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1. An Investigation of Maladaptive Health Behavior Engagement and Neurobehavioral and Neurocognitive Outcomes in Former Elite American Football Players (P10-9.016)

Author

Bragg, Tahlia, primary, Baldwin, Shania, additional, Holleck, Minna, additional, Pettway, Erika, additional, Tuz-Zahra, Fatima, additional, Tripodis, Yorghos, additional, Bernick, Charles, additional, Adler, Charles, additional, Belcer, Laura, additional, Ritter, Aaron, additional, Reiman, Eric, additional, Cummings, Jeffrey, additional, Shenton, Martha E., additional, Stern, Robert, additional, Alosco, Michael, additional, and Turner, Robert, additional

Published
2024
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2. A phase 3 trial of IV immunoglobulin for Alzheimer disease

Author

Relkin, Norman R, Thomas, Ronald G, Rissman, Robert A, Brewer, James B, Rafii, Michael S, van Dyck, Christopher H, Jack, Clifford R, Sano, Mary, Knopman, David S, Raman, Rema, Szabo, Paul, Gelmont, David M, Fritsch, Sandor, Aisen, Paul S, Ahern, Geoffrey, Yaari, Roy, Sabbagh, Marwan, Mirza, Nadeem, Bernick, Charles, Bell, Karen, Turner, R Scott, Obisesan, Thomas, Chertkow, Howard, Zabar, Yuval, Knopman, David, Mintzer, Jacobo, Grossman, Hillel, Sadowski, Martin, Wu, Chuang-Kuo, Quinn, Joseph, Borrie, Michael, Petrie, William, Ott, Brian, Keegan, Andrew, Grossberg, George, Bari, Moammed, Cohen, Sharon, Richter, Ralph, Lerner, Alan, Mulnard, Ruth, Potkin, Steven, Rafii, Michael, Brockington, John, Hsiung, Robin, Schultz, Susan, Burns, Jeffrey, Jicha, Gregory, Burke, William, Arnold, Steven, Porsteinsson, Anton, Smith, Amanda, Schneider, Lon, Quiceno, Mary, Zamrini, Edward, Asthana, Sanjay, Burgat, FT, Duara, Ranjan, and van Dyck, Christopher

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Aging, Clinical Trials and Supportive Activities, Alzheimer's Disease, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Neurodegenerative, Clinical Research, Dementia, Acquired Cognitive Impairment, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Neurological, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Apolipoprotein E4, Biomarkers, Brain, Canada, Cognition, Double-Blind Method, Female, Humans, Immunoglobulins, Intravenous, Male, Middle Aged, Nootropic Agents, Peptide Fragments, Treatment Failure, United States, Alzheimer's Disease Cooperative Study, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveWe tested biweekly infusions of IV immunoglobulin (IVIg) as a possible treatment for mild to moderate Alzheimer disease (AD) dementia.MethodsIn a phase 3, double-blind, placebo-controlled trial, we randomly assigned 390 participants with mild to moderate AD to receive placebo (low-dose albumin) or IVIg (Gammagard Liquid; Baxalta, Bannockburn, IL) administered IV at doses of 0.2 or 0.4 g/kg every 2 weeks for 18 months. The primary cognitive outcome was change from baseline to 18 months on the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale; the primary functional outcome was 18-month change on the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. Safety and tolerability data, as well as serial MRIs and plasma samples, were collected throughout the study from all enrolled participants.ResultsNo beneficial effects were observed in the dual primary outcome measures for the 2 IVIg doses tested. Significant decreases in plasma Aβ42 (but not Aβ40) levels were observed in IVIg-treated participants. Analysis of safety data showed no difference between IVIg and placebo in terms of the rate of occurrence of amyloid-related imaging abnormalities (brain edema or microhemorrhage). IVIg-treated participants had more systemic reactions (chills, rashes) but fewer respiratory infections than participants receiving placebo.ConclusionsParticipants with mild to moderate AD showed good tolerability of treatment with low-dose human IVIg for 18 months but did not show beneficial effects on cognition or function relative to participants who received placebo.Clinicaltrialsgov identifierNCT00818662.Classification of evidenceThis study provides Class II evidence that IVIg infusions performed every 2 weeks do not improve cognition or function at 18 months in patients with mild to moderate AD.

Published
2017

4. Association of Vascular Risk Factors and CSF and Imaging Biomarkers With White Matter Hyperintensities in Former American Football Players.

Author

Ly, Monica T., Tuz-Zahra, Fatima, Tripodis, Yorghos, Adler, Charles H., Balcer, Laura J., Bernick, Charles, Zetterberg, Henrik, Blennow, Kaj, Peskind, Elaine R., Au, Rhoda, Banks, Sarah J., Barr, William B., Wethe, Jennifer V., Bondi, Mark W., Delano-Wood, Lisa M., Cantu, Robert C., Coleman, Michael J., Dodick, David W., McClean, Michael D., and Mez, Jesse B.

Published
2024
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6. Type 2 diabetes mellitus, brain atrophy, and cognitive decline

Author

Moran, Chris, Beare, Richard, Wang, Wei, Callisaya, Michele, Srikanth, Velandai, Weiner, Michael, Aisen, Paul, Weiner, Michael, Aisen, Paul, Petersen, Ronald, Jack, Clifford R., Jr., Jagust, William, Trojanowki, John Q., Toga, Arthur W., Beckett, Laurel, Green, Robert C., Saykin, Andrew J., Morris, John, Liu, Enchi, Green, Robert C., Montine, Tom, Petersen, Ronald, Aisen, Paul, Gamst, Anthony, Thomas, Ronald G., Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Beckett, Laurel, Harvey, Danielle, Gamst, Anthony, Donohue, Michael, Kornak, John, Jack, Clifford R., Jr., Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, DeCarli, Charles, Jagust, William, Bandy, Dan, Koeppe, Robert A., Foster, Norm, Reiman, Eric M., Chen, Kewei, Mathis, Chet, Morris, John, Cairns, Nigel J., Taylor-Reinwald, Lisa, Trojanowki, J.Q., Shaw, Les, Lee, Virginia M.Y., Korecka, Magdalena, Toga, Arthur W., Crawford, Karen, Neu, Scott, Saykin, Andrew J., Foroud, Tatiana M., Potkin, Steven, Shen, Li, Kachaturian, Zaven, Frank, Richard, Snyder, Peter J., Molchan, Susan, Kaye, Jeffrey, Quinn, Joseph, Lind, Betty, Dolen, Sara, Schneider, Lon S., Pawluczyk, Sonia, Spann, Bryan M., Brewer, James, Vanderswag, Helen, Heidebrink, Judith L., Lord, Joanne L., Petersen, Ronald, Johnson, Kris, Doody, Rachelle S., Villanueva-Meyer, Javier, Chowdhury, Munir, Stern, Yaakov, Honig, Lawrence S., Bell, Karen L., Morris, John C., Ances, Beau, Carroll, Maria, Leon, Sue, Mintun, Mark A., Schneider, Stacy, Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, Mitsis, Effie, Romirowsky, Aliza, deToledo-Morrell, Leyla, Shah, Raj C., Duara, Ranjan, Varon, Daniel, Roberts, Peggy, Albert, Marilyn, Onyike, Chiadi, Kielb, Stephanie, Rusinek, Henry, de Leon, Mony J, Glodzik, Lidia, De Santi, Susan, Doraiswamy, P. Murali, Petrella, Jeffrey R., Coleman, R. Edward, Arnold, Steven E., Karlawish, Jason H., Wolk, David, Smith, Charles D., Jicha, Greg, Hardy, Peter, Lopez, Oscar L., Oakley, MaryAnn, Simpson, Donna M., Porsteinsson, Anton P., Goldstein, Bonnie S., Martin, Kim, Makino, Kelly M., Ismail, M. Saleem, Brand, Connie, Mulnard, Ruth A., Thai, Gaby, McAdams-Ortiz, Catherine, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Diaz-Arrastia, Ramon, King, Richard, Weiner, Myron, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I., Lah, James J., Cellar, Janet S., Burns, Jeffrey M., Anderson, Heather S., Swerdlow, Russell H., Apostolova, Liana, Lu, Po H., Bartzokis, George, Silverman, Daniel H.S., Graff-Radford, Neill R, Parfitt, Francine, Johnson, Heather, Farlow, Martin R., Hake, Ann Marie, Matthews, Brandy R., Herring, Scott, van Dyck, Christopher H., Carson, Richard E., MacAvoy, Martha G., Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Caldwell, Curtis, Robin Hsiung, Ging-Yuek, Feldman, Howard, Mudge, Benita, Assaly, Michele, Kertesz, Andrew, Rogers, John, Trost, Dick, Bernick, Charles, Munic, Donna, Kerwin, Diana, Mesulam, Marek-Marsel, Lipowski, Kristina, Wu, Chuang-Kuo, Johnson, Nancy, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Sperling, Reisa A., Johnson, Keith A., Marshall, Gad, Frey, Meghan, Yesavage, Jerome, Taylor, Joy L., Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Sabbagh, Marwan, Belden, Christine, Jacobson, Sandra, Kowall, Neil, Killiany, Ronald, Budson, Andrew E., Norbash, Alexander, Johnson, Patricia Lynn, Obisesan, Thomas O., Wolday, Saba, Bwayo, Salome K., Lerner, Alan, Hudson, Leon, Ogrocki, Paula, Fletcher, Evan, Carmichael, Owen, Olichney, John, DeCarli, Charles, Kittur, Smita, Borrie, Michael, Lee, T-Y, Bartha, Dr Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M., Potkin, Steven G., Preda, Adrian, Nguyen, Dana, Tariot, Pierre, Fleisher, Adam, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Scharre, Douglas W., Kataki, Maria, Zimmerman, Earl A., Celmins, Dzintra, Brown, Alice D., Pearlson, Godfrey D., Blank, Karen, Anderson, Karen, Saykin, Andrew J., Santulli, Robert B., Schwartz, Eben S., Sink, Kaycee M., Williamson, Jeff D., Garg, Pradeep, Watkins, Franklin, Ott, Brian R., Querfurth, Henry, Tremont, Geoffrey, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J., Miller, Bruce L., Mintzer, Jacobo, Longmire, Crystal Flynn, Spicer, Kenneth, Finger, Elizabether, Rachinsky, Irina, Rogers, John, Kertesz, Andrew, Drost, Dick, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Schultz, Susan K., Boles Ponto, Laura L., Shim, Hyungsub, Smith, Karen Elizabeth, Relkin, Norman, Chaing, Gloria, Raudin, Lisa, Smith, Amanda, Fargher, Kristin, and Raj, Balebail Ashok

Published
2019
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15. National Institute of Neurological Disorders and Stroke Consensus Diagnostic Criteria for Traumatic Encephalopathy Syndrome

Author

Katz, Douglas I., primary, Bernick, Charles, additional, Dodick, David W., additional, Mez, Jesse, additional, Mariani, Megan L., additional, Adler, Charles H., additional, Alosco, Michael L., additional, Balcer, Laura J., additional, Banks, Sarah J., additional, Barr, William B., additional, Brody, David L., additional, Cantu, Robert C., additional, Dams-O'Connor, Kristen, additional, Geda, Yonas E., additional, Jordan, Barry D., additional, McAllister, Thomas W., additional, Peskind, Elaine R., additional, Petersen, Ronald C., additional, Wethe, Jennifer V., additional, Zafonte, Ross D., additional, Foley, Éimear M., additional, Babcock, Debra J., additional, Koroshetz, Walter J., additional, Tripodis, Yorghos, additional, McKee, Ann C., additional, Shenton, Martha E., additional, Cummings, Jeffrey L., additional, Reiman, Eric M., additional, and Stern, Robert A., additional

Published
2021
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17. In vivo staging of regional amyloid deposition

Author

Grothe, Michel J, Barthel, Henryk, Aisen, Paul, Romirowsky, Aliza, deToledo-Morrell, Leyla, Shah, Raj C, Duara, Ranjan, Varon, Daniel, Roberts, Peggy, Albert, Marilyn, Onyike, Chiadi, Kielb, Stephanie, Rusinek, Henry, Petersen, Ronald, de Leon, Mony J, Glodzik, Lidia, De Santi, Susan, Doraiswamy, P Murali, Petrella, Jeffrey R, Coleman, R Edward, Arnold, Steven E, Karlawish, Jason H, Wolk, David, Smith, Charles D, Jack, Clifford R, Jicha, Greg, Hardy, Peter, Lopez, Oscar L, Oakley, MaryAnn, Simpson, Donna M, Porsteinsson, Anton P, Goldstein, Bonnie S, Martin, Kim, Makino, Kelly M, Ismail, M Saleem, Jagust, William, Brand, Connie, Mulnard, Ruth A, Thai, Gaby, Mc-Adams-Ortiz, Catherine, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Diaz-Arrastia, Ramon, King, Richard, Weiner, Myron, Trojanowki, John Q, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I, Lah, James J, Cellar, Janet S, Burns, Jeffrey M, Anderson, Heather S, Swerdlow, Russell H, Apostolova, Liana, Lu, Po H, Toga, Arthur W, Bartzokis, George, Silverman, Daniel H S, Parfitt, Francine, Johnson, Heather, Farlow, Martin R, Hake, Ann Marie, Matthews, Brandy R, Herring, Scott, van Dyck, Christopher H, Carson, Richard E, Beckett, Laurel, MacAvoy, Martha G, Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Caldwell, Curtis, Robin Hsiung, Ging-Yuek, Feldman, Howard, Mudge, Benita, Green, Robert C, Assaly, Michele, Kertesz, Andrew, Rogers, John, Trost, Dick, Bernick, Charles, Munic, Donna, Kerwin, Diana, Mesulam, Marek-Marsel, Lipowski, Kristina, Wu, Chuang-Kuo, Saykin, Andrew J, Johnson, Nancy, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Sperling, Reisa A, Johnson, Keith A, Marshall, Gad, Morris, John, Frey, Meghan, Yesavage, Jerome, Taylor, Joy L, Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Sabbagh, Marwan, Belden, Christine, Jacobson, Sandra, Kowall, Neil, Sepulcre, Jorge, Liu, Enchi, Killiany, Ronald, Budson, Andrew E, Norbash, Alexander, Johnson, Patricia Lynn, Obisesan, Thomas O, Wolday, Saba, Bwayo, Salome K, Lerner, Alan, Hudson, Leon, Ogrocki, Paula, Fletcher, Evan, Carmichael, Owen, Olichney, John, DeCarli, Charles, Kittur, Smita, Borrie, Michael, Lee, T-Y, Bartha, Rob, Johnson, Sterling, Asthana, Sanjay, Montine, Tom, Carlsson, Cynthia M, Potkin, Steven G, Preda, Adrian, Nguyen, Dana, Tariot, Pierre, Fleisher, Adam, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Scharre, Douglas W, Kataki, Maria, Zimmerman, Earl A, Celmins, Dzintra, Brown, Alice D, Pearlson, Godfrey D, Blank, Karen, Anderson, Karen, Santulli, Robert B, Schwartz, Eben S, Sink, Kaycee M, Williamson, Jeff D, Garg, Pradeep, Watkins, Franklin, Ott, Brian R, Querfurth, Henry, Tremont, Geoffrey, Salloway, Stephen, Malloy, Paul, Gamst, Anthony, Correia, Stephen, Rosen, Howard J, Miller, Bruce L, Mintzer, Jacobo, Longmire, Crystal Flynn, Spicer, Kenneth, Finger, Elizabether, Rachinsky, Irina, Thomas, Ronald G, Drost, Dick, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Schultz, Susan K, Boles Ponto, Laura L, Shim, Hyungsub, Smith, Karen Elizabeth, Relkin, Norman, Chaing, Gloria, Donohue, Michael, Raudin, Lisa, Smith, Amanda, Fargher, Kristin, Raj, Balebail Ashok, Walter, Sarah, Gessert, Devon, Dyrba, Martin, Sather, Tamie, Harvey, Danielle, Kornak, John, Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Sabri, Osama, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, Bandy, Dan, Koeppe, Robert A, Foster, Norm, Reiman, Eric M, Teipel, Stefan J, Chen, Kewei, Mathis, Chet, Cairns, Nigel J, Taylor-Reinwald, Lisa, Trojanowki, J. Q., Shaw, Les, Lee, Virginia M Y, Korecka, Magdalena, Initiative, Alzheimer's Disease Neuroimaging, Crawford, Karen, Neu, Scott, Foroud, Tatiana M, Potkin, Steven, Shen, Li, Kachaturian, Zaven, Frank, Richard, Snyder, Peter J, Molchan, Susan, Weiner, Michael, Kaye, Jeffrey, Quinn, Joseph, Lind, Betty, Dolen, Sara, Schneider, Lon S, Pawluczyk, Sonia, Spann, Bryan M, Brewer, James, Vanderswag, Helen, Heidebrink, Judith L, Lord, Joanne L, Johnson, Kris, Doody, Rachelle S, Villanueva-Meyer, Javier, Chowdhury, Munir, Stern, Yaakov, Honig, Lawrence S, Bell, Karen L, Morris, John C, Ances, Beau, Carroll, Maria, Leon, Sue, Mintun, Mark A, Schneider, Stacy, Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, and Mitsis, Effie

Subjects
0301 basic medicine, Male, Pathology, Aging, diagnostic imaging [Cognitive Dysfunction], cerebrospinal fluid [Amyloid beta-Peptides], metabolism [Cognitive Dysfunction], 0302 clinical medicine, diagnostic imaging [Cerebral Cortex], metabolism [Neostriatum], Aged, 80 and over, Cerebral Cortex, Neocortex, Aniline Compounds, methods [Positron-Emission Tomography], amyloid beta-protein (1-42), medicine.anatomical_structure, diagnostic imaging [Neostriatum], Cerebral cortex, Cohort, Disease Progression, florbetapir, Ethylene Glycols, Female, Alzheimer's disease, metabolism [Alzheimer Disease], metabolism [Biomarkers], medicine.medical_specialty, Amyloid, metabolism [Amyloid beta-Peptides], Article, Temporal lobe, 03 medical and health sciences, Neuroimaging, Alzheimer Disease, mental disorders, medicine, Dementia, Humans, Cognitive Dysfunction, ddc:610, metabolism [Aging], cerebrospinal fluid [Peptide Fragments], Aged, Amyloid beta-Peptides, business.industry, metabolism [Cerebral Cortex], medicine.disease, Peptide Fragments, Neostriatum, 030104 developmental biology, Cross-Sectional Studies, Positron-Emission Tomography, Neurology (clinical), business, diagnostic imaging [Alzheimer Disease], 030217 neurology & neurosurgery, Biomarkers
Abstract

Objectives:To estimate a regional progression pattern of amyloid deposition from cross-sectional amyloid-sensitive PET data and evaluate its potential for in vivo staging of an individual's amyloid pathology.Methods:Multiregional analysis of florbetapir (18F-AV45)–PET data was used to determine individual amyloid distribution profiles in a sample of 667 participants from the Alzheimer's Disease Neuroimaging Initiative cohort, including cognitively normal older individuals (CN) as well as patients with mild cognitive impairment and Alzheimer disease (AD) dementia. The frequency of regional amyloid positivity across CN individuals was used to construct a 4-stage model of progressing amyloid pathology, and individual distribution profiles were used to evaluate the consistency of this hierarchical stage model across the full cohort.Results:According to a 4-stage model, amyloid deposition begins in temporobasal and frontomedial areas, and successively affects the remaining associative neocortex, primary sensory-motor areas and the medial temporal lobe, and finally the striatum. Amyloid deposition in these brain regions showed a highly consistent hierarchical nesting across participants, where only 2% exhibited distribution profiles that deviated from the staging scheme. The earliest in vivo amyloid stages were mostly missed by conventional dichotomous classification approaches based on global florbetapir-PET signal, but were associated with significantly reduced CSF Aβ42 levels. Advanced in vivo amyloid stages were most frequent in patients with AD and correlated with cognitive impairment in individuals without dementia.Conclusions:The highly consistent regional hierarchy of PET-evidenced amyloid deposition across participants resembles neuropathologic observations and suggests a predictable regional sequence that may be used to stage an individual's progress of amyloid pathology in vivo.

Published
2017

19. Multimodal characterization of older APOE2 carriers reveals selective reduction of amyloid load

Author

Grothe, Michel J, Villeneuve, Sylvia, Petersen, Ronald, Leyla deToledo-Morrell, PhD, Shah, Raj C, Duara, Ranjan, Varon, Daniel, Roberts Cna, Peggy, Albert, Marilyn, Onyike, Chiadi, Kielb, Stephanie, Rusinek, Henry, de Leon, Mony J, Jack, Clifford R, Glodzik, Lidia, De Santi, Susan, Doraiswamy, P Murali, Petrella, Jeffrey R, Coleman, R Edward, Arnold, Steven E, Karlawish, Jason H, Wolk, David, Smith, Charles D, Jicha, Greg, Jagust, William, Hardy, Peter, Lopez, Oscar L, Oakley, MaryAnn, Simpson, Donna M, Porsteinsson, Anton P, Goldstein, Bonnie S, Martin, Kim, Makino, Kelly M, Ismail, M Saleem, Brand, Connie, Trojanowki, John Q, Mulnard, Ruth A, Thai, Gaby, Mc-Adams-Ortiz, Catherine, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Diaz-Arrastia, Ramon, King, Richard, Weiner, Myron, Martin-Cook, Kristen, Toga, Arthur W, DeVous, Michael, Levey, Allan I, Lah, James J, Cellar, Janet S, Burns, Jeffrey M, Anderson, Heather S, Swerdlow, Russell H, Apostolova, Liana, Lu, Po H, Bartzokis, George, Beckett, Laurel, Silverman, Daniel H S, Graff-Radford Mbbch, Neill R, Parfitt, Francine, Johnson, Heather, Farlow, Martin R, Hake, Ann Marie, Matthews, Brandy R, Herring, Scott, van Dyck, Christopher H, Carson, Richard E, Green, Robert C, MacAvoy, Martha G, Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Caldwell, Curtis, Robin Hsiung, Ging-Yuek, Feldman, Howard, Mudge, Benita, Saykin, Andrew J, Assaly, Michele, Kertesz, Andrew, Rogers, John, Trost, Dick, Bernick, Charles, Munic, Donna, Kerwin, Diana, Mesulam, Marek-Marsel, Lipowski, Kristina, Wu, Chuang-Kuo, Morris, John, Johnson, Nancy, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Sperling, Reisa A, Johnson, Keith A, Marshall, Gad, Liu, Enchi, Frey, Meghan, Yesavage, Jerome, Taylor, Joy L, Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Sabbagh, Marwan, Belden, Christine, Jacobson, Sandra, Kowall, Neil, Dyrba, Martin, Killiany, Ronald, Budson, Andrew E, Norbash, Alexander, Johnson, Patricia Lynn, Obisesan, Thomas O, Wolday, Saba, Bwayo, Salome K, Lerner, Alan, Hudson, Leon, Ogrocki, Paula, Montine, Tom, Fletcher, Evan, Carmichael, Owen, Olichney, John, DeCarli, Charles, Kittur, Smita, Borrie, Michael, Lee, T-Y, Bartha, Dr Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M, Potkin, Steven G, Preda, Adrian, Nguyen, Dana, Tariot, Pierre, Fleisher, Adam, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Aisen, Paul, Scharre, Douglas W, Kataki, Maria, Zimmerman, Earl A, Celmins, Dzintra, Brown, Alice D, Pearlson, Godfrey D, Blank, Karen, Anderson, Karen, Santulli, Robert B, Gamst, Anthony, Schwartz, Eben S, Sink, Kaycee M, Williamson, Jeff D, Garg, Pradeep, Watkins, Franklin, Ott, Brian R, Querfurth, Henry, Tremont, Geoffrey, Salloway, Stephen, Malloy, Paul, Thomas, Ronald G, Correia, Stephen, Rosen, Howard J, Miller, Bruce L, Mintzer, Jacobo, Longmire, Crystal Flynn, Spicer, Kenneth, Finger, Elizabether, Rachinsky, Irina, Donohue, Michael, Drost, Dick, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Schultz, Susan K, Boles Ponto, Laura L, Shim, Hyungsub, Smith, Karen Elizabeth, Relkin, Norman, Chaing, Gloria, Walter, Sarah, Raudin, Lisa, Smith, Amanda, Fargher, Kristin, Raj, Balebail Ashok, Gessert, Devon, Sather, Tamie, Bartrés-Faz, David, Harvey, Danielle, Kornak, John, Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Wirth, Miranka, Thompson, Paul, Schuff, Norbert, Alexander, Gene, Bandy, Dan, Koeppe, Robert A, Foster, Norm, Reiman, Eric M, Chen, Kewei, Initiative, Alzheimer's Disease Neuroimaging, Mathis, Chet, Cairns, Nigel J, Taylor-Reinwald, Lisa, Trojanowki, J. Q., Shaw, Les, Lee, Virginia M Y, Korecka, Magdalena, Crawford, Karen, Weiner, Michael, Neu, Scott, Foroud, Tatiana M, Potkin, Steven, Shen, Li, Kachaturian, Zaven, Frank, Richard, Snyder, Peter J, Molchan, Susan, Kaye, Jeffrey, Quinn, Joseph, Lind, Betty, Dolen, Sara, Schneider, Lon S, Pawluczyk, Sonia, Spann, Bryan M, Brewer, James, Vanderswag, Helen, Heidebrink, Judith L, Lord, Joanne L, Johnson, Kris, Doody, Rachelle S, Villanueva-Meyer, Javier, Chowdhury, Munir, Stern, Yaakov, Honig, Lawrence S, Bell, Karen L, Morris, John C, Ances, Beau, Carroll, Maria, Leon, Sue, Mintun, Mark A, Schneider, Stacy, Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, Mitsis, Effie, and Romirowsky, Aliza

Subjects
0301 basic medicine, Oncology, Male, Aging, Apolipoprotein E2, diagnostic imaging [Cognitive Dysfunction], Apolipoprotein E3, metabolism [Gray Matter], Disease, Multimodal Imaging, metabolism [Cognitive Dysfunction], pathology [Aging], 0302 clinical medicine, Genotype, Medicine, Gray Matter, medicine.diagnostic_test, Brain, Organ Size, Magnetic Resonance Imaging, metabolism [Glucose], cerebrospinal fluid [Biomarkers], Positron emission tomography, genetics [Aging], genetics [Apolipoprotein E3], Female, Alzheimer's disease, medicine.medical_specialty, Amyloid, Heterozygote, Neuroimaging, Article, 03 medical and health sciences, Fluorodeoxyglucose F18, Internal medicine, genetics [Apolipoprotein E2], Dementia, Humans, Cognitive Dysfunction, ddc:610, metabolism [Aging], Allele, diagnostic imaging [Brain], metabolism [Amyloid], Aged, business.industry, diagnostic imaging [Gray Matter], Magnetic resonance imaging, medicine.disease, 030104 developmental biology, Glucose, metabolism [Brain], Positron-Emission Tomography, Neurology (clinical), Radiopharmaceuticals, business, 030217 neurology & neurosurgery, Biomarkers
Abstract

Objective:To comprehensively assess neurobiological effects of the protective APOE2 allele in the aged brain using a cross-sectional multimodal neuroimaging approach.Methods:Multimodal neuroimaging data were obtained from a total of 572 older individuals without dementia (cognitively normal and mild cognitive impairment) enrolled in the Alzheimer's Disease Neuroimaging Initiative and included assessments of regional amyloid load with AV45-PET, glucose metabolism with fluorodeoxyglucose-PET, and gray matter volume with structural MRI. Imaging indexes of APOE2 carriers were contrasted to risk-neutral APOE3 homozygotes, and analyses were controlled for age, sex, education, and clinical diagnosis. Additional models examined genotype-specific effects of age on the imaging markers.Results:In region-of-interest–based analyses, APOE2 carriers had significantly less precuneal amyloid pathology and did not show the typical age-related increase in amyloid load, although the age × genotype interaction was only trend-level significant. In contrast, parietal metabolism and hippocampal volume did not differ between APOE2 and APOE3 genotypes, and both groups showed comparable negative effects of age on these markers. The amyloid specificity of APOE2-related brain changes was corroborated in 2 complementary analyses: spatially unbiased voxel-wise analyses showing widespread reductions in amyloid deposition but no differences in gray matter volume or metabolism and an analysis of CSF-based biomarkers showing a significant effect on amyloid but not on tau pathology.Conclusions:Regarding the range of Alzheimer disease biomarkers considered in the present study, the APOE2 allele appears to have a relatively selective effect on reduced accumulation of amyloid pathology in the aged brain.

Published
2016

31. Vascular burden and Alzheimer disease pathologic progression

Author

Lo, Raymond Y., primary, Jagust, William J., additional, Weiner, Michael, additional, Aisen, Paul, additional, Petersen, Ronald, additional, Jack, Clifford R., additional, Jagust, William, additional, Trojanowki, John Q., additional, Toga, Arthur W., additional, Beckett, Laurel, additional, Green, Robert C., additional, Saykin, Andrew J., additional, Morris, John, additional, Liu, Enchi, additional, Montine, Tom, additional, Gamst, Anthony, additional, Thomas, Ronald G., additional, Donohue, Michael, additional, Walter, Sarah, additional, Gessert, Devon, additional, Sather, Tamie, additional, Harvey, Danielle, additional, Kornak, John, additional, Dale, Anders, additional, Bernstein, Matthew, additional, Felmlee, Joel, additional, Fox, Nick, additional, Thompson, Paul, additional, Schuff, Norbert, additional, Alexander, Gene, additional, DeCarli, Charles, additional, Bandy, Dan, additional, Koeppe, Robert A., additional, Foster, Norm, additional, Reiman, Eric M., additional, Chen, Kewei, additional, Mathis, Chet, additional, Cairns, Nigel J., additional, Taylor-Reinwald, Lisa, additional, Trojanowki, J.Q., additional, Shaw, Les, additional, Lee, Virginia M.Y., additional, Korecka, Magdalena, additional, Crawford, Karen, additional, Neu, Scott, additional, Foroud, Tatiana M., additional, Potkin, Steven, additional, Shen, Li, additional, Kachaturian, Zaven, additional, Frank, Richard, additional, Snyder, Peter J., additional, Molchan, Susan, additional, Kaye, Jeffrey, additional, Quinn, Joseph, additional, Lind, Betty, additional, Dolen, Sara, additional, Schneider, Lon S., additional, Pawluczyk, Sonia, additional, Spann, Bryan M., additional, Brewer, James, additional, Vanderswag, Helen, additional, Heidebrink, Judith L., additional, Lord, Joanne L., additional, Johnson, Kris, additional, Doody, Rachelle S., additional, Villanueva-Meyer, Javier, additional, Chowdhury, Munir, additional, Stern, Yaakov, additional, Honig, Lawrence S., additional, Bell, Karen L., additional, Morris, John C., additional, Ances, Beau, additional, Carroll, Maria, additional, Leon, Sue, additional, Mintun, Mark A., additional, Schneider, Stacy, additional, Marson, Daniel, additional, Griffith, Randall, additional, Clark, David, additional, Grossman, Hillel, additional, Mitsis, Effie, additional, Romirowsky, Aliza, additional, deToledo-Morrell, Leyla, additional, Shah, Raj C., additional, Duara, Ranjan, additional, Varon, Daniel, additional, Roberts, Peggy, additional, Albert, Marilyn, additional, Onyike, Chiadi, additional, Kielb, Stephanie, additional, Rusinek, Henry, additional, de Leon, Mony J, additional, Glodzik, Lidia, additional, De Santi, Susan, additional, Doraiswamy, P. Murali, additional, Petrella, Jeffrey R., additional, Coleman, R. Edward, additional, Arnold, Steven E., additional, Karlawish, Jason H., additional, Wolk, David, additional, Smith, Charles D., additional, Jicha, Greg, additional, Hardy, Peter, additional, Lopez, Oscar L., additional, Oakley, MaryAnn, additional, Simpson, Donna M., additional, Porsteinsson, Anton P., additional, Goldstein, Bonnie S., additional, Martin, Kim, additional, Makino, Kelly M., additional, Ismail, M. Saleem, additional, Brand, Connie, additional, Mulnard, Ruth A., additional, Thai, Gaby, additional, Mc-Adams-Ortiz, Catherine, additional, Womack, Kyle, additional, Mathews, Dana, additional, Quiceno, Mary, additional, Diaz-Arrastia, Ramon, additional, King, Richard, additional, Weiner, Myron, additional, Martin-Cook, Kristen, additional, DeVous, Michael, additional, Levey, Allan I., additional, Lah, James J., additional, Cellar, Janet S., additional, Burns, Jeffrey M., additional, Anderson, Heather S., additional, Swerdlow, Russell H., additional, Apostolova, Liana, additional, Lu, Po H., additional, Bartzokis, George, additional, Silverman, Daniel H.S., additional, Graff-Radford, Neill R, additional, Parfitt, Francine, additional, Johnson, Heather, additional, Farlow, Martin R., additional, Hake, Ann Marie, additional, Matthews, Brandy R., additional, Herring, Scott, additional, van Dyck, Christopher H., additional, Carson, Richard E., additional, MacAvoy, Martha G., additional, Chertkow, Howard, additional, Bergman, Howard, additional, Hosein, Chris, additional, Black, Sandra, additional, Stefanovic, Dr Bojana, additional, Caldwell, Curtis, additional, Hsiung, Ging-Yuek Robin, additional, Feldman, Howard, additional, Mudge, Benita, additional, Assaly, Michele, additional, Kertesz, Andrew, additional, Rogers, John, additional, Trost, Dick, additional, Bernick, Charles, additional, Munic, Donna, additional, Kerwin, Diana, additional, Mesulam, Marek-Marsel, additional, Lipowski, Kristina, additional, Wu, Chuang-Kuo, additional, Johnson, Nancy, additional, Sadowsky, Carl, additional, Martinez, Walter, additional, Villena, Teresa, additional, Turner, Raymond Scott, additional, Johnson, Kathleen, additional, Reynolds, Brigid, additional, Sperling, Reisa A., additional, Johnson, Keith A., additional, Marshall, Gad, additional, Frey, Meghan, additional, Yesavage, Jerome, additional, Taylor, Joy L., additional, Lane, Barton, additional, Rosen, Allyson, additional, Tinklenberg, Jared, additional, Sabbagh, Marwan, additional, Belden, Christine, additional, Jacobson, Sandra, additional, Kowall, Neil, additional, Killiany, Ronald, additional, Budson, Andrew E., additional, Norbash, Alexander, additional, Johnson, Patricia Lynn, additional, Obisesan, Thomas O., additional, Wolday, Saba, additional, Bwayo, Salome K., additional, Lerner, Alan, additional, Hudson, Leon, additional, Ogrocki, Paula, additional, Fletcher, Evan, additional, Carmichael, Owen, additional, Olichney, John, additional, Kittur, Smita, additional, Borrie, Michael, additional, Lee, T-Y, additional, Bartha, Dr Rob, additional, Johnson, Sterling, additional, Asthana, Sanjay, additional, Carlsson, Cynthia M., additional, Potkin, Steven G., additional, Preda, Adrian, additional, Nguyen, Dana, additional, Tariot, Pierre, additional, Fleisher, Adam, additional, Reeder, Stephanie, additional, Bates, Vernice, additional, Capote, Horacio, additional, Rainka, Michelle, additional, Scharre, Douglas W., additional, Kataki, Maria, additional, Zimmerman, Earl A., additional, Celmins, Dzintra, additional, Brown, Alice D., additional, Pearlson, Godfrey D., additional, Blank, Karen, additional, Anderson, Karen, additional, Santulli, Robert B., additional, Schwartz, Eben S., additional, Sink, Kaycee M., additional, Williamson, Jeff D., additional, Garg, Pradeep, additional, Watkins, Franklin, additional, Ott, Brian R., additional, Querfurth, Henry, additional, Tremont, Geoffrey, additional, Salloway, Stephen, additional, Malloy, Paul, additional, Correia, Stephen, additional, Rosen, Howard J., additional, Miller, Bruce L., additional, Mintzer, Jacobo, additional, Longmire, Crystal Flynn, additional, Spicer, Kenneth, additional, Finger, Elizabether, additional, Rachinsky, Irina, additional, and Drost, Dick, additional

Published
2012
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