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202. Impact of Potential Modifications to Alzheimer’s Disease Clinical Trials in Response to Disruption by COVID-19

Author

Schneider, Lon S, primary, Qiu, Yuqi, additional, Thomas, Ronald G, additional, Evans, Carol, additional, Jacobs, Diane M., additional, Jin, Shelia, additional, Kaye, Jeffrey A., additional, LaCroix, Andrea Z., additional, Messer, Karen, additional, Salmon, David P, additional, Sano, Mary, additional, Schafer, Kimberly A., additional, and Feldman, Howard H., additional

Published
2021
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203. Neuropathology of nondemented aging: Presumptive evidence for preclinical Alzheimer disease

Author

Price, Joseph L., McKeel, Daniel W., Jr., Buckles, Virginia D., Roe, Catherine M., Xiong, Chengjie, Grundman, Michael, Hansen, Lawrence A., Petersen, Ronald C., Parisi, Joseph E., Dickson, Dennis W., Smith, Charles D., Davis, Daron G., Schmitt, Frederick A., Markesbery, William R., Kaye, Jeffrey, Kurlan, Roger, Hulette, Christine, Kurland, Brenda F., Higdon, Roger, Kukull, Walter, and Morris, John C.

Published
2009
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204. Amyloid beta peptides in human plasma and tissues and their significance for Alzheimer's disease

Author

Roher, Alex E., Esh, Chera L., Kokjohn, Tyler A., Castaño, Eduardo M., Van Vickle, Gregory D., Kalback, Walter M., Patton, R. Lyle, Luehrs, Dean C., Daugs, Ian D., Kuo, Yu-Min, Emmerling, Mark R., Soares, Holly, Quinn, Joseph F., Kaye, Jeffrey, Connor, Donald J., Silverberg, Nina B., Adler, Charles H., Seward, James D., Beach, Thomas G., and Sabbagh, Marwan N.

Published
2009
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205. Assessing the Clinical Meaningfulness of the Alzheimer's Disease Composite Score (ADCOMS) Tool.

Author

Tahami Monfared, Amir Abbas, Lenderking, William R., Savva, Yulia, Ladd, Mary Kate, Zhang, Quanwu, for the Alzheimer's Disease Neuroimaging Initiative, Brewer, James, Lopez, Oscar, Hyman, Bradley, Grabowski, Thomas, Sano, Mary, Chui, Helena, Albert, Marilyn, Morris, John, Kaye, Jeffrey, Wisniewski, Thomas, Small, Scott, Trojanowski, John, DeCarli, Charles, and Saykin, Andrew

Published
2022
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206. Unobtrusive, in-home assessment of older adults' everyday activities and health events: associations with cognitive performance over a brief observation period.

Author

Bernstein, John P.K., Dorociak, Katherine, Mattek, Nora, Leese, Mira, Trapp, Chelsea, Beattie, Zachary, Kaye, Jeffrey, and Hughes, Adriana

Subjects
OLDER people, COGNITIVE ability, COGNITION, HYPNOTICS, NEUROPSYCHOLOGICAL tests
Abstract

In-home assessment of everyday activities over many months to years may be useful in predicting cognitive decline in older adulthood. This study examined whether a comparatively brief data collection period (3 months) may yield similar diagnostic information. A total of 91 community-dwelling older adults without dementia underwent baseline neuropsychological testing and completed weekly computer-based surveys assessing health-related events/activities. A subset of participants wore fitness tracker watches assessing daily sleep and physical activity patterns, used a sensor-instrumented pillbox, and had their computer use frequency recorded on a daily basis. Similar patterns in computer use, sleep and medication use were noted in comparison to prior literature with more extensive data collection periods. Greater computer use and sleep, as well as self-reported pain and independence, were also linked to better cognition. These activities and symptoms may be useful correlates of cognitive function even when assessed over a relatively brief monitoring period. [ABSTRACT FROM AUTHOR]

Published
2022
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207. Assessment of the genetic variance of late-onset Alzheimer's disease

Author

Adams, Perrie M., Albert, Marilyn S., Albin, Roger L., Apostolova, Liana G., Arnold, Steven E., Asthana, Sanjay, Atwood, Craig S., Baldwin, Clinton T., Barber, Robert C., Barmada, Michael M., Barnes, Lisa L., Barral, Sandra, Beach, Thomas G., Becker, James T., Beecham, Gary W., Beekly, Duane, Bennett, David A., Bigio, Eileen H., Bird, Thomas D., Blacker, Deborah, Boeve, Bradley F., Bowen, James D., Boxer, Adam, Burke, James R., Burns, Jeffrey M., Buxbaum, Joseph D., Cairns, Nigel J., Cantwell, Laura B., Cao, Chuanhai, Carlson, Chris S., Carlsson, Cynthia M., Carney, Regina M., Carrasquillo, Minerva M., Carroll, Steven L., Chui, Helena C., Clark, David G., Corneveaux, Jason, Crane, Paul K., Cribbs, David H., Crocco, Elizabeth A., Cruchaga, Carlos, De Jager, Philip L., DeCarli, Charles, Demirci, F. Yesim, Dick, Malcolm, Dickson, Dennis W., Doody, Rachelle S., Duara, Ranjan, Ertekin-Taner, Nilufer, Evans, Denis A., Faber, Kelley M., Fairchild, Thomas J., Fallon, Kenneth B., Fardo, David W., Farlow, Martin R., Ferris, Steven, Foroud, Tatiana M., Frosch, Matthew P., Galasko, Douglas R., Gearing, Marla, Geschwind, Daniel H., Ghetti, Bernardino, Gilbert, John R., Goate, Alison M., Graff-Radford, Neill R., Green, Robert C., Growdon, John H., Hakonarson, Hakon, Hamilton, Ronald L., Hamilton-Nelson, Kara L., Hardy, John, Harrell, Lindy E., Honig, Lawrence S., Huebinger, Ryan M., Huentelman, Matthew J., Hulette, Christine M., Hyman, Bradley T., Jarvik, Gail P., Jicha, Gregory A., Jin, Lee-Way, Jun, Gyungah, Kamboh, M. Ilyas, Karydas, Anna, Katz, Mindy J., Kauwe, John S.K., Kaye, Jeffrey A., Kim, Ronald, Kowall, Neil W., Kramer, Joel H., Kukull, Walter A., Kunkle, Brian W., LaFerla, Frank M., Lah, James J., Larson, Eric B., Leverenz, James B., Levey, Allan I., Li, Ge, Lieberman, Andrew P., Lin, Chiao-Feng, Lipton, Richard B., Lopez, Oscar L., Lunetta, Kathryn L., Lyketsos, Constantine G., Mack, Wendy J., Marson, Daniel C., Martin, Eden R., Martiniuk, Frank, Mash, Deborah C., Masliah, Eliezer, McCormick, Wayne C., McCurry, Susan M., McDavid, Andrew N., McKee, Ann C., Mesulam, Marsel, Miller, Bruce L., Miller, Carol A., Miller, Joshua W., Montine, Thomas J., Morris, John C., Mukherjee, Shubhabrata, Murrell, Jill R., Myers, Amanda J., Naj, Adam C., O'Bryant, Sid, Olichney, John M., Pankratz, Vernon S., Parisi, Joseph E., Partch, Amanda, Paulson, Henry L., Perry, William, Peskind, Elaine, Petersen, Ronald C., Pierce, Aimee, Poon, Wayne W., Potter, Huntington, Quinn, Joseph F., Raj, Ashok, Raskind, Murray, Reiman, Eric M., Reisberg, Barry, Reisch, Joan S., Reitz, Christiane, Ringman, John M., Roberson, Erik D., Rogaeva, Ekaterina, Rosen, Howard J., Rosenberg, Roger N., Royall, Donald R., Sager, Mark A., Sano, Mary, Saykin, Andrew J., Schneider, Julie A., Schneider, Lon S., Seeley, William W., Smith, Amanda G., Sonnen, Joshua A., Spina, Salvatore, St George-Hyslop, Peter, Stern, Robert A., Swerdlow, Russell H., Tanzi, Rudolph E., Thornton-Wells, Tricia A., Trojanowski, John Q., Troncoso, Juan C., Tsuang, Debby W., Valladares, Otto, Van Deerlin, Vivianna M., Van Eldik, Linda J., Vardarajan, Badri N., Vinters, Harry V., Vonsattel, Jean Paul, Wang, Li-San, Weintraub, Sandra, Welsh-Bohmer, Kathleen A., Wendland, Jens R., Wilhelmsen, Kirk C., Williamson, Jennifer, Wingo, Thomas S., Winslow, Ashley R., Wishnek, Sarah, Woltjer, Randall L., Wright, Clinton B., Wu, Chuang-Kuo, Younkin, Steven G., Yu, Chang-En, Yu, Lei, Ridge, Perry G., Hoyt, Kaitlyn B., Boehme, Kevin, Haines, Jonathan L., Mayeux, Richard, Farrer, Lindsay A., Pericak-Vance, Margaret A., and Schellenberg, Gerard D.

Published
2016
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208. Effects of Multiple Genetic Loci on Age at Onset in Late-Onset Alzheimer Disease: A Genome-Wide Association Study

Author

Naj, Adam C., Jun, Gyungah, Reitz, Christiane, Kunkle, Brian W., Perry, William, Park, Yo Son, Beecham, Gary W., Rajbhandary, Ruchita A., Hamilton-Nelson, Kara L., Wang, Li-San, Kauwe, John S. K., Huentelman, Matthew J., Myers, Amanda J., Bird, Thomas D., Boeve, Bradley F., Baldwin, Clinton T., Jarvik, Gail P., Crane, Paul K., Rogaeva, Ekaterina, Barmada, Michael M., Demirci, Yesim F., Cruchaga, Carlos, Kramer, Patricia L., Ertekin-Taner, Nilufer, Hardy, John, Graff-Radford, Neill R., Green, Robert C., Larson, Eric B., St. George-Hyslop, Peter H., Buxbaum, Joseph D., Evans, Denis A., Schneider, Julie A., Lunetta, Kathryn L., Kamboh, Ilyas M., Saykin, Andrew J., Reiman, Eric M., De Jager, Philip L., Bennett, David A., Morris, John C., Montine, Thomas J., Goate, Alison M., Blacker, Deborah, Tsuang, Debby W., Hakonarson, Hakon, Kukull, Walter A., Foroud, Tatiana M., Martin, Eden R., Haines, Jonathan L., Mayeux, Richard P., Farrer, Lindsay A., Schellenberg, Gerard D., Pericak-Vance, Margaret A., Albert, Marilyn S., Albin, Roger L., Apostolova, Liana G., Arnold, Steven E., Barber, Robert, Barnes, Lisa L., Beach, Thomas G., Becker, James T., Beekly, Duane, Bigio, Eileen H., Bowen, James D., Boxer, Adam, Burke, James R., Cairns, Nigel J., Cantwell, Laura B., Cao, Chuanhai, Carlson, Chris S., Carney, Regina M., Carrasquillo, Minerva M., Carroll, Steven L., Chui, Helena C., Clark, David G., Corneveaux, Jason, Cribbs, David H., Crocco, Elizabeth A., DeCarli, Charles, DeKosky, Steven T., Dick, Malcolm, Dickson, Dennis W., Duara, Ranjan, Faber, Kelley M., Fallon, Kenneth B., Farlow, Martin R., Ferris, Steven, Frosch, Matthew P., Galasko, Douglas R., Ganguli, Mary, Gearing, Marla, Geschwind, Daniel H., Ghetti, Bernardino, Gilbert, John R., Glass, Jonathan D., Growdon, John H., Hamilton, Ronald L., Harrell, Lindy E., Head, Elizabeth, Honig, Lawrence S., Hulette, Christine M., Hyman, Bradley T., Jicha, Gregory A., Jin, Lee-Way, Karydas, Anna, Kaye, Jeffrey A., Kim, Ronald, Koo, Edward H., Kowall, Neil W., Kramer, Joel H., LaFerla, Frank M., Lah, James J., Leverenz, James B., Levey, Allan I., Li, Ge, Lieberman, Andrew P., Lin, Chiao-Feng, Lopez, Oscar L., Lyketsos, Constantine G., Mack, Wendy J., Martiniuk, Frank, Mash, Deborah C., Masliah, Eliezer, McCormick, Wayne C., McCurry, Susan M., McDavid, Andrew N., McKee, Ann C., Mesulam, Marsel, Miller, Bruce L., Miller, Carol A., Miller, Joshua W., Murrell, Jill R., Olichney, John M., Pankratz, Vernon S., Parisi, Joseph E., Paulson, Henry L., Peskind, Elaine, Petersen, Ronald C., Pierce, Aimee, Poon, Wayne W., Potter, Huntington, Quinn, Joseph F., Raj, Ashok, Raskind, Murray, Reisberg, Barry, Ringman, John M., Roberson, Erik D., Rosen, Howard J., Rosenberg, Roger N., Sano, Mary, Schneider, Lon S., Seeley, William W., Smith, Amanda G., Sonnen, Joshua A., Spina, Salvatore, Stern, Robert A., Tanzi, Rudolph E., Thornton-Wells, Tricia A., Trojanowski, John Q., Troncoso, Juan C., Valladares, Otto, Van Deerlin, Vivianna M., Van Eldik, Linda J., Vardarajan, Badri N., Vinters, Harry V., Vonsattel, Jean Paul, Weintraub, Sandra, Welsh-Bohmer, Kathleen A., Williamson, Jennifer, Wishnek, Sarah, Woltjer, Randall L., Wright, Clinton B., Younkin, Steven G., Yu, Chang-En, and Yu, Lei

Published
2014
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211. Predictors of cognitive impairment in primary age-related tauopathy: an autopsy study

Author

Iida, Megan A., primary, Farrell, Kurt, additional, Walker, Jamie M., additional, Richardson, Timothy E., additional, Marx, Gabe, additional, Bryce, Clare H., additional, Purohit, Dushyant, additional, Ayalon, Gai, additional, Beach, Thomas G., additional, Bigio, Eileen H., additional, Cortes, Etty, additional, Gearing, Marla, additional, Haroutunian, Vahram, additional, McMillan, Corey T., additional, Lee, Eddie B., additional, Dickson, Dennis, additional, McKee, Ann C., additional, Stein, Thor D., additional, Trojanowski, John Q., additional, Woltjer, Randall L., additional, Kovacs, Gabor G., additional, Kofler, Julia K., additional, Kaye, Jeffrey, additional, White, Charles L., additional, and Crary, John F., additional

Published
2021
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218. The necessity of diplomacy in brain health

Author

Dawson, Walter D, Bobrow, Kirsten, Ibanez, Agustin, Booi, Laura, Pintado-Caipa, Maritza, Yamamoto, Stacey, Tarnanas, Ioannis, Evans, Timothy, Comas-Herrera, Adelina, Cummings, Jeffrey, Kaye, Jeffrey, Yaffe, Kristine, Miller, Bruce L, and Eyre, Harris A

Published
2020
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221. The ageing systemic milieu negatively regulates neurogenesis and cognitive function

Author

Villeda, Saul A., Luo, Jian, Mosher, Kira I., Zou, Bende, Britschgi, Markus, Bieri, Gregor, Stan, Trisha M., Fainberg, Nina, Ding, Zhaoqing, Eggel, Alexander, Lucin, Kurt M., Czirr, Eva, Park, Jeong-Soo, Couillard-Despres, Sebastien, Aigner, Ludwig, Li, Ge, Peskind, Elaine R., Kaye, Jeffrey A., Quinn, Joseph F., Galasko, Douglas R., Xie, Xinmin S., Rando, Thomas A., and Wyss-Coray, Tony

Subjects
Cognition in children -- Research, Neurogenesis -- Research, Neuroplasticity -- Research, Cerebrospinal fluid -- Physiological aspects -- Research, Chemokines -- Physiological aspects -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

In the central nervous system, ageing results in a precipitous decline in adult neural stem/progenitor cells and neurogenesis, with concomitant impairments in cognitive functions (1). Interestingly, such impairments can be ameliorated through systemic perturbations such as exercise (1). Here, using heterochronic parabiosis we show that blood-borne factors present in the systemic milieu can inhibit or promote adult neurogenesis in an age-dependent fashion in mice. Accordingly, exposing a young mouse to an old systemic environment or to plasma from old mice decreased synaptic plasticity, and impaired contextual fear conditioning and spatial learning and memory. We identify chemokines--including CCL11 (also known as eotaxin)--the plasma levels of which correlate with reduced neurogenesis in heterochronic parabionts and aged mice, and the levels of which are increased in the plasma and cerebrospinal fluid of healthy ageing humans. Lastly, increasing peripheral CCL11 chemokine levels in vivo in young mice decreased adult neurogenesis and impaired learning and memory. Together our data indicate that the decline in neurogenesis and cognitive impairments observed during ageing can be in part attributed to changes in blood-borne factors., Adult neurogenesis occurs in local microenvironments, or neurogenic niches, in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the hippocampus (2,3). Permissive cues within [...]

Published
2011
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225. Comparisons of plasma/serum micronutrients between Okinawan and Oregonian elders: a pilot study

Author

Dodge, Hiroko H., Katsumata, Yuriko, Todoriki, Hidemi, Yasura, Shoutoku, Willcox, D. Craig, Bowman, Gene L., Willcox, Bradley, Leonard, Scott, Clemons, Aaron, Oken, Barry S., Kaye, Jeffrey A., and Traber, Maret G.

Subjects
Aged -- Physiological aspects, Aged -- Psychological aspects, Cognition disorders -- Demographic aspects, Cognition disorders -- Diagnosis, Health, Seniors
Abstract

Certain micronutrients are protective against cognitive decline. We examined whether there is any uniform pattern of circulating micronutrients cross--culturally that are associated with successful cognitive aging. For the U.S. sample, we used the stored serum/plasma of 115 participants, collected in Oregon, USA. The Okinawa sample consisted of 49 participants selected using similar inclusion criteria as the Oregon sample, from the Keys to Optimal Cognitive Aging Project. All participants were aged 85 years and older without cognitive impairment. We found that the Okinawan elders used fewer vitamin supplements but had similar levels of vitamin [B.sub.12] and [alpha]-tocopherol, lower folate and [gamma]-tocopherol, compared with Oregonian elders. That is, we did not find a uniform pattern of circulating micronutrients, suggesting that micronutrients other than those examined here or other lifestyle factors than nutrition could play an important role in achieving successful cognitive aging. Key Words: Oldest old--Circulating micronutrients--Healthy cognitive aging--Okinawa--Oregon. doi: 10.1093/gerona/glq124

Published
2010

228. Predictors of normal and successful aging among urban-dwelling elderly Brazilians

Author

Chaves, Marcia Lorena, Camozzato, Ana Luiza, Eizirik, Claudio Laks, and Kaye, Jeffrey

Subjects
Aged -- Research, Aged -- Social aspects, Dementia -- Research, Danger perception -- Research, Health, Psychology and mental health, Seniors
Abstract

The association of successful aging with demographic, socioeconomic, and medical characteristics in healthy community-dwelling Brazilian individuals aged 60 years and older (N = 345) was investigated. Participants were classified as successful (n = 214, 62%) or normal (n = 131, 38%) agers. Successful agers participated in significantly more leisure activities (34%) than did normal agers (21%). Multivariate logistic regression analysis revealed that the number of living children was a risk factor, whereas confidants and family income were protective factors for successful aging. Key Words: Aging--Brazil--Community-dwelling elderly--Successful aging.

Published
2009

229. Remote Assessment and Dynamic Response Program: Development of an In-Home Dementia-Related Care Needs Assessment to Improve Well-Being.

Author

Miller, Lyndsey M, Solomon, Diane N, Whitlatch, Carol J, Hiatt, Shirin O, Wu, Chao-Yi, Reynolds, Christina, Au-Yeung, Wan-Tai Michael, Kaye, Jeffrey, and Steele, Joel S

Subjects
DEMENTIA, DIGITAL technology
Abstract

Background and Objectives The Remote Assessment and Dynamic Response (READyR) Program was developed in order to address the current lack of early-stage dementia care planning programs that assess the care needs of persons with dementia. The goal was to create a program informed by care values and ongoing ecologically valid data. The objectives of this study are to describe the development and design process of the READyR Program, and to evaluate the utility of the READyR Program for identifying dementia-related care needs. Research Design and Methods A prototype of the web-based READyR Program tool was first created using digital activity data that were collected by previous studies using a platform of multimodal sensors installed in the homes of older adult couples with and without dementia. Digital activity data were then mapped onto potential care values (e.g. safety & autonomy) to create a values-based needs assessment that is tailored to the individual care dyad. Next, evaluation of the READyR Program by 11 professional dementia care coordinators and case managers (across 3 semistructured focus groups) was used to explore the utility of READyR for assessing dementia-related needs. Qualitative description using conventional content analysis was used to iteratively code focus group data and to describe prevalent themes. Results Prevalent focus groups themes included barriers to (e.g. family relationship strain) and facilitators of (e.g. tailored assessments) the optimal process for assessing dementia-related care needs by care coordinators, as well as advantages to (e.g. providing new objective insights into function, and routines) and disadvantages of (e.g. bringing up new questions about care) incorporating the remote monitoring data into a values-based needs assessment. Discussion and Implications READyR has the potential to help family members, as well as care coordinators and providers, gain insight into the values-based care needs of persons with early-stage dementia. Clinical Trials Registration Number: NCT04542109 [ABSTRACT FROM AUTHOR]

Published
2022
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230. The Survey for Memory, Attention, and Reaction Time (SMART): Development and Validation of a Brief Web-Based Measure of Cognition for Older Adults

Author

Dorociak, Katherine E., primary, Mattek, Nora, additional, Lee, Jonathan, additional, Leese, Mira I, additional, Bouranis, Nicole, additional, Imtiaz, Danish, additional, Doane, Bridget M., additional, Bernstein, John P.K., additional, Kaye, Jeffrey A., additional, and Hughes, Adriana M., additional

Published
2021
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231. Omega-3 PUFA for Cerebral White Matter Hyperintensities, Medial Temporal Lobe Atrophy and White Matter Integrity in Older Adults:  A 3-Year Randomized-Controlled Phase 2 Trial

Author

Bowman, Gene L., primary, Murchison, Charles F., additional, Silbert, Lisa C., additional, Dodge, Hiroko H., additional, Hagen, Kirsten, additional, Lahna, David, additional, Harris, William S., additional, Kaye, Jeffrey, additional, Quinn, Joseph F., additional, and Shinto, Lynne, additional

Published
2021
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233. Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases

Author

Nakashima-Yasuda, Hanae, Uryu, Kunihiro, Robinson, John, Xie, Sharon X., Hurtig, Howard, Duda, John E., Arnold, Steven E., Siderowf, Andrew, Grossman, Murray, Leverenz, James B., Woltjer, Randy, Lopez, Oscar L., Hamilton, Ronald, Tsuang, Debby W., Galasko, Douglas, Masliah, Eliezer, Kaye, Jeffrey, Clark, Christopher M., Montine, Thomas J., Lee, Virginia M. -Y., and Trojanowski, John Q.

Published
2007
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235. Higher CSF sTREM2 attenuates ApoE4-related risk for cognitive decline and neurodegeneration

Author

Franzmeier, Nicolai, Suárez-Calvet, M., Kleinberger, Gernot, Doraiswamy, P Murali, Petrella, Jeffrey R, Arnold, Steven E, Karlawish, Jason H, Wolk, David, Smith, Charles D, Jicha, Greg, Hardy, Peter, Lopez, Oscar L, Oakley, Mary Ann, Haass, Christian, Simpson, Donna M, Ismail, M Saleem, Brand, Connie, Mulnard, Ruth A, Thai, Gaby, Mc-Adams-Ortiz, Catherine, Diaz-Arrastia, Ramon, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I, Ewers, Michael, Lah, James J, Cellar, Janet S, Burns, Jeffrey M, Anderson, Heather S, Swerdlow, Russell H, Bartzokis, George, Silverman, Daniel H S, Lu, Po H, Apostolova, Liana, Graff-Radford, Neill R, Initiative, Alzheimer’s Disease Neuroimaging, Parfitt, Francine, Johnson, Heather, Farlow, Martin, Herring, Scott, Hake, Ann M, van Dyck, Christopher H, Carson, Richard E, MacAvoy, Martha G, Chertkow, Howard, Bergman, Howard, Weiner, Michael, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Caldwell, Curtis, Hsiung, Ging-Yuek Robin, Feldman, Howard, Assaly, Michele, Kertesz, Andrew, Rogers, John, Trost, Dick, Aisen, Paul, Bernick, Charles, Munic, Donna, Wu, Chuang-Kuo, Johnson, Nancy, Mesulam, Marsel, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Raymond Scott, Johnson, Kathleen, Novak, Gerald, Reynolds, Brigid, Sperling, Reisa A, Frey, Meghan, Johnson, Keith A, Rosen, Allyson, Tinklenberg, Jared, Ashford, Wes, Sabbagh, Marwan, Belden, Christine, Jacobson, Sandra, Green, Robert C, Killiany, Ronald, Norbash, Alexander, Nair, Anil, Obisesan, Thomas O, Wolday, Saba, Bwayo, Salome K, Lerner, Alan, Hudson, Leon, Ogrocki, Paula, Fletcher, Evan, Montine, Tom, Carmichael, Owen, Kittur, Smita, Borrie, Michael, Lee, T-Y, Bartha, Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M, Potkin, Steven G, Preda, Adrian, Petersen, Ronald, Nguyen, Dana, Tariot, Pierre, Fleisher, Adam, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Hendin, Barry A, Scharre, Douglas W, Kataki, Maria, Frontzkowski, Lukas, Gamst, Anthony, Zimmerman, Earl A, Celmins, Dzintra, Brown, Alice D, Hosp, Hartford, Pearlson, Godfrey D, Blank, Karen, Anderson, Karen, Santulli, Robert B, Schwartz, Eben S, Williamson, Jeff D, Thomas, Ronald G, Sink, Kaycee M, Watkins, Franklin, Ott, Brian R, Querfurth, Henry, Tremont, Geoffrey, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J, Miller, Bruce L, Donohue, Michael, Mintzer, Jacobo, Longmire, Crystal Flynn, Spicer, Kenneth, Walter, Sarah, Gessert, Devon, Sather, Tamie, Beckett, Laurel, Harvey, Danielle, Kornak, John, Jack, Clifford R, Moore, Annah, Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, DeCarli, Charles, Jagust, William, Bandy, Dan, Hohman, Timothy J, 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, Morenas-Rodriguez, Estrella, 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, Nuscher, Brigitte, Frank, Richard, Snyder, Peter J, Molchan, Susan, Kaye, Jeffrey, Dolen, Sara, Quinn, Joseph, Schneider, Lon S, Pawluczyk, Sonia, Spann, Bryan M, Brewer, James, Shaw, Leslie, 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, Trojanowski, John Q, Morris, John C, Mintun, Mark A, Schneider, Stacy, Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, Mitsis, Effie, Romirowsky, Aliza, deToledo-Morrell, Leyla, Dichgans, Martin, Shah, Raj C, Duara, Ranjan, Varon, Daniel, Roberts, Peggy, Albert, Marilyn, Onyike, Chiadi, Kielb, Stephanie, Rusinek, Henry, de Leon, Mony J, and Glodzik, Lidia

Subjects
Male, Aging, pathology [Cognitive Dysfunction], Apolipoprotein E4, Cognitive decline, genetics [Alzheimer Disease], Neurodegenerative, lcsh:Geriatrics, Alzheimer's Disease, lcsh:RC346-429, pathology [Alzheimer Disease], Immunologic, Receptors, 80 and over, 2.1 Biological and endogenous factors, sTREM2, Microglial activation, Aetiology, Receptors, Immunologic, genetics [Apolipoprotein E4], Aged, 80 and over, Membrane Glycoproteins, pathology [Nerve Degeneration], cerebrospinal fluid [Alzheimer Disease], cerebrospinal fluid [Cognitive Dysfunction], Neurological, Female, cerebrospinal fluid [Membrane Glycoproteins], Alzheimer’s disease, Research Article, Clinical Sciences, ApoE4, Clinical Research, Alzheimer Disease, ddc:570, Acquired Cognitive Impairment, Genetics, Humans, Cognitive Dysfunction, Genetic Predisposition to Disease, Neurodegeneration, lcsh:Neurology. Diseases of the nervous system, Aged, Neurology & Neurosurgery, Neurosciences, genetics [Cognitive Dysfunction], Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer’s Disease Neuroimaging Initiative, Brain Disorders, lcsh:RC952-954.6, Nerve Degeneration, Dementia
Abstract

Background The Apolipoprotein E ε4 allele (i.e. ApoE4) is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD). TREM2 (i.e. Triggering receptor expressed on myeloid cells 2) is a microglial transmembrane protein brain that plays a central role in microglia activation in response to AD brain pathologies. Whether higher TREM2-related microglia activity modulates the risk to develop clinical AD is an open question. Thus, the aim of the current study was to assess whether higher sTREM2 attenuates the effects of ApoE4-effects on future cognitive decline and neurodegeneration. Methods We included 708 subjects ranging from cognitively normal (CN, n = 221) to mild cognitive impairment (MCI, n = 414) and AD dementia (n = 73) from the Alzheimer’s disease Neuroimaging Initiative. We used linear regression to test the interaction between ApoE4-carriage by CSF-assessed sTREM2 levels as a predictor of longitudinally assessed cognitive decline and MRI-assessed changes in hippocampal volume changes (mean follow-up of 4 years, range of 1.7-7 years). Results Across the entire sample, we found that higher CSF sTREM2 at baseline was associated with attenuated effects of ApoE4-carriage (i.e. sTREM2 x ApoE4 interaction) on longitudinal global cognitive (p = 0.001, Cohen’s f 2 = 0.137) and memory decline (p = 0.006, Cohen’s f 2 = 0.104) as well as longitudinally assessed hippocampal atrophy (p = 0.046, Cohen’s f 2 = 0.089), independent of CSF markers of primary AD pathology (i.e. Aβ1–42, p-tau181). While overall effects of sTREM2 were small, exploratory subanalyses stratified by diagnostic groups showed that beneficial effects of sTREM2 were pronounced in the MCI group. Conclusion Our results suggest that a higher CSF sTREM2 levels are associated with attenuated ApoE4-related risk for future cognitive decline and AD-typical neurodegeneration. These findings provide further evidence that TREM2 may be protective against the development of AD.

Published
2020

236. Neuropathologic features associated with basal forebrain atrophy in Alzheimer disease

Author

Teipel, Stefan J, Fritz, H-Christian, Toga, Arthur W., 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., Beckett, Laurel, 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., Green, Robert C., Porsteinsson, Anton P., Goldstein, Bonnie S., Martin, Kim, Makino, Kelly M., Ismail, M. Saleem, Brand, Connie, Mulnard, Ruth A., Thai, Gaby, Mc-Adams-Ortiz, Catherine, Womack, Kyle, Saykin, Andrew J., 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., Morris, John, 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, Liu, Enchi, 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, Hsiung, Ging-Yuek Robin, Feldman, Howard, Mudge, Benita, Assaly, Michele, Kertesz, Andrew, Rogers, John, Trost, Dick, Montine, Tom, Bernick, Charles, Munic, Donna, Kerwin, Diana, Mesulam, Marek-Marsel, Lipowski, Kristina, Wu, Chuang-Kuo, Johnson, Nancy, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Petersen, Ronald, Scott Turner, Raymond, Johnson, Kathleen, Reynolds, Brigid, Sperling, Reisa A., Johnson, Keith A., Marshall, Gad, Frey, Meghan, Yesavage, Jerome, Taylor, Joy L., Lane, Barton, Aisen, Paul, Rosen, Allyson, Tinklenberg, Jared, Sabbagh, Marwan, Belden, Christine, Jacobson, Sandra, Kowall, Neil, Killiany, Ronald, Budson, Andrew E., Norbash, Alexander, Johnson, Patricia Lynn, Grothe, Michel, Gamst, Anthony, Obisesan, Thomas O., Wolday, Saba, Bwayo, Salome K., Lerner, Alan, Hudson, Leon, Ogrocki, Paula, Fletcher, Evan, Carmichael, Owen, Olichney, John, DeCarli, Charles, Thomas, Ronald G., Kittur, Smita, Borrie, Michael, Lee, T-Y, Bartha, Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M., Potkin, Steven G., Preda, Adrian, Nguyen, Dana, Donohue, Michael, Tariot, Pierre, Fleisher, Adam, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Scharre, Douglas W., Kataki, Maria, Zimmerman, Earl A., Celmins, Dzintra, Walter, Sarah, Brown, Alice D., Pearlson, Godfrey D., Blank, Karen, Anderson, Karen, Santulli, Robert B., Schwartz, Eben S., Sink, Kaycee M., Williamson, Jeff D., Garg, Pradeep, Gessert, Devon, Watkins, Franklin, Ott, Brian R., Querfurth, Henry, Tremont, Geoffrey, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J., Miller, Bruce L., Mintzer, Jacobo, Sather, Tamie, Longmire, Crystal Flynn, Spicer, Kenneth, Finger, Elizabether, Rachinsky, Irina, 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, Raj, Balebail Ashok, Harvey, Danielle, Initiative, Alzheimer's Disease Neuroimaging, Kornak, John, Jack, Clifford R., Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, Weiner, Michael, Jagust, William, Bandy, Dan, Koeppe, Robert A., Foster, Norm, Reiman, Eric M., Chen, Kewei, Mathis, Chet, Cairns, Nigel J., Taylor-Reinwald, Lisa, Trojanowki, J. Q., Shaw, Les, Lee, Virginia M Y, Korecka, Magdalena, Crawford, Karen, 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, Trojanowki, John Q., Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, Mitsis, Effie, Romirowsky, Aliza, deToledo-Morrell, Leyla, Shah, Raj C., Duara, Ranjan, Varon, Daniel, Instituto de Salud Carlos III, European Commission, and Ministerio de Ciencia, Innovación y Universidades (España)

Subjects
0301 basic medicine, Male, medicine.medical_specialty, Multivariate analysis, diagnostic imaging [Basal Forebrain], Basal Forebrain, pathology [Basal Forebrain], Logistic regression, Article, 03 medical and health sciences, pathology [Alzheimer Disease], 0302 clinical medicine, Atrophy, Alzheimer Disease, Internal medicine, Ischaemic stroke, Medicine, Humans, ddc:610, Stroke, Cost implications, Aged, Aged, 80 and over, pathology [Atrophy], business.industry, medicine.disease, Magnetic Resonance Imaging, 030104 developmental biology, Charlson comorbidity index, Female, Neurology (clinical), Alzheimer's disease, business, diagnostic imaging [Alzheimer Disease], 030217 neurology & neurosurgery
Abstract

Alzheimer's Disease Neuroimaging Initiative., [Objective] To study the neuropathologic correlates of cholinergic basal forebrain (BF) atrophy as determined using antemortem MRI in the Alzheimer disease (AD) spectrum., [Methods] We determined associations between BF volume from antemortem MRI brain scans and postmortem assessment of neuropathologic features, including neuritic plaques, neurofibrillary tangles (NFTs), Lewy body (LB) pathology, and TDP-43, in 64 cases of the Alzheimer's Disease Neuroimaging Initiative cohort. For comparison, we assessed neuropathologic features associated with hippocampal and parahippocampal gyrus atrophy. In addition to region of interest–based analysis, we determined the association of neuropathologic features with whole brain gray matter volume using regionally unbiased voxel-based volumetry., [Results] BF atrophy was associated with Thal amyloid phases (95% confidence interval [CI] −0.49 to −0.01, p = 0.049) and presence of LB pathology (95% CI −0.54 to −0.06, p = 0.015), as well as with the degree of LB pathology within the nucleus basalis Meynert (95% CI −0.54 to −0.07, p = 0.025). These effects were no longer significant after false discovery rate (FDR) correction. Hippocampal atrophy was significantly associated with the presence of TDP-43 pathology (95% CI −0.61 to −0.17, p = 0.003; surviving FDR correction), in addition to dentate gyrus NFT load (95% CI −0.49 to −0.01, p = 0.044; uncorrected). Voxel-based analysis confirmed spatially restricted effects of Thal phases and presence of LB pathology on BF volume., [Conclusions] These findings indicate that neuropathologic correlates of regional atrophy differ substantially between different brain regions that are typically involved in AD-related neurodegeneration, including different susceptibilities to common comorbid pathologies., M.J.G. is supported by the “Miguel Servet” program [CP19/00031] of the Spanish Instituto de Salud Carlos III (ISCIII-FEDER).

Published
2020

237. The genetic architecture of the human cerebral cortex

Author

Grasby, Katrina L, Jahanshad, Neda, Shatokhina, Natalia, Mirza-Schreiber, Nazanin, Moreira, Jose C V, Mühleisen, Thomas W, Müller-Myhsok, Bertram, Najt, Pablo, Nakahara, Soichiro, Nho, Kwangsik, Olde Loohuis, Loes M, Orfanos, Dimitri Papadopoulos, Pearson, John F, Zsembik, Leo C P, Pitcher, Toni L, Pütz, Benno, Quidé, Yann, Ragothaman, Anjanibhargavi, Rashid, Faisal M, Reay, William R, Redlich, Ronny, Reinbold, Céline S, Repple, Jonathan, Richard, Geneviève, Thomopoulos, Sophia I, Riedel, Brandalyn C, Risacher, Shannon L, Rocha, Cristiane S, Mota, Nina Roth, Salminen, Lauren, Saremi, Arvin, Saykin, Andrew J, Schlag, Fenja, Schmaal, Lianne, Schofield, Peter R, Zhu, Alyssa H, Secolin, Rodrigo, Shapland, Chin Yang, Shen, Li, Shin, Jean, Shumskaya, Elena, Sønderby, Ida E, Sprooten, Emma, Tansey, Katherine E, Teumer, Alexander, Thalamuthu, Anbupalam, Strike, Lachlan T, Tordesillas-Gutiérrez, Diana, Turner, Jessica A, Uhlmann, Anne, Vallerga, Costanza Ludovica, van der Meer, Dennis, van Donkelaar, Marjolein M J, van Eijk, Liza, van Erp, Theo G M, van Haren, Neeltje E M, van Rooij, Daan, Agartz, Ingrid, van Tol, Marie-José, Veldink, Jan H, Verhoef, Ellen, Walton, Esther, Wang, Mingyuan, Wang, Yunpeng, Wardlaw, Joanna M, Wen, Wei, Westlye, Lars T, Whelan, Christopher D, Alhusaini, Saud, Witt, Stephanie H, Wittfeld, Katharina, Wolf, Christiane, Wolfers, Thomas, Wu, Jing Qin, Yasuda, Clarissa L, Zaremba, Dario, Zhang, Zuo, Zwiers, Marcel P, Artiges, Eric, Almeida, Marcio A A, Assareh, Amelia A, Ayesa-Arriola, Rosa, Belger, Aysenil, Brandt, Christine L, Brown, Gregory G, Cichon, Sven, Curran, Joanne E, Davies, Gareth E, Degenhardt, Franziska, Dennis, Michelle F, Alnæs, Dag, Dietsche, Bruno, Djurovic, Srdjan, Doherty, Colin P, Espiritu, Ryan, Garijo, Daniel, Gil, Yolanda, Gowland, Penny A, Green, Robert C, Häusler, Alexander N, Heindel, Walter, Amlien, Inge K, Ho, Beng-Choon, Hoffmann, Wolfgang U, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Jack, Clifford R, Jang, MiHyun, Jansen, Andreas, Kimbrel, Nathan A, Kolskår, Knut, Painter, Jodie N, Andersson, Micael, Koops, Sanne, Krug, Axel, Lim, Kelvin O, Luykx, Jurjen J, Mathalon, Daniel H, Mather, Karen A, Mattay, Venkata S, Matthews, Sarah, Mayoral Van Son, Jaqueline, McEwen, Sarah C, Ard, Tyler, Melle, Ingrid, Morris, Derek W, Mueller, Bryon A, Nauck, Matthias, Nordvik, Jan E, Nöthen, Markus M, O'Leary, Daniel S, Opel, Nils, Martinot, Marie-Laure Paillère, Pike, G Bruce, Armstrong, Nicola J, Preda, Adrian, Quinlan, Erin B, Rasser, Paul E, Ratnakar, Varun, Reppermund, Simone, Steen, Vidar M, Tooney, Paul A, Torres, Fábio R, Veltman, Dick J, Voyvodic, James T, Ashley-Koch, Allison, Whelan, Robert, White, Tonya, Yamamori, Hidenaga, Adams, Hieab H H, Bis, Joshua C, Debette, Stephanie, Decarli, Charles, Fornage, Myriam, Gudnason, Vilmundur, Hofer, Edith, Atkins, Joshua R, Ikram, M Arfan, Launer, Lenore, Longstreth, W. 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Marissa Natelson, Ikeda, Masashi, Mintun, Mark A, Frasier, Mark, Logue, Mark, Minton, Mark, Loeffler, Markus, Scholz, Markus, Baca, Marne, Farlow, Martin R, Sadowski, Martin, Janowitz, Deborah, Creech, Mary L, Hynes, Mary L, Quiceno, Mary, Oakley, MaryAnn, Harris, Mat, Senjem, Matt, Bernstein, Matthew, Panizzon, Matthew S, Stern, Matthew, Becerra, Mauricio, Jansen, Iris E, Witbracht, Megan, Vernooij, Meike W, Brandabur, Melanie, Keltz, Melanie, Lamar, Melissa, Yang, Mia, Ahlijanian, Michael, Borrie, Michael, Neale, Michael C, Donohue, Michael, Jia, Tianye, Lyons, Michael J, Lin, Michael, Rapp, Michael, Smolka, Michael, Weiner, Michael W, Weiner, Michael, Figurski, Michal, Perron, Michel, Assaly, Michele, Luciano, Michelle, Jockwitz, Christiane, Rainka, Michelle, Dang, Mimi, Sheikh, Mohammed O, Ghanbari, Mohsen, Gaikwad, Mrunalini, Chowdhury, Munir, Trncic, Nadira, Amin, Najaf, Johnson, Nancy, Kanai, Ryota, Kowalksi, Nancy, Monahan, Nancy, Gillespie, Nathan A, Pacini, Nathaniel, 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Silverstein, Rebecca, Sperling, Reisa A, Wilson, Renee, Carson, Richard E, Frank, Richard, El Khouli, Riham, Koeppe, Robert A, Santulli, Robert B, Knapp, Michael, Hauser, Robert, Umek, Robert, Radtke, Rodney, Killiany, Ronald, Petersen, Ronald, Rodriguez, Rosemarie, Miranda, Ruben, Knodt, Annchen R, Bruehl, Ruediger, Xia, Rui, Swerdlow, Russell H, Ottmann, Ruth, Millenet, Sabina, Borges-Neto, Salvador, Frank, Samuel, Black, Sandra, Weintraub, Sandra, Obradov, Sanja, Krämer, Bernd, Asthana, Sanjay, Vaishnavi, Sanjeev, Dolen, Sara, Mason, Sara S, Hohmann, Sarah, Kremen, Sarah, Miller, Sarah, Walter, Sarah, Herring, Scott, Neu, Scott, Lam, Max, Aydin, Semiha, Ahmad, Shahzad, Harlan, Sherry, Sirrel, Sherye A, Lasch, Shirley, Hu, Shu-Ching, Li, Shuo, Kittur, Smita, Chowdhury, Sohini, Lancaster, Thomas M, Pawluczyk, Sonia, Maingault, Sophie, Schneider, Stacy, Seiler, Stephan, Guthrie, Stephanie, Kielb, Stephanie, Reeder, Stephanie, Correia, Stephen, Pasternak, Stephen, McMahon, Mary Agnes B, Lee, Phil H, Salloway, Stephen, Johnson, Sterling, Williams, Steve, Chao, Steven, Arnold, Steven E, Paul, Steven, Potkin, Steven, Factor, Stewart, Isaacson, Stuart, Lett, Tristram A, Kim, Sungeun, Ainscough, Susan, Schultz, Susan K, Landau, Susan, Mendick, Susan, Rountree, Susan, Ostrowizki, Suzanne, Veillette, Suzanne, van der Lee, Sven J, Desrivieres, Sylvane, Lewis, Lindsay B, Lee, T-Y, Simuni, Tanya, Foroud, Tatiana, Foroud, Tatiana M, Wong, Terence Z, Villena, Teresa, Comery, Thomas, Obisesan, Thomas O, Lopes-Cendes, Iscia, Banaschewski, Tobias, Sherer, Todd, Montine, Tom, Paus, Tomáš, Robbins, Trevor, Bromberg, Uli, Völker, Uwe, Pavlik, Valory, Arnedo, Vanessa, Kiyasova, Vera, Bates, Vernice, Logovinsky, Veronika, Sossi, Vesna, Shibley, Victoria, Frouin, Vincent, Lee, Virginia, Poewe, Werner, Jagust, William, Brooks, William M, Macciardi, Fabio, Pavlosky, William, Potter, William, Kremen, William S, Longstreth, William T, Niessen, Wiro J, Jian, Xueqiu, Stern, Yaakov, Saba, Yasaman, Cabrera, Yuliana, Grimmer, Yvonne, Marquand, Andre F, Khachaturian, Zaven, Mari, Zoltan, Mathias, Samuel R, Melzer, Tracy R, Milaneschi, Yuri, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Movement Disorder (MD), Alzheimer’s Disease Neuroimaging Initiative, CHARGE Consortium, EPIGEN Consortium, IMAGEN Consortium, SYS Consortium, Parkinson’s Progression Markers Initiative, Stochastics, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, Science and Society, Cognitive Psychology, IBBA, APH - Personalized Medicine, Complex Trait Genetics, APH - Methodology, Clinical Neuropsychology, Sociology and Social Gerontology, Amsterdam Neuroscience - Complex Trait Genetics, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, Klinische Genetica, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA Klinische Genetica (5), Neurology, Psychiatry, Pediatric surgery, Amsterdam Reproduction & Development (AR&D), Human genetics, APH - Digital Health, Psychology, Precision Medicine Institute of Psychiatry, Child and Adolescent Psychiatry / Psychology, Radiology & Nuclear Medicine, Clinical Genetics, Epidemiology, Medical Informatics, Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Neurodegeneratives Diseases Institute (IMN-UMR CNRS 5293), Centre National de la Recherche Scientifique (CNRS), General Paediatrics, ARD - Amsterdam Reproduction and Development, Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), [SDV]Life Sciences [q-bio], LOCI, Genome-wide association study, Brain mapping, 0302 clinical medicine, Cognition, Cortex (anatomy), ComputingMilieux_MISCELLANEOUS, Cerebral Cortex, 0303 health sciences, Brain Mapping, Multidisciplinary, COMMON VARIANTS, Parkinson Disease, Organ Size, Central sulcus, Magnetic Resonance Imaging, medicine.anatomical_structure, Cerebral cortex, Neuroinformatics, EXPRESSION, endocrine system, central sulcus, SURFACE-AREA, Biology, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Genetic variation, medicine, Attention deficit hyperactivity disorder, Humans, General, Gene, METAANALYSIS, 030304 developmental biology, Progenitor, CORTICAL SULCI, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Genetic variants, Genetic Variation, Attention Deficit Disorder with Hyperactivity, Genetic Loci, Genome-Wide Association Study, functional annotation, medicine.disease, Genetic architecture, 030104 developmental biology, Evolutionary biology, OBSERVER-INDEPENDENT CHARACTERIZATION, Multiple comparisons problem, ddc:320, genome-wide association, Neuroscience, 030217 neurology & neurosurgery
Abstract

Enhancing NeuroImaging Genetics through Meta-Analysis Consortium (ENIGMA)—Genetics working group., The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.

Published
2020

238. Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins

Author

Ray, Sandip, Britschgi, Markus, Herbert, Charles, Takeda-Uchimura, Yoshiko, Boxer, Adam, Blennow, Kaj, Friedman, Leah F, Galasko, Douglas R, Jutel, Marek, Karydas, Anna, Kaye, Jeffrey A, Leszek, Jerzy, Miller, Bruce L, Minthon, Lennart, Quinn, Joseph F, Rabinovici, Gil D, Robinson, William H, Sabbagh, Marwan N, So, Yuen T, Sparks, D Larry, Tabaton, Massimo, Tinklenberg, Jared, Yesavage, Jerome A, Tibshirani, Robert, and Wyss-Coray, Tony

Abstract

Author(s): Sandip Ray [1, 16]; Markus Britschgi [2, 16]; Charles Herbert [1]; Yoshiko Takeda-Uchimura [2]; Adam Boxer [3]; Kaj Blennow [4]; Leah F Friedman [5]; Douglas R Galasko [6]; Marek [...]

Published
2007
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239. Genome-wide association analysis of hippocampal volume identifies enrichment of neurogenesis-related pathways

Author

Horgusluoglu-Moloch, Emrin, Risacher, Shannon L., Crane, Paul K., Hibar, Derrek, Thompson, Paul M., Saykin, Andrew J., Nho, Kwangsik, Weiner, Michael W., Aisen, Paul, Petersen, Ronald, Jack, Clifford R., Jagust, William, Trojanowki, John Q., Toga, Arthur W., Beckett, Laurel, Green, Robert C., Morris, John, Shaw, Leslie M., Kaye, Jeffrey, Quinn, Joseph, Silbert, Lisa, Lind, Betty, Carter, Raina, Dolen, Sara, Schneider, Lon S., Pawluczyk, Sonia, Beccera, Mauricio, Teodoro, Liberty, Spann, Bryan M., Brewer, James, Vanderswag, Helen, and Fleisher, Adam

Subjects
Male, Aging, Activin Receptors, Type I, Hippocampus, lcsh:Medicine, Genome-wide association study, Hippocampal formation, Adult neurogenesis, Genome-wide association studies, 0302 clinical medicine, Cognition, 2.1 Biological and endogenous factors, Aetiology, lcsh:Science, Neurons, 0303 health sciences, Multidisciplinary, Neurogenesis, Cell Differentiation, Organ Size, Phenotype, Mental Health, Neurological, Female, Signal Transduction, Dipeptidyl Peptidase 4, Biology, Article, Biological pathway, 03 medical and health sciences, Neuroimaging, Alzheimer Disease, Genetics, Humans, Genetic Predisposition to Disease, 030304 developmental biology, Aged, Dentate gyrus, lcsh:R, Human Genome, Calcium-Binding Proteins, Neurosciences, Alzheimer’s Disease Neuroimaging Initiative, Stem Cell Research, Brain Disorders, Gene Expression Regulation, Methionine Sulfoxide Reductases, Dentate Gyrus, lcsh:Q, Neuroscience, Activin Receptors, Type I, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Adult neurogenesis occurs in the dentate gyrus of the hippocampus during adulthood and contributes to sustaining the hippocampal formation. To investigate whether neurogenesis-related pathways are associated with hippocampal volume, we performed gene-set enrichment analysis using summary statistics from a large-scale genome-wide association study (N = 13,163) of hippocampal volume from the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium and two year hippocampal volume changes from baseline in cognitively normal individuals from Alzheimer’s Disease Neuroimaging Initiative Cohort (ADNI). Gene-set enrichment analysis of hippocampal volume identified 44 significantly enriched biological pathways (FDR corrected p-value TESC, ACVR1, MSRB3, and DPP4 as significantly associated with hippocampal volume. Furthermore, co-expression network-based functional analysis of gene expression data in the hippocampal subfields, CA1 and CA3, from 32 normal controls showed that distinct co-expression modules were mostly enriched in neurogenesis related pathways. Our results suggest that neurogenesis-related pathways may be enriched for hippocampal volume and that hippocampal volume may serve as a potential phenotype for the investigation of human adult neurogenesis.

Published
2019

240. Dementia-free survival among centenarians: an evidence-based review

Author

Calvert, James F., Jr., Hollander-Rodriguez, Joyce, Kaye, Jeffrey, and Leahy, Marjorie

Subjects
Centenarians -- Health aspects, Centenarians -- Research, Dementia -- Prevention, Dementia -- Research, Gerontology -- Research, Health, Seniors
Abstract

Background. The 2000 U.S. census identified 50,454 Americans older than 100 years (18 per 100,000). Increased longevity is only of benefit if accompanied by the maintenance of physical, social, and cognitive function into advanced age. The goal of this review was to identify research describing centenarians to find the prevalence of dementia-free survival. Methods. We reviewed 650 publications to find studies that described the prevalence of dementia in centenarians, were community-based, had data that were specific to persons older than 100 years, and were published in peer-reviewed journals. For each study, we identified the prevalence of dementia, the completeness of the sample, the number of study participants, the method used to diagnose dementia, and the duration of the study. Results. We identified 20 research groups from 14 countries with publications meeting our search criteria. The studies showed substantial variation in methods of assessing cognitive status, assuring a complete cohort, and sample size. Few studies reported longitudinal data or attempted diagnosis of the cause of dementia. The prevalence of dementia-flee survival past 100 years of age varied between 0 and 50 percent. Conclusions. The methodology used in studies regarding dementia prevalence among centenarians is sufficiently varied that combination of existing studies into a meta-analysis is not possible. Suggestions for assuring quality in future centenarian research are presented.

Published
2006

242. Vitamin E and donepezil for the treatment of mild cognitive impairment

Author

Petersen, Ronald C., Thomas, Ronald G., Grudman, Michael, Galasko, Douglas, Kaye, Jeffrey, Doody, Rachelle, Sano, Mary, Ferris, Steven, Dyck, Christopher H. van, Bennet, David, Jin, Shelia, Levey, Allan, Thal, Leon J., and Pfeiffer, Eric

Subjects
Vitamin E -- Dosage and administration, Cognition disorders -- Care and treatment
Abstract

Subjects were randomly assigned to receive 2000 IU of vitamin E daily, 10 mg of donepezil daily or placebo for three years and were evaluated with the amnestic subtype of mild cognitive impairment. The findings indicate that vitamin E had no benefit in patients with mild cognitive impairment and the rate of progression to Alzheimer's disease after three years was not lower among patients treated with donepezil than among those given placebo.

Published
2005

250. Effects of omega‐3 fatty acids on cerebral white matter hyperintensities and medial temporal lobe atrophy in older non‐demented adults: A 3‐year randomized‐controlled phase 2 trial

Author

Bowman, Gene L, primary, Silbert, Lisa C, additional, Dodge, Hiroko H, additional, Hagen, Kirsten, additional, David, Jason C, additional, Murchison, Charles F, additional, Lahna, David, additional, Kaye, Jeffrey, additional, Quinn, Joseph F, additional, and Shinto, Lynne, additional

Published
2020
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