Alzheimer's disease
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Stephanie A. Schultz, Jeremy F. Strain, Adedamola Adedokun, Qing Wang, Oliver Preische, Jens Kuhle, Shaney Flores, Sarah Keefe, Aylin Dincer, Beau M. Ances, Sarah B. Berman, Adam M. Brickman, David M. Cash, Jasmeer Chhatwal, Carlos Cruchaga, Michael Ewers, Nick N. Fox, Bernardino Ghetti, Alison Goate, Neill R. Graff-Radford, Jason J. Hassenstab, Russ Hornbeck, Clifford Jack, Jr, Keith Johnson, Nelly Joseph-Mathurin, Celeste M. Karch, Robert A. Koeppe, Athene K.W. Lee, Johannes Levin, Colin Masters, Eric McDade, Richard J. Perrin, Christopher C. Rowe, Stephen Salloway, Andrew J. Saykin, Reisa Sperling, Yi Su, Victor L. Villemagne, Jonathan Vöglein, Michael Weiner, Chengjie Xiong, Anne M. Fagan, John C. Morris, Randall J. Bateman, Tammie L.S. Benzinger, Mathias Jucker, and Brian A. Gordon
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Neurofilament ,Alzheimer's disease ,Neurodegeneration ,White matter ,Blood-based biomarkers ,Neuroimaging ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Neurofilament light chain (NfL) is a protein that is selectively expressed in neurons. Increased levels of NfL measured in either cerebrospinal fluid or blood is thought to be a biomarker of neuronal damage in neurodegenerative diseases. However, there have been limited investigations relating NfL to the concurrent measures of white matter (WM) decline that it should reflect. White matter damage is a common feature of Alzheimer's disease. We hypothesized that serum levels of NfL would associate with WM lesion volume and diffusion tensor imaging (DTI) metrics cross-sectionally in 117 autosomal dominant mutation carriers (MC) compared to 84 non-carrier (NC) familial controls as well as in a subset (N = 41) of MC with longitudinal NfL and MRI data.In MC, elevated cross-sectional NfL was positively associated with WM hyperintensity lesion volume, mean diffusivity, radial diffusivity, and axial diffusivity and negatively with fractional anisotropy. Greater change in NfL levels in MC was associated with larger changes in fractional anisotropy, mean diffusivity, and radial diffusivity, all indicative of reduced WM integrity. There were no relationships with NfL in NC. Our results demonstrate that blood-based NfL levels reflect WM integrity and supports the view that blood levels of NfL are predictive of WM damage in the brain. This is a critical result in improving the interpretability of NfL as a marker of brain integrity, and for validating this emerging biomarker for future use in clinical and research settings across multiple neurodegenerative diseases.
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- 2020
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9. Creating three dimensional models of Alzheimer’s disease
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Matthew Marks, Amy Alexander, Joseph Matsumoto, Jane Matsumoto, Jonathan Morris, Ronald Petersen, Clifford Jack, Tatsuya Oishi, and David Jones
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Hippocampus ,3D printing ,Alzheimer’s disease ,Dementia ,Brain ,Additive manufacturing ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Abstract
Abstract Background Alzheimer’s disease prevalence will reach epidemic proportions in coming decades. There is a need for impactful educational materials to help patients, families, medical practitioners, and policy makers understand the nature and impact of the disease. Defining an effective workflow to create such models from existing segmentation tools will be a valuable contribution in creating these patient-specific models. Results A step-by-step workflow was developed and used to take patients’ Digital Imaging and Computing in Medicine magnetic resonance brain images through a process resulting in illustrative 3D–printed brain and hippocampus models that clearly demonstrate the progressive degenerative changes caused by Alzheimer’s disease. We outline the specific technical steps of auto-segmentation, manual smoothing, Standard Triangle Language file customization, and 3D printing used to create these models. Conclusions Our explicated workflow can create effective models of Alzheimer’s brains that can be used in patient education, medical education, and policy forums.
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- 2017
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10. Decline in Visual and Posterior Cortical Functions in Logopenic Progressive Aphasia (P5-6.001)
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Neha Atulkumar Singh, Jonathan Graff-Radford, Arenn Carlos, Mary Machulda, Christopher Schwarz, Matthew Senjem, Clifford Jack, Val Lowe, Keith Josephs, and Jennifer Whitwell
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- 2023
11. The Experience of The COVID-19 Pandemic in a Population-Based Study of Cognitive Aging (P5-10.001)
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Khaled Ghoniem, Jeremiah Aakre, Anna Castillo, Mohamed Elminawy, Mary Machulda, Yonas Geda, Prashanthi Vemuri, Clifford Jack, Jonathan Graff-Radford, David Knopman, Ronald Petersen, and Maria Vassilaki
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- 2023
12. Identifying Key Patterns of Social and Structural Determinants of Health and Their Association with Dementia Risk in a Population-Based Study of Cognitive Aging (P1-12.007)
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Maria Vassilaki, Jeremiah Aakre, Anna Castillo, Timothy Lesnick, Jonathan Graff-Radford, David Knopman, Clifford Jack, Ronald Petersen, and Prashanthi Vemuri
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- 2023
13. Eligibility for Anti-Amyloid Treatment in a Population-Based Cohort Study of Aging (P5-6.006)
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Rioghna Pittock, Jeremiah Aakre, Anna Castillo, Vijay Ramanan, Clifford Jack, Prashanthi Vemuri, David Knopman, Ronald Petersen, Jonathan Graff-Radford, and Maria Vassilaki
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- 2023
14. Volumetric Analysis of Hippocampal Subregions and Subfields in Left and Right Predominant Semantic Dementia (P11-6.002)
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Arenn F. Carlos, Stephen D. Weigand, Rene Utianski, Joseph Duffy, Heather M. Clark, Mary Machulda, Nha Trang Thu Pham, Christopher Schwarz, Clifford Jack, Jennifer Whitwell, and Keith A. Josephs
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- 2023
15. APOE and cortical superficial siderosis in CAA: Meta-analysis and potential mechanisms
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Charidimou, Andreas, Zonneveld, Hazel I., Shams, Sara, Kantarci, Kejal, Shoamanesh, Ashkan, Hilal, Saima, Yates, Paul A., Boulouis, Gregoire, Na, Han Kyu, Pasi, Marco, Biffi, Allesandro, Chai, Yuek Ling, Chong, Joyce Ruifen, Wahlund, Lars-Olof, Clifford, Jack R., Chen, Christopher, Gurol, M. Edip, Goldstein, Joshua N., Na, Duk L., Barkhof, Frederik, Seo, Sang Won, Rosand, Jonathan, Greenberg, Steven M., and Viswanathan, Anand
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- 2019
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16. Complete Genome Sequences of Ezakiella coagulans C0061C1 and Fenollaria massiliensis C0061C2
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France, Michael T., primary, Clifford, Jack, additional, Narina, Shilpa, additional, Rutt, Lindsay, additional, and Ravel, Jacques, additional
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- 2022
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17. Neuroimaging within the Dominantly Inherited Alzheimer’s Network (DIAN): PET and MRI
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Diana Hobbs, Brian Gordon, Nelly Joseph-Mathurin, Austin McCullough, Peter Millar, Clifford Jack, Russ Hornbeck, David Cash, Nicole McKay, and Gregory Day
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The Dominantly Inherited Alzheimer Network (DIAN) Observational Study is an international collaboration studying autosomal dominant Alzheimer disease (ADAD). This rare form of Alzheimer disease (AD) is caused by mutations in the presenilin 1 (PSEN1), presenilin 2 (PSEN2), or amyloid precursor protein (APP) genes. As individuals from these families have a 50% chance of inheriting the familial mutation, this provides researchers with a well-matched cohort of carriers vs non-carriers for case-control studies. An important trait of ADAD is that the age at symptom onset is highly predictable and consistent for each specific mutation, allowing researchers to estimate an individual’s point in their disease time course prior to symptom onset. Although ADAD represents only a small proportion (approximately 0.1%) of all AD cases, studying this form of AD allows researchers to investigate preclinical AD and the progression of changes that occur within the brain prior to AD symptom onset. Furthermore, the young age at symptom onset (typically 30-60 years) means age-related comorbidities are much less prevalent than in sporadic AD, thereby allowing AD pathophysiology to be studied independent of these confounds. A major goal of the DIAN Observational Study is to create a global resource for AD researchers. To that end, the current manuscript provides an overview of the DIAN magnetic resonance imaging (MRI) and positron emission tomography (PET) protocols and highlights the key imaging results of this study to date.
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- 2022
18. Comparison of amyloid burden in individuals with Down syndrome versus autosomal dominant Alzheimer's disease: a cross-sectional study
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Anna H Boerwinkle, Brian A Gordon, Julie Wisch, Shaney Flores, Rachel L Henson, Omar H Butt, Nicole McKay, Charles D Chen, Tammie L S Benzinger, Anne M Fagan, Benjamin L Handen, Bradley T Christian, Elizabeth Head, Mark Mapstone, Michael S Rafii, Sid O'Bryant, Florence Lai, H Diana Rosas, Joseph H Lee, Wayne Silverman, Adam M Brickman, Jasmeer P Chhatwal, Carlos Cruchaga, Richard J Perrin, Chengjie Xiong, Jason Hassenstab, Eric McDade, Randall J Bateman, Beau M Ances, Howard J Aizenstein, Howard F Andrews, Karen Bell, Rasmus M Birn, Peter Bulova, Amrita Cheema, Kewei Chen, Isabel Clare, Lorraine Clark, Ann D Cohen, John N Constantino, Eric W Doran, Eleanor Feingold, Tatiana M Foroud, Sigan L Hartley, Christy Hom, Lawrence Honig, Milos D Ikonomovic, Sterling C Johnson, Courtney Jordan, M Ilyas Kamboh, David Keator, William E Klunk MD, Julia K Kofler, William C Kreisl, Sharon J Krinsky- McHale, Patrick Lao, Charles Laymon, Ira T Lott, Victoria Lupson, Chester A Mathis, Davneet S Minhas, Neelesh Nadkarni, Deborah Pang, Melissa Petersen, Julie C Price, Margaret Pulsifer, Eric Reiman, Batool Rizvi, Marwan N Sabbagh, Nicole Schupf, Dana L Tudorascu, Rameshwari Tumuluru, Benjamin Tycko, Badri Varadarajan, Desiree A White, Michael A Yassa, Shahid Zaman, Fan Zhang, Sarah Adams, Ricardo Allegri, Aki Araki, Nicolas Barthelemy, Jacob Bechara, Sarah Berman, Courtney Bodge, Susan Brandon, William Brooks, Jared Brosch, Jill Buck, Virginia Buckles, Kathleen Carter, Lisa Cash, Patricio C Mendez, Jasmin Chua, Helena Chui, Laura Courtney, Gregory Day, Chrismary DeLaCruz, Darcy Denner, Anna Diffenbacher, Aylin Dincer, Tamara Donahue, Jane Douglas, Duc Duong, Noelia Egido, Bianca Esposito, Marty Farlow, Becca Feldman, Colleen Fitzpatrick, Nick Fox, Erin Franklin, Nelly Joseph-Mathurin, Hisako Fujii, Samantha Gardener, Bernardino Ghetti, Alison Goate, Sarah Goldberg, Jill Goldman, Alyssa Gonzalez, Susanne Gräber-Sultan, Neill Graff-Radford, Morgan Graham, Julia Gray, Emily Gremminger, Miguel Grilo, Alex Groves, Christian Haass, Lisa Häslerc, Cortaiga Hellm, Elizabeth Herries, Laura Hoechst-Swisher, Anna Hofmann, David Holtzman, Russ Hornbeck, Yakushev Igor, Ryoko Ihara, Takeshi Ikeuchi, Snezana Ikonomovic, Kenji Ishii, Clifford Jack, Gina Jerome, Erik Johnson, Mathias Jucker, Celeste Karch, Stephan Käser, Kensaku Kasuga, Sarah Keefe, William Klunk, Robert Koeppe, Deb Koudelis, Elke Kuder-Buletta, Christoph Laske, Allan Levey, Johannes Levin, Yan Li, Oscar Lopez, Jacob Marsh, Ralph Martins, Neal S Mason, Colin Masters, Kwasi Mawuenyega, Austin McCullough, Arlene Mejia, Estrella Morenas-Rodriguez, John C Morris, James Mountz, Catherine Mummery, Akemi Nagamatsu, Katie Neimeyer, Yoshiki Niimi, James Noble, Joanne Norton, Brigitte Nuscher, Ulricke Obermüller, Antoinette O'Connor, Riddhi Patira, Lingyan Ping, Oliver Preische, Alan Renton, John Ringman, Stephen Salloway, Peter Schofield, Michio Senda, Nicholas T Seyfried, Kristine Shady, Hiroyuki Shimada, Wendy Sigurdson, Jennifer Smith, Lori Smith, Beth Snitz, Hamid Sohrabi, Sochenda Stephens, Kevin Taddei, Sarah Thompson, Jonathan Vöglein, Peter Wang, Qing Wang, Elise Weamer, Jinbin Xu, and Xiong Xu
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Adult ,Cerebral Cortex ,Amyloid beta-Peptides ,Apolipoproteins E ,Cross-Sectional Studies ,Alzheimer Disease ,Positron-Emission Tomography ,Humans ,Neurology (clinical) ,Middle Aged ,Down Syndrome ,Biomarkers ,Aged - Abstract
Important insights into the early pathogenesis of Alzheimer's disease can be provided by studies of autosomal dominant Alzheimer's disease and Down syndrome. However, it is unclear whether the timing and spatial distribution of amyloid accumulation differs between people with autosomal dominant Alzheimer's disease and those with Down syndrome. We aimed to directly compare amyloid changes between these two groups of people.In this cross-sectional study, we included participants (aged ≥25 years) with Down syndrome and sibling controls who had MRI and amyloid PET scans in the first data release (January, 2020) of the Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) study. We also included carriers of autosomal dominant Alzheimer's disease genetic mutations and non-carrier familial controls who were within a similar age range to ABC-DS participants (25-73 years) and had MRI and amyloid PET scans at the time of a data freeze (December, 2020) of the Dominantly Inherited Alzheimer Network (DIAN) study. Controls from the two studies were combined into a single group. All DIAN study participants had genetic testing to determine PSEN1, PSEN2, or APP mutation status. APOE genotype was determined from blood samples. CSF samples were collected in a subset of ABC-DS and DIAN participants and the ratio of amyloid β42 (Aβ42) to Aβ40 (Aβ42/40) was measured to evaluate its Spearman's correlation with amyloid PET. Global PET amyloid burden was compared with regards to cognitive status, APOE ɛ4 status, sex, age, and estimated years to symptom onset. We further analysed amyloid PET deposition by autosomal dominant mutation type. We also assessed regional patterns of amyloid accumulation by estimated number of years to symptom onset. Within a subset of participants the relationship between amyloid PET and CSF Aβ42/40 was evaluated.192 individuals with Down syndrome and 33 sibling controls from the ABC-DS study and 265 carriers of autosomal dominant Alzheimer's disease mutations and 169 non-carrier familial controls from the DIAN study were included in our analyses. PET amyloid centiloid and CSF Aβ42/40 were negatively correlated in carriers of autosomal dominant Alzheimer's disease mutations (n=216; r=-0·565; p0·0001) and in people with Down syndrome (n=32; r=-0·801; p0·0001). There was no difference in global PET amyloid burden between asymptomatic people with Down syndrome (mean 18·80 centiloids [SD 28·33]) versus asymptomatic mutation carriers (24·61 centiloids [30·27]; p=0·11) and between symptomatic people with Down syndrome (77·25 centiloids [41·76]) versus symptomatic mutation carriers (69·15 centiloids [51·10]; p=0·34). APOE ɛ4 status and sex had no effect on global amyloid PET deposition. Amyloid deposition was elevated significantly earlier in mutation carriers than in participants with Down syndrome (estimated years to symptom onset -23·0 vs -17·5; p=0·0002). PSEN1 mutations primarily drove this difference. Early amyloid accumulation occurred in striatal and cortical regions for both mutation carriers (n=265) and people with Down syndrome (n=128). Although mutation carriers had widespread amyloid accumulation in all cortical regions, the medial occipital regions were spared in people with Down syndrome.Despite minor differences, amyloid PET changes were similar between people with autosomal dominant Alzheimer's disease versus Down syndrome and strongly supported early amyloid dysregulation in individuals with Down syndrome. Individuals with Down syndrome aged at least 35 years might benefit from early intervention and warrant future inclusion in clinical trials, particularly given the relatively high incidence of Down syndrome.The National Institute on Aging, Riney and Brennan Funds, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the German Center for Neurodegenerative Diseases, and the Japan Agency for Medical Research and Development.
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- 2022
19. Problematic historiography: The case of the Spanish Civil War
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Clifford, Jack
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- 2011
20. Abstract 10133: Cerebrovascular Imaging Biomarkers, Neuropsychiatric Symptoms, and Mild Cognitive Impairment
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Maria Vassilaki, Jeremy Syrjanen, Eugene Scharf, Janina Krell-Roesch, Prashanthi Vemuri, Jonathan Graff-radford, Michelle Mielke, Mary M. Machulda, Walter Kremers, Val Lowe, Clifford Jack, David Knopman, Ronald Petersen, and Yonas E. Geda
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Physiology (medical) ,mental disorders ,Cardiology and Cardiovascular Medicine ,behavioral disciplines and activities - Abstract
Introduction: Cerebrovascular disease (CVD) and neuropsychiatric symptoms (NPS) are common in older adults and are independently associated with cognitive impairment. In addition, vascular depression (a late-life depression) is hypothesized to be associated with cerebrovascular pathology. Hypothesis: CVD pathology imaging biomarkers (e.g., white matter hyperintensities (WMH), infarctions) are associated with depression and anxiety, and both (depression/anxiety and CVD imaging biomarkers) are independently associated with mild cognitive impairment (MCI). Methods: This cross-sectional study included 1739 Mayo Clinic Study of Aging participants (≥50 years old) without dementia, with comprehensive cognitive evaluations and available data on the Beck Depression Inventory II (BDI), the Beck Anxiety Inventory (BAI) and imaging CVD biomarkers via FLAIR-MRI (i.e., WMH% of total intracranial volume (TIV) and brain infarctions). We used linear and logistic regression models to examine the associations adjusting for age, sex, education, and apolipoprotein E ε4 status. Results: Participants’ mean age (SD) was 71.11 (10.61) years (53.3% males). Higher WMH% TIV burden was significantly associated with higher BDI (b= 0.082, 95%CI: 0.031, 0.133), p=0.002) and BAI scores (b= 0.088, 95%CI: 0.037, 0.140), p=0.001); the presence of infarctions was also associated with a higher BDI score. Both WMH %TIV burden (OR: 1.20 (95%CI:1.05, 1.38), p=0.008) and BDI score (OR: 1.38 (95%CI:1.21, 1.57), p Conclusions: CVD imaging biomarkers and NPS, as measured by BDI and BAI scores, could represent two distinct processes associated with cognitive impairment. Studies are ongoing to further examine these associations and delineate how CVD, NPS, and other pathophysiology processes (e.g., Alzheimer’s disease) interact and are associated with cognitive impairment.
- Published
- 2021
21. ASSOCIATIONS OF AUDIOMETRIC HEARING, BRAIN MRI, AND COGNITIVE PERFORMANCE WITH SPEECH-IN-NOISE PERFORMANCE
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Kening Jiang, Josef Coresh, Kathleen Hayden, Clifford Jack, Jr., Thomas Mosley, James Pankow, Frank Lin, and Jennifer Deal
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Health (social science) ,Life-span and Life-course Studies ,Health Professions (miscellaneous) - Abstract
Speech-in-noise performance is fundamental to daily communications and comprehensive characterization is needed. We studied 590 dementia-free participants aged 70-84 years, including 428 hearing-impaired participants from the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study baseline (2018-19), which is a randomized controlled trial partially nested within the Atherosclerosis Risk in Communities (ARIC) Study, and 162 normal-hearing ARIC Visit 6/7 (2016-17/2018-19) participants. The Quick Speech-in-Noise (QuickSIN) test was used to measure speech-in-noise performance. Predictors included (1) Four-frequency better-ear pure-tone average (PTA); (2) Magnetic resonance imaging (MRI) measures (total and lobar volumes, diffusion tensor imaging, white matter hyperintensities); (3) Global and domain-specific (language, memory, executive function) cognitive performance. All predictors were standardized to Z-scores. We used multivariable-adjusted linear regression, adjusting for demographic and disease covariates. PTA and cognitive performance, but not MRI measures, were independently associated with speech-in-noise performance, with PTA explaining the largest variance, indicating the promising role of hearing aids.
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- 2022
22. Service Station Attendant and Light Automotive Maintenance, Course Description.
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Minneapolis Public Schools, Minn. Work Opportunity Center. and Clifford, Jack W.
- Abstract
Prepared by instructors and curriculum specialists, this course of study was designed to meet the individual needs of the dropout and/or hard-core unemployed youth by providing training as a service station attendant and light automotive maintenance mechanic. The achievement level of each student is determined at entry, and small instructional units are used to provide continuing positive reinforcement to minimize frustration. Training in this area is conducted in a public service station operated by the Work Opportunity Center. Instruction is provided in driveway sales, lubrication engine tune-up, brake work, and other repair and maintenance tasks short of major overhaul or body work. Students may receive such related instruction as mathematics, sales, accounting, and communications at the Center in addition to the related units taught at the station. Brief descriptions of other instructional areas, teaching techniques, material utilization, motivational devices, and case studies are appended. Related materials are available as VT 011 518-VT 011 533 in this issue. (GR)
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- 1969
23. Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease
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Preische, Oliver, Schultz, Stephanie A, Vöglein, Jonathan, Raichle, Marc, Ringman, John, Roh, Jee Hoon, Salloway, Stephen, Schofield, Peter, Shimada, Hiroyuki, Shiroto, Tomoyo, Shoji, Mikio, Sigurdson, Wendy, Sohrabi, Hamid, Levin, Johannes, Sparks, Paige, Suzuki, Kazushi, Swisher, Laura, Taddei, Kevin, Wang, Jen, Wang, Peter, Weiner, Mike, Wolfsberger, Mary, Xiong, Chengjie, Xu, Xiong, Masters, Colin L, Martins, Ralph, Schofield, Peter R, Rossor, Martin N, Graff-Radford, Neill R, Ghetti, Bernardino, Ringman, John M, Apel, Anja, Noble, James M, Chhatwal, Jasmeer, Goate, Alison M, Benzinger, Tammie L S, Morris, John C, Bateman, Randall J, Wang, Guoqiao, Fagan, Anne M, McDade, Eric M, Gordon, Brian A, Kuhle, Jens, Jucker, Mathias, Network, Dominantly Inherited Alzheimer, Allegri, Ricardo, Amtashar, Fatima, Bateman, Randall, Benzinger, Tammie, Berman, Sarah, Bodge, Courtney, Brandon, Susan, Brooks, William, Kaeser, Stephan A, Buck, Jill, Buckles, Virginia, Chea, Sochenda, Chrem, Patricio, Chui, Helena, Cinco, Jake, Clifford, Jack, Cruchaga, Carlos, D'Mello, Mirelle, Barro, Christian, Donahue, Tamara, Douglas, Jane, Edigo, Noelia, Erekin-Taner, Nilufer, Fagan, Anne, Farlow, Marty, Farrar, Angela, Feldman, Howard, Flynn, Gigi, Fox, Nick, Gräber, Susanne, Franklin, Erin, Fujii, Hisako, Gant, Cortaiga, Gardener, Samantha, Goate, Alison, Goldman, Jill, Gordon, Brian, Graff-Radford, Neill, Gray, Julia, Kuder-Buletta, Elke, Gurney, Jenny, Hassenstab, Jason, Hirohara, Mie, Holtzman, David, Hornbeck, Russ, DiBari, Siri Houeland, Ikeuchi, Takeshi, Ikonomovic, Snezana, Jerome, Gina, Karch, Celeste, la Fougère, Christian, Kasuga, Kensaku, Kawarabayashi, Takeshi, Klunk, William, Koeppe, Robert, Lee, Jae-Hong, Marcus, Daniel, Mason, Neal Scott, Masters, Colin, Laske, Christoph, Maue-Dreyfus, Denise, McDade, Eric, Montoya, Lucy, Mori, Hiroshi, Morris, John, Nagamatsu, Akem, Neimeyer, Katie, Noble, James, Norton, Joanne, and Perrin, Richard
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0301 basic medicine ,Oncology ,Aging ,blood [Neurofilament Proteins] ,Neurofilament ,Medicina Clínica ,Disease ,Neurodegenerative ,Alzheimer's Disease ,Medical and Health Sciences ,pathology [Alzheimer Disease] ,0302 clinical medicine ,Cerebrospinal fluid ,Neurofilament Proteins ,2.1 Biological and endogenous factors ,Aetiology ,screening and diagnosis ,medicine.diagnostic_test ,Neurodegeneration ,General Medicine ,genetics [Neurofilament Proteins] ,cerebrospinal fluid [Alzheimer Disease] ,Detection ,Editorial Commentary ,Positron emission tomography ,030220 oncology & carcinogenesis ,Neurological ,Disease Progression ,Biomarker (medicine) ,Alzheimer's disease ,medicine.medical_specialty ,CIENCIAS MÉDICAS Y DE LA SALUD ,Immunology ,blood [Nerve Degeneration] ,genetics [Mutation] ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,blood [Alzheimer Disease] ,Clinical Research ,Alzheimer Disease ,Internal medicine ,Acquired Cognitive Impairment ,medicine ,Humans ,ddc:610 ,neurofilament protein L ,business.industry ,Multiple sclerosis ,Neurosciences ,Neurología Clínica ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Magnetic resonance imaging ,medicine.disease ,Brain Disorders ,4.1 Discovery and preclinical testing of markers and technologies ,cerebrospinal fluid [Neurofilament Proteins] ,Good Health and Well Being ,030104 developmental biology ,Dominantly Inherited Alzheimer Network ,Mutation ,Nerve Degeneration ,Alzheimer ,Dementia ,business ,Biomarkers - Abstract
Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer's disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-β deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini-Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer's disease, which supports its potential utility as a clinically useful biomarker. Fil: Preische, Oliver. German Center For Neurodegenerative Disease; Alemania. Eberhard Karls Universität Tübingen.; Alemania Fil: Schultz, Stephanie A.. Washington University in St. Louis; Estados Unidos Fil: Apel, Anja. German Center For Neurodegenerative Disease; Alemania. Eberhard Karls Universität Tübingen.; Alemania Fil: Kuhle, Jens. University of Basel; Suiza Fil: Kaeser, Stephan A.. German Center For Neurodegenerative Disease; Alemania. Eberhard Karls Universität Tübingen.; Alemania Fil: Barro, Christian. University of Basel; Suiza Fil: Gräber, Susanne. German Center For Neurodegenerative Disease; Alemania Fil: Kuder Buletta, Elke. German Center For Neurodegenerative Disease; Alemania Fil: LaFougere, Christian. German Center For Neurodegenerative Disease; Alemania Fil: Laske, Christoph. German Center For Neurodegenerative Disease; Alemania. Eberhard Karls Universität Tübingen.; Alemania Fil: Vöglein, Jonathan. German Center for Neurodegenerative Diseases; Alemania. Ludwig Maximilians Universitat; Alemania Fil: Levin, Johannes. German Center for Neurodegenerative Diseases; Alemania. Ludwig Maximilians Universitat; Alemania Fil: Masters, Colin. University of Melbourne; Australia Fil: Martins, Ralph. Edith Cowan University; Australia. Macquarie University; Australia Fil: Schofield, Peter. Neuroscience Research Australia; Australia. University of New South Wales; Australia Fil: Rossor, Martin N.. University College London; Estados Unidos Fil: Graff Radford, Neill. Mayo Clinic Jacksonville. Department of Neurology; Estados Unidos Fil: Salloway, Stephen. Brown University; Estados Unidos Fil: Ghetti, Bernardino. Indiana University. School of Medicine; Estados Unidos Fil: Ringman, John M.. Indiana University. School of Medicine; Estados Unidos Fil: Noble, James M.. Columbia University; Estados Unidos Fil: Chhatwal, Jasmeer. Harvard Medical School; Estados Unidos Fil: Goate, Alison. Icahn School of Medicine at Mount Sinai. Department of Neuroscience; Estados Unidos Fil: Benzinger, Tammie L. S.. Washington University in St. Louis; Estados Unidos Fil: Morris, John. Washington University in St. Louis; Estados Unidos Fil: Bateman, Randall J.. Washington University in St. Louis; Estados Unidos Fil: Wang, Guoqiao. Washington University in St. Louis; Estados Unidos Fil: Fagan, Anne M.. Washington University in St. Louis; Estados Unidos Fil: McDade, Eric M.. Washington University in St. Louis; Estados Unidos Fil: Gordon, Brian. Washington University in St. Louis; Estados Unidos Fil: Jucker, Mathias. University of Tübingen. Hertie Institute for Clinical Brain Research. Department of Cellular Neurology and Department of Psychiatry and Psychotherapy; Alemania. German Center For Neurodegenerative Disease; Alemania Fil: Allegri, Ricardo Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
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- 2019
24. Associations of Central Auditory Processing With Brain Volumes
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Kening Jiang, Josef Coresh, Kathleen Hayden, Clifford Jack, Thomas Mosley, James Pankow, Frank Lin, and Jennifer Deal
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Health (social science) ,Life-span and Life-course Studies ,Health Professions (miscellaneous) - Abstract
We investigated the cross-sectional associations of speech-in-noise performance with magnetic resonance imaging brain volumes among 588 cognitively normal participants (77±4 years, 56% female) from the Aging and Cognitive Health Evaluation in Elders Study (randomized trial embedded in the Atherosclerosis Risk in Communities (ARIC) Study) baseline in 2018-19 (N=427, with hearing loss) and ARIC (N=161, normal hearing) Visit 6/7 in 2016-17/2018-19. Central auditory processing was measured by Quick Speech-in-Noise (QuickSIN) test; range: 0 to 30, lower scores=worse performance. In models adjusted for demographic and disease covariates, every 5-point decrease in QuickSIN score was associated with smaller volumes of the temporal lobe overall (-0.07SD, 95% CI:-0.13,-0.01) as well as subregions including but not limited to those important for auditory processing (amygdala:-0.13SD, 95% CI:-0.21,-0.04; middle temporal gyrus:-0.08SD, 95% CI:-0.15,-0.00; superior temporal gyrus:-0.08SD, 95% CI:-0.15,-0.01). Further research is needed to understand the mechanisms underlying these observed associations.
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- 2021
25. 0264 Sleepiness in cognitively unimpaired older adults is associated with CSF biomarkers of inflammation and axonal integrity
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Diego Carvalho, Erik St Louis, Scott Przybelski, Timothy Morgenthaler, Bradley Boeve, Ronald Petersen, Clifford Jack, Jonathan Graff-Radford, Prashanthi Vemuri, and Michele Mielke
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Physiology (medical) ,Neurology (clinical) - Abstract
Introduction We have previously shown that older adults with excessive daytime sleepiness (EDS) appear to be more vulnerable to longitudinal amyloid PET accumulation before the onset of the dementia. It remains unclear whether this vulnerability is specific to amyloid or extends to other biomarkers of Alzheimer’s disease pathology, or axonal integrity and inflammation, which can also contribute to neurodegeneration and cognitive changes. Methods For this cross-sectional analysis, we identified 260 cognitively unimpaired adults (>60 years old) without neurologic disorder who underwent CSF quantification of AD biomarkers (CSF Aβ-42, p-tau181, p-tau217) along with at least one other biomarker of interest (neurofilament light chain [NfL], IL-6, IL-10, and TNF-α) from the Mayo Clinic Study of Aging – a longitudinal population-based cohort in Olmsted County, Minnesota. CSF biomarkers were available in 251-260 individuals, depending on the biomarker. We fit linear regression models to assess whether the CSF biomarkers were associated with sleepiness as measured by the Epworth Sleepiness Scale (ESS), after controlling for age, sex, APOE4 genotype, BMI, hypertension, dyslipidemia, and OSA diagnosis (by chart review). Results Higher ESS scores were independently associated with higher CSF IL-6 and NfL, but not with the other biomarkers in the whole sample. For every single-point increase in the ESS score, there was a .008 ([95% CI .001-.016], p=0.033) increase in the log of IL-6 and .01 ([95% CI .002-.018], p=0.016) increase in the log of NfL. A sensitivity analysis showed a correlation between ESS scores and log of p-tau/Aβ-42 ratio only in participants with abnormal ratio (>0.023), after controlling for APOE4 (partial r=.27, p=039). Conclusion Our results corroborate previous literature suggesting that higher inflammatory milieu reflected by increased CSF IL-6 is associated with sleepiness. The association between NfL and sleepiness suggests that sleepiness may be related to disturbed connectivity due to axonal damage. Alternatively, NfL may be a surrogate of active axonal injury associated with more disrupted sleep. A correlation between sleepiness and CSF p-tau/ab-42 ratio was only seen in patients with abnormal ratio, suggesting a stronger association between sleepiness and AD pathology as the disease progresses, possibly because AD pathology worsens sleep quality and/or vice-versa. Support (If Any) NIH/NIA
- Published
- 2022
26. Amyloid and Tau Pathology Associations With Personality Traits, Neuropsychiatric Symptoms, and Cognitive Lifestyle in the Preclinical Phases of Sporadic and Autosomal Dominant Alzheimer’s Disease
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Pichet Binette, Alexa, primary, Vachon-Presseau, Étienne, additional, Morris, John, additional, Bateman, Randall, additional, Benzinger, Tammie, additional, Collins, D. Louis, additional, Poirier, Judes, additional, Breitner, John C.S., additional, Villeneuve, Sylvia, additional, Allegri, Ricardo, additional, Amtashar, Fatima, additional, Bateman, Randy, additional, Berman, Sarah, additional, Bodge, Courtney, additional, Brandon, Susan, additional, Brooks, William (Bill), additional, Buck, Jill, additional, Buckles, Virginia, additional, Chea, Sochenda, additional, Chhatwal, Jasmeer, additional, Chrem, Patricio, additional, Chui, Helena, additional, Cinco, Jake, additional, Clifford, Jack, additional, Cruchaga, Carlos, additional, D‘Mello, Mirelle, additional, Donahue, Tamara, additional, Douglas, Jane, additional, Edigo, Noelia, additional, Erekin-Taner, Nilufer, additional, Fagan, Anne, additional, Farlow, Marty, additional, Farrar, Angela, additional, Feldman, Howard, additional, Flynn, Gigi, additional, Fox, Nick, additional, Franklin, Erin, additional, Fujii, Hisako, additional, Gant, Cortaiga, additional, Gardener, Samantha, additional, Ghetti, Bernardino, additional, Goate, Alison, additional, Goldman, Jill, additional, Gordon, Brian, additional, Graff-Radford, Neill, additional, Gray, Julia, additional, Gurney, Jenny, additional, Hassenstab, Jason, additional, Hirohara, Mie, additional, Holtzman, David, additional, Hornbeck, Russ, additional, DiBari, Siri Houeland, additional, Ikeuchi, Takeshi, additional, Ikonomovic, Snezana, additional, Jerome, Gina, additional, Jucker, Mathias, additional, Karch, Celeste, additional, Kasuga, Kensaku, additional, Kawarabayashi, Takeshi, additional, Klunk, William (Bill), additional, Koeppe, Robert, additional, Kuder-Buletta, Elke, additional, Laske, Christoph, additional, Lee, Jae-Hong, additional, Levin, Johannes, additional, Marcus, Daniel, additional, Martins, Ralph, additional, Mason, Neal Scott, additional, Masters, Colin, additional, Maue-Dreyfus, Denise, additional, McDade, Eric, additional, Montoya, Lucy, additional, Mori, Hiroshi, additional, Nagamatsu, Akem, additional, Neimeyer, Katie, additional, Noble, James, additional, Norton, Joanne, additional, Perrin, Richard, additional, Raichle, Marc, additional, Ringman, John, additional, Roh, Jee Hoon, additional, Salloway, Stephen, additional, Schofield, Peter, additional, Shimada, Hiroyuki, additional, Shiroto, Tomoyo, additional, Shoji, Mikio, additional, Sigurdson, Wendy, additional, Sohrabi, Hamid, additional, Sparks, Paige, additional, Suzuki, Kazushi, additional, Swisher, Laura, additional, Taddei, Kevin, additional, Wang, Jen, additional, Wang, Peter, additional, Weiner, Mike, additional, Wolfsberger, Mary, additional, Xiong, Chengjie, additional, Xu, Xiong, additional, Tam, Angela, additional, Labonté, Anne, additional, Pichet Binette, Alexa, additional, Faubert, Anne-Marie, additional, Mathieu, Axel, additional, Madjar, Cécile, additional, Carrier, Charles Edouard, additional, Dansereau, Christian, additional, Kazazian, Christina, additional, Lepage, Claude, additional, Picard, Cynthia, additional, Maillet, David, additional, Michaud, Diane, additional, Couture, Doris, additional, Dea, Doris, additional, Cuello, Claudio, additional, Barkun, Alan, additional, Evans, Alan, additional, Courcot, Blandine, additional, Tardif, Christine, additional, Debacker, Clément, additional, Jack, Clifford R., additional, Fontaine, David, additional, Knopman, David S., additional, Maultaup, Gerhard, additional, Near, Jamie, additional, Leoutsakos, Jeannie-Marie, additional, Maltais, Jean-Robert, additional, Brandt, Jason, additional, Pruessner, Jens, additional, Morris, John C., additional, Cheewakriengkrai, Laksanun, additional, Münter, Lisa-Marie, additional, Collins, Louis, additional, Chakravarty, Mallar, additional, Sager, Mark A., additional, Dauar-Tedeschi, Marina, additional, Eisenberg, Mark, additional, Rajah, Natasha, additional, Aisen, Paul, additional, Toussaint, Joanne, additional, Rosa-Neto, Pedro, additional, Bellec, Pierre, additional, Kostopoulos, Penelope, additional, Etienne, Pierre, additional, Tariot, Pierre N., additional, Orban, Pierre, additional, Sperling, Reisa A., additional, Hoge, Rick, additional, Thomas, Ronald G., additional, Gauthier, Serge, additional, Craft, Suzanne, additional, Montine, Thomas J., additional, Nair, Vasavan, additional, Bohbot, Véronique, additional, Venugopalan, Vinod, additional, Fonov, Vladimir, additional, Ituria-Medina, Yasser, additional, Khachaturian, Zaven S., additional, Teigner, Eduard, additional, Anthal, Elena, additional, Yu, Elsa, additional, Ferdinand, Fabiola, additional, Pogossova, Galina, additional, Mayrand, Ginette, additional, Duclair, Guerda, additional, Gagné, Guylaine, additional, Newbold-Fox, Holly, additional, Leppert, Illana, additional, Vallée, Isabelle, additional, Vogel, Jacob W., additional, Tremblay-Mercier, Jennifer, additional, Frenette, Joanne, additional, Frappier, Josée, additional, Kat, Justin, additional, Miron, Justin, additional, Wan, Karen, additional, Mahar, Laura, additional, Carmo, Leopoldina, additional, Théroux, Louise, additional, Dadar, Mahsa, additional, Dufour, Marianne, additional, Lafaille-Magnan, Marie-Elyse, additional, Appleby, Melissa, additional, Savard, Mélissa, additional, Tuwaig, Miranda, additional, Petkova, Mirela, additional, Rioux, Pierre, additional, Meyer, Pierre-François, additional, El-Khoury, Rana, additional, Gordon, Renee, additional, Giles, Renuka, additional, Das, Samir, additional, Wang, Seqian, additional, Tabrizi, Shirin, additional, Mathotaarachchi, Sulantha, additional, Dubuc, Sylvie, additional, Lee, Tanya, additional, Beaudry, Thomas, additional, Gervais, Valérie, additional, Pagé, Véronique, additional, Gonneaud, Julie, additional, Ayranci, Gülebru, additional, Pascoal, Tharick A., additional, Desautels, René, additional, Benbouhoud, Fatiha, additional, Saint-Fort, Eunice Farah, additional, Verfaillie, Sander C.J., additional, Farzin, Sarah, additional, Salaciak, Alyssa, additional, Tullo, Stephanie, additional, Vachon-Presseau, Etienne, additional, Daoust, Leslie-Ann, additional, Köbe, Theresa, additional, Spreng, Nathan, additional, McSweeney, Melissa, additional, Nilsson, Nathalie, additional, Pishnamazi, Morteza, additional, and Bedetti, Christophe, additional
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- 2021
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27. Early indications of future cognitive decline: stable versus declining controls.
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Angela Rizk-Jackson, Philip Insel, Ronald Petersen, Paul Aisen, Clifford Jack, and Michael Weiner
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Medicine ,Science - Abstract
This study aimed to identify baseline features of normal subjects that are associated with subsequent cognitive decline. Publicly available data from the Alzheimer's Disease Neuroimaging Initiative was used to find differences in baseline clinical assessments (ADAScog, AVLT, FAQ) between cognitively healthy individuals who will suffer cognitive decline within 48 months and those who will remain stable for that period. Linear regression models indicated an individual's conversion status was significantly associated with certain baseline neuroimaging measures, including posterior cingulate glucose metabolism. Linear Discriminant Analysis models built with baseline features derived from MRI and FDG-PET measures were capable of successfully predicting whether an individual will convert to MCI within 48 months or remain cognitively stable. The findings from this study support the idea that there exist informative differences between normal people who will later develop cognitive impairments and those who will remain cognitively stable for up to four years. Further, the feasibility of developing predictive models that can detect early states of cognitive decline in seemingly normal individuals was demonstrated.
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- 2013
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28. A telescope GWAS analysis strategy, based on SNPs-genes-pathways ensamble and on multivariate algorithms, to characterize late onset Alzheimer's disease
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Squillario, Margherita, Abate, Giulia, Tomasi, Federico, Tozzo, Veronica, Barla, Annalisa, Uberti, Daniela, Weiner, Michael W., Aisen, Paul, Petersen, Ronald, Clifford, Jack R., Jagust, William, Trojanowki, John Q., Toga, Arthur W., Beckett, Laurel, Green, Robert C., Saykin, Andrew J., Morris, John, Shaw, Leslie M., Khachaturian, Zaven, Sorensen, Greg, Carrillo, Maria, Kuller, Lew, Raichle, Marc, Paul, Steven, Davies, Peter, Fillit, Howard, Hefti, Franz, Holtzman, Davie, Mesulam, M. Marcel, Potter, William, Snyder, Peter, and Montine, Tom
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0301 basic medicine ,Aging ,Multivariate statistics ,Gene regulatory network ,lcsh:Medicine ,Genome-wide association study ,Neurodegenerative ,Alzheimer's Disease ,Machine Learning ,0302 clinical medicine ,Genetics research ,2.1 Biological and endogenous factors ,Gene Regulatory Networks ,Aetiology ,lcsh:Science ,Multidisciplinary ,Single Nucleotide ,Alzheimer's disease ,Magnetic Resonance Imaging ,Neurological ,Algorithm ,Algorithms ,Biotechnology ,Alzheimer's Disease Neuroimaging Initiative ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Article ,03 medical and health sciences ,Alzheimer Disease ,Genetics ,Acquired Cognitive Impairment ,Humans ,Genetic Predisposition to Disease ,Allele ,Polymorphism ,Alleles ,Genetic association ,Gene Expression Profiling ,Human Genome ,lcsh:R ,Neurosciences ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Alzheimer’s Disease Neuroimaging Initiative ,Brain Disorders ,Gene expression profiling ,030104 developmental biology ,Positron-Emission Tomography ,Dementia ,lcsh:Q ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Genome–wide association studies (GWAS) have revealed a plethora of putative susceptibility genes for Alzheimer’s disease (AD), with the sole exception of APOE gene unequivocally validated in independent study. Considering that the etiology of complex diseases like AD could depend on functional multiple genes interaction network, here we proposed an alternative GWAS analysis strategy based on (i) multivariate methods and on a (ii) telescope approach, in order to guarantee the identification of correlated variables, and reveal their connections at three biological connected levels. Specifically as multivariate methods, we employed two machine learning algorithms and a genetic association test and we considered SNPs, Genes and Pathways features in the analysis of two public GWAS dataset (ADNI-1 and ADNI-2). For each dataset and for each feature we addressed two binary classifications tasks: cases vs. controls and the low vs. high risk of developing AD considering the allelic status of APOEe4. This complex strategy allowed the identification of SNPs, genes and pathways lists statistically robust and meaningful from the biological viewpoint. Among the results, we confirm the involvement of TOMM40 gene in AD and we propose GRM7 as a novel gene significantly associated with AD.
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- 2020
29. A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease
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Barthélemy, Nicolas R, Li, Yan, Morris, John C, Neimeyer, Katie, Noble, James, Norton, Joanne, Perrin, Richard, Raichle, Marc, Renton, Alan, Ringman, John, Roh, Jee Hoon, Salloway, Stephen, Schofield, Peter, Karch, Celeste M, Shimada, Hiroyuki, Sigurdson, Wendy, Sohrabi, Hamid, Sparks, Paige, Suzuki, Kazushi, Taddei, Kevin, Wang, Peter, Xiong, Chengjie, Xu, Xiong, Allegri, Ricardo, Mendez, Patricio Chrem, Berman, Sarah B, Ikeuchi, Takeshi, Mori, Hiroshi, Shoji, Mikio, Joseph-Mathurin, Nelly, Farlow, Martin, Chhatwal, Jasmeer, Graff-Radford, Neill R, Schofield, Peter R, Masters, Colin L, Martins, Ralph N, O'Connor, Antoinette, Gordon, Brian A, Fox, Nick C, Levin, Johannes, Jucker, Mathias, Gabelle, Audrey, Lehmann, Sylvain, Sato, Chihiro, Bateman, Randall J, McDade, Eric, Network, Dominantly Inherited Alzheimer, Hassenstab, Jason, Bateman, Randy, Bechara, Jacob, Benzinger, Tammie, Berman, Sarah, Bodge, Courtney, Brandon, Susan, Brooks, William Bill, Buck, Jill, Buckles, Virginia, Chea, Sochenda, Benzinger, Tammie L S, Chrem Mendez, Patricio, Chui, Helena, Cinco, Jake, Clifford, Jack, Cruchaga, Carlos, Donahue, Tamara, Douglas, Jane, Edigo, Noelia, Erekin-Taner, Nilufer, Fagan, Anne, Fitzpatrick, Colleen, Flynn, Gigi, Fox, Nick, Franklin, Erin, Fujii, Hisako, Gant, Cortaiga, Gardener, Samantha, Ghetti, Bernardino, Fagan, Anne M, Goate, Alison, Goldman, Jill, Gordon, Brian, Graff-Radford, Neill, Gray, Julia, Groves, Alexander, Hoechst-Swisher, Laura, Holtzman, David, Hornbeck, Russ, Perrin, Richard J, DiBari, Siri Houeland, Ikonomovic, Snezana, Jerome, Gina, Karch, Celeste, Kasuga, Kensaku, Kawarabayashi, Takeshi, Klunk, William Bill, Koeppe, Robert, Kuder-Buletta, Elke, Goate, Alison M, Laske, Christoph, Lee, Jae-Hong, Martins, Ralph, Mason, Neal Scott, Masters, Colin, Maue-Dreyfus, Denise, Morris, John, Nagamatsu, Akem, Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia [Buenos Aires] (FLENI), FLENI, University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Niigata University, Osaka City University (OCU), Hirosaki University, The University of Tokyo (UTokyo), Columbia University [New York], Indiana University - Purdue University Indianapolis (IUPUI), Indiana University System, Harvard Medical School [Boston] (HMS), Mayo Clinic [Jacksonville], Brown University, Neuroscience Research Australia (NeuRA), University of New South Wales [Sydney] (UNSW), The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Edith Cowan University (ECU), Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO)-Planning and Transport Research Centre (PATREC), University College of London [London] (UCL), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Ludwig-Maximilians-Universität München (LMU), Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU), University of Tübingen, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), BioCampus Montpellier (BCM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Dominantly Inherited Alzheimer Network: Ricardo Allegri, Randy Bateman, Jacob Bechara, Tammie Benzinger, Sarah Berman, Courtney Bodge, Susan Brandon, William Bill Brooks, Jill Buck, Virginia Buckles, Sochenda Chea, Jasmeer Chhatwal, Patricio Chrem Mendez, Helena Chui, Jake Cinco, Jack Clifford, Carlos Cruchaga, Tamara Donahue, Jane Douglas, Noelia Edigo, Nilufer Erekin-Taner, Anne Fagan, Martin Farlow, Colleen Fitzpatrick, Gigi Flynn, Nick Fox, Erin Franklin, Hisako Fujii, Cortaiga Gant, Samantha Gardener, Bernardino Ghetti, Alison Goate, Jill Goldman, Brian Gordon, Neill Graff-Radford, Julia Gray, Alexander Groves, Jason Hassenstab, Laura Hoechst-Swisher, David Holtzman, Russ Hornbeck, Siri Houeland DiBari, Takeshi Ikeuchi, Snezana Ikonomovic, Gina Jerome, Mathias Jucker, Celeste Karch, Kensaku Kasuga, Takeshi Kawarabayashi, William Bill Klunk, Robert Koeppe, Elke Kuder-Buletta, Christoph Laske, Jae-Hong Lee, Johannes Levin, Ralph Martins, Neal Scott Mason, Colin Masters, Denise Maue-Dreyfus, Eric McDade, Hiroshi Mori, John Morris, Akem Nagamatsu, Katie Neimeyer, James Noble, Joanne Norton, Richard Perrin, Marc Raichle, Alan Renton, John Ringman, Jee Hoon Roh, Stephen Salloway, Peter Schofield, Hiroyuki Shimada, Wendy Sigurdson, Hamid Sohrabi, Paige Sparks, Kazushi Suzuki, Kevin Taddei, Peter Wang, Chengjie Xiong, Xiong Xu, Technische Universität München [München] (TUM)-Ludwig-Maximilians-Universität München (LMU), BioCampus (BCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Michel-Avella, Amandine
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0301 basic medicine ,Male ,[SDV]Life Sciences [q-bio] ,Inheritance Patterns ,genetics [Alzheimer Disease] ,Plaque, Amyloid ,Disease ,0302 clinical medicine ,Cerebrospinal fluid ,Cognition ,pathology [Brain] ,Phosphorylation ,biology ,Neurodegeneration ,Brain ,General Medicine ,Middle Aged ,Magnetic Resonance Imaging ,3. Good health ,[SDV] Life Sciences [q-bio] ,cerebrospinal fluid [Alzheimer Disease] ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,Alzheimer's disease ,metabolism [Alzheimer Disease] ,Adult ,Amyloid ,genetics [Inheritance Patterns] ,Tau protein ,Neuroimaging ,tau Proteins ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Atrophy ,Alzheimer Disease ,Fluorodeoxyglucose F18 ,mental disorders ,medicine ,Humans ,ddc:610 ,pathology [Plaque, Amyloid] ,chemistry [Fluorodeoxyglucose F18] ,metabolism [Amyloid] ,Aged ,medicine.disease ,metabolism [tau Proteins] ,030104 developmental biology ,cerebrospinal fluid [tau Proteins] ,Solubility ,biology.protein ,diagnostic imaging [Alzheimer Disease] ,Neuroscience - Abstract
International audience; Development of tau-based therapies for Alzheimer's disease requires an understanding of the timing of disease-related changes in tau. We quantified the phosphorylation state at multiple sites of the tau protein in cerebrospinal fluid markers across four decades of disease progression in dominantly inherited Alzheimer's disease. We identified a pattern of tau staging where site-specific phosphorylation changes occur at different periods of disease progression and follow distinct trajectories over time. These tau phosphorylation state changes are uniquely associated with structural, metabolic, neurodegenerative and clinical markers of disease, and some (p-tau217 and p-tau181) begin with the initial increases in aggregate amyloid-β as early as two decades before the development of aggregated tau pathology. Others (p-tau205 and t-tau) increase with atrophy and hypometabolism closer to symptom onset. These findings provide insights into the pathways linking tau, amyloid-β and neurodegeneration, and may facilitate clinical trials of tau-based treatments.
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- 2020
30. An atlas of cortical circular RNA expression in Alzheimer disease brains demonstrates clinical and pathological associations
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Dube, Umber, Del-Aguila, Jorge L, Gentsch, Jen, Wang, Peter, Weiner, Mike, Wolfsberger, Mary, Xiong, Chengjie, Xu, Xiong, Wang, Fengxian, Network, Dominantly Inherited Alzheimer, Salloway, Stephen, Masters, Colin L, Lee, Jae-Hong, Graff-Radford, Neill R, Chhatwal, Jasmeer P, Bateman, Randall J, Morris, John C, Li, Zeran, Karch, Celeste M, Harari, Oscar, Cruchaga, Carlos, Allegri, Ricardo, Amtashar, Fatima, Benzinger, Tammie, Berman, Sarah, Bodge, Courtney, Brandon, Susan, Brooks, William, Budde, John P, Buck, Jill, Buckles, Virginia, Chea, Sochenda, Chrem, Patricio, Chui, Helena, Cinco, Jake, Clifford, Jack, D'Mello, Mirelle, Donahue, Tamara, Douglas, Jane, Jiang, Shan, Edigo, Noelia, Erekin-Taner, Nilufer, Fagan, Anne, Farlow, Marty, Farrar, Angela, Feldman, Howard, Flynn, Gigi, Fox, Nick, Franklin, Erin, Fujii, Hisako, Hsu, Simon, Gant, Cortaiga, Gardener, Samantha, Ghetti, Bernardino, Goate, Alison, Goldman, Jill, Gordon, Brian, Gray, Julia, Gurney, Jenny, Hassenstab, Jason, Hirohara, Mie, Ibanez, Laura, Holtzman, David, Hornbeck, Russ, DiBari, Siri Houeland, Ikeuchi, Takeshi, Ikonomovic, Snezana, Jerome, Gina, Jucker, Mathias, Kasuga, Kensaku, Kawarabayashi, Takeshi, Klunk, William, Fernandez, Maria Victoria, Koeppe, Robert, Kuder-Buletta, Elke, Laske, Christoph, Levin, Johannes, Marcus, Daniel, Martins, Ralph, Mason, Neal Scott, Maue-Dreyfus, Denise, McDade, Eric, Montoya, Lucy, Farias, Fabiana, Mori, Hiroshi, Nagamatsu, Akem, Neimeyer, Katie, Noble, James, Norton, Joanne, Perrin, Richard, Raichle, Marc, Ringman, John, Roh, Jee Hoon, Schofield, Peter, Shimada, Hiroyuki, Shiroto, Tomoyo, Shoji, Mikio, Sigurdson, Wendy, Sohrabi, Hamid, Sparks, Paige, Suzuki, Kazushi, Swisher, Laura, Taddei, Kevin, and Wang, Jen
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0301 basic medicine ,metabolism [Parietal Lobe] ,Posterior parietal cortex ,Biology ,Severity of Illness Index ,Article ,Pathogenesis ,03 medical and health sciences ,pathology [Alzheimer Disease] ,0302 clinical medicine ,Atlases as Topic ,Alzheimer Disease ,Circular RNA ,metabolism [MicroRNAs] ,Parietal Lobe ,ddc:570 ,microRNA ,medicine ,Dementia ,Humans ,RNA, Messenger ,Gene ,Messenger RNA ,biosynthesis [RNA, Messenger] ,Sequence Analysis, RNA ,General Neuroscience ,Gene Expression Profiling ,diagnosis [Alzheimer Disease] ,RNA, Circular ,medicine.disease ,biosynthesis [RNA, Circular] ,MicroRNAs ,030104 developmental biology ,Case-Control Studies ,Alzheimer's disease ,Neuroscience ,030217 neurology & neurosurgery ,metabolism [Alzheimer Disease] - Abstract
Parietal cortex RNA-sequencing (RNA-seq) data were generated from individuals with and without Alzheimer disease (AD; ncontrol = 13; nAD = 83) from the Knight Alzheimer Disease Research Center (Knight ADRC). Using this and an independent (Mount Sinai Brain Bank (MSBB)) AD RNA-seq dataset, cortical circular RNA (circRNA) expression was quantified in the context of AD. Significant associations were identified between circRNA expression and AD diagnosis, clinical dementia severity and neuropathological severity. It was demonstrated that most circRNA-AD associations are independent of changes in cognate linear messenger RNA expression or estimated brain cell-type proportions. Evidence was provided for circRNA expression changes occurring early in presymptomatic AD and in autosomal dominant AD. It was also observed that AD-associated circRNAs co-expressed with known AD genes. Finally, potential microRNA-binding sites were identified in AD-associated circRNAs for miRNAs predicted to target AD genes. Together, these results highlight the importance of analyzing non-linear RNAs and support future studies exploring the potential roles of circRNAs in AD pathogenesis.
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- 2019
31. Subjective Cognitive Decline Is Associated With Altered Default Mode Network Connectivity in Individuals With a Family History of Alzheimer's Disease
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Sander C.J. Verfaillie, Alexa Pichet Binette, Etienne Vachon-Presseau, Shirin Tabrizi, Mélissa Savard, Pierre Bellec, Rik Ossenkoppele, Philip Scheltens, Wiesje M. van der Flier, John C.S. Breitner, Sylvia Villeneuve, Paul Aisen, Elena Anthal, Melissa Appleby, Gülebru Ayranci, Alan Barkun, Thomas Beaudry, Fatiha Benbouhoud, Veronique Bohbot, Jason Brandt, John Breitner, Leopoldina Carmo, Edouard Carrier Charles, Mallar Chakravarty, Laksanun Cheewakriengkrai, Louis Collins, Blandine Courcot, Doris Couture, Suzanne Craft, Claudio Cuello, Mahsa Dadar, Christian Dansereau, null DasSamir, Dauar-Tedeschi Marina, Doris Dea, Clement Debacker, Rene Desautels, Sylvie Dubuc, Guerda Duclair, Marianne Dufour, Mark Eisenberg, Rana El-Khoury, Pierre Etienne, Alan Evans, Anne-Marie Faubert, Fabiola Ferdinand, Vladimir Fonov, David Fontaine, Josée Frappier, Frenette Joanne, Guylaine Gagne, Serge Gauthier, Valérie Gervais, Renuka Giles, Julie Gonneaud, Renee Gordon, Rick Hoge, Bradley Hyman, Yasser Ituria-Medina, Clifford Jack, Justin Kat, Christina Kazazian, Zaven Khachaturian, David Knopman, Penelope Kostopoulos, Anne Labonte, Marie-Elyse Lafaille-Magnan, Tanya Lee, Jeannie-Marie Leoutsakos, Claude Lepage, Illana Leppert, Cécile Madjar, Laura Mahar, David Maillet, Jean-Robert Maltais, Axel Mathieu, Sulantha Mathotaarachchi, Gerhard Maultaup, Ginette Mayrand, Pierre-François Meyer, Diane Michaud, Justin Miron, Thomas Montine, John Morris, Lisa-Marie Münter, Vasavan Nair, Jamie Near, Holly Newbold-Fox, Pierre Orban, Véronique Page, Tharick Pascoal, Mirela Petkova, Cynthia Picard, Galina Pogossova, Judes Poirier, Jens Pruessner, Natasha Rajah, Pierre Rioux, Pedro Rosa-Neto, Mark Sager, Eunice Farah Saint-Fort, Reisa Sperling, Angela Tam, Christine Tardif, Pierre Tariot, Eduard Teigner, Louise Theroux, Ronald Thomas, Paule-Joanne Toussaint, Jennifer Tremblay-Mercier, Miranda Tuwaig, Isabelle Vallee, Vinod Venugopalan, Sander Verfaillie, Jacob Vogel, Karen Wan, Seqian Wang, Elsa Yu, Radiology and nuclear medicine, Amsterdam Neuroscience - Neurodegeneration, Neurology, APH - Personalized Medicine, and APH - Methodology
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0301 basic medicine ,Male ,medicine.medical_specialty ,Cognitive Neuroscience ,Audiology ,Neuropsychological Tests ,Asymptomatic ,03 medical and health sciences ,0302 clinical medicine ,Cognition ,Alzheimer Disease ,Neural Pathways ,Medicine ,Dementia ,Humans ,Radiology, Nuclear Medicine and imaging ,Cognitive Dysfunction ,Effects of sleep deprivation on cognitive performance ,Neuropsychological assessment ,Cognitive decline ,Family history ,Biological Psychiatry ,Default mode network ,Aged ,Brain Mapping ,medicine.diagnostic_test ,business.industry ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,030104 developmental biology ,Disease Progression ,Female ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Background: Both subjective cognitive decline (SCD) and a family history of Alzheimer's disease (AD) portend risk of brain abnormalities and progression to dementia. Posterior default mode network (pDMN) connectivity is altered early in the course of AD. It is unclear whether SCD predicts similar outcomes in cognitively normal individuals with a family history of AD. Methods: We studied 124 asymptomatic individuals with a family history of AD (age 64 ± 5 years). Participants were categorized as having SCD if they reported that their memory was becoming worse (SCD+). We used extensive neuropsychological assessment to investigate five different cognitive domain performances at baseline (n = 124) and 1 year later (n = 59). We assessed interconnectivity among three a priori defined ROIs: pDMN, anterior ventral DMN, medial temporal memory system (MTMS), and the connectivity of each with the rest of brain. Results: Sixty-eight (55%) participants reported SCD. Baseline cognitive performance was comparable between groups (all false discovery rate-adjusted p values >.05). At follow-up, immediate and delayed memory improved across groups, but the improvement in immediate memory was reduced in SCD+ compared with SCD− (all false discovery rate–adjusted p values −, SCD+ subjects showed increased pDMN–MTMS connectivity (false discovery rate–adjusted p
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- 2018
32. Multisite study of the relationships between antemortem [
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Renaud, La Joie, Nagehan, Ayakta, William W, Seeley, Ewa, Borys, Adam L, Boxer, Charles, DeCarli, Vincent, Doré, Lea T, Grinberg, Eric, Huang, Ji-Hye, Hwang, Milos D, Ikonomovic, Clifford, Jack, William J, Jagust, Lee-Way, Jin, William E, Klunk, Julia, Kofler, Orit H, Lesman-Segev, Samuel N, Lockhart, Val J, Lowe, Colin L, Masters, Chester A, Mathis, Catriona L, McLean, Bruce L, Miller, Daniel, Mungas, James P, O'Neil, John M, Olichney, Joseph E, Parisi, Ronald C, Petersen, Howard J, Rosen, Christopher C, Rowe, Salvatore, Spina, Prashanthi, Vemuri, Victor L, Villemagne, Melissa E, Murray, and Gil D, Rabinovici
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Male ,Thiazoles ,Aniline Compounds ,Alzheimer Disease ,Positron-Emission Tomography ,Humans ,Female ,Plaque, Amyloid ,Autopsy ,Neuropathology ,Article ,Aged ,Retrospective Studies - Abstract
INTRODUCTION: We sought to establish the relationships between standard post mortem measures of AD neuropathology and ante mortem [(11)C]PIB-PET analyzed with the Centiloid (CL) method, a standardized scale for Aβ-PET quantification. METHODS: Four centers contributed 179 participants encompassing a broad range of clinical diagnoses, PET data and autopsy findings. RESULTS: CL values increased with each CERAD neuritic plaque score increment (median −3 CL for no plaques, 92 CL for frequent plaques) and non-linearly with Thal Aβ phases (increases were detected starting at phase 2) with overlap between scores/phases. Findings were comparable across sites and when restricted to 56 patients who died within 2 years of PET. A threshold of 12.2 CL detected CERAD moderate-to-frequent neuritic plaques (AUC=0.910, Sensitivity=89.2%, Specificity=86.4%) while 24.4 CL identified intermediate-to-high AD neuropathological changes (AUC=0.894, Sensitivity=84.1%, Specificity=87.9%). DISCUSSION: Our study demonstrated the robustness of a multi-site Centiloid [(11)C]PIBPET study and established a range of pathology-based CL thresholds.
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- 2018
33. Abstract P082: Arterial Stiffness and Pressure Amplification are Associated with Lower Cognition Among Older Caucasian Adults: The Atherosclerosis Risk in Communities (ARIC) Study
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Jingkai Wei, Priya Palta, Michelle Meyer, Hirofumi Tanaka, Jennifer Deal, Clifford Jack, David Knopman, Jacqueline Wright, Michael Griswold, Thomas H Mosley, and Gerardo Heiss
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Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Introduction: Accelerated cognitive decline is influenced by vascular aging. Arterial stiffness and pressure amplification, measures of vascular aging, are associated with lower cognitive performance though their association with cognitive domains has been understudied. Hypothesis: Arterial stiffness and pressure amplification are associated with lower global and domain-specific cognition among a sample of Caucasian and African American (AA) older adults. Methods: In a cross-sectional study of 4618 members from visit 5 (2011-2013) of ARIC (mean age: 75 years, 41% men, 20% AA), we measured arterial stiffness (carotid-femoral pulse wave velocity (cfPWV)) and pressure amplification (pulse pressure amplification (PPA), central pulse pressure (cPP) and carotid systolic blood pressure (cSBP)) using the Omron VP-1000 Plus device. Race-specific 25th percentile cut points were estimated for each measure. Domain-specific cognitive function was examined using the Delayed Word Recall Test (memory), Digit Symbol Substitution Test (executive function/processing speed), and Word Fluency Test (language). Test-specific z scores were calculated from sample means and standard deviations. A global cognition z score was generated by averaging the test-specific z scores. Linear regression was used to estimate the associations between race-specific 25th percentile dichotomies for arterial stiffness and pressure amplification measures with test-specific and global cognition z scores, adjusted for age, sex, education, ApoE4, heart rate, smoking and body mass index. Results: Among AAs, there was no significant association between measures of arterial stiffness and pressure amplification with either global or the domain-specific measures of cognition. Among Caucasians, all measures of arterial stiffness and pressure amplification were associated with lower global cognitive z scores (cfPWV: Beta (β) =-0.11, 95% Confidence Interval (CI): -0.19, -0.04; PPA: β=-0.11, 95% CI: -0.19, -0.03; cPP: β=-0.11, 95% CI: -0.18, -0.04; cSBP: β=-0.12, 95% CI: -0.20, -0.05). All measures of arterial stiffness and pressure amplification also were associated with lower executive function/processing speed (cfPWV: β=-0.09, 95% CI: -0.16, -0.03; PPA: β=-0.15, 95% CI: -0.22, -0.08; cPP: β=-0.14, 95% CI: -0.21, -0.07; cSBP: β=-0.13, 95% CI: -0.20, -0.07). High cfPWV was associated with lower memory (β=-0.12, 95% CI: -0.20, -0.04); and high cSBP was associated with lower language (β=-0.12, 95% CI: -0.20, -0.04). Conclusions: Arterial stiffness and measures of pressure amplification are inversely associated with global and domain-specific cognition in Caucasian older adults, but not in a smaller sample of AAs. Further study of the role of modifiable components of arterial aging on the preservation of cognition, particularly executive function/psychomotor speed, in older adulthood is warranted.
- Published
- 2016
34. Abstract MP56: Association of Arterial Stiffness and Pressure Amplification with Mild Cognitive Impairment and Dementia: The Atherosclerosis Risk in Communities Study - Neurocognitive Study (ARIC-NCS)
- Author
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Michelle L Meyer, Priya Palta, Hirofumi Tanaka, Jennifer A Deal, Jacqueline Wright, Clifford Jack, David Knopman, Michael Griswold, Thomas H Mosley, and Gerardo Heiss Heiss
- Subjects
Physiology (medical) ,mental disorders ,Cardiology and Cardiovascular Medicine - Abstract
Background: As a high-flow, low-impedance organ, the brain is sensitive to excessive pressure and flow pulsatility. Increased pulsatility and arterial stiffness are hypothesized to contribute to cerebral microvascular damage linked to cognitive impairment. The association of arterial stiffness with mild cognitive impairment (MCI) and dementia in a biethnic population is not well characterized, and the association of pressure amplification with MCI and dementia is relatively unexplored. Objectives: To quantify the cross-sectional association of arterial stiffness, measured by aortic pulse wave velocity (PWV), and pressure amplification with MCI and dementia in a biethnic population of older adults. Methods: We included 4,945 adults (2,903 females; 1,069 African Americans; mean age 75 years) from the population-based ARIC-NCS. The Omron VP-1000 plus system was used to measure arterial stiffness (carotid-femoral PWV (cfPWV)) and pressure amplification measures (central systolic blood pressure (cSBP), central pulse pressure (cPP), and pulse pressure amplification (PPA)). A neurologist and neuropsychologist classified MCI and dementia using psychometric assessments, medical history, cerebral magnetic resonance imaging, and physical examinations, with adjudication by a third reviewer. We used multinomial logistic regression to evaluate associations of race-specific 25th percentile cut points of PWV and pressure amplification with normal cognition (reference), MCI and dementia. We stratified by race and adjusted for age, sex, and heart rate, ApoE4, education, smoking status, and study center. Results: There were 760 Caucasians with MCI and 110 with dementia, and 201 African Americans with MCI and 47 with dementia. Among Caucasians, those with lower PPA had a higher prevalence of dementia, odds ratio (OR)=1.84 (95% confidence interval (CI): 1.15, 2.97), comparing participants below the 25th percentile to those above it, and those with higher cSBP had a higher prevalence of MCI, OR=1.33 (95% CI: 1.09, 1.63), comparing participants above the 75th percentile to those below it. Also among Caucasians, those with higher cPP had a higher prevalence of MCI, OR=1.25 (95%CI: 1.01, 1.55), and dementia, OR=1.66 (95% CI: 1.00, 2.73), comparing participants above the 75th percentile to those below it. There were no statistically significant associations with cfPWV, among African Americans, and no evidence for effect modification by hypertension or diabetes. Conclusion: Arterial stiffness and components of pressure amplification were associated with MCI and dementia in Caucasians but not in African Americans, possibly due to the limited sample size. Longitudinal characterization of the observed associations is warranted to determine whether these measures are independent predictors of MCI and dementia among Caucasian and African American older adults.
- Published
- 2016
35. The clinical use of structural MRI in Alzheimer disease
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Giovanni B. Frisoni, Clifford Jack, Philip Scheltens, Nick Fox, Paul Thompson, Giovanni Frisoni, Neurology, and NCA - Neurodegeneration
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medicine.medical_specialty ,Disease ,Article ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Atrophy ,Alzheimer Disease ,medicine ,Humans ,Stage (cooking) ,Intensive care medicine ,030304 developmental biology ,0303 health sciences ,medicine.diagnostic_test ,business.industry ,Neurodegeneration ,Brain ,Magnetic resonance imaging ,medicine.disease ,Magnetic Resonance Imaging ,Hyperintensity ,3. Good health ,Neurology (clinical) ,Differential diagnosis ,Alzheimer's disease ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Structural imaging based on magnetic resonance is an integral part of the clinical assessment of patients with suspected Alzheimer dementia. Prospective data on the natural history of change in structural markers from preclinical to overt stages of Alzheimer disease are radically changing how the disease is conceptualized, and will influence its future diagnosis and treatment. Atrophy of medial temporal structures is now considered to be a valid diagnostic marker at the mild cognitive impairment stage. Structural imaging is also included in diagnostic criteria for the most prevalent non-Alzheimer dementias, reflecting its value in differential diagnosis. In addition, rates of whole-brain and hippocampal atrophy are sensitive markers of neurodegeneration, and are increasingly used as outcome measures in trials of potentially disease-modifying therapies. Large multicenter studies are currently investigating the value of other imaging and nonimaging markers as adjuncts to clinical assessment in diagnosis and monitoring of progression. The utility of structural imaging and other markers will be increased by standardization of acquisition and analysis methods, and by development of robust algorithms for automated assessment.
- Published
- 2010
36. Abstract 44: Associations of Atrial Fibrillation, Neuroimaging Measures of Cerebrovascular Disease and Alzheimer’S Disease-related Pathology, and Cognitive Impairment
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Jonathan Graff-Radford, Rosebud Roberts, Malini Madhavan, Alejandro Rabinstein, Ruth Cha, Prashanthi Vemuri, Kejal Kantarci, Michelle Mielke, Val Lowe, Jeffrey Gunter, Matthew Senjem, Vernon S Pankratz, David Knopman, Ronald C Petersen, and Clifford Jack
- Subjects
Advanced and Specialized Nursing ,cardiovascular system ,cardiovascular diseases ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine - Abstract
The objective of this study was to investigate the cross-sectional associations of atrial fibrillation with neuroimaging measures of cerebrovascular disease and Alzheimer’s disease-related pathology, and their interaction with cognitive impairment. MRI scans of non-demented individuals (n=1044) from the population-based Mayo Clinic Study of Aging were analyzed for infarctions, total grey matter, hippocampal and white matter hyperintensity volumes. A subset of 496 individuals underwent FDG and C-11 Pittsburgh compound B (PiB) PET scans. We assessed the associations of atrial fibrillation with i) categorical MRI measures (cortical and subcortical infarctions) using multivariable logistic regression models, and with ii) continuous MRI measures ( hippocampal, total grey matter, and white matter hyperintensity volumes) and FDG-PET and PiB-PET measures using multivariable linear regression models, and adjusting for confounders. Among participants who underwent MRI (median age, 77.8, 51.6% male), 13.5% had atrial fibrillation. Presence of atrial fibrillation was associated with subcortical infarctions (odds ratio [OR], 1.83; p=0.002), cortical infarctions (OR, 1.91; p=0.03), total grey matter volume (Beta [β], -.025, p
- Published
- 2015
37. and cortical superficial siderosis in CAA: Meta-analysis and potential mechanisms.
- Author
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Charidimou, Andreas, Zonneveld, Hazel I., Shams, Sara, Kantarci, Kejal, Shoamanesh, Ashkan, Hilal, Saima, Yates, Paul A., Boulouis, Gregoire, Na, Han Kyu, Pasi, Marco, Biffi, Allesandro, Chai, Yuek Ling, Chong, Joyce Ruifen, Wahlund, Lars-Olof, Clifford, Jack R., Chen, Christopher, Gurol, M. Edip, Goldstein, Joshua N., Na, Duk L., and Barkhof, Frederik
- Published
- 2019
- Full Text
- View/download PDF
38. P1‐264: LONGITUDINAL CHANGES IN BRAIN MRI AND NEUROPSYCHOMETRICS IN ASYMPTOMATIC AND SYMPTOMATIC FAMILIAL FRONTOTEMPORAL LOBAR DEGENERATION WITH MUTATIONS IN MAPT
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David Thomas Jones, Stephen Weigand, Scott Przybelski, Jonathan Graff‐Radford, Mathew Senjem, Jeffrey Gunter, Jennifer Louise Whitwell, David S. Knopman, Neill R. Graff‐Radford, Keith Josephs, Zbigniew Wszolek, Prashanthi Vemuri, Julie A. Fields, Mary M. Machulda, Tanis Ferman, John Lucas, Val J. Lowe, Ralitza Gavrilova, Kuntz Karen, Mariely DeJesus Hernandez, Matthew Baker, Rosa Rademakers, Ronald Carl Petersen, Kejal Kantarci, Clifford Jack, and Bradley F. Boeve
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2014
39. S4‐01‐01: HARP: THE EADC‐ADNI HARMONIZED PROTOCOL FOR MANUAL HIPPOCAMPAL SEGMENTATION: A STANDARD OF REFERENCE FROM A GLOBAL WORKING GROUP
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Giovanni B. Frisoni and Clifford Jack
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2014
40. P1‐234: IMPAIRED SEGREGATION OF THE VENTRAL DEFAULT MODE NETWORK IN ALZHEIMER'S DISEASE
- Author
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David Thomas Jones, Jeffrey Gunter, Heather Wiste, Jonathan Graff‐Radford, Mary M. Machulda, Prashanthi Vemuri, Bradley F. Boeve, David S. Knopman, Ronald Petersen, and Clifford Jack
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2014
41. IC‐P‐066: PATHOLOGIC INVESTIGATION OF MICROINFARCTS AND ASSOCIATION WITH GRAY MATTER ATROPHY ON ANTEMORTEM MRI
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Mekala Raman, Ross Reichard, Christopher George Schwarz, Mathew Senjem, Scott Przybelski, Jeffrey Gunter, Prashanthi Vemuri, Melissa Erin Murray, Bradley F. Boeve, David S. Knopman, Ronald Petersen, Joseph Parisi, Dennis W. Dickson, Clifford Jack, and Kejal Kantarci
- Subjects
Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2014
42. P1‐224: SPONTANEOUS ARIA WITH EDEMA AND MICROHEMORRHAGES IN A COGNITIVELY NORMAL SUBJECT FROM ADNI
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Mekala Raman, Heather Wiste, Matthew Senjem, Chad Ward, Clifford Jack, and Kejal Kantarci
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2014
43. O4‐07‐03: PATHOLOGIC VALIDATION OF THE EADC‐ADNI HARMONIZED HIPPOCAMPAL PROTOCOL
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Liana Apostolova, Chris Zarow, Kristina Biado, Sona Hurtz, Marina Boccardi, Johanne Somme, Hedieh Honarpisheh, Anna Blanken, Jenny Brook, Spencer Tung, Denise Ng, Jeffrey Alger, Harry Vinters, Martina Bocchetta, Henri Duvernoy, Clifford Jack, and Giovanni Frisoni
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2014
44. P4‐137: THE TRANSITIONAL ASSOCIATION BETWEEN BETA‐AMYLOID PATHOLOGY AND REGIONAL BRAIN ATROPHY
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Philip Insel, Niklas Mattsson, Michael C. Donohue, Scott Mackin, Paul Aisen, Clifford Jack, Leslie Shaw, John Q. Trojanowski, and Michael Walter Weiner
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2014
45. Preclinical trials in autosomal dominant AD: Implementation of the DIAN-TU trial
- Author
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Peter R. Schofield, D. Heinrichs, Richard P. Mayeux, John C. Morris, Martin N. Rossor, Mathias Jucker, Anne M. Fagan, Bernardino Ghetti, Chengjie Xiong, CM Masters, M. C. Althage, John M. Ringman, Reisa A. Sperling, Randall J. Bateman, Stephen Salloway, Christopher C. Stewart, Nick C. Fox, William E. Klunk, David B. Clifford, Martin R. Farlow, M. Carril, A Danek, Tammie L.S. Benzinger, P. Snyder, Virginia Buckles, A. Fuqua, Ronald G. Thomas, Alison Goate, Daniel S. Marcus, Jeremy Snider, Clifford Jack, Ralph N. Martins, Sarah M. Mills, Russ C. Hornbeck, J. Mallmann, Anna Santacruz, William S. Brooks, Paul S. Aisen, Angela Oliver, Nigel J. Cairns, Eric McDade, and S. Belyew
- Subjects
Research design ,medicine.medical_specialty ,Medication Systems, Hospital ,Biomedical Research ,Population ,genetics [Alzheimer Disease] ,Disease ,Article ,methods [Clinical Trials as Topic] ,Alzheimer Disease ,medicine ,Humans ,Medical physics ,ddc:610 ,education ,Psychiatry ,Genes, Dominant ,Monitoring, Physiologic ,education.field_of_study ,Clinical Trials as Topic ,therapy [Alzheimer Disease] ,business.industry ,Patient Selection ,Cognition ,methods [Monitoring, Physiologic] ,medicine.disease ,Home Care Services ,Magnetic Resonance Imaging ,Clinical trial ,Neurology ,Research Design ,Biomarker (medicine) ,Observational study ,Neurology (clinical) ,Alzheimer's disease ,methods [Biomedical Research] ,business - Abstract
The Dominantly Inherited Alzheimer's Network Trials Unit (DIAN-TU) was formed to direct the design and management of interventional therapeutic trials of international DIAN and autosomal dominant Alzheimer's disease (ADAD) participants. The goal of the DIAN-TU is to implement safe trials that have the highest likelihood of success while advancing scientific understanding of these diseases and clinical effects of proposed therapies. The DIAN-TU has launched a trial design that leverages the existing infrastructure of the ongoing DIAN observational study, takes advantage of a variety of drug targets, incorporates the latest results of biomarker and cognitive data collected during the observational study, and implements biomarkers measuring Alzheimer's disease (AD) biological processes to improve the efficiency of trial design. The DIAN-TU trial design is unique due to the sophisticated design of multiple drugs, multiple pharmaceutical partners, academics servings as sponsor, geographic distribution of a rare population and intensive safety and biomarker assessments. The implementation of the operational aspects such as home health research delivery, safety magnetic resonance imagings (MRIs) at remote locations, monitoring clinical and cognitive measures, and regulatory management involving multiple pharmaceutical sponsors of the complex DIAN-TU trial are described.
- Published
- 2013
46. O2–02–04: Hypometabolism in PiB‐positive, population‐based, cognitively normal subjects with and without APOE‐ε4
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Stephen Weigand, Val Lowe, Matthew Senjem, Prashanthi Vemuri, Kejal Kantarci, David Knopman, Bradley Boeve, Ronald Petersen, and Clifford Jack
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2013
47. IC‐P‐032: Effect of measurement variability on hippocampal volume‐based clinical trial enrichment
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Peng Yu, Jia Sun, Robin Wolz, Diane Stephenson, Clifford Jack, Patricia Cole, Derek Hill, and Adam Schwarz
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2013
48. P3–125: Rates of atrophy differ across pathologically defined subtypes of Alzheimer's disease: A longitudinal MRI study
- Author
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Jennifer Whitwell, Dennis Dickson, Melissa Murray, Matthew Senjem, Jeffrey Gunter, Anthony Spychalla, Ronald Petersen, Clifford Jack, and Keith Josephs
- Subjects
Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2013
49. P3–093: FDG‐PET and PiB‐PET imaging in asymptomatic at‐risk carriers of a novel octapeptide repeat insertion in PRNP
- Author
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Bradley Boeve, Val Lowe, Kejal Kantarci, Scott Przybelski, Stephen Weigand, Anthony Spychalla, Prashanthi Vemuri, David Jones, Eric McDade, Neeraj Kumar, Rosa Rademakers, Matthew Baker, David Knopman, Ronald Petersen, Joseph Parisi, Dennis Dickson, and Clifford Jack
- Subjects
Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2013
50. P1–269: Are early atrophy patterns in autosomal dominant familial Alzheimer's disease gene‐dependent?
- Author
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Kirsi Kinnunen, Natalie Ryan, David Cash, António Bastos Leite, Sarah Finnegan, Manuel Cardoso, Kelvin Leung, Marc Modat, Tammie Benzinger, Clifford Jack, Daniel Marcus, Marcus Raichle, Paul Thompson, John Ringman, Bernardino Ghetti, Stephen Salloway, Reisa Sperling, Peter Schofield, Colin Masters, Richard Mayeux, Ralph Martins, Michael Weiner, Randall Bateman, Alison Goate, Anne Fagan, Nigel Cairns, Virginia Buckles, John Morris, Martin Rossor, Sebastien Ourselin, and Nick Fox
- Subjects
Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2013
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