"Shah, Raj" / Search Limiters: Full Text / Topic: aging - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Shah, Raj"' showing total 17 results

Start Over "Shah, Raj" Search Limiters Full Text Topic aging

17 results on '"Shah, Raj"'

1. Impact of Cognitive Impairment Across Specialties: Summary of a Report From the U13 Conference Series

Author: Carpenter, Christopher R, McFarland, Frances, Avidan, Michael, Berger, Miles, Inouye, Sharon K, Karlawish, Jason, Lin, Frank R, Marcantonio, Edward, Morris, John C, Reuben, David B, Shah, Raj C, Whitson, Heather E, Asthana, Sanjay, and Verghese, Joe
Subjects: Health Services and Systems, Health Sciences, Brain Disorders, Aging, Dementia, Alzheimer's Disease, Acquired Cognitive Impairment, Neurodegenerative, Behavioral and Social Science, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Mental health, Good Health and Well Being, Alzheimer Disease, Biomarkers, Biomedical Research, Cognitive Dysfunction, Datasets as Topic, Delirium, Ethics Committees, Research, Ethics, Research, Humans, Interdisciplinary Research, Interprofessional Relations, Mental Competency, Research Subjects, delirium, dementia, interdisciplinary research, research ethics, Medical and Health Sciences, Geriatrics, Biomedical and clinical sciences, Health sciences, Psychology
Abstract: Although declines in cognitive capacity are assumed to be a characteristic of aging, increasing evidence shows that it is age-related disease, rather than age itself, that causes cognitive impairment. Even so, older age is a primary risk factor for cognitive decline, and with individuals living longer as a result of medical advances, cognitive impairment and dementia are increasing in prevalence. On March 26 to 27, 2018, the American Geriatrics Society convened a conference in Bethesda, MD, to explore cognitive impairment across the subspecialties. Bringing together representatives from several subspecialties, this was the third of three conferences, supported by a U13 grant from the National Institute on Aging, to aid recipients of Grants for Early Medical/Surgical Specialists' Transition to Aging Research (GEMSSTAR) in integrating geriatrics into their subspecialties. Scientific sessions focused on the impact of cognitive impairment, sensory contributors, comorbidities, links between delirium and dementia, and issues of informed consent in cognitively impaired populations. Discussions highlighted the complexity not only of cognitive health itself, but also of the bidirectional relationship between cognitive health and the health of other organ systems. Thus, conference participants noted the importance of multidisciplinary team science in future aging research. This article summarizes the full conference report, "The Impact of Cognitive Impairment Across Specialties," and notes areas where GEMSSTAR scholars can contribute to progress as they embark on their careers in aging research. J Am Geriatr Soc 67:2011-2017, 2019.
Published: 2019

2. Willingness to Be a Brain Donor

Author: Boise, Linda, Hinton, Ladson, Rosen, Howard J, Ruhl, Mary C, Dodge, Hiroko, Mattek, Nora, Albert, Marilyn, Denny, Andrea, Grill, Joshua D, Hughes, Travonia, Lingler, Jennifer H, Morhardt, Darby, Parfitt, Francine, Peterson-Hazan, Susan, Pop, Viorela, Rose, Tara, and Shah, Raj C
Subjects: Biomedical and Clinical Sciences, Biological Psychology, Clinical Sciences, Neurosciences, Psychology, Acquired Cognitive Impairment, Alzheimer's Disease, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Clinical Research, Neurodegenerative, Dementia, Aging, Brain Disorders, Neurological, Aged, Autopsy, Biomedical Research, Brain, Ethnicity, Female, Health Knowledge, Attitudes, Practice, Humans, Male, Racial Groups, Surveys and Questionnaires, Tissue Donors, Volunteers, Cognitive Sciences, Geriatrics, Clinical sciences, Biological psychology
Abstract: IntroductionRacial and ethnic groups are under-represented among research subjects who assent to brain donation in Alzheimer disease research studies. There has been little research on this important topic. Although there are some studies that have investigated the barriers to brain donation among African American study volunteers, there is no known research on the factors that influence whether or not Asians or Latinos are willing to donate their brains for research.MethodsAfrican American, Caucasian, Asian, and Latino research volunteers were surveyed at 15 Alzheimer Disease Centers to identify predictors of willingness to assent to brain donation.ResultsPositive predictors included older age, Latino ethnicity, understanding of how the brain is used by researchers, and understanding of what participants need to do to ensure that their brain will be donated. Negative predictors included African/African American race, belief that the body should remain whole at burial, and concern that researchers might not be respectful of the body during autopsy.DiscussionThe predictive factors identified in this study may be useful for researchers seeking to increase participation of diverse ethnic groups in brain donation.
Published: 2017

3. Brain amyloidosis ascertainment from cognitive, imaging, and peripheral blood protein measures

Author: Apostolova, Liana G, Hwang, Kristy S, Avila, David, Elashoff, David, Kohannim, Omid, Teng, Edmond, Sokolow, Sophie, Jack, Clifford R, Jagust, William J, Shaw, Leslie, Trojanowski, John Q, Weiner, Michael W, Thompson, Paul M, Weiner, Michael, Aisen, Paul, Petersen, Ronald, Jagust, Wiliam, Trojanowki, JQ, Toga, Arthur W, Beckett, Laurel, Green, Robert C, Gamst, Anthony, Sakin, Andrew J, Morris, John, Potter, William Z, Montine, Tom, Donohue, Michael, Walter, Sarah, Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, DeCarli, Charles, Bandy, Dan, Koeppe, Robert A, Foster, Norm, Reiman, Eric M, Chen, Kewei, Mathis, Chet, Cairns, Nigel J, Taylor-Reinwald, Lisa, Shaw, Lee, Lee, Virginia M-Y, Korecka, Magdalena, Crawford, Karen, Neu, Scott, Harvey, Danielle, Kornak, John, Foroud, Tatiana M, Potkin, Steven, Shen, Li, Kachaturian, Zaven, Frank, Richard, Snyder, Peter J, Molchan, Susan, Kaye, Jeffrey, Dolen, Sara, Quinn, Joseph, Schneider, Lon, 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, Mintun, Mark A, Schneider, Stacy, Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, Tang, Cheuk, Marzloff, George, deToledo-Morrell, Leyla, Shah, Raj C, Duara, Ranjan, Varon, Daniel, Robers, Peggy, Albert, Marilyn S, Kozauer, Nicholas, Zerrate, Maria, Rusinek, Henry, de Leon, Mony J, De Santi, Susan M, Doraiswamy, P Murali, Petrella, Jeffrey R, Aiello, Marilyn, Arnold, Steve, and Karlawish, Jason H
Subjects: Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Biomedical Imaging, Aging, Behavioral and Social Science, Clinical Research, Alzheimer's Disease, Acquired Cognitive Impairment, Brain Disorders, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, 4.2 Evaluation of markers and technologies, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Neurological, Aged, Algorithms, Alzheimer Disease, Amyloid beta-Peptides, Amyloidosis, Aniline Compounds, Biomarkers, Brain, Cognition, Cognitive Dysfunction, Cohort Studies, Databases, Factual, Disease Progression, Female, Humans, Male, Neuropsychological Tests, Pattern Recognition, Automated, Peptide Fragments, Positron-Emission Tomography, Sensitivity and Specificity, Thiazoles, Alzheimer's Disease Neuroimaging Initiative, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract: BackgroundThe goal of this study was to identify a clinical biomarker signature of brain amyloidosis in the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) mild cognitive impairment (MCI) cohort.MethodsWe developed a multimodal biomarker classifier for predicting brain amyloidosis using cognitive, imaging, and peripheral blood protein ADNI1 MCI data. We used CSF β-amyloid 1-42 (Aβ42) ≤ 192 pg/mL as proxy measure for Pittsburgh compound B (PiB)-PET standard uptake value ratio ≥ 1.5. We trained our classifier in the subcohort with CSF Aβ42 but no PiB-PET data and tested its performance in the subcohort with PiB-PET but no CSF Aβ42 data. We also examined the utility of our biomarker signature for predicting disease progression from MCI to Alzheimer dementia.ResultsThe CSF training classifier selected Mini-Mental State Examination, Trails B, Auditory Verbal Learning Test delayed recall, education, APOE genotype, interleukin 6 receptor, clusterin, and ApoE protein, and achieved leave-one-out accuracy of 85% (area under the curve [AUC] = 0.8). The PiB testing classifier achieved an AUC of 0.72, and when classifier self-tuning was allowed, AUC = 0.74. The 36-month disease-progression classifier achieved AUC = 0.75 and accuracy = 71%.ConclusionsAutomated classifiers based on cognitive and peripheral blood protein variables can identify the presence of brain amyloidosis with a modest level of accuracy. Such methods could have implications for clinical trial design and enrollment in the near future.Classification of evidenceThis study provides Class II evidence that a classification algorithm based on cognitive, imaging, and peripheral blood protein measures identifies patients with brain amyloid on PiB-PET with moderate accuracy (sensitivity 68%, specificity 78%).
Published: 2015

4. Dementia Prevention: optimizing the use of observational data for personal, clinical, and public health decision-making.

Author: Dacks, Penny A, Andrieu, Sandrine, Blacker, Deborah, Carman, Aaron J, Green, Allan M, Grodstein, Francine, Henderson, Victor W, James, Bryan D, Lane, Rachel F, Lau, Joseph, Lin, Pei-Jung, Reeves, Barnaby C, Shah, Raj C, Vellas, Bruno, Yaffe, Kristine, Yurko-Mauro, Karin, Shineman, Diana W, Bennett, David A, and Fillit, Howard M
Subjects: Biomedical and Clinical Sciences, Biological Psychology, Cognitive and Computational Psychology, Neurosciences, Psychology, Nutrition, Alzheimer's Disease, Brain Disorders, Dementia, Acquired Cognitive Impairment, Behavioral and Social Science, Aging, Neurodegenerative, Clinical Research, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Comparative Effectiveness Research, Prevention, Clinical Trials and Supportive Activities, 7.3 Management and decision making, Management of diseases and conditions, Neurological, Good Health and Well Being, Alzheimer’s, communication, low-risk, non-randomized studies, primary prevention, Biological psychology, Cognitive and computational psychology
Abstract: Worldwide, over 35 million people suffer from Alzheimer's disease and related dementias. This number is expected to triple over the next 40 years. How can we improve the evidence supporting strategies to reduce the rate of dementia in future generations? The risk of dementia is likely influenced by modifiable factors such as exercise, cognitive activity, and the clinical management of diabetes and hypertension. However, the quality of evidence is limited and it remains unclear whether specific interventions to reduce these modifiable risk factors can, in turn, reduce the risk of dementia. Although randomized controlled trials are the gold-standard for causality, the majority of evidence for long-term dementia prevention derives from, and will likely continue to derive from, observational studies. Although observational research has some unavoidable limitations, its utility for dementia prevention might be improved by, for example, better distinction between confirmatory and exploratory research, higher reporting standards, investment in effectiveness research enabled by increased data-pooling, and standardized exposure and outcome measures. Informed decision-making by the general public on low-risk health choices that could have broad potential benefits could be enabled by internet-based tools and decision-aids to communicate the evidence, its quality, and the estimated magnitude of effect.
Published: 2014

5. Vascular burden and Alzheimer disease pathologic progression

Author: Lo, Raymond Y, Jagust, William J, Weiner, Michael, Aisen, Paul, Petersen, Ronald, Jack, Clifford R, Jagust, William, Trojanowki, John Q, Toga, Arthur W, Beckett, Laurel, Green, Robert C, Saykin, Andrew J, Morris, John, Liu, Enchi, Montine, Tom, Gamst, Anthony, Thomas, Ronald G, Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Harvey, Danielle, Kornak, John, Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, DeCarli, Charles, Bandy, Dan, Koeppe, Robert A, Foster, Norm, Reiman, Eric M, Chen, Kewei, Mathis, Chet, Cairns, Nigel J, Taylor-Reinwald, Lisa, Trojanowki, JQ, Shaw, Les, Lee, Virginia MY, 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, Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, Mitsis, Effie, Romirowsky, Aliza, deToledo-Morrell, Leyla, Shah, Raj C, Duara, Ranjan, and Varon, Daniel
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Aging, Biomedical Imaging, Dementia, Brain Disorders, Clinical Research, Vascular Cognitive Impairment/Dementia, Alzheimer's Disease, Neurosciences, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Neurological, Cardiovascular, Aged, Alzheimer Disease, Atrophy, Brain, Cognitive Dysfunction, Disease Progression, Female, Genotype, Humans, Leukoencephalopathies, Longitudinal Studies, Magnetic Resonance Imaging, Male, Positron-Emission Tomography, Alzheimer's Disease Neuroimaging Initiative, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract: ObjectiveTo investigate the vascular contribution to longitudinal changes in Alzheimer disease (AD) biomarkers.MethodsThe Alzheimer's Disease Neuroimaging Initiative is a clinic based, longitudinal study with CSF, PET, and MRI biomarkers repeatedly measured in participants with normal cognition (NC), mild cognitive impairment (MCI), and mild AD. Participants with severe cerebrovascular risks were excluded. Cardiovascular risk scores and MRI white matter hyperintensities (WMHs) were treated as surrogate markers for vascular burden. Generalized estimating equations were applied, and both vascular burden and its interaction with time (vascular burden × time) or time-varying WMHs were entered into regression models to assess whether biomarker rates of change were modified by vascular burden.ResultsCardiovascular risk profiles were not predictive of progression in CSF β₄₂-amyloid, [¹⁸F]fluorodeoxyglucose (FDG) PET uptake, and MRI hippocampal atrophy. Greater baseline cardiovascular risks or WMHs were generally associated with cognitive impairment, particularly poor executive function. WMHs increased over time with a faster rate in MCI and AD than in NC. Increased time-varying WMH was associated with faster decline in executive function and lower FDG uptake in NC. Otherwise, WMH was not associated with CSF and MRI biomarkers in the 3 groups. These findings remained unchanged after accounting for APOE4.ConclusionIncreased WMHs are associated with aging, decreased glucose metabolism, and decline in executive function but do not affect AD-specific pathologic progression, suggesting that the vascular contribution to dementia is probably additive although not necessarily independent of the amyloid pathway.
Published: 2012

6. Glucose metabolism patterns: A potential index to characterize brain ageing and predict high conversion risk into cognitive impairment

Author: Jiang, Jiehui, Sheng, Can, Aisen, Paul, Dang, Mimi, Stern, Yaakov, Honig, Lawrence S, Bell, Karen L, Ances, Beau, Carroll, Maria, Leon, Sue, Mintun, Mark A, Schneider, Stacy, Oliver, Angela, Petersen, Ronald, Marson, Daniel, Griffith, Randall, Clark, David, Geldmacher, David, Brockington, John, Roberson, Erik, Grossman, Hillel, Mitsis, Effie, de Toledo-Morrell, Leyla, Shah, Raj C, Jack, Clifford R, Duara, Ranjan, Varon, Daniel, Greig, Maria T, Roberts, Peggy, Onyike, Chiadi, D'Agostino, Daniel, Kielb, Stephanie, Galvin, James E, Cerbone, Brittany, Michel, Christina A, Jagust, William, Rusinek, Henry, de Leon, Mony J, Glodzik, Lidia, De Santi, Susan, Murali Doraiswamy, P., Petrella, Jeffrey R, Wong, Terence Z, Arnold, Steven E, Karlawish, Jason H, Wolk, David, Trojanowski, John Q, Smith, Charles D, Jicha, Greg, Hardy, Peter, Sinha, Partha, Oates, Elizabeth, Conrad, Gary, Lopez, Oscar L, Oakley, MaryAnn, Simpson, Donna M, Porsteinsson, Anton P, Toga, Arthur W, Goldstein, Bonnie S, Martin, Kim, Makino, Kelly M, Saleem Ismail, M., Brand, Connie, Mulnard, Ruth A, Thai, Gaby, McAdams-Ortiz, Catherine, Womack, Kyle, Mathews, Dana, Beckett, Laurel, Quiceno, Mary, Diaz-Arrastia, Ramon, King, Richard, Weiner, Myron, Martin-Cook, Kristen, DeVous, Michael, I Levey, Allan, Lah, James J, Cellar, Janet S, Burns, Jeffrey M, Green, Robert C, Anderson, Heather S, Swerdlow, Russell H, Apostolova, Liana, Tingus, Kathleen, Woo, Ellen, Silverman, Daniel H S, Lu, Po H, Bartzokis, George, Graff-Radford, Neill R, Parfitt, Francine, Saykin, Andrew J, Kendall, Tracy, Johnson, Heather, Farlow, Martin R, Hake, Ann Marie, Matthews, Brandy R, Herring, Scott, Hunt, Cynthia, van Dyck, Christopher H, Carson, Richard E, MacAvoy, Martha G, Morris, John, Chertkow, Howard, Bergman, Howard, Hosein, Chris, Robin Hsiung, Ging-Yuek, Feldman, Howard, Mudge, Benita, Assaly, Michele, Bernick, Charles, Munic, Donna, Kertesz, Andrew, Chen, Guanqun, Shaw, Leslie, Rogers, John, Trost, Dick, Kerwin, Diana, Lipowski, Kristine, Wu, Chuang-Kuo, Johnson, Nancy, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Raymond Scott, Khachaturian, Zaven, Johnson, Kathleen, Reynolds, Brigid, Sperling, Reisa A, Johnson, Keith A, Marshall, Gad, Frey, Meghan, Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Sabbagh, Marwan N, Sorensen, Greg, Belden, Christine M, Jacobson, Sandra A, Sirrel, Sherye A, Kowall, Neil, Killiany, Ronald, Budson, Andrew E, Norbash, Alexander, Johnson, Patricia Lynn, Allard, Joanne, Lerner, Alan, Kuller, Lew, Ogrocki, Paula, Hudson, Leon, Fletcher, Evan, Carmichae, Owen, Olichney, John, DeCarli, Charles, Kittur, Smita, Borrie, Michael, Lee, T-Y, Bartha, Rob, Raichle, Marcus, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M, Preda, Adrian, Nguyen, Dana, Tariot, Pierre, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Paul, Steven, Scharre, Douglas W, Kataki, Maria, Adeli, Anahita, Zimmerman, Earl A, Celmins, Dzintra, Brown, Alice D, Pearlson, Godfrey D, Blank, Karen, Anderson, Karen, Santulli, Robert B, Davies, Peter, Kitzmiller, Tamar J, Schwartz, Eben S, Sink, Kaycee M, Williamson, Jeff D, Garg, Pradeep, Watkins, Franklin, Ott, Brian R, Querfurth, Henry, Tremont, Geoffrey, Salloway, Stephen, Fillit, Howard, Malloy, Paul, Correia, Stephen, Rosen, Howard J, Miller, Bruce L, Mintzer, Jacobo, Spicer, Kenneth, Bachman, David, Pasternak, Stephen, Rachinsky, Irina, Drost, Dick, Hefti, Franz, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Schultz, Susan K, Ponto, Laura L Boles, Shim, Hyungsub, Elizabeth Smith, Karen, Relkin, Norman, Chaing, Gloria, Raudin, Lisa, Holtzman, David, Smith, Amanda, Fargher, Kristin, Raj, Balebail Ashok, Neylan, Thomas, Grafman, Jordan, Davis, Melissa, Morrison, Rosemary, Hayes, Jacqueline, Finley, Shannon, Friedl, Karl, Liu, Chunhua, Mesulam, Marek M, Fleischman, Debra, Arfanakis, Konstantinos, James, Olga, Massoglia, Dino, Jay Fruehling, J., Harding, Sandra, Peskind, Elaine R, Petrie, Eric C, Li, Gail, Yesavage, Jerome A, Potter, William, Taylor, Joy L, Furst, Ansgar J, Snyder, Peter, Schwartz, Adam, Montine, Tom, Thomas, Ronald G, Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Jin, Shichen, Jiminez, Gus, Harvey, Danielle, Bernstein, Matthew, Thompson, Paul, Schuff, Norbert, Borowski, Bret, Gunter, Jeff, Senjem, Matt, Vemuri, Prashanthi, Jones, David, Li, Lanlan, Kantarci, Kejal, Ward, Chad, Koeppe, Robert A, Foster, Norm, Reiman, Eric M, Chen, Kewei, Mathis, Chet, Landau, Susan, Cairns, Nigel J, Householder, Erin, Jiang, Xueyan, Taylor-Reinwald, Lisa, Lee, Virginia, Korecka, Magdalena, Figurski, Michal, Crawford, Karen, Neu, Scott, Foroud, Tatiana M, Potkin, Steven G, Shen, Li, Faber, Kelley, Han, Ying, Kim, Sungeun, Nho, Kwangsik, Thal, Leon, Buckholtz, Neil, Albert, Marylyn, Frank, Richard, Hsiao, John, Kaye, Jeffrey, Quinn, Joseph, Lind, Betty, Initiative, Alzheimer’s Disease Neuroimaging, Carter, Raina, Dolen, Sara, Schneider, Lon S, Pawluczyk, Sonia, Beccera, Mauricio, Teodoro, Liberty, Spann, Bryan M, Brewer, James, Vanderswag, Helen, Fleisher, Adam, Weiner, Michael W, Heidebrink, Judith L, Lord, Joanne L, Mason, Sara S, Albers, Colleen S, Knopman, David S, Johnson, Kris, Doody, Rachelle S, Villanueva-Meyer, Javier, Chowdhury, Munir, and Rountree, Susan
Subjects: Glucose metabolism, Positron emission tomography, Aging, Pattern, Brain, Glucose, Brain ageing, Alzheimer Disease, Fluorodeoxyglucose F18, Positron-Emission Tomography, Humans, Original Article, Cognitive Dysfunction, ddc:610, Geriatrics and Gerontology, Aged
Abstract: Exploring individual hallmarks of brain ageing is important. Here, we propose the age-related glucose metabolism pattern (ARGMP) as a potential index to characterize brain ageing in cognitively normal (CN) elderly people. We collected (18)F-fluorodeoxyglucose ((18)F-FDG) PET brain images from two independent cohorts: the Alzheimer’s Disease Neuroimaging Initiative (ADNI, N = 127) and the Xuanwu Hospital of Capital Medical University, Beijing, China (N = 84). During follow-up (mean 80.60 months), 23 participants in the ADNI cohort converted to cognitive impairment. ARGMPs were identified using the scaled subprofile model/principal component analysis method, and cross-validations were conducted in both independent cohorts. A survival analysis was further conducted to calculate the predictive effect of conversion risk by using ARGMPs. The results showed that ARGMPs were characterized by hypometabolism with increasing age primarily in the bilateral medial superior frontal gyrus, anterior cingulate and paracingulate gyri, caudate nucleus, and left supplementary motor area and hypermetabolism in part of the left inferior cerebellum. The expression network scores of ARGMPs were significantly associated with chronological age (R = 0.808, p
Published: 2022

7. Potential modifiable factors associated with late-life cognitive trajectories.

Author: Zimu Wu, Woods, Robyn L., Chong, Trevor T.-J., Orchard, Suzanne G., McNeil, John J., Shah, Raj C., Wolfe, Rory, Murray, Anne M., Storey, Elsdon, and Ryan, Joanne
Subjects: STRUCTURAL equation modeling, COGNITIVE ability, COGNITIVE aging, HEALTH behavior, LIVING alone
Abstract: Objective: There is variability across individuals in cognitive aging. To investigate the associations of several modifiable factors with high and low cognitive performance. Methods: Data came from 17,724 community-dwelling individuals aged 65–98 years. Global cognition, verbal fluency, episodic memory, and psychomotor speed were assessed over up to seven years. Group-based multi-trajectory modeling identified distinct cognitive trajectories. Structural equation modeling examined the direct/indirect associations of social/behavioral factors and several chronic conditions with cognitive trajectories. Results: Seven trajectory subgroups were identified. In the structural equation modeling we compared two subgroups-participants with the highest (14.2%) and lowest (4.1%) cognitive performance with the average subgroup. Lower education, never alcohol intake, and frailty directly predicted increased risk of low performance, and decreased likelihood of high performance. Hypertension (RR: 0.69, 95%CI: 0.60–0.80), obesity (RR: 0.84, 95%CI: 0.73–0.97), diabetes (RR: 0.69, 95%CI: 0.56–0.86) and depression (RR: 0.68, 95%CI: 0.54–0.85) only predicted lower likelihood of high cognitive performance, while dyslipidemia was only associated with low performance (RR: 1.30, 95%CI: 1.07–1.57). Living alone predicted increased risk of low cognitive performance and several comorbidities. Smoking did not predict cognitive trajectories but was associated with increased risk of diabetes, obesity and frailty. Findings were similar when examining the direct associations between modifiable risk factors and all seven cognitive subgroups. Conclusions: Although several modifiable factors were associated with high performance, and reversely with low performance, this was not observed for obesity, hypertension and dyslipidemia. Further, health behaviors may affect cognitive function indirectly, via geriatric conditions. This indicates that strategies to promote healthy cognitive aging, may be distinct from those targeting dementia prevention. [ABSTRACT FROM AUTHOR]
Published: 2022
Full Text: View/download PDF

8. 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

9. The Health Equity through Aging Research and Discussion (HEARD) study: A proposed two-phase sequential mixed-methods research design to understand barriers and facilitators of brain donation among diverse older adults

Author: Glover, Crystal M., Shah, Raj C., Bennett, David A., Wilson, Robert S., and Barnes, Lisa L.
Subjects: Aging, Health Equity, Brain, Hispanic or Latino, Focus Groups, Middle Aged, Article, Tissue Donors, White People, Black or African American, Research Design, Surveys and Questionnaires, Income, Humans, Minority Groups
Abstract: BACKGROUND: Brain donation in studies on aging remains a critical pathway to discovering and improving preventive measures and treatments for Alzheimer’s dementia and related disorders. Brain donation for research is almost exclusively obtained from non-Latinx Whites of higher socioeconomic status in the United States. Despite persistent efforts, it has been difficult to obtain consent for brain donation among diverse participants. Hence, our understanding of Alzheimer’s dementia and related disorders remains incomplete. The purpose of this methodological paper was to propose and outline a two-phase sequential mixed-methods research study design to identify barriers and facilitators of brain donation among diverse older adults. METHODS: The first phase will consist of qualitative focus groups using a three (participant minority status: African American, Latinx, or White of lower income) by two (participant brain donation decision: consented or declined) design. The second phase will include statistical analyses of quantitative measures of existing data representing categories of variables that may be associated with decision making regarding brain donation. DISCUSSION: Next steps must include conducting qualitative focus groups and subsequent data analyses, resulting in overarching themes. Afterward, qualitative themes will be operationalized using quantitative variables for statistical analyses. This proposed study design can provide the foundation for designing and implementing effective and culturally competent survey instruments, educational tools, and intervention strategies in an effort to facilitate brain donation among diverse older adults.
Published: 2020

10. 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

11. 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

12. Does posterior cingulate hypometabolism result from disconnection or local pathology across preclinical and clinical stages of Alzheimer's disease?

Author: Teipel, Stefan, Grothe, Michel J, Trojanowki, John Q, Quinn, Joseph, Silbert, Lisa, Lind, Betty, Carter, Raina, Dolen, Sara, Schneider, Lon S, Pawluczyk, Sonia, Becerra, Mauricio, Teodoro, Liberty, Spann, Bryan M, Toga, Arthur W, Brewer, James, Vanderswag, Helen, Fleisher, Adam, Heidebrink, Judith L, Lord, Joanne L, Petersen, Ronald, Mason, Sara S, Albers, Colleen S, Knopman, David, Johnson, Kris, Beckett, Laurel, Doody, Rachelle S, Villanueva-Meyer, Javier, Pavlik, Valory, Shibley, Victoria, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Stern, Yaakov, Honig, Lawrence S, Bell, Karen L, Green, Robert C, Ances, Beau, Morris, John C, Carroll, Maria, Creech, Mary L, Franklin, Erin, Mintun, Mark A, Schneider, Stacy, Oliver, Angela, Marson, Daniel, Geldmacher, David, Saykin, Andrew J, Love, Marissa Natelson, Griffith, Randall, Clark, David, Brockington, John, Roberson, Erik, Grossman, Hillel, Mitsis, Effie, Shah, Raj C, deToledo-Morrell, Leyla, Duara, Ranjan, Morris, John, Greig-Custo, Maria T, Barker, Warren, Albert, Marilyn, Onyike, Chiadi, D'Agostino, Daniel, Kielb, Stephanie, Sadowski, Martin, Sheikh, Mohammed O, Ulysse, Anaztasia, Gaikwad, Mrunalini, Shaw, Leslie M, Doraiswamy, P Murali, Petrella, Jeffrey R, Borges-Neto, Salvador, Wong, Terence Z, Coleman, Edward, Arnold, Steven E, Karlawish, Jason H, Wolk, David A, Clark, Christopher M, Smith, Charles D, Khachaturian, Zaven, Jicha, Greg, Hardy, Peter, Sinha, Partha, Oates, Elizabeth, Conrad, Gary, Lopez, Oscar L, Oakley, MaryAnn, Simpson, Donna M, Porsteinsson, Anton P, Goldstein, Bonnie S, Sorensen, Greg, Martin, Kim, Makino, Kelly M, Ismail, M Saleem, Brand, Connie, Potkin, Steven G, Preda, Adrian, Nguyen, Dana, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Carrillo, Maria, Levey, Allan I, Lah, James J, Cellar, Janet S, Burns, Jeffrey M, Swerdlow, Russell H, Brooks, William M, Apostolova, Liana, Tingus, Kathleen, Woo, Ellen, Silverman, Daniel H S, Initiative, Alzheimer´s Disease Neuroimaging, Kuller, Lew, Lu, Po H, Bartzokis, George, Graff-Radford, Neill R, Parfitt, Francine, Poki-Walker, Kim, Farlow, Martin R, Hake, Ann Marie, Matthews, Brandy R, Brosch, Jared R, Herring, Scott, Raichle, Marc, van Dyck, Christopher H, Carson, Richard E, MacAvoy, Martha G, Varma, Pradeep, Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Caldwell, Curtis, Paul, Steven, Hsiung, Ging-Yuek Robin, Feldman, Howard, Mudge, Benita, Assaly, Michele, Finger, Elizabeth, Pasternack, Stephen, Rachisky, Irina, Trost, Dick, Kertesz, Andrew, Bernick, Charles, Davies, Peter, Munic, Donna, Mesulam, Marek-Marsel, Rogalski, Emily, Lipowski, Kristine, Weintraub, Sandra, Bonakdarpour, Borna, Kerwin, Diana, Wu, Chuang-Kuo, Johnson, Nancy, Sadowsky, Carl, Fillit, Howard, Villena, Teresa, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Sperling, Reisa A, Johnson, Keith A, Marshall, Gad, Yesavage, Jerome, Taylor, Joy L, Lane, Barton, Hefti, Franz, Rosen, Allyson, Tinklenberg, Jared, Sabbagh, Marwan N, Belden, Christine M, Jacobson, Sandra A, Sirrel, Sherye A, Kowall, Neil, Killiany, Ronald, Budson, Andrew E, Norbash, Alexander, Holtzman, David, Johnson, Patricia Lynn, Obisesan, Thomas O, Wolday, Saba, Allard, Joanne, Lerner, Alan, Ogrocki, Paula, Tatsuoka, Curtis, Fatica, Parianne, Fletcher, Evan, Maillard, Pauline, Mesulam, M Marcel, Olichney, John, DeCarli, Charles, Carmichael, Owen, Kittur, Smita, Borrie, Michael, Lee, T-Y, Bartha, Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M, Potter, William, Tariot, Pierre, Burke, Anna, Milliken, Ann Marie, Trncic, Nadira, Reeder, Stephanie, Bates, Vernice, Snyder, Peter, Capote, Horacio, Rainka, Michelle, Scharre, Douglas W, Kataki, Maria, Kelley, Brendan, Zimmerman, Earl A, Celmins, Dzintra, Brown, Alice D, Pearlson, Godfrey D, Blank, Karen, Weiner, Michael W, Schwartz, Adam, Anderson, Karen, Flashman, Laura A, Seltzer, Marc, Hynes, Mary L, Santulli, Robert B, Sink, Kaycee M, Gordineer, Leslie, Williamson, Jeff D, Garg, Pradeep, Watkins, Franklin, Ott, Brian R, Tremont, Geoffrey, Daiello, Lori A, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J, Miller, Bruce L, Perry, David, Mintzer, Jacobo, Montine, Tom, Spicer, Kenneth, Bachman, David, Pasternak, Stephen, Rachinsky, Irina, Rogers, John, Drost, Dick, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Schultz, Susan K, Smith, Karen Ekstam, Koleva, Hristina, Nam, Ki Won, Shim, Hyungsub, Relkin, Norman, Chiang, Gloria, Lin, Michael, Ravdin, Lisa, Aisen, Paul, Smith, Amanda, Raj, Balebail Ashok, Fargher, Kristin, Weiner, Michael, Harvey, Danielle, Thomas, Ronald G, Jack, Clifford R, Jagust, William, Neylan, Thomas, Grafman, Jordan, Donohue, Michael, Gessert, Devon, Sather, Tamie, Davis, Melissa, Morrison, Rosemary, Walter, Sarah, Jiminez, Gus, Hayes, Jacqueline, Finley, Shannon, Bernstein, Matthew, Borowski, Bret, Gunter, Jeff, Senjem, Matt, Kantarci, Kejal, Ward, Chad, Koeppe, Robert A, Foster, Norm, Reiman, Eric M, Chen, Kewei, Landau, Susan, Cairns, Nigel J, Householder, Erin, Lee, Virginia, Korecka, Magdalena, Figurski, Michal, Crawford, Karen, Neu, Scott, Foroud, Tatiana M, Potkin, Steven, Shen, Li, Faber, Kelley, Kim, Sungeun, Nho, Kwangsik, Friedl, Karl, Balasubramanian, Archana B, Fleischman, Debra, Arfanakis, Konstantinos, Mason, Jennifer, Varon, Daniel, Greig, Maria T, James, Olga, Goldstein, Bonnie, Martin, Kimberly S, Sim, Iris, Massoglia, Dino, Brawman-Mintzer, Olga, Martinez, Walter, Rosen, Howard, Behan, Kelly, Johnson, Sterling C, Fruehling, J Jay, Harding, Sandra, Peskind, Elaine R, Petrie, Eric C, Li, Gail, Yesavage, Jerome A, Furst, Ansgar J, Chao, Steven, Fox, Nick, Thompson, Paul, Schuff, Norbert, DeCArli, Charles, Vemuri, Prashanthi, Jones, David, Mathis, Chet, Taylor-Reinwald, Lisa, Thal, Lean, Thal, Leon, Buckholtz, Neil, Snyder, Peter J, Frank, Richard, Hsiao, John, and Kaye, Jeffrey
Subjects: Male, Pathology, Aging, physiopathology [Cognitive Dysfunction], diagnostic imaging [Cognitive Dysfunction], Hippocampus, 030218 nuclear medicine & medical imaging, metabolism [Cognitive Dysfunction], 0302 clinical medicine, Cognition, pathology [Gray Matter], Cortex (anatomy), Image Processing, Computer-Assisted, Gray Matter, diagnostic imaging [Hippocampus], General Medicine, Middle Aged, Magnetic Resonance Imaging, medicine.anatomical_structure, Female, metabolism [Alzheimer Disease], medicine.medical_specialty, Amyloid, Grey matter, Gyrus Cinguli, physiopathology [Alzheimer Disease], Article, 03 medical and health sciences, Atrophy, Neuroimaging, Alzheimer Disease, Fluorodeoxyglucose F18, mental disorders, metabolism [Gyrus Cinguli], medicine, Dementia, Humans, Cognitive Dysfunction, Radiology, Nuclear Medicine and imaging, ddc:610, chemistry [Fluorodeoxyglucose F18], physiopathology [Gyrus Cinguli], Aged, business.industry, diagnostic imaging [Gray Matter], medicine.disease, pathology [Hippocampus], Posterior cingulate, Positron-Emission Tomography, bacteria, business, diagnostic imaging [Alzheimer Disease], 030217 neurology & neurosurgery
Abstract: Posterior cingulate cortex (PCC) hypometabolism as measured by FDG PET is an indicator of Alzheimer’s disease (AD) in prodromal stages, such as in mild cognitive impairment (MCI), and has been found to be closely associated with hippocampus atrophy in AD dementia. We studied the effects of local and remote atrophy and of local amyloid load on the PCC metabolic signal in patients with different preclinical and clinical stages of AD. We determined the volume of the hippocampus and PCC grey matter based on volumetric MRI scans, PCC amyloid load based on AV45 PET, and PCC metabolism based on FDG PET in 667 subjects participating in the Alzheimer’s Disease Neuroimaging Initiative spanning the range from cognitively normal ageing through prodromal AD to AD dementia. In cognitively normal individuals and those with early MCI, PCC hypometabolism was exclusively associated with hippocampus atrophy, whereas in subjects with late MCI it was associated with both local and remote effects of atrophy as well as local amyloid load. In subjects with AD dementia, PCC hypometabolism was exclusively related to local atrophy. Our findings suggest that the effects of remote pathology on PCC hypometabolism decrease and the effects of local pathology increase from preclinical to clinical stages of AD, consistent with a progressive disconnection of the PCC from downstream cortical and subcortical brain regions.
Published: 2016

13. Body mass index is associated with biological CSF markers of core brain pathology of Alzheimer's disease

Author: Ewers, Michael, Schmitz, Susanne, Vellas, Bruno, Morris, John C, Ances, Beau, Carroll, Maria, Leon, Sue, Mintun, Mark A, Schneider, Stacy, Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, Dubois, Bruno, Mitsis, Effie, Romirowsky, Aliza, deToledo-Morrell, Leyla, Shah, Raj C, Duara, Ranjan, Varon, Daniel, Roberts, Peggy, Albert, Marilyn, Onyike, Chiadi, Kielb, Stephanie, Blennow, Kaj, Rusinek, Henry, de Leon, Mony J, Glodzik, Lidia, Doraiswamy, P Murali, Petrella, Jeffrey R, Coleman, R Edward, Arnold, Steven E, Karlawish, Jason H, Wolk, David, Smith, Charles D, Buerger, Katharina, 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, Teipel, Stefan J, Brand, Connie, 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, Weiner, Michael, 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, Hampel, Harald, Farlow, Martin, Herring, Scott, Hake, Ann M, van Dyck, Christopher H, Carson, Richard E, MacAvoy, Martha G, Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Initiative, Alzheimer's Disease Neuroimaging, Stefanovic, Bojana, Caldwell, Curtis, Hsiung, Ging-Yuek Robin, Feldman, Howard, 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, Aisen, Paul, Reynolds, Brigid, Sperling, Reisa A, Johnson, Keith A, Marshall, Gad, Frey, Meghan, Rosen, Allyson, Tinklenberg, Jared, Sabbagh, Marwan, Belden, Christine, Jacobson, Sandra, Hansson, Oskar, 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, Rob, Johnson, Sterling, Petersen, Ronald, Asthana, Sanjay, Carlsson, Cynthia M, Potkin, Steven G, Preda, Adrian, Nguyen, Dana, Tariot, Pierre, Fleisher, Adam, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Jack, Clifford R, Rainka, Michelle, Hendin, Barry A, Scharre, Douglas W, Kataki, Maria, Zimmerman, Earl A, Celmins, Dzintra, Brown, Alice D, Pearlson, Godfrey D, Blank, Karen, Anderson, Karen, Jagust, William, 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, Trojanowki, John Q, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J, Miller, Bruce L, Mintzer, Jacobo, Longmire, Crystal Flynn, Spicer, Kenneth, Toga, Arthur W, Beckett, Laurel, Green, Robert C, Walsh, Cathal, Morris, John, Liu, Enchi, Montine, Tom, Gamst, Anthony, Thomas, Ronald G, Donohue, Michael, Walter, Sarah, Fitzpatrick, Annette, Gessert, Devon, Sather, Tamie, Harvey, Danielle, Kornak, John, Dale, Anders, Bernstein, Matthew, Bennett, David, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, Bandy, Dan, Koeppe, Robert A, Foster, Norm, Minthon, Lennart, Reiman, Eric M, Chen, Kewei, Mathis, Chet, Cairns, Nigel J, Taylor-Reinwald, Lisa, Trojanowki, J. Q., Shaw, Les, Lee, Virginia M Y, Korecka, Magdalena, Trojanowski, John Q, Crawford, Karen, Neu, Scott, Foroud, Tatiana M, Potkin, Steven, Shen, Li, Kachaturian, Zaven, Frank, Richard, Snyder, Peter J, Shaw, Leslie M, Molchan, Susan, Kaye, Jeffrey, Quinn, Joseph, Lind, Betty, Dolen, Sara, Schneider, Lon S, Pawluczyk, Sonia, Spann, Bryan M, Brewer, James, Vanderswag, Helen, Faluyi, Yetunde O, Heidebrink, Judith L, Lord, Joanne L, Johnson, Kris, Doody, Rachelle S, Villanueva-Meyer, Javier, Chowdhury, Munir, Stern, Yaakov, Honig, Lawrence S, and Bell, Karen L
Subjects: Male, Apolipoprotein E, Aging, Pathology, Neurology, epidemiology [Alzheimer Disease], Statistics as Topic, cerebrospinal fluid [Amyloid beta-Peptides], Comorbidity, Body Mass Index, Cerebrospinal fluid, pathology [Brain], Prevalence, Aged, 80 and over, biology, General Neuroscience, Brain, Middle Aged, Prognosis, amyloid beta-protein (1-42), cerebrospinal fluid [Cognition Disorders], cerebrospinal fluid [Alzheimer Disease], cerebrospinal fluid [Biomarkers], Biomarker (medicine), Female, epidemiology [United States], Alzheimer's disease, Psychology, Alzheimer's Disease Neuroimaging Initiative, epidemiology [Cognition Disorders], medicine.medical_specialty, Tau protein, tau Proteins, Alzheimer Disease, medicine, Humans, ddc:610, cerebrospinal fluid [Peptide Fragments], Aged, Amyloid beta-Peptides, medicine.disease, United States, Peptide Fragments, cerebrospinal fluid [tau Proteins], metabolism [Brain], biology.protein, pathology [Cognition Disorders], Neurology (clinical), Geriatrics and Gerontology, Cognition Disorders, Body mass index, Biomarkers, Developmental Biology
Abstract: Weight changes are common in aging and Alzheimer's disease (AD) and postmortem findings suggest a relation between lower body mass index (BMI) and increased AD brain pathology. In the current multicenter study, we tested whether lower BMI is associated with higher core AD brain pathology as assessed by cerebrospinal fluid (CSF)-based biological markers of AD in 751 living subjects: 308 patients with AD, 296 subjects with amnestic mild cognitive impairment (MCI), and 147 elderly healthy controls (HC). Based upon a priori cutoff values on CSF concentration of total tau and beta-amyloid (Aβ(1-42)), subjects were binarized into a group with abnormal CSF biomarker signature (CSF+) and those without (CSF-). Results showed that BMI was significantly lower in the CSF+ when compared with the CSF- group (F = 27.7, df = 746, p0.001). There was no interaction between CSF signature and diagnosis or apolipoprotein E (ApoE) genotype. In conclusion, lower BMI is indicative of AD pathology as assessed with CSF-based biomarkers in demented and nondemented elderly subjects.
Published: 2012

14. Common genetic variants influence human subcortical brain structures

Author: Hibar, Derrek P, Stein, Jason L, Aribisala, Benjamin S, de Zubicaray, Greig I, Dillman, Allissa, Duggirala, Ravi, Dyer, Thomas D, Erk, Susanne, Fedko, Iryna O, Ferrucci, Luigi, Foroud, Tatiana M, Fox, Peter T, Fukunaga, Masaki, Armstrong, Nicola J, Gibbs, J Raphael, Göring, Harald H H, Green, Robert C, Guelfi, Sebastian, Hansell, Narelle K, Hartman, Catharina A, Hegenscheid, Katrin, Heinz, Andreas, Hernandez, Dena G, Heslenfeld, Dirk J, Bernard, Manon, Hoekstra, Pieter J, Holsboer, Florian, Homuth, Georg, Hottenga, Jouke-Jan, Ikeda, Masashi, Jack, Clifford R, Jenkinson, Mark, Johnson, Robert, Kanai, Ryota, Keil, Maria, Bohlken, Marc M, Kent, Jack W, Kochunov, Peter, Kwok, John B, Lawrie, Stephen M, Liu, Xinmin, Longo, Dan L, McMahon, Katie L, Meisenzahl, Eva, Melle, Ingrid, Mohnke, Sebastian, Boks, Marco P, Montgomery, Grant W, Mostert, Jeanette C, Mühleisen, Thomas W, Nalls, Michael A, Nichols, Thomas E, Nilsson, Lars G, Nöthen, Markus M, Ohi, Kazutaka, Olvera, Rene L, Perez-Iglesias, Rocio, Bralten, Janita, Pike, G Bruce, Potkin, Steven G, Reinvang, Ivar, Reppermund, Simone, Rietschel, Marcella, Romanczuk-Seiferth, Nina, Rosen, Glenn D, Rujescu, Dan, Schnell, Knut, Schofield, Peter R, Brown, Andrew A, Smith, Colin, Steen, Vidar M, Sussmann, Jessika E, Thalamuthu, Anbupalam, Toga, Arthur W, Traynor, Bryan J, Troncoso, Juan, Turner, Jessica A, Valdés Hernández, Maria C, van 't Ent, Dennis, Chakravarty, M Mallar, van der Brug, Marcel, van der Wee, Nic J A, van Tol, Marie-Jose, Veltman, Dick J, Wassink, Thomas H, Westman, Eric, Zielke, Ronald H, Zonderman, Alan B, Ashbrook, David G, Hager, Reinmar, Chen, Qiang, Lu, Lu, McMahon, Francis J, Morris, Derek W, Williams, Robert W, Brunner, Han G, Buckner, Randy L, Buitelaar, Jan K, Cahn, Wiepke, Calhoun, Vince D, Cavalleri, Gianpiero L, Ching, Christopher R K, Crespo-Facorro, Benedicto, Dale, Anders M, Davies, Gareth E, Delanty, Norman, Depondt, Chantal, Djurovic, Srdjan, Drevets, Wayne C, Espeseth, Thomas, Gollub, Randy L, Ho, Beng-Choon, Renteria, Miguel E, Cuellar-Partida, Gabriel, Hoffmann, Wolfgang, Hosten, Norbert, Kahn, René S, Le Hellard, Stephanie, Meyer-Lindenberg, Andreas, Müller-Myhsok, Bertram, Nauck, Matthias, Nyberg, Lars, Pandolfo, Massimo, Penninx, Brenda W J H, den Braber, Anouk, Roffman, Joshua L, Sisodiya, Sanjay M, Smoller, Jordan W, van Bokhoven, Hans, van Haren, Neeltje E M, Völzke, Henry, Walter, Henrik, Weiner, Michael W, Wen, Wei, White, Tonya, Giddaluru, Sudheer, Agartz, Ingrid, Andreassen, Ole A, Blangero, John, Boomsma, Dorret I, Brouwer, Rachel M, Cannon, Dara M, Cookson, Mark R, de Geus, Eco J C, Deary, Ian J, Donohoe, Gary, Goldman, Aaron L, Fernández, Guillén, Fisher, Simon E, Francks, Clyde, Glahn, David C, Grabe, Hans J, Gruber, Oliver, Hardy, John, Hashimoto, Ryota, Hulshoff Pol, Hilleke E, Jönsson, Erik G, Grimm, Oliver, Kloszewska, Iwona, Lovestone, Simon, Mattay, Venkata S, Mecocci, Patrizia, McDonald, Colm, McIntosh, Andrew M, Ophoff, Roel A, Paus, Tomas, Pausova, Zdenka, Ryten, Mina, Guadalupe, Tulio, Sachdev, Perminder S, Saykin, Andrew J, Simmons, Andy, Singleton, Andrew, Soininen, Hilkka, Wardlaw, Joanna M, Weale, Michael E, Weinberger, Daniel R, Adams, Hieab H H, Launer, Lenore J, Hass, Johanna, Seiler, Stephan, Schmidt, Reinhold, Chauhan, Ganesh, Satizabal, Claudia L, Becker, James T, Yanek, Lisa, van der Lee, Sven J, Ebling, Maritza, Fischl, Bruce, Longstreth, W. T., Woldehawariat, Girma, Greve, Douglas, Schmidt, Helena, Nyquist, Paul, Vinke, Louis N, van Duijn, Cornelia M, Xue, Luting, Mazoyer, Bernard, Bis, Joshua C, Gudnason, Vilmundur, Seshadri, Sudha, Holmes, Avram J, Ikram, M Arfan, Initiative, Alzheimer’s Disease Neuroimaging, Consortium, CHARGE, EPIGEN, IMAGEN, SYS, Martin, Nicholas G, Wright, Margaret J, Schumann, Gunter, Franke, Barbara, Hoogman, Martine, Thompson, Paul M, Medland, Sarah E, Weiner, Michael, Aisen, Paul, Petersen, Ronald, Jagust, William, Trojanowki, John Q, Beckett, Laurel, Arias-Vasquez, Alejandro, Janowitz, Deborah, Morris, John, Shaw, Leslie M, Khachaturian, Zaven, Sorensen, Greg, Carrillo, Maria, Kuller, Lew, Raichle, Marc, Paul, Steven, Jia, Tianye, Davies, Peter, Fillit, Howard, Hefti, Franz, Holtzman, Davie, Mesulman, M Marcel, Potter, William, Snyder, Peter, Schwartz, Adam, Montine, Tom, Kim, Sungeun, Thomas, Ronald G, Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Jiminez, Gus, Harvey, Danielle, Klein, Marieke, Bernstein, Matthew, Fox, Nick, Thompson, Paul, Schuff, Norbert, DeCarli, Charles, Borowski, Bret, Gunter, Jeff, Senjem, Matt, Kraemer, Bernd, Vemuri, Prashanthi, Jones, David, Kantarci, Kejal, Ward, Chad, Koeppe, Robert A, Foster, Norm, Reiman, Eric M, Chen, Kewei, Mathis, Chet, Lee, Phil H, Landau, Susan, Cairns, Nigel J, Householder, Erin, Taylor-Reinwald, Lisa, Trojanowki, J. Q., Shaw, Les, Lee, Virginia M Y, Korecka, Magdalena, Figurski, Michal, Olde Loohuis, Loes M, Crawford, Karen, Neu, Scott, Potkin, Steven, Shen, Li, Faber, Kelley, Nho, Kwangsik, Luciano, Michelle, Thal, Leon, Frank, Richard, Snyder, Peter J, Buckholtz, Neil, Macare, Christine, Albert, Marilyn, Hsiao, John, Kaye, Jeffrey, Quinn, Joseph, Lind, Betty, Carter, Raina, Dolen, Sara, Gutman, Boris A, Schneider, Lon S, Mather, Karen A, Pawluczyk, Sonia, Beccera, Mauricio, Teodoro, Liberty, Spann, Bryan M, Brewer, James, Vanderswag, Helen, Fleisher, Adam, Heidebrink, Judith L, Lord, Joanne L, Desrivières, Sylvane, Mattheisen, Manuel, Mason, Sara S, Albers, Colleen S, Knopman, David, Johnson, Kris, Doody, Rachelle S, Villanueva-Meyer, Javier, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Stern, Yaakov, Milaneschi, Yuri, Honig, Lawrence S, Bell, Karen L, Ances, Beau, Morris, John C, Carroll, Maria, Leon, Sue, Mintun, Mark A, Schneider, Stacy, Oliver, Angela, Marson, Daniel, Griffith, Randall, Clark, David, Geldmacher, David, Brockington, John, Roberson, Erik, Grossman, Hillel, Mitsis, Effie, deToledo-Morrell, Leyla, Shah, Raj C, Papmeyer, Martina, Duara, Ranjan, Varon, Daniel, Greig, Maria T, Roberts, Peggy, Onyike, Chiadi, D'Agostino, Daniel, Kielb, Stephanie, Galvin, James E, Pogorelec, Dana M, Ramasamy, Adaikalavan, Cerbone, Brittany, Michel, Christina A, Rusinek, Henry, de Leon, Mony J, Glodzik, Lidia, De Santi, Susan, Doraiswamy, P Murali, Petrella, Jeffrey R, Wong, Terence Z, Arnold, Steven E, Risacher, Shannon L, Karlawish, Jason H, Wolk, David, Smith, Charles D, Jicha, Greg, Hardy, Peter, Sinha, Partha, Oates, Elizabeth, Conrad, Gary, Lopez, Oscar L, Oakley, MaryAnn, Roiz-Santiañez, Roberto, Simpson, Donna M, 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, Rose, Emma J, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Diaz-Arrastia, Ramon, King, Richard, Weiner, Myron, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I, Lah, James J, Salami, Alireza, Cellar, Janet S, Burns, Jeffrey M, Anderson, Heather S, Swerdlow, Russell H, Apostolova, Liana, Tingus, Kathleen, Woo, Ellen, Silverman, Daniel H S, Lu, Po H, Bartzokis, George, Sämann, Philipp G, Graff-Radford, Neill R, Parfitt, Francine, Kendall, Tracy, Johnson, Heather, Farlow, Martin R, Hake, Ann Marie, Matthews, Brandy R, Herring, Scott, Hunt, Cynthia, van Dyck, Christopher H, Jahanshad, Neda, Schmaal, Lianne, Carson, Richard E, MacAvoy, Martha G, Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Caldwell, Curtis, Hsiung, Yuek Robin, Feldman, Howard, Schork, Andrew J, Mudge, Benita, Assaly, Michele, Kertesz, Andrew, Rogers, John, Trost, Dick, Bernick, Charles, Munic, Donna, Kerwin, Diana, Mesulam, Marek-Marsel, Lipowski, Kristine, Shin, Jean, Wu, Chuang-Kuo, Johnson, Nancy, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Sperling, Reisa A, Johnson, Keith A, Strike, Lachlan T, Marshall, Gad, Frey, Meghan, Yesavage, Jerome, Taylor, Joy L, Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Sabbagh, Marwan N, Belden, Christine M, Jacobson, Sandra A, Teumer, Alexander, Sirrel, Sherye A, Kowall, Neil, Killiany, Ronald, Budson, Andrew E, Norbash, Alexander, Johnson, Patricia Lynn, Obisesan, Thomas O, Wolday, Saba, Allard, Joanne, Lerner, Alan, van Donkelaar, Marjolein M J, Ogrocki, Paula, Hudson, Leon, Fletcher, Evan, Carmichael, Owen, Olichney, John, Kittur, Smita, Borrie, Michael, Lee, T-Y, Bartha, Rob, van Eijk, Kristel R, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M, Preda, Adrian, Nguyen, Dana, Tariot, Pierre, Reeder, Stephanie, Bates, Vernice, Walters, Raymond K, Capote, Horacio, Rainka, Michelle, Scharre, Douglas W, Kataki, Maria, Adeli, Anahita, Zimmerman, Earl A, Celmins, Dzintra, Brown, Alice D, Pearlson, Godfrey D, Blank, Karen, Westlye, Lars T, Anderson, Karen, Santulli, Robert B, Kitzmiller, Tamar J, Schwartz, Eben S, Sink, Kaycee M, Williamson, Jeff D, Garg, Pradeep, Watkins, Franklin, Ott, Brian R, Querfurth, Henry, Whelan, Christopher D, Tremont, Geoffrey, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J, Miller, Bruce L, Mintzer, Jacobo, Spicer, Kenneth, Bachman, David, Finger, Elizabether, Toro, Roberto, Winkler, Anderson M, Pasternak, Stephen, Rachinsky, Irina, Drost, Dick, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Schultz, Susan K, Ponto, Laura L Boles, Zwiers, Marcel P, Shim, Hyungsub, Smith, Karen Elizabeth, Relkin, Norman, Chaing, Gloria, Raudin, Lisa, Smith, Amanda, Fargher, Kristin, Raj, Balebail Ashok, Amin, Najaf, Becker, Diane, Alhusaini, Saud, Beiser, Alexa, Debette, Stéphanie, DeStefano, Anita, Hofer, Edith, Hofman, Albert, Niessen, Wiro J, Smith, Albert, Tzourio, Christophe, Vaidya, Dhananjay, Athanasiu, Lavinia, Vernooij, Meike W, Goldstein, David B, Heinzen, Erin L, Shianna, Kevin, Radtke, Rodney, Ottmann, Ruth, Albrecht, Lisa, Andrew, Chris, Arroyo, Mercedes, Artiges, Eric, Ehrlich, Stefan, Aydin, Semiha, Bach, Christine, Banaschewski, Tobias, Barbot, Alexis, Barker, Gareth, Boddaert, Nathalie, Bokde, Arun, Bricaud, Zuleima, Bromberg, Uli, Bruehl, Ruediger, Hakobjan, Marina M H, Büchel, Christian, Cachia, Arnaud, Cattrell, Anna, Conrod, Patricia, Constant, Patrick, Crombag, Hans, Czech, Katharina, Dalley, Jeffrey, Decideur, Benjamin, Desrivieres, Sylvane, Hartberg, Cecilie B, Fadai, Tahmine, Flor, Herta, Frouin, Vincent, Fuchs, Birgit, Gallinat, Jürgen, Garavan, Hugh, Briand, Fanny Gollier, Gowland, Penny, Head, Kay, Heinrichs, Bert, Haukvik, Unn K, Heym, Nadja, Hübner, Thomas, Ihlenfeld, Albrecht, Ireland, James, Ittermann, Bernd, Ivanov, Nikolay, Jones, Jennifer, Klaassen, Arno, Heister, Angelien J G A M, Lalanne, Christophe, Lathrop, Mark, Lanzerath, Dirk, Lemaitre, Hervé, Lüdemann, Katharina, Mallik, Catherine, Mangin, Jean-François, Mann, Karl, Mar, Adam, Hoehn, David, Martinot, Jean-Luc, Massicotte, Jessica, Mennigen, Eva, Mesquita de Carvahlo, Fabiana, Mignon, Xavier, Miranda, Ruben, Müller, Kathrin, Nees, Frauke, Nymberg, Charlotte, Paillere, Marie-Laure, Wittfeld, Katharina, Kasperaviciute, Dalia, Pena-Oliver, Yolanda, Poline, Jean-Baptiste, Poustka, Luise, Rapp, Michael, Reed, Laurence, Robert, Gabriel, Reuter, Jan, Liewald, David C M, Ripke, Stephan, Ripley, Tamzin, Robbins, Trevor, Rodehacke, Sarah, Romanowski, Alexander, Ruggeri, Barbara, Schilling, Christina, Schmäl, Christine, Schmidt, Dirk, Lopez, Lorna M, Schneider, Sophia, Schroeder, Markus, Schubert, Florian, Schwartz, Yannick, Smolka, Michael, Sommer, Wolfgang, Spanagel, Rainer, Speiser, Claudia, Spranger, Tade, Stedman, Alicia, Makkinje, Remco R R, Steiner, Sabina, Stephens, Dai, Strache, Nicole, Ströhle, Andreas, Struve, Maren, Subramaniam, Naresh, Theobald, David, Topper, Lauren, Vollstaedt-Klein, Sabine, Walaszek, Bernadeta, Matarin, Mar, Weiß, Katharina, Werts, Helen, Whelan, Robert, Williams, Steve, Yacubian, Juliana, Ziesch, Veronika, Zilbovicius, Monica, Wong, C Peng, Lubbe, Steven, Naber, Marlies A M, Martinez-Medina, Lourdes, Kepa, Agnes, Fernandes, Alinda, Tahmasebi, Amir, Abrahamowicz, Michal, Gaudet, Daniel, Leonard, Gabriel, Perron, Michel, Richer, Louis, Seguin, Jean, McKay, D Reese, Veillette, Suzanne, Needham, Margaret, Nugent, Allison C, Pütz, Benno, Abramovic, Lucija, Royle, Natalie A, Sprooten, Emma, Trabzuni, Daniah, van der Marel, Saskia S L, van Hulzen, Kimm J E, Walton, Esther, Wolf, Christiane, Almasy, Laura, Ames, David, Andersson, Micael, Arepalli, Sampath, Assareh, Amelia A, Bastin, Mark E, Brodaty, Henry, Bulayeva, Kazima B, Carless, Melanie A, Cichon, Sven, Corvin, Aiden, Curran, Joanne E, Czisch, Michael, MUMC+: DA Klinische Genetica (5), RS: GROW - Developmental Biology, RS: GROW - R4 - Reproductive and Perinatal Medicine, Université de Montréal. Faculté de médecine. Département de psychiatrie et d'addictologie, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), QIMR Berghofer Medical Research Institute, Department of Psychiatry, Donders Centre for Neuroscience, Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen], Department of Human Genetics, Radboud University Medical Center [Nijmegen], Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, PRES Sorbonne Paris Cité, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Gènes, Synapses et Cognition (CNRS - UMR3571 ), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Greifswald University Hospital, University Medical Center [Utrecht], European Commission, University of Edinburgh, Lagos State University (LASU), Heriot-Watt University [Edinburgh] (HWU), Unité d'expérimentation sur les Ruminants de Theix, Institut National de la Recherche Agronomique (INRA), Donders Institute for Brain, Cognition and Behaviour, Radboud University [Nijmegen], University of Oslo (UiO), Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], School of Technical Physics, Xidian University, Dept. of Mechanical Engineering, McMaster University [Hamilton, Ontario], Biological Psychology, Neuroscience Campus Amsterdam & EMGO Institute for Health and Care Research, VU University & VU Medical Center, Amsterdam 1081 BT, The Netherlands, Haukeland University Hospital, University of Bergen (UiB), Physicochimie des Processus de Combustion et de l’Atmosphère - UMR 8522 (PC2A), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Universität Heidelberg [Heidelberg] = Heidelberg University, Language and Genetics Department [Nijmegen], Max Planck Institute for Psycholinguistics, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, International Max Planck Research School for Language Sciences (IMPRS ), Georgia Institute of Technology [Atlanta], National Institutes of Health [Bethesda] (NIH), Yale University [New Haven], Massachusetts General Hospital [Boston], Mental Health Sciences Unit, University College of London [London] (UCL), Beijing Normal University (BNU), Indiana University School of Medicine, Indiana University System, Indiana Alzheimer Disease Center, Indiana University System-Indiana University System, Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen 37075, Germany, Scottish Fish Immunology Research Centre, School of Biological Sciences, University of Aberdeen, University of California (UC), Medstar Research Institute, Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia, Department of Genomics, Life and Brain Center, Universität Bonn = University of Bonn, Institute of Human Genetics, Department of Biomedicine and the Centre for Integrative Sequencing, Aarhus University [Aarhus], VU University Medical Center [Amsterdam], Respiratory Epidemiology and Public Health, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-MRC-HPA Centre for Environment and Health, Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Institut Parisien de Chimie Moléculaire (IPCM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Umeå Centre for Functional Brain Imaging (UFBI), Umeå University, Umeå 901 87, Sweden, Aging Research Center [Karolinska Institutet] (ARC ), Stockholm University-Karolinska Institutet [Stockholm], Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Department of Neurosciences [Univ California San Diego] (Neuro - UC San Diego), School of Medicine [Univ California San Diego] (UC San Diego), University of California [San Diego] (UC San Diego), University of California (UC)-University of California (UC)-University of California [San Diego] (UC San Diego), Department of Cognitive Sciences [Univ California San Diego] (CogSci - UC San Diego), The Hospital for sick children [Toronto] (SickKids), Queensland Institute of Medical Research, School of Psychology, University of Queensland, Brisbane 4072, Australia, University of Queensland [Brisbane], Centre for Advanced Imaging, University of Queensland, Brisbane 4072, Australia, Department of Genomics of Common Disease, Imperial College London, Department of Psychology [Oslo], Faculty of Social Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Deutsche Bundesbank, Department of Neurology and Neurosurgery [Montreal], McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland (RCSI), MetaGenoPolis, Department of Psychiatric Research and Development, Diakonhjemmet Hospital, Oslo 0319, Norway, UCL Institute of Neurology and Epilepsy Society, Department of Medicine, Clinical And Experimental Epilepsy, Dpt of Psychiatry [New Haven], Yale School of Medicine [New Haven, Connecticut] (YSM), Hartford Hospital, Neuropsychiatric Genetics Research Group and Department of Psychiatry, Trinity College Institute of Psychiatry, Trinity College Dublin, Dublin 2, Ireland, Institute of Food & Health, University College Dublin, University College Dublin [Dublin] (UCD), Statistical Genetics Group, State Key Laboratory of Lead Compound Research, WuXi AppTec, Co., Ltd, Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL, Institute of Neurology [London], Department of Genetics, King Faisal Specialist Hospital and Research Centre (KFSH & RC), Centre épigénétique et destin cellulaire (EDC), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Dundee Technopole, CXR Biosciences Ltd, Ninewells Hospital and Medical School, Biomedical Research Centre, University of Dundee, Southwest Foundation for Biomedical Research, Department of Psychiatry and National Ageing Research Institute, University of Melbourne, Department of Clinical Genetics, Department of Medical Parasitology and Mycology, School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-Tehran University of Medical Siences, Centre for Healthy Brain Ageing, University of New South Wales [Sydney] (UNSW), Dementia Collaborative Research Centre, N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119333, Russia, Texas Biomedical Research Institute [San Antonio, TX], Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Division of Medical Genetics, University of Basel (Unibas), Trinity College Dublin-St. James's Hospital, Neuropsychiatric Genetics Research Group, Trinity College Dublin, Department of Materials Science & Metallurgy, University of Cambridge [UK] (CAM), Bijvoet Center of Biomolecular Research [Utrecht], Utrecht University [Utrecht], School of Psychology, University of Queensland, Laboratory of Neurogenetics, The University of Texas Health Science Center at Houston (UTHealth), Department of Genomics, Department of Medical and Molecular Genetics, South Texas Veterans Health Care System, San Antonio, Texas 78229, USA, Biofunctional Imaging, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan, Public Health Genomics Unit, Department of Biomolecular Engineering, Rheinische Friedrich-Wilhelms-Universität Bonn, Estación Experimental de Pastos y Forrajes 'Indio Hatuey', University Medical Center Groningen [Groningen] (UMCG), Neuronal Plasticity / Mouse Behaviour, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Department of Psychiatry, Fujita Health University School of Medicine, Toyoake 470-1192, Japan, Department of Radiology, Mayo Clinic, Department of Clinical Neurology [Oxford], University of Oxford-FMRIB Centre- John Radcliffe Hospital [Oxford University Hospital], University of Maryland School of Medicine, University of Maryland System, University of Sussex, Institute of Cognitive Neuroscience, United Kingdom Met Office [Exeter], University of Maryland [Baltimore County] (UMBC), University of Maryland System-University of Maryland System-University of Maryland School of Medicine, Department of Civil and Structural Engineering, The Hong Kong Polytechnic University [Hong Kong] (POLYU)-The Hong Kong Polytechnic University [Hong Kong] (POLYU), Columbia University Irving Medical Center (CUIMC), Lymphocyte Cell Biology Unit, Laboratory of Genetics, Centre for Advanced Imaging, Psychiatry and Psychotherapy, KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Division of Mental Health and Addiction, Oslo University Hospital [Oslo], Institute of Clinical Medicine [Oslo], Faculty of Medicine [Oslo], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Genetic Epidemiology Unit, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Statistics [Warwick], University of Warwick [Coventry], Osaka University [Osaka], Institute of Psychiatry, King’s College London, London SE5 8AF, UK, University of Calgary, Psychiatry and Human Behavior, University of California, Irvine, California 92617, USA, University of California [Irvine] (UC Irvine), Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health [Mannheim], University Hospital Mannheim | Universitätsmedizin Mannheim-University Hospital Mannheim | Universitätsmedizin Mannheim, Space and Naval Warfare Systems Center, Klinik für Psychiatrie, Martin-Luther-University Halle-Wittenberg, Department of Psychiatry, Division of Medical Psychology, Genetics of Mental Illness and Brain Function, Neuroscience Research Australia, Développement et amélioration des plantes (UMR DAP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia, Laboratory of Neuro Imaging [Los Angeles] (LONI), Departamento de Física Aplicada, Universidade de Vigo, Georgia State University, University System of Georgia (USG), Genentech, Inc. [San Francisco], Psychiatry and Leiden Institute for Brain and Cognition, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Universiteit Leiden, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], Department of Neurobiology, Care Sciences and Society, Karolinska Institutet [Stockholm], University of Manchester [Manchester], The University of Tennessee Health Science Center [Memphis] (UTHSC), iangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong 226001, China, Centre for Ultrahigh Bandwidth Devices for Optical Systems (CUDOS), Macquarie University, Cognitive Neuroscience Laboratory (CNL), Harvard University, Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud University [Nijmegen]-Radboud University [Nijmegen], Icahn School of Medicine at Mount Sinai [New York] (MSSM), The Mind Research Network, Department of Electrical and Computer Engineering [Albuquerque] (ECE Department), The University of New Mexico [Albuquerque], Division of Molecular and Cellular Therapeutics, Scottish Association for Marine Science (SAMS), Structural Biology Laboratory, Department of Chemistry, University of York, Neurology Division, Beaumont Hospital, Dublin 9, Ireland, Beaumont Hospital, Department of Neurology, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Deparment of Medical Genetics, Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Department of Psychiatry, University of Iowa, University of Iowa [Iowa City], Institute for Community Medicine, Department Epidemiology of Health Care and Community Health, Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig-Universität Leipzig, Institute of Clinical Chemistry and Laboratory Medicine, Department of Health Science, Division of Health and Rehabilitation, Luleå University of Technology (LUT), Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Psychiatric and Neurodevelopmental Genetics Unit, 849 Department of Human Genetics, Institute for Community Medicine, Institute for Energy Systems and Thermodynamics, Renyi Institute, Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, NSW, Department of Child and Adolescent Psychiatry, Erasmus University Medical Centre, Rotterdam 3000 CB, The Netherlands, Department of Radiology, Erasmus University Medical Centre, Rotterdam 3015 CN, The Netherlands, Vrije Universiteit Amsterdam [Amsterdam] (VU), Cell Biology and Gene Expression Section, National Institute of Health, Bethesda, Dept of Psychology, Laboratoire de Recherche Magellan, Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Institut d'Administration des Entreprises (IAE) - Lyon, Institut de Socio-économie des Entreprises et des ORganisations (ISEOR), Institut de socio-économie des entreprises et des organisations, Department of Psychiatry and Psychotherapy, HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, Laboratoire d'Informatique de Grenoble (LIG), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Centre for Allergy Research, Department of Medicine, Clinical Pharmacology Unit, Karolinska University Hospital [Stockholm], Medical University of Łódź (MUL), Psychiatry Institute, Department of Health and Human Services, Institute of Gerontology and Geriatrics, Università degli Studi di Perugia = University of Perugia (UNIPG), Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), Australian Centre for Research into Injury in Sport and its Prevention, Monash University [Clayton], University Medical Center [Utrecht]-Brain Center Rudolf Magnus, School of Psychology [Nottingham], University of Nottingham, UK (UON), McConnell Brain Imaging Centre (MNI), SickKids - The Hospital for sick children, European Centre for Medium-Range Weather Forecasts (ECMWF), University of Eastern Finland, Centre for Population Health Sciences, Lieber Institute for Brain Development [Baltimore] (LIBD), Johns Hopkins University (JHU), Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz 8010, Austria, Austrian Institute of Technology [Vienna] (AIT), INSERM Research Center for Epidemiology and Biostatistics (U897) Team Neuroepidemiology, Bordeaux, France College of Health Sciences, University of Bordeaux, Bordeaux, France, INSERM, Neuroepidemiology U708, Bordeaux, France, Karlsruhe Institute of Technology (KIT), General Internal Medicine, Johns Hopkins School of Medicine, Johns Hopkins University School of Medicine [Baltimore], Harvard Medical School [Boston] (HMS), Computer Science and Artificial Intelligence Laboratory [Cambridge] (CSAIL), Massachusetts Institute of Technology (MIT), University of Washington [Seattle], Department of Physics [Stockholm], Stockholm University, Center for Medical Systems Biology, Netherlands Genomics Initiative, Leiden University Medical Center, Leiden, The Netherlands, Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, Boston University [Boston] (BU), Groupe d'Imagerie Neurofonctionnelle (GIN - UMR 5296), 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)-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)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Faculty of Medicine, University of Iceland [Reykjavik], Icelandic Heart Association, Kopavogur, Iceland., Boston University School of Medicine (BUSM), Laboratoire d'Ingénierie des Matériaux de Bretagne (LIMATB), Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université de Brest (UBO), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University of California-University of California, Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen], Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Gènes, Synapses et Cognition, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), UE 1354 Unité d'expérimentation sur les Ruminants de Theix, Institut National de la Recherche Agronomique (INRA)-Physiologie Animale et Systèmes d'Elevage (PHASE), Institut National de la Recherche Agronomique (INRA)-Unité d'expérimentation sur les Ruminants de Theix (UE RT), Radboud university [Nijmegen], McGill University, University of Bergen (UIB), Universität Heidelberg [Heidelberg], Beijing Normal University, University of California, University of Bonn, Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Department of Neurosciences [San Diego], Department of Cognitive Sciences [San Diego], The Hospital for Sick Children, University of Toronto, Toronto M5G 1X8, Canada, McGill University-McGill University, US 1367 MetaGénoPolis, Institut National de la Recherche Agronomique (INRA)-Département Microbiologie et Chaîne Alimentaire (MICA), Institut National de la Recherche Agronomique (INRA)-MetaGénoPolis (MGP), Yale University School of Medicine, King Faisal Specialist Hospital and Research Centre, Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Texas Biomedical Research Institute [San Antonio, Texas], Bijvoet Center of Biomolecular Research, Academic Unit for Psychiatry of Old Age, University of Melbourne, Melbourne 3101, Australia, Department of Genomics, Life & Brain Center, University of Bonn, Bonn D-53127, Germany, University of Oxford [Oxford]-FMRIB Centre- John Radcliffe Hospital [Oxford University Hospital], School of Psychology, University of Sussex, Brighton BN1 9QH, UK, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Department of Neurology [University of Calgary], Department of Clinical Neuroscience [University of Calgary], University of California [Irvine] (UCI), Medical Faculty [Mannheim]-Medical Faculty [Mannheim], Centre National de la Recherche Scientifique (CNRS)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Universidate de Vigo, Harvard University [Cambridge], Radboud university [Nijmegen]-Radboud university [Nijmegen], Université Libre de Bruxelles [Bruxelles] (ULB)-Hôpital Erasme (Bruxelles), Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Centre de Recherche Magellan, Institut d'Administration des Entreprises (IAE) - Lyon-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon, Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Università degli Studi di Perugia (UNIPG), Department of neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland, Department of neurology, University of Eastern Finland-University Hospital of Kuopio-University of Eastern Finland-University Hospital of Kuopio, Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Service NEUROSPIN (NEUROSPIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université de Bretagne Sud (UBS)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), The Alzheimer’s Disease Neuroimaging Initiative, The CHARGE Consortium, EPIGEN, IMAGEN, SYS, Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen], Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), FMRIB Centre- John Radcliffe Hospital [Oxford University Hospital]-University of Oxford [Oxford], Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF), 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)-Université Paris-Saclay, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), University of Oxford [Oxford]- John Radcliffe Hospital [Oxford University Hospital]-FMRIB Centre, Neurology, Psychiatry, Anatomy and neurosciences, NCA - Neurobiology of mental health, EMGO - Mental health, NCA - Brain imaging technology, Biological Psychology, Cognitive Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Neuroscience Campus Amsterdam - Brain Imaging Technology, EMGO+ - Mental Health, Child and Adolescent Psychiatry / Psychology, Epidemiology, Radiology & Nuclear Medicine, Laboratory of Neuro Imaging, David Geffen School of Medicine, University of California, Los Angeles, California, USA, Donders Centre for Neuroscience, Radboud University Nijmegen Medical Centre, MRC- SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE5 8AF, UK, Génétique humaine et Fonctions cognitives - Human Genetics and Cognitive Functions, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Greifswald 17487, Germany, Department of Psychiatry, University Medicine Greifswald, Greifswald 17489, Germany, Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands, Brain Research Imaging Centre, University of Edinburgh, Edinburgh EH4 2XU, UK, Department of Computer Science, Lagos State University, Lagos, Nigeria, Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK, Heriot-Watt University [Edinburgh] ( HWU ), Institut National de la Recherche Agronomique ( INRA ) -Physiologie Animale et Systèmes d'Elevage ( PHASE ) -Unité d'expérimentation sur les Ruminants de Theix ( UE RT ), Department of Human Genetics, Radboud university medical center, Nijmegen 6500 HB, The Netherlands, Department of Cognitive Neuroscience, Radboud university medical center, Nijmegen 6500 HB, The Netherlands, NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway, NORMENT - KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0424, Norway, Montreal Neurological Institute [Montréal], NORMENT - KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway, Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen 5021, Norway, Physicochimie des Processus de Combustion et de l’Atmosphère - UMR 8522 ( PC2A ), Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen 6525 XD, The Netherlands, International Max Planck Research School for Language Sciences, Nijmegen 6525 XD, The Netherlands, Human Genetics Branch and Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland 20892, USA, Department of Psychology, Yale University, New Haven, Connecticut 06511, USA, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA, University College of London [London] ( UCL ), Center for Neuroimaging, Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA, Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA, Center for Neurobehavioral Genetics, University of California, Los Angeles, California 90095, USA, Université de Bonn, Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, Amsterdam 1081 HL, The Netherlands, Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh EH10 5HF, UK, Imperial College London-School of public health-MRC-HPA Centre for Environment and Health, Cibersam (Centro Investigación Biomédica en Red Salud Mental), Madrid 28029, Spain, Institut Parisien de Chimie Moléculaire ( IPCM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Aging Research Center [Karolinska Institutet] ( ARC ), Max Planck Institute of Psychiatry, Munich 80804, Germany, Multimodal Imaging Laboratory, Department of Neurosciences, University of California, San Diego, California 92093, USA, Department of Cognitive Sciences, University of California, San Diego, California 92161, USA, Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia, Department of Psychology, University of Oslo, Oslo 0373, Norway, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal H3A 2B4, Canada, Molecular and Cellular Therapeutics, The Royal College of Surgeons, Dublin 2, Ireland, Institut National de la Recherche Agronomique ( INRA ) -MetaGénoPolis ( MGP ) -Microbiologie et Chaîne Alimentaire ( MICA ), UCL Institute of Neurology, London, United Kingdom and Epilepsy Society, London WC1N 3BG, UK, Department of Medicine, Imperial College London, London W12 0NN, UK, Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK, Yale School of Medicine, Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, Connecticut 06106, USA, University College Dublin [Dublin] ( UCD ), Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK, Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia, Centre épigénétique et destin cellulaire ( EDC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), School of public health-Tehran University of Medical Siences, University of New South Wales [Sydney] ( UNSW ), Texas Biomedical Research Institute, San Antonio, Texas 78245, USA, Institute of Neuroscience and Medicine ( INM-1 ), University of Basel ( Unibas ), Cambridge University, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA, University of Texas Health Science Center, San Antonio, Texas 78229, USA, Clinical Research Branch, National Institute on Aging, Baltimore, Maryland 20892, USA, Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald 17475, Germany, University Medical Center Groningen, University of Groningen, University of Greifswald, Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA, NICHD Brain and Tissue Bank for Developmental Disorders, University of Maryland Medical School, Baltimore, Maryland 21201, USA, nstitute of Cognitive Neuroscience, University College London, London WC1N 3AR, UK, Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland, Baltimore, Maryland 21201, USA, Department of Pathology and Cell Biology, Columbia University Medical Center, New York 10032, USA, Lymphocyte Cell Biology Unit, Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA, University of Oslo ( UiO ) -Institute of Clinical Medicine-Oslo University Hospital, Oslo University Hospital, Institute of Clinical Medicine, University of Oslo ( UiO ) -European Network of Bipolar Research Expert Centers (ENBREC) Group, Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, CCM, Berlin 10117, Germany, Erasmus MC, Laboratory of Neurogenetics, Intramural Research Program, National Institute on Aging, National Institutes of Health (NIH), Bethesda, Maryland, USA, Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA, Central Institute of Mental Health, UMR 1098 Développement et Amélioration des Plantes, Institut National de la Recherche Agronomique ( INRA ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -MontpellierSupAgro ( MontpellierSupAgro ) -Génétique et amélioration des plantes ( G.A.P. ) -Développement et Amélioration des Plantes ( DAP ), Laboratory of Neuro Imaging [Los Angeles] ( LONI ), University of California at Los Angeles [Los Angeles] ( UCLA ), Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK, Genentech, South San Francisco, California 94080, USA, Psychiatry and Leiden Institute for Brain and Cognition, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands, LUMC, Carver College of Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm SE-141 83, Sweden, Behavioral Epidemiology Section, National Institute on Aging Intramural Research Program, Baltimore, Maryland 20892, USA, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK, Center for Integrative and Translational Genomics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA, Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA, Centre Interlangues - Texte, Image, Langage ( TIL ), Université de Bourgogne ( UB ), Centre for Ultrahigh Bandwidth Devices for Optical Systems ( CUDOS ), Icahn School of Medicine at Mount Sinai [New York], The Mind Research Network & LBERI, Albuquerque, New Mexico 87106, USA, Department of ECE, University of New Mexico, Albuquerque, New Mexico 87131, USA, Scottish Association for Marine Science ( SAMS ), Department of Neurology, Hopital Erasme, Universite Libre de Bruxelles, Brussels 1070, Belgium, National Institutes of Health ( NIH ) -National Institute of Mental Health (NIMH), Harvard Medical School [Boston] ( HMS ) -Massachusetts General Hospital [Boston], Department of Psychiatry, University of Iowa, Iowa City, Iowa 52242, USA, Luleå University of Technology ( LUT ), Broad Institute of MIT and Harvard, Massachusetts General Hospital, Vrije Universiteit Amsterdam [Amsterdam] ( VU ), Université Jean Moulin - Lyon III-Institut d'Administration des Entreprises (IAE) - Lyon, Institut de Socio-économie des Entreprises et des ORganisations ( ISEOR ), University Medicine Greifswald,-HELIOS Hospital Stralsund, Laboratoire d'Informatique de Grenoble ( LIG ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National Polytechnique de Grenoble ( INPG ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Osaka University, Osaka 565-0871, Japan, Karolinska University Hospital (Solna), Medical University of Łódź ( MUL ), National Institutes of Health ( NIH ), University of Perugia, Commonwealth Scientific and Industrial Research Organisation, University Medical Center Utrecht-Brain Center Rudolf Magnus, University of Nottingham, UK ( UON ), McConnell Brain Imaging Centre ( MNI ), The Hospital for sick children [Toronto] ( SickKids ), Department of Medical and Molecular Genetics, King’s College London, London SE1 9RT, UK, European Centre for Medium-Range Weather Forecasts ( ECMWF ), Lieber Institute for Brain Development, Baltimore, Maryland 21205, USA, Departments of Psychiatry, Neurology, Neuroscience and the Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique ( CNRS ), Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, Austrian Institute of Technology [Vienna] ( AIT ), Karlsruhe Institute of Technology ( KIT ), General Internal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA, Department of Radiology, Erasmus Medical Center University Medical Center, Rotterdam, The Netherlands, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA, Computer Science and Artificial Intelligence Laboratory [Cambridge] ( CSAIL ), Massachusetts Institute of Technology ( MIT ), Department of Epidemiology, University of Washington, Seattle, Washington, USA, Department of Neurology, University of Washington, Seattle, Washington, USA, Department of Physics, Stockholm University ( Department of Physics, Stockholm University ), Université de Lille, Sciences Humaines et Sociales, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA, Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center University Medical Center, Rotterdam, The Netherlands, Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA, Groupe d'Imagerie Neurofonctionnelle ( GIN - UMR 5296 ), Service NEUROSPIN ( NEUROSPIN ), Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université de Bordeaux ( UB ), Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA, Faculty of Medicine, University of Iceland, Reykjavik, Iceland, Department of Neurology, Boston University School of Medicine, Framingham Heart Study, Boston, MA, Department of Neurology, Erasmus Medical Center University Medical Center, Rotterdam, The Netherlands, Laboratoire d'Ingénierie des Matériaux de Bretagne ( LIMATB ), Université de Bretagne Sud ( UBS ) -Institut Brestois du Numérique et des Mathématiques ( IBNM ), Université de Brest ( UBO ) -Université de Brest ( UBO ) -Université de Brest ( UBO ), King's College, Department of Psychiatry, Radboud university medical center, Nijmegen 6500 HB, The Netherlands, and Broad Institute of © 2012 Nature America, Inc. All rights reserved. Nature Ge N etics aDV a NCE ONLINE PUBLIC a TION 7 l e t t e r s Harvard and MIT, Cambridge, Massachusetts, US
Subjects: CHROMATIN, Male, Netherlands Twin Register (NTR), Aging, Identification, nervous-system, human geography, SEGMENTATION, Caudate nucleus, Apoptosis, Expression, Genome-wide association study, Striatum, Hippocampal formation, Hippocampus, BASAL GANGLIA, 130 000 Cognitive Neurology & Memory, Basal ganglia, genetics [Gene Expression Regulation, Developmental], Hippocampal, Child, anatomy & histology [Skull], Aged, 80 and over, Genetics, Sex Characteristics, KINECTIN, Genome-wide association, Multidisciplinary, Putamen, Brain, Gene Expression Regulation, Developmental, blood, brain, disease incidence, genetic variation, neurology, Organ Size, Human brain, Middle Aged, organization, Magnetic Resonance Imaging, genetics [Genetic Variation], Chromatin, Dynamics, genetics [Membrane Proteins], medicine.anatomical_structure, genetics [Aging], Anatomy & histology, [ SCCO.NEUR ] Cognitive science/Neuroscience, Female, ddc:500, anatomy & histology [Caudate Nucleus], Neuroinformatics, EXPRESSION, Adult, Adolescent, Evolution, anatomy & histology [Hippocampus], ORGANIZATION, genetics [Genetic Loci], Biology, Article, Young Adult, SDG 3 - Good Health and Well-being, Journal Article, medicine, Humans, GENOME-WIDE ASSOCIATION, General, genetics [Apoptosis], Kinectin, Aged, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], HIPPOCAMPAL, IDENTIFICATION, genetics [Organ Size], [SCCO.NEUR]Cognitive science/Neuroscience, Skull, segmentation, Genetic Variation, Membrane Proteins, NERVOUS-SYSTEM, anatomy & histology [Putamen], Genetic Loci, KTN1 protein, human, Caudate Nucleus, anatomy & histology [Brain], Neuroscience, Genome-Wide Association Study
Abstract: Contains fulltext : 144426.pdf (Publisher’s version ) (Closed access) Contains fulltext : 144426pre.pdf (Author’s version preprint ) (Open Access) The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 x 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. 6 p.
Published: 2015

15. Applying automated MR-based diagnostic methods to the memory clinic: A prospective study

Author: Klöppel, Stefan, Peter, Jessica, Schroeter, Matthias L, Nho, Kwangsik, Weiner, Michael W, Thal, Lean, Khachaturian, Zaven, Thal, Leon, Buckholtz, Neil, Snyder, Peter J, Potter, William, Paul, Steven, Perneczky, Robert, Albert, Marylyn, Frank, Richard, Hsiao, John, Kaye, Jeffrey, Quinn, Joseph, Silbert, Lisa, Lind, Betty, Carter, Raina, Dolen, Sara, Häussermann, Peter, Schneider, Lon S, Pawluczyk, Sonia, Beccera, Mauricio, Teodoro, Liberty, Spann, Bryan M, Brewer, James, Vanderswag, Helen, Fleisher, Adam, Heidebrink, Judith L, Lord, Joanne L, Vach, Werner, Petersen, Ronald, Mason, Sara S, Albers, Colleen S, Knopman, David, Johnson, Kris, Doody, Rachelle S, Villanueva-Meyer, Javier, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Urbach, Horst, Stern, Yaakov, Honig, Lawrence S, Bell, Karen L, Ances, Beau, Morris, John C, Carroll, Maria, Creech, Mary L, Franklin, Erin, Mintun, Mark A, Schneider, Stacy, Teipel, Stefan, Oliver, Angela, Marson, Daniel, Griffith, Randall, Clark, David, Geldmacher, David, Brockington, John, Roberson, Erik, Love, Marissa Natelson, Grossman, Hillel, Mitsis, Effie, Hüll, Michael, Shah, Raj C, deToledo-Morrell, Leyla, Duara, Ranjan, Varon, Daniel, Greig, Maria T, Roberts, Peggy, Albert, Marilyn, Onyike, Chiadi, D'Agostino, Daniel, Kielb, Stephanie, Abdulkadir, Ahmed, Galvin, James E, Cerbone, Brittany, Michel, Christina A, Pogorelec, Dana M, Rusinek, Henry, de Leon, Mony J, Glodzik, Lidia, De Santi, Susan, Doraiswamy, P Murali, Petrella, Jeffrey R, Initiative, Alzheimer’s Disease Neuroimaging, Wong, Terence Z, Coleman, Edward, Arnold, Steven E, Karlawish, Jason H, Wolk, David, Clark, Christopher M, Smith, Charles D, Jicha, Greg, Hardy, Peter, Sinha, Partha, Oates, Elizabeth, Conrad, Gary, Lopez, Oscar L, Oakley, MaryAnn, Simpson, Donna M, Porsteinsson, Anton P, Goldstein, Bonnie S, Martin, Kim, Makino, Kelly M, Ismail, M Saleem, Ludl, Anna, Aisen, Paul, Brand, Connie, Mulnard, Ruth A, Thai, Gaby, Mc-Adams-Ortiz, Catherine, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Levey, Allan I, Lah, James J, Cellar, Janet S, Weiner, Michael, Burns, Jeffrey M, Swerdlow, Russell H, Brooks, William M, Apostolova, Liana, Tingus, Kathleen, Woo, Ellen, Silverman, Daniel H S, Lu, Po H, Bartzokis, George, Graff-Radford, Neill R, Parfitt, Francine, Kendall, Tracy, Johnson, Heather, Farlow, Martin R, Hake, Ann Marie, Matthews, Brandy R, Brosch, Jared R, Herring, Scott, Hunt, Cynthia, van Dyck, Christopher H, Carson, Richard E, MacAvoy, Martha G, Varma, Pradeep, Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Caldwell, Curtis, Hsiung, Ging-Yuek Robin, Jack, Clifford R, Feldman, Howard, Mudge, Benita, Assaly, Michele, Finger, Elizabeth, Pasternack, Stephen, Rachisky, Irina, Trost, Dick, Kertesz, Andrew, Bernick, Charles, Munic, Donna, Jagust, William, Mesulam, Marek-Marsel, Lipowski, Kristine, Weintraub, Sandra, Bonakdarpour, Borna, Kerwin, Diana, Wu, Chuang-Kuo, Johnson, Nancy, Sadowsky, Carl, Villena, Teresa, Turner, Raymond Scott, Trojanowki, John Q, Johnson, Kathleen, Reynolds, Brigid, Sperling, Reisa A, Johnson, Keith A, Marshall, Gad, Yesavage, Jerome, Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Sabbagh, Marwan N, Toga, Arthur W, Belden, Christine M, Jacobson, Sandra A, Sirrel, Sherye A, Kowall, Neil, Killiany, Ronald, Budson, Andrew E, Norbash, Alexander, Johnson, Patricia Lynn, Obisesan, Thomas O, Wolday, Saba, Beckett, Laurel, Allard, Joanne, Lerner, Alan, Ogrocki, Paula, Tatsuoka, Curtis, Fatica, Parianne, Fletcher, Evan, Maillard, Pauline, Olichney, John, DeCarli, Charles, Carmichael, Owen, Green, Robert C, Kittur, Smita, Borrie, Michael, Lee, T-Y, Bartha, Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M, Potkin, Steven G, Preda, Adrian, Nguyen, Dana, Pilatus, Anne, Saykin, Andrew J, Tariot, Pierre, Burke, Anna, Trncic, Nadira, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Scharre, Douglas W, Kataki, Maria, Morris, John, Adeli, Anahita, Zimmerman, Earl A, Celmins, Dzintra, Brown, Alice D, Neuropsychiatry, Olin, Pearlson, Godfrey D, Blank, Karen, Anderson, Karen, Flashman, Laura A, Seltzer, Marc, Shaw, Leslie M, Hynes, Mary L, Santulli, Robert B, Sink, Kaycee M, Gordineer, Leslie, 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, Perry, David, Mintzer, Jacobo, Spicer, Kenneth, Bachman, David, Finger, Elizabether, Sorensen, Greg, Pasternak, Stephen, Rachinsky, Irina, Rogers, John, Drost, Dick, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Schultz, Susan K, Ponto, Laura L Boles, Carrillo, Maria, Shim, Hyungsub, Smith, Karen Ekstam, Relkin, Norman, Chaing, Gloria, Lin, Michael, Ravdin, Lisa, Smith, Amanda, Raj, Balebail Ashok, Fargher, Kristin, Kuller, Lew, Harvey, Danielle, Raichle, Marc, Neylan, Thomas, Grafman, Jordan, Montine, Tom, Thomas, Ronald G, Donohue, Michael, Gessert, Devon, Sather, Tamie, Davis, Melissa, Morrison, Rosemary, Jiminez, Gus, Hayes, Jacqueline, Finley, Shannon, Davies, Peter, Bernstein, Matthew, Borowski, Bret, Gunter, Jeff, Senjem, Matt, Kantarci, Kejal, Koeppe, Robert A, Foster, Norm, Maier, Sabrina, Fillit, Howard, Reiman, Eric M, Chen, Kewei, Landau, Susan, Cairns, Nigel J, Householder, Erin, Lee, Virginia, Korecka, Magdalena, Hefti, Franz, Figurski, Michal, Crawford, Karen, Neu, Scott, Foroud, Tatiana M, Potkin, Steven, Shen, Li, Faber, Kelley, Kim, Sungeun, Holtzman, Davie, Friedl, Karl, Mesulam, M Marcel, Fleischman, Debra, Arfanakis, Konstantinos, James, Olga, Goldstein, Bonnie, Martin, Kimberly S, McAdams-Ortiz, Catherine, Massoglia, Dino, Brawman-Mintzer, Olga, Snyder, Peter, Martinez, Walter, Rosen, Howard, Behan, Kelly, Schwartz, Adam, Johnson, Sterling C, Fruehling, J Jay, Harding, Sandra, Peskind, Elaine R, Petrie, Eric C, Li, Gail, Yesavage, Jerome A, Taylor, Joy L, Furst, Ansgar J, Chao, Steven, Mader, Irina, Walter, Sarah, Balasubramanian, Archana B, Mason, Jennifer, Sim, Iris, Heimbach, Bernhard, Fox, Nick, Thompson, Paul, Schuff, Norbert, DeCArli, Charles, Frings, Lars, Vemuri, Prashanthi, Jones, David, Ward, Chad, Egger, Karl, Mathis, Chet, Taylor-Reinwald, Lisa, and Dukart, Juergen
Subjects: Male, Aging, Support Vector Machine, 030218 nuclear medicine & medical imaging, pathology [Alzheimer Disease], pathology [Aging], diagnosis [Frontotemporal Dementia], methods [Magnetic Resonance Imaging], 0302 clinical medicine, pathology [Brain], pathology [White Matter], Prospective Studies, Medical diagnosis, Prospective cohort study, General Neuroscience, diagnosis [Alzheimer Disease], Brain, General Medicine, Middle Aged, Magnetic Resonance Imaging, White Matter, Psychiatry and Mental health, Clinical Psychology, machine learning, Frontotemporal Dementia, Disease Progression, Female, Alzheimer's disease, Psychology, diagnosis [Lewy Body Disease], methods [Imaging, Three-Dimensional], Research Article, Frontotemporal dementia, Lewy Body Disease, medicine.medical_specialty, Diagnosis, Differential, Dementia diagnostics, 03 medical and health sciences, Imaging, Three-Dimensional, Physical medicine and rehabilitation, Alzheimer Disease, mental disorders, medicine, Humans, Dementia, ddc:610, Psychiatry, Aged, Lewy body, Memory clinic, pathology [Lewy Body Disease], medicine.disease, Hyperintensity, pathology [Frontotemporal Dementia], Linear Models, prognosis, Geriatrics and Gerontology, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Several studies have demonstrated that fully automated pattern recognition methods applied to structural magnetic resonance imaging (MRI) aid in the diagnosis of dementia, but these conclusions are based on highly preselected samples that significantly differ from that seen in a dementia clinic. At a single dementia clinic, we evaluated the ability of a linear support vector machine trained with completely unrelated data to differentiate between Alzheimer’s disease (AD), frontotemporal dementia (FTD), Lewy body dementia, and healthy aging based on 3D-T1 weighted MRI data sets. Furthermore, we predicted progression to AD in subjects with mild cognitive impairment (MCI) at baseline and automatically quantified white matter hyperintensities from FLAIR-images. Separating additionally recruited healthy elderly from those with dementia was accurate with an area under the curve (AUC) of 0.97 (according to Fig. 4). Multi-class separation of patients with either AD or FTD from other included groups was good on the training set (AUC > 0.9) but substantially less accurate (AUC = 0.76 for AD, AUC = 0.78 for FTD) on 134 cases from the local clinic. Longitudinal data from 28 cases with MCI at baseline and appropriate follow-up data were available. The computer tool discriminated progressive from stable MCI with AUC = 0.73, compared to AUC = 0.80 for the training set. A relatively low accuracy by clinicians (AUC = 0.81) illustrates the difficulties of predicting conversion in this heterogeneous cohort. This first application of a MRI-based pattern recognition method to a routine sample demonstrates feasibility, but also illustrates that automated multi-class differential diagnoses have to be the focus of future methodological developments and application studies
Published: 2015

16. 1195Brain-predicted age difference is associated with cognitive processing and delayed recall in later life.

Author: Wrigglesworth, Jo, Yaacob, Nurathifah, Ward, Phillip, Woods, Robyn, McNeil, John, Storey, Elsdon, Egan, Gary, Murray, Anne, Shah, Raj, Jamadar, Sharna, Trevaks, Ruth, Ward, Stephanie, Harding, Ian, and Ryan, Joanne
Subjects: AGE differences, OLDER people, MAGNETIC resonance imaging, COGNITIVE ability, AGE, AGING
Abstract: Background Brain age is a novel neuroimaging-based marker of ageing that uses machine learning to predict a person's biological brain age. A higher brain age relative to chronological age (i.e. brain-predicted age difference [brain-PAD]) is considered a sign of accelerated ageing. We examined whether brain-PAD is associated with cognition and the change in cognitive function over time. Methods This study involved 531 cognitively healthy community-dwelling older adults (70+ years). Using a previously trained algorithm, brain age was estimated using T1-weighted structural magnetic resonance images acquired at baseline. Psychomotor speed, delayed recall, verbal fluency and global cognition were assessed at baseline, years 1 and 3. Results At baseline, a significant negative association was observed between brain-PAD and psychomotor speed (r=-0.14, p = 0.001), delayed recall (r=-0.09, p = 0.04), and the three-year change in delayed recall (r=-0.15, p = 0.02), which persisted after adjusting for covariates. Conclusions These findings indicate that accelerated brain ageing in cognitively unimpaired older people is associated with worse psychomotor speed, and delayed recall. This study also provides new evidence that accelerated brain ageing is a risk factor for progressive memory decline. Future research would benefit from further prospective analyses of associations between brain-PAD and cognitive function in community dwelling older adults. Key messages Brain age is a neuroimaging-based marker of biological ageing. A higher estimate of brain age relative to chronological age (i.e. accelerated ageing) is associated with worse psychomotor speed and memory, and memory decline. [ABSTRACT FROM AUTHOR]
Published: 2021
Full Text: View/download PDF

17. No Modulation of the Effect of Aspirin by Body Weight in Healthy Older Men and Women.

Author: Woods, Robyn L., Polekhina, Galina, Wolfe, Rory, Nelson, Mark R., Ernst, Michael E., Reid, Christopher M., Shah, Raj C., Lockery, Jessica E., Orchard, Suzanne G., Murray, Anne M., McNeil, John J., and ASPREE Investigator Group†
Subjects: *BODY weight, *OLDER men, *OLDER women, *ASPIRIN, *CEREBROVASCULAR disease, *RESEARCH, *AGE distribution, *RESEARCH methodology, *EVALUATION research, *MEDICAL cooperation, *COMPARATIVE studies, *CARDIOVASCULAR diseases, *RESEARCH funding
Abstract: Keywords: aging; aspirin; body weight EN aging aspirin body weight 1110 1112 3 04/20/20 20200331 NES 200331 A recent meta-analysis[1] of individual patient data from several randomized, controlled trials evaluating aspirin for the prevention of primary or secondary cardiovascular events found that the protective effect of low-dose aspirin (<=100 mg) was limited to individuals weighing <70 kg, driven by lean body mass (LBM) but not body mass index (BMI).[1] Given the limited number of people >=70 years of age who were included in the meta-analysis[1] and calls for validation of these findings,[2],[3] we investigated whether body habitus modulated the efficacy of aspirin in a post hoc analysis of the ASPREE trial (Aspirin in Reducing Events in the Elderly).[4] ASPREE randomized 19 114 older participants to daily 100-mg enteric-coated aspirin (9525) or matched placebo (9589) and followed them up for a median of 4.7 years for disability-free survival and other clinical outcomes.[4] Trial participants were community-dwelling Australian (16 703) and US (2411) men and women who were >=70 years of age at enrollment or >=65 years of age for US blacks and Hispanics. At baseline, anthropometric indexes (mean±SD) of body weight, BMI, waist circumference, and LBM in the aspirin versus placebo groups were 77.0±15.1 kg versus 77.0±14.8 kg, 28.1±4.8 kg/m SP 2 sp versus 28.1±4.7 kg/m SP 2 sp , 97±13 cm versus 97±13 cm, and 49.8±8.3 kg versus 49.9±8.2 kg, respectively. Larger BMI or waist circumference or LBM also did not alter the effect of aspirin on the risk of cardiovascular disease or major hemorrhage (Figure). [Extracted from the article]
Published: 2020
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources

Refine your results

17 results on '"Shah, Raj"'

1. Impact of Cognitive Impairment Across Specialties: Summary of a Report From the U13 Conference Series

2. Willingness to Be a Brain Donor

3. Brain amyloidosis ascertainment from cognitive, imaging, and peripheral blood protein measures

4. Dementia Prevention: optimizing the use of observational data for personal, clinical, and public health decision-making.

5. Vascular burden and Alzheimer disease pathologic progression

6. Glucose metabolism patterns: A potential index to characterize brain ageing and predict high conversion risk into cognitive impairment

7. Potential modifiable factors associated with late-life cognitive trajectories.

8. Higher CSF sTREM2 attenuates ApoE4-related risk for cognitive decline and neurodegeneration

9. The Health Equity through Aging Research and Discussion (HEARD) study: A proposed two-phase sequential mixed-methods research design to understand barriers and facilitators of brain donation among diverse older adults

10. In vivo staging of regional amyloid deposition

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

12. Does posterior cingulate hypometabolism result from disconnection or local pathology across preclinical and clinical stages of Alzheimer's disease?

13. Body mass index is associated with biological CSF markers of core brain pathology of Alzheimer's disease

14. Common genetic variants influence human subcortical brain structures

15. Applying automated MR-based diagnostic methods to the memory clinic: A prospective study

16. 1195Brain-predicted age difference is associated with cognitive processing and delayed recall in later life.

17. No Modulation of the Effect of Aspirin by Body Weight in Healthy Older Men and Women.

Catalog

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

17 results on '"Shah, Raj"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources