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1. Treatment satisfaction significantly improves in patients with multiple sclerosis switching from interferon beta therapy to peginterferon beta-1a every 2 weeks

Author

Hendin,Barry, Naismith,Robert, Wray,Sibyl E, Huang,Deren, Dong,Qunming, Livingston,Terrie, Jones,Daniel, Watson,Crystal, Jhaveri,Mehul, Hendin,Barry, Naismith,Robert, Wray,Sibyl E, Huang,Deren, Dong,Qunming, Livingston,Terrie, Jones,Daniel, Watson,Crystal, and Jhaveri,Mehul

Abstract

Barry Hendin,1 Robert T Naismith,2 Sibyl E Wray,3 Deren Huang,4 Qunming Dong,5 Terrie Livingston,6 Daniel L Jones,6 Crystal Watson,7 Mehul Jhaveri6 1Phoenix Neurological Associates, Phoenix, AZ, USA; 2Department of Neurology, Washington University School of Medicine, St Louis, MO, USA; 3Hope Neurology MS Center, Knoxville, TN, USA; 4Mount Carmel Neuroscience and MDH Research, Westerville, OH, USA; 5Biostatistics, Biogen, Cambridge, MA, USA; 6US Medical, Biogen, Cambridge, MA, USA; 7Global Value and Access, Biogen, Cambridge, MA, USA Objectives: Posthoc analysis of treatment satisfaction in patients switching to subcutaneous (SC) peginterferon beta-1a in the ALLOW study.Patients and methods: Patients with relapsing multiple sclerosis treated with intramuscular interferon (IFN) beta-1a or SC IFN beta-1a or beta-1b remained on their current therapy for a 4-week run-in period, followed by a switch to SC peginterferon beta-1a 125 mcg every 2 weeks for 48 weeks. Treatment satisfaction was measured using the Treatment Satisfaction Questionnaire for Medication (TSQM), which covers effectiveness, side effects, convenience, and global satisfaction. Patients completed the TSQM at baseline (prior to starting the 4-week run-in period) and 4, 12, 24, 36, and 48 weeks after switching, and scores were analyzed for the overall population and compared to baseline. Patients reported the severity of flu-like symptoms (FLS) at baseline and with each peginterferon beta-1a injection; clinicians evaluated the occurrence of injection-site reactions (ISRs) after the first dose of peginterferon beta-1a and every 12 weeks thereafter. TSQM scores were stratified by the presence of FLS or ISRs during the study period and by prior IFN therapy use.Results: For the overall population (n=194), convenience and global satisfaction scores significantly improved from baseline at all time points, and side effect satisfaction scores significantly improved up to week 36. Convenience scores significantly im

Published
2018

2. Predicting missing biomarker data in a longitudinal study of Alzheimer disease

Author

Lo, Raymond Y., Jagust, William J., Aisen, Paul, Jack, Clifford R., Toga, Arthur W., Beckett, Laurel, Gamst, Anthony, Soares, Holly, C. Green, Robert, Montine, Tom, Thomas, Ronald G., Donohue, Michael, Walter, Sarah, Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, DeCarli, Charles, Bandy, Dan, Chen, Kewei, Morris, John, Lee, Virginia M.-Y., Korecka, Magdalena, Crawford, Karen, Neu, Scott, Harvey, Danielle, Kornak, John, Saykin, Andrew J., Foroud, Tatiana M., Potkin, Steven, Shen, Li, Buckholtz, Neil, Kaye, Jeffrey, Dolen, Sara, Quinn, Joseph, Schneider, Lon, 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., Mintun, Mark A., Schneider, Stacy, Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, Tang, Cheuk, Marzloff, George, Toledo-Morrell, Leylade, Shah, Raj C., Duara, Ranjan, Varon, Daniel, Roberts, Peggy, Albert, Marilyn S., Pedroso, Julia, Toroney, Jaimie, Rusinek, Henry, de Leon, Mony J, De Santi, Susan M, Doraiswamy, P. Murali, Petrella, Jeffrey R., Aiello, Marilyn, Clark, Christopher M., Pham, Cassie, Nunez, Jessica, Smith, Charles D., Given, Curtis A., Hardy, Peter, Lopez, Oscar L., Oakley, MaryAnn, Simpson, Donna M., Ismail, M. Saleem, Brand, Connie, Richard, Jennifer, Mulnard, Ruth A., Thai, Gaby, Mc-Adams-Ortiz, Catherine, Diaz-Arrastia, Ramon, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I., Lah, James J., Cellar, Janet S., Burns, Jeffrey M., Anderson, Heather S., Laubinger, Mary M., Bartzokis, George, Silverman, Daniel H.S., Lu, Po H., Graff-Radford MBBCH, Neill R, Parfitt, Francine, Johnson, Heather, Farlow, Martin, Herring, Scott, Hake, Ann M., van Dyck, Christopher H., MacAvoy, Martha G., Benincasa, Amanda L., Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Graham, Simon, Caldwell, Curtis, Hsiung, Ging-Yuek Robin, Feldman, Howard, Assaly, Michele, Kertesz, Andrew, Rogers, John, Trost, Dick, Bernick, Charles, Munic, Donna, Wu, Chuang-Kuo, Johnson, Nancy, Mesulam, Marsel, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Scott, Johnson, Kathleen B., Behan, Kelly E., Sperling, Reisa A., Rentz, Dorene M., Johnson, Keith A., Rosen, Allyson, Tinklenberg, Jared, Ashford, Wes, Sabbagh, Marwan, Connor, Donald, Jacobson, Sandra, Killiany, Ronald, Norbash, Alexander, Nair, Anil, Obisesan, Thomas O., Jayam-Trouth, Annapurni, Wang, Paul, Lerner, Alan, Hudson, Leon, Ogrocki, Paula, Fletcher, Evan, Carmichael, Owen, Kittur, Smita, Mirje, Seema, 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, Hendin, Barry A., Scharre, Douglas W., Kataki, Maria, Zimmerman, Earl A., Celmins, Dzintra, Brown, Alice D., Gandy, Sam, Marenberg, Marjorie E., Rovner, Barry W., Pearlson, Godfrey, Anderson, Karen, Santulli, Robert B., Englert, Jessica, Williamson, Jeff D., Sink, Kaycee M., Watkins, Franklin, Ott, Brian R., Cohen, Ronald, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J., Miller, Bruce L., Mintzer, Jacobo, Lo, Raymond Y., Jagust, William J., Aisen, Paul, Jack, Clifford R., Toga, Arthur W., Beckett, Laurel, Gamst, Anthony, Soares, Holly, C. Green, Robert, Montine, Tom, Thomas, Ronald G., Donohue, Michael, Walter, Sarah, Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, DeCarli, Charles, Bandy, Dan, Chen, Kewei, Morris, John, Lee, Virginia M.-Y., Korecka, Magdalena, Crawford, Karen, Neu, Scott, Harvey, Danielle, Kornak, John, Saykin, Andrew J., Foroud, Tatiana M., Potkin, Steven, Shen, Li, Buckholtz, Neil, Kaye, Jeffrey, Dolen, Sara, Quinn, Joseph, Schneider, Lon, 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., Mintun, Mark A., Schneider, Stacy, Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, Tang, Cheuk, Marzloff, George, Toledo-Morrell, Leylade, Shah, Raj C., Duara, Ranjan, Varon, Daniel, Roberts, Peggy, Albert, Marilyn S., Pedroso, Julia, Toroney, Jaimie, Rusinek, Henry, de Leon, Mony J, De Santi, Susan M, Doraiswamy, P. Murali, Petrella, Jeffrey R., Aiello, Marilyn, Clark, Christopher M., Pham, Cassie, Nunez, Jessica, Smith, Charles D., Given, Curtis A., Hardy, Peter, Lopez, Oscar L., Oakley, MaryAnn, Simpson, Donna M., Ismail, M. Saleem, Brand, Connie, Richard, Jennifer, Mulnard, Ruth A., Thai, Gaby, Mc-Adams-Ortiz, Catherine, Diaz-Arrastia, Ramon, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I., Lah, James J., Cellar, Janet S., Burns, Jeffrey M., Anderson, Heather S., Laubinger, Mary M., Bartzokis, George, Silverman, Daniel H.S., Lu, Po H., Graff-Radford MBBCH, Neill R, Parfitt, Francine, Johnson, Heather, Farlow, Martin, Herring, Scott, Hake, Ann M., van Dyck, Christopher H., MacAvoy, Martha G., Benincasa, Amanda L., Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Graham, Simon, Caldwell, Curtis, Hsiung, Ging-Yuek Robin, Feldman, Howard, Assaly, Michele, Kertesz, Andrew, Rogers, John, Trost, Dick, Bernick, Charles, Munic, Donna, Wu, Chuang-Kuo, Johnson, Nancy, Mesulam, Marsel, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Scott, Johnson, Kathleen B., Behan, Kelly E., Sperling, Reisa A., Rentz, Dorene M., Johnson, Keith A., Rosen, Allyson, Tinklenberg, Jared, Ashford, Wes, Sabbagh, Marwan, Connor, Donald, Jacobson, Sandra, Killiany, Ronald, Norbash, Alexander, Nair, Anil, Obisesan, Thomas O., Jayam-Trouth, Annapurni, Wang, Paul, Lerner, Alan, Hudson, Leon, Ogrocki, Paula, Fletcher, Evan, Carmichael, Owen, Kittur, Smita, Mirje, Seema, 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, Hendin, Barry A., Scharre, Douglas W., Kataki, Maria, Zimmerman, Earl A., Celmins, Dzintra, Brown, Alice D., Gandy, Sam, Marenberg, Marjorie E., Rovner, Barry W., Pearlson, Godfrey, Anderson, Karen, Santulli, Robert B., Englert, Jessica, Williamson, Jeff D., Sink, Kaycee M., Watkins, Franklin, Ott, Brian R., Cohen, Ronald, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J., Miller, Bruce L., and Mintzer, Jacobo

Abstract

Objective:To investigate predictors of missing data in a longitudinal study of Alzheimer disease (AD).Methods:The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a clinic-based, multicenter, longitudinal study with blood, CSF, PET, and MRI scans repeatedly measured in 229 participants with normal cognition (NC), 397 with mild cognitive impairment (MCI), and 193 with mild AD during 2005–2007. We used univariate and multivariable logistic regression models to examine the associations between baseline demographic/clinical features and loss of biomarker follow-ups in ADNI.Results:CSF studies tended to recruit and retain patients with MCI with more AD-like features, including lower levels of baseline CSF Aβ42. Depression was the major predictor for MCI dropouts, while family history of AD kept more patients with AD enrolled in PET and MRI studies. Poor cognitive performance was associated with loss of follow-up in most biomarker studies, even among NC participants. The presence of vascular risk factors seemed more critical than cognitive function for predicting dropouts in AD.Conclusion:The missing data are not missing completely at random in ADNI and likely conditional on certain features in addition to cognitive function. Missing data predictors vary across biomarkers and even MCI and AD groups do not share the same missing data pattern. Understanding the missing data structure may help in the design of future longitudinal studies and clinical trials in AD.

Published
2012

3. Predicting missing biomarker data in a longitudinal study of Alzheimer disease

Author

Lo, Raymond Y., Jagust, William J., Aisen, Paul, Jack, Clifford R., Toga, Arthur W., Beckett, Laurel, Gamst, Anthony, Soares, Holly, C. Green, Robert, Montine, Tom, Thomas, Ronald G., Donohue, Michael, Walter, Sarah, Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, DeCarli, Charles, Bandy, Dan, Chen, Kewei, Morris, John, Lee, Virginia M.-Y., Korecka, Magdalena, Crawford, Karen, Neu, Scott, Harvey, Danielle, Kornak, John, Saykin, Andrew J., Foroud, Tatiana M., Potkin, Steven, Shen, Li, Buckholtz, Neil, Kaye, Jeffrey, Dolen, Sara, Quinn, Joseph, Schneider, Lon, 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., Mintun, Mark A., Schneider, Stacy, Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, Tang, Cheuk, Marzloff, George, Toledo-Morrell, Leylade, Shah, Raj C., Duara, Ranjan, Varon, Daniel, Roberts, Peggy, Albert, Marilyn S., Pedroso, Julia, Toroney, Jaimie, Rusinek, Henry, De Leon, Mony J, De Santi, Susan M, Doraiswamy, P. Murali, Petrella, Jeffrey R., Aiello, Marilyn, Clark, Christopher M., Pham, Cassie, Nunez, Jessica, Smith, Charles D., Given, Curtis A., Hardy, Peter, Lopez, Oscar L., Oakley, MaryAnn, Simpson, Donna M., Ismail, M. Saleem, Brand, Connie, Richard, Jennifer, Mulnard, Ruth A., Thai, Gaby, Mc-Adams-Ortiz, Catherine, Diaz-Arrastia, Ramon, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I., Lah, James J., Cellar, Janet S., Burns, Jeffrey M., Anderson, Heather S., Laubinger, Mary M., Bartzokis, George, Silverman, Daniel H.S., Lu, Po H., Graff-Radford MBBCH, Neill R, Parfitt, Francine, Johnson, Heather, Farlow, Martin, Herring, Scott, Hake, Ann M., Van Dyck, Christopher H., MacAvoy, Martha G., Benincasa, Amanda L., Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Graham, Simon, Caldwell, Curtis, Hsiung, Ging-Yuek Robin, Feldman, Howard, Assaly, Michele, Kertesz, Andrew, Rogers, John, Trost, Dick, Bernick, Charles, Munic, Donna, Wu, Chuang-Kuo, Johnson, Nancy, Mesulam, Marsel, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Scott, Johnson, Kathleen B., Behan, Kelly E., Sperling, Reisa A., Rentz, Dorene M., Johnson, Keith A., Rosen, Allyson, Tinklenberg, Jared, Ashford, Wes, Sabbagh, Marwan, Connor, Donald, Jacobson, Sandra, Killiany, Ronald, Norbash, Alexander, Nair, Anil, Obisesan, Thomas O., Jayam-Trouth, Annapurni, Wang, Paul, Lerner, Alan, Hudson, Leon, Ogrocki, Paula, Fletcher, Evan, Carmichael, Owen, Kittur, Smita, Mirje, Seema, 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, Hendin, Barry A., Scharre, Douglas W., Kataki, Maria, Zimmerman, Earl A., Celmins, Dzintra, Brown, Alice D., Gandy, Sam, Marenberg, Marjorie E., Rovner, Barry W., Pearlson, Godfrey, Anderson, Karen, Santulli, Robert B., Englert, Jessica, Williamson, Jeff D., Sink, Kaycee M., Watkins, Franklin, Ott, Brian R., Cohen, Ronald, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J., Miller, Bruce L., Mintzer, Jacobo, Lo, Raymond Y., Jagust, William J., Aisen, Paul, Jack, Clifford R., Toga, Arthur W., Beckett, Laurel, Gamst, Anthony, Soares, Holly, C. Green, Robert, Montine, Tom, Thomas, Ronald G., Donohue, Michael, Walter, Sarah, Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, DeCarli, Charles, Bandy, Dan, Chen, Kewei, Morris, John, Lee, Virginia M.-Y., Korecka, Magdalena, Crawford, Karen, Neu, Scott, Harvey, Danielle, Kornak, John, Saykin, Andrew J., Foroud, Tatiana M., Potkin, Steven, Shen, Li, Buckholtz, Neil, Kaye, Jeffrey, Dolen, Sara, Quinn, Joseph, Schneider, Lon, 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., Mintun, Mark A., Schneider, Stacy, Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, Tang, Cheuk, Marzloff, George, Toledo-Morrell, Leylade, Shah, Raj C., Duara, Ranjan, Varon, Daniel, Roberts, Peggy, Albert, Marilyn S., Pedroso, Julia, Toroney, Jaimie, Rusinek, Henry, De Leon, Mony J, De Santi, Susan M, Doraiswamy, P. Murali, Petrella, Jeffrey R., Aiello, Marilyn, Clark, Christopher M., Pham, Cassie, Nunez, Jessica, Smith, Charles D., Given, Curtis A., Hardy, Peter, Lopez, Oscar L., Oakley, MaryAnn, Simpson, Donna M., Ismail, M. Saleem, Brand, Connie, Richard, Jennifer, Mulnard, Ruth A., Thai, Gaby, Mc-Adams-Ortiz, Catherine, Diaz-Arrastia, Ramon, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I., Lah, James J., Cellar, Janet S., Burns, Jeffrey M., Anderson, Heather S., Laubinger, Mary M., Bartzokis, George, Silverman, Daniel H.S., Lu, Po H., Graff-Radford MBBCH, Neill R, Parfitt, Francine, Johnson, Heather, Farlow, Martin, Herring, Scott, Hake, Ann M., Van Dyck, Christopher H., MacAvoy, Martha G., Benincasa, Amanda L., Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Graham, Simon, Caldwell, Curtis, Hsiung, Ging-Yuek Robin, Feldman, Howard, Assaly, Michele, Kertesz, Andrew, Rogers, John, Trost, Dick, Bernick, Charles, Munic, Donna, Wu, Chuang-Kuo, Johnson, Nancy, Mesulam, Marsel, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Scott, Johnson, Kathleen B., Behan, Kelly E., Sperling, Reisa A., Rentz, Dorene M., Johnson, Keith A., Rosen, Allyson, Tinklenberg, Jared, Ashford, Wes, Sabbagh, Marwan, Connor, Donald, Jacobson, Sandra, Killiany, Ronald, Norbash, Alexander, Nair, Anil, Obisesan, Thomas O., Jayam-Trouth, Annapurni, Wang, Paul, Lerner, Alan, Hudson, Leon, Ogrocki, Paula, Fletcher, Evan, Carmichael, Owen, Kittur, Smita, Mirje, Seema, 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, Hendin, Barry A., Scharre, Douglas W., Kataki, Maria, Zimmerman, Earl A., Celmins, Dzintra, Brown, Alice D., Gandy, Sam, Marenberg, Marjorie E., Rovner, Barry W., Pearlson, Godfrey, Anderson, Karen, Santulli, Robert B., Englert, Jessica, Williamson, Jeff D., Sink, Kaycee M., Watkins, Franklin, Ott, Brian R., Cohen, Ronald, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J., Miller, Bruce L., and Mintzer, Jacobo

Published
2012

4. A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly

Author

Ho, April J., Stein, Jason L., Hua, Xue, Lee, Suh, Hibar, Derrek P., Leow, Alex D., Dinov, Ivo D., Toga, Arthur W., Saykin, Andrew J., Shen, Li, Foroud, Tatiana, Pankratz, Nathan, Huentelman, Matthew J., Craig, David W., Gerber, Jill D., Allen, April N., Corneveaux, Jason J., Stephan, Dietrich A., DeCarli, Charles S., DeChairo, Bryan M., Potkin, Steven G., Jack, Clifford R., Weiner, Michael W., Raji, Cyrus A., Lopez, Oscar L., Becker, James T., Carmichael, Owen T., Thompson, Paul M., Weiner, Michael, Thal, Leon, Petersen, Ronald, Jagust, William, Trojanowki, John, Beckett, Laurel, Green, Robert C., Gamst, Anthony, Potter, William Z., Montine, Tom, Anders, Dale, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, Bandy, Dan, Koeppe, Robert A., Foster, Norm, Reiman, Eric M., Chen, Kewei, Shaw, Les, Lee, Virginia M.-Y., Korecka, Magdalena, Crawford, Karen, Neu, Scott, Harvey, Danielle, Kornak, John, Kachaturian, Zaven, Frank, Richard, Snyder, Peter J., Molchan, Susan, Kaye, Jeffrey, Vorobik, Remi, Quinn, Joseph, Schneider, Lon, Pawluczyk, Sonia, Spann, Bryan, Fleisher, Adam S., 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., Mintun, Mark A., Schneider, Stacy, Marson, Daniel, Griffith, Randall, Badger, Beverly, Grossman, Hillel, Tang, Cheuk, Stern, Jessica, deToledo-Morrell, Leyla, Shah, Raj C., Bach, Julie, Duara, Ranjan, Isaacson, Richard, Strauman, Silvia, Albert, Marilyn S., Pedroso, Julia, Toroney, Jaimie, Rusinek, Henry, de Leon, Mony J, De Santi, Susan M, Doraiswamy, P. Murali, Petrella, Jeffrey R., Aiello, Marilyn, Clark, Christopher M., Pham, Cassie, Nunez, Jessica, Smith, Charles D., Given II, Curtis A., Hardy, Peter, DeKosky, Steven T., Oakley, MaryAnn, Simpson, Donna M., Ismail, M. Saleem, Porsteinsson, Anton, McCallum, Colleen, Cramer, Steven C., Mulnard, Ruth A., McAdams-Ortiz, Catherine, Diaz-Arrastia, Ramon, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I., Lah, James J., Cellar, Janet S., Burns, Jeffrey M., Anderson, Heather S., Laubinger, Mary M., Bartzokis, George, Silverman, Daniel H.S., Lu, Po H., Fletcher, Rita, Parfitt, Francine, Johnson, Heather, Farlow, Martin, Herring, Scott, Hake, Ann M., van Dyck, Christopher H., MacAvoy, Martha G., Bifano, Laurel A., Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Graham, Simon, Caldwell, Curtis, Feldman, Howard, Assaly, Michele, Hsiung, Ging-Yuek R., Kertesz, Andrew, Rogers, John, Trost, Dick, Bernick, Charles, Gitelman, Darren, Johnson, Nancy, Mesulam, Marsel, Sadowsky, Carl, Villena, Teresa, Mesner, Scott, Aisen, Paul S., Johnson, Kathleen B., Behan, Kelly E., Sperling, Reisa A., Rentz, Dorene M., Johnson, Keith A., Rosen, Allyson, Tinklenberg, Jared, Ashford, Wes, Sabbagh, Marwan, Connor, Donald, Obradov, Sanja, Killiany, Ron, Norbash, Alex, Obisesan, Thomas O., Jayam-Trouth, Annapurni, Wang, Paul, Auchus, Alexander P., Huang, Juebin, Friedland, Robert P., DeCarli, Charles, Fletcher, Evan, Carmichael, Owen, Kittur, Smita, Mirje, Seema, Johnson, Sterling C., Borrie, Michael, Lee, T-Y, Asthana, Sanjay, Carlsson, Cynthia M., Highum, Diane, Preda, Adrian, Nguyen, Dana, Tariot, Pierre N., Hendin, Barry A., Scharre, Douglas W., Kataki, Maria, Beversdorf, David Q., Zimmerman, Earl A., Celmins, Dzintra, Brown, Alice D., Gandy, Sam, Marenberg, Marjorie E., Rovner, Barry W., Pearlson, Godfrey, Blank, Karen, Anderson, Karen, Santulli, Robert B., Pare, Nadia, Williamson, Jeff D., Sink, Kaycee M., Potter, Huntington, Ashok Raj, B., Giordano, Amy, Ott, Brian R., Wu, Chuang-Kuo, Cohen, Ronald, Wilks, Kerri L., Ho, April J., Stein, Jason L., Hua, Xue, Lee, Suh, Hibar, Derrek P., Leow, Alex D., Dinov, Ivo D., Toga, Arthur W., Saykin, Andrew J., Shen, Li, Foroud, Tatiana, Pankratz, Nathan, Huentelman, Matthew J., Craig, David W., Gerber, Jill D., Allen, April N., Corneveaux, Jason J., Stephan, Dietrich A., DeCarli, Charles S., DeChairo, Bryan M., Potkin, Steven G., Jack, Clifford R., Weiner, Michael W., Raji, Cyrus A., Lopez, Oscar L., Becker, James T., Carmichael, Owen T., Thompson, Paul M., Weiner, Michael, Thal, Leon, Petersen, Ronald, Jagust, William, Trojanowki, John, Beckett, Laurel, Green, Robert C., Gamst, Anthony, Potter, William Z., Montine, Tom, Anders, Dale, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, Bandy, Dan, Koeppe, Robert A., Foster, Norm, Reiman, Eric M., Chen, Kewei, Shaw, Les, Lee, Virginia M.-Y., Korecka, Magdalena, Crawford, Karen, Neu, Scott, Harvey, Danielle, Kornak, John, Kachaturian, Zaven, Frank, Richard, Snyder, Peter J., Molchan, Susan, Kaye, Jeffrey, Vorobik, Remi, Quinn, Joseph, Schneider, Lon, Pawluczyk, Sonia, Spann, Bryan, Fleisher, Adam S., 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., Mintun, Mark A., Schneider, Stacy, Marson, Daniel, Griffith, Randall, Badger, Beverly, Grossman, Hillel, Tang, Cheuk, Stern, Jessica, deToledo-Morrell, Leyla, Shah, Raj C., Bach, Julie, Duara, Ranjan, Isaacson, Richard, Strauman, Silvia, Albert, Marilyn S., Pedroso, Julia, Toroney, Jaimie, Rusinek, Henry, de Leon, Mony J, De Santi, Susan M, Doraiswamy, P. Murali, Petrella, Jeffrey R., Aiello, Marilyn, Clark, Christopher M., Pham, Cassie, Nunez, Jessica, Smith, Charles D., Given II, Curtis A., Hardy, Peter, DeKosky, Steven T., Oakley, MaryAnn, Simpson, Donna M., Ismail, M. Saleem, Porsteinsson, Anton, McCallum, Colleen, Cramer, Steven C., Mulnard, Ruth A., McAdams-Ortiz, Catherine, Diaz-Arrastia, Ramon, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I., Lah, James J., Cellar, Janet S., Burns, Jeffrey M., Anderson, Heather S., Laubinger, Mary M., Bartzokis, George, Silverman, Daniel H.S., Lu, Po H., Fletcher, Rita, Parfitt, Francine, Johnson, Heather, Farlow, Martin, Herring, Scott, Hake, Ann M., van Dyck, Christopher H., MacAvoy, Martha G., Bifano, Laurel A., Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Graham, Simon, Caldwell, Curtis, Feldman, Howard, Assaly, Michele, Hsiung, Ging-Yuek R., Kertesz, Andrew, Rogers, John, Trost, Dick, Bernick, Charles, Gitelman, Darren, Johnson, Nancy, Mesulam, Marsel, Sadowsky, Carl, Villena, Teresa, Mesner, Scott, Aisen, Paul S., Johnson, Kathleen B., Behan, Kelly E., Sperling, Reisa A., Rentz, Dorene M., Johnson, Keith A., Rosen, Allyson, Tinklenberg, Jared, Ashford, Wes, Sabbagh, Marwan, Connor, Donald, Obradov, Sanja, Killiany, Ron, Norbash, Alex, Obisesan, Thomas O., Jayam-Trouth, Annapurni, Wang, Paul, Auchus, Alexander P., Huang, Juebin, Friedland, Robert P., DeCarli, Charles, Fletcher, Evan, Carmichael, Owen, Kittur, Smita, Mirje, Seema, Johnson, Sterling C., Borrie, Michael, Lee, T-Y, Asthana, Sanjay, Carlsson, Cynthia M., Highum, Diane, Preda, Adrian, Nguyen, Dana, Tariot, Pierre N., Hendin, Barry A., Scharre, Douglas W., Kataki, Maria, Beversdorf, David Q., Zimmerman, Earl A., Celmins, Dzintra, Brown, Alice D., Gandy, Sam, Marenberg, Marjorie E., Rovner, Barry W., Pearlson, Godfrey, Blank, Karen, Anderson, Karen, Santulli, Robert B., Pare, Nadia, Williamson, Jeff D., Sink, Kaycee M., Potter, Huntington, Ashok Raj, B., Giordano, Amy, Ott, Brian R., Wu, Chuang-Kuo, Cohen, Ronald, and Wilks, Kerri L.

Abstract

A recently identified variant within the fat mass and obesity-associated (FTO) gene is carried by 46% of Western Europeans and is associated with an ~1.2 kg higher weight, on average, in adults and an ~1 cm greater waist circumference. With >1 billion overweight and 300 million obese persons worldwide, it is crucial to understand the implications of carrying this very common allele for the health of our aging population. FTO is highly expressed in the brain and elevated body mass index (BMI) is associated with brain atrophy, but it is unknown how the obesity-associated risk allele affects human brain structure. We therefore generated 3D maps of regional brain volume differences in 206 healthy elderly subjects scanned with MRI and genotyped as part of the Alzheimer's Disease Neuroimaging Initiative. We found a pattern of systematic brain volume deficits in carriers of the obesity-associated risk allele versus noncarriers. Relative to structure volumes in the mean template, FTO risk allele carriers versus noncarriers had an average brain volume difference of ~8% in the frontal lobes and 12% in the occipital lobes—these regions also showed significant volume deficits in subjects with higher BMI. These brain differences were not attributable to differences in cholesterol levels, hypertension, or the volume of white matter hyperintensities; which were not detectably higher in FTO risk allele carriers versus noncarriers. These brain maps reveal that a commonly carried susceptibility allele for obesity is associated with structural brain atrophy, with implications for the health of the elderly.

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