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2. Can We Use Blood Biomarkers as Entry Criteria and for Monitoring Drug Treatment Effects in Clinical Trials? A Report from the EU/US CTAD Task Force

Author

Angioni, D., Hansson, O., Bateman, R. J., Rabe, C., Toloue, M., Braunstein, J. B., Agus, S., Sims, J. R., Bittner, T., Carrillo, M. C., Fillit, H., Masters, C. L., Salloway, S., Aisen, P., Weiner, M., Vellas, B., Gauthier, S., Abushakra, Susan, Afshar, Mohammad, Alam, John, Algeciras-Schimnich, Alicia, Andrieu, Sandrine, Ballard, Clive, Baruch, Amos, Batrla, Richard, Baudler, Monika, Bell, Joanne, Bozeat, Sasha, Brooks, Dawn, Brooks, Tricia, Bullain, Szofia, Burmeister, Jan, Cho, Min, Collins, Emily, Cook, Gavin, Cummings, Jeffrey, Dague, Chris, De Santi, Susan, Doody, Rachelle, Dunn, Billy, Egan, Michael, Eriksson, Sven, Esquivel, Rianne, Fagan, Tom, Ferrell, Phyllis, Gallagher, Michela, Grönblad, Anna-Kaija, Hains, Avis, Hampel, Harald, Hefting, Nanco, Hendrix, Suzanne, Ho, Carole, Hu, Helen, Ismail, Zahinoor, Jones, Daryl, Kinney, Gene, Kinnon, Paul, Kurzman, Ricky, Lannfelt, Lars, Lawson, John, LeBastard, Nathalie, Legrand, Valérie, Lewandowski, Nicole, Lim, Carine, Lyketsos, Costantine, Masterman, Donna, Lu, Ming, Mintun, Mark, Molinuevo, José Luis, Monteiro, Cecilia, Navia, Bradford, Odergren, Tomas, Osswald, Gunilla, Penny, Lewis, Pontecorvo, Michael, Porsteinsson, Anton, Raman, Rema, Respondek, Gesine, Reyderman, Larisa, Rogers, Sharon, Rosenberg, Paul, Rosenzweig-Lipson, Sharon, Roskey, Mark, Carrie, Rubel, Saad, Ziad, Schindler, Rachel, Selkoe, Dennis, Shulman, Melanie, Sink, Kaycee, Sipe, Lisa, Skovronsky, Daniel, Somers, Elizabeth, Soto, Maria, Streffer, Johannes, Such, Pedro, Suhy, Joyce, Touchon, Jacques, Vandijck, Manu, White, Anne, Wilson, David, Zago, Wagner, and Zhou, Jin

Published
2023
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3. Blood Biomarkers from Research Use to Clinical Practice: What Must Be Done? A Report from the EU/US CTAD Task Force

Author

Angioni, Davide, Delrieu, J, Hansson, O, Fillit, H, Aisen, P, Cummings, J, Sims, JR, Braunstein, JB, Sabbagh, M, Bittner, T, Pontecorvo, M, Bozeat, S, Dage, JL, Largent, E, Mattke, S, Correa, O, Gutierrez Robledo, LM, Baldivieso, V, Willis, DR, Atri, A, Bateman, RJ, Ousset, P-J, Vellas, B, and Weiner, M

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Prevention, Clinical Research, Aging, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Good Health and Well Being, Humans, Alzheimer Disease, Biomarkers, Advisory Committees, Alzheimer’s disease, amyloid, blood biomarkers, clinical trials, diagnostic, neurofilament light, p-tau, Neurosciences, Biological psychology, Cognitive and computational psychology
Abstract

Timely and accurate diagnosis of Alzheimer's disease (AD) in clinical practice remains challenging. PET and CSF biomarkers are the most widely used biomarkers to aid diagnosis in clinical research but present limitations for clinical practice (i.e., cost, accessibility). Emerging blood-based markers have the potential to be accurate, cost-effective, and easily accessible for widespread clinical use, and could facilitate timely diagnosis. The EU/US CTAD Task Force met in May 2022 in a virtual meeting to discuss pathways to implementation of blood-based markers in clinical practice. Specifically, the CTAD Task Force assessed: the state-of-art for blood-based markers, the current use of blood-based markers in clinical trials, the potential use of blood-based markers in clinical practice, the current challenges with blood-based markers, and the next steps needed for broader adoption in clinical practice.

Published
2022

4. Using Digital Tools to Advance Alzheimer’s Drug Trials During a Pandemic: The EU/US CTAD Task Force

Author

Kaye, Jeffrey, Aisen, P, Amariglio, R, Au, R, Ballard, C, Carrillo, M, Fillit, H, Iwatsubo, T, Jimenez-Maggiora, G, Lovestone, S, Natanegara, F, Papp, K, Soto, ME, Weiner, M, and Vellas, B

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Brain Disorders, Clinical Research, Neurosciences, Aging, Neurodegenerative, Clinical Trials and Supportive Activities, Alzheimer's Disease, Acquired Cognitive Impairment, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Neurological, Good Health and Well Being, Advisory Committees, Alzheimer Disease, Biomedical Research, COVID-19, Clinical Trials as Topic, Digital Technology, European Union, Humans, United States, Alzheimer’s disease, clinical outcomes, digital tools, remote assessments, Biological psychology, Cognitive and computational psychology
Abstract

The 2020 COVID-19 pandemic has disrupted Alzheimer's disease (AD) clinical studies worldwide. Digital technologies may help minimize disruptions by enabling remote assessment of subtle cognitive and functional changes over the course of the disease. The EU/US Clinical Trials in Alzheimer's Disease (CTAD) Task Force met virtually in November 2020 to explore the opportunities and challenges associated with the use of digital technologies in AD clinical research. While recognizing the potential of digital tools to accelerate clinical trials, improve the engagement of diverse populations, capture clinically meaningful data, and lower costs, questions remain regarding the stability, validity, generalizability, and reproducibility of digital data. Substantial concerns also exist regarding regulatory acceptance and privacy. Nonetheless, the Task Force supported further exploration of digital technologies through collaboration and data sharing, noting the need for standardization of digital readouts. They also concluded that while it may be premature to employ remote assessments for trials of novel experimental medications, remote studies of non-invasive, multi-domain approaches may be feasible at this time.

Published
2021

6. Progress toward standardized diagnosis of vascular cognitive impairment: Guidelines from the Vascular Impairment of Cognition Classification Consensus Study

Author

Taragano, F.E., Kril, J., Cavalieri, M., Jellinger, K.A., Kovacs, G.G., Engelborghs, S., Lafosse, C., Bertolucci, P.H., Brucki, S., Caramelli, P., de Toledo Ferraz Alves, T.C., Bocti, C., Fulop, T., Hogan, D.B., Hsiung, G.R., Kirk, A., Leach, L., Robillard, A., Sahlas, D.J., Guo, Q., Tian, J., Hokkanen, L., Jokinen, H., Benisty, S., Deramecourt, V., Hauw, J., Lenoir, H., Tsatali, M., Tsolaki, M., Sundar, U., Coen, R.F., Korczyn, A.D., Altieri, M., Baldereschi, M., Caltagirone, C., Caravaglios, G., Di Carlo, A., Di Piero, V., Gainotti, G., Galluzzi, S., Logroscino, G., Mecocci, P., Moretti, D.V., Padovani, A., Fukui, T., Ihara, M., Mizuno, T., Kim, S.Y., Akinyemi, R., Baiyewu, O., Ogunniyi, A., Szczudlik, A., Bastos-Leite, A.J., Firmino, H., Massano, J., Verdelho, A., Kruglov, L.S., Ikram, M.K., Kandiah, N., Arana, E., Barroso-Ribal, J., Calatayud, T., Cruz-Jentoft, A.J., López-Pousa, S., Martinez-Lage, P., Mataro, M., Börjesson-Hanson, A., Englund, E., Laukka, E.J., Qiu, C., Viitanen, M., Biessels, G.J., de Leeuw, F.-E., den Heijer, T., Exalto, L.G., Kappelle, L.J., Prins, N.D., Richard, E., Schmand, B., van den Berg, E., van der Flier, W.M., Bilgic, B., Allan, L.M., Archer, J., Attems, J., Bayer, A., Blackburn, D., Brayne, C., Bullock, R., Connelly, P.J., Farrant, A., Fish, M., Harkness, K., Ince, P.G., Langhorne, P., Mann, J., Matthews, F.E., Mayer, P., Pendlebury, S.T., Perneczky, R., Peters, R., Smithard, D., Stephan, B.C., Swartz, J.E., Todd, S., Werring, D.J., Wijayasiri, S.N., Wilcock, G., Zamboni, G., Au, R., Borson, S., Bozoki, A., Browndyke, J.N., Corrada, M.M., Crane, P.K., Diniz, B.S., Etcher, L., Fillit, H., Greenberg, S.M., Grinberg, L.T., Hurt, S.W., Lamar, M., Mielke, M., Ott, B.R., Perry, G., Powers, W.J., Ramos-Estebanez, C., Reed, B., Roberts, R.O., Romero, J.R., Saykin, A.J., Seshadri, S., Silbert, L., Stern, Y., Zarow, C., Skrobot, Olivia A., Black, Sandra E., Chen, Christopher, DeCarli, Charles, Erkinjuntti, Timo, Ford, Gary A., Kalaria, Rajesh N., O'Brien, John, Pantoni, Leonardo, Pasquier, Florence, Roman, Gustavo C., Wallin, Anders, Sachdev, Perminder, Skoog, Ingmar, Ben-Shlomo, Yoav, Passmore, Anthony P., Love, Seth, and Kehoe, Patrick G.

Published
2018
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9. The Vascular Impairment of Cognition Classification Consensus Study

Author

Taragano, F.E., Kril, J., Cavalieri, M., Jellinger, K.A., Kovacs, G.G., Engelborghs, S., Lafosse, C., Bertolucci, P.H., Brucki, S., Caramelli, P., de Toledo Ferraz Alves, T.C., Bocti, C., Fulop, T., Hogan, D.B., Hsiung, G.R., Kirk, A., Leach, L., Robillard, A., Sahlas, D.J., Guo, Q., Tian, J., Hokkanen, L., Jokinen, H., Benisty, S., Deramecourt, V., Hauw, J., Lenoir, H., Tsatali, M., Tsolaki, M., Sundar, U., Coen, R.F., Korczyn, A.D., Altieri, M., Baldereschi, M., Caltagirone, C., Caravaglios, G., Di Carlo, A., DI Piero, V., Gainotti, G., Galluzzi, S., Logroscino, G., Mecocci, P., Moretti, D.V., Padovani, A., Fukui, T., Ihara, M., Mizuno, T., Kim, S.Y., Akinyemi, R., Baiyewu, O., Ogunniyi, A., Szczudlik, A., Bastos-Leite, A.J., Firmino, H., Massano, J., Verdelho, A., Kruglov, L.S., Ikram, M.K., Kandiah, N., Arana, E., Barroso-Ribal, J., Calatayud, T., Cruz-Jentoft, A.J., López-Pousa, S., Martinez-Lage, P., Mataro, M., Börjesson-Hanson, A., Englund, E., Laukka, E.J., Qiu, C., Viitanen, M., Biessels, G.J., de Leeuw, F.-E., den Heijer, T., Exalto, L.G., Kappelle, L.J., Prins, N.D., Richard, E., Schmand, B., van den Berg, E., van der Flier, W.M., Bilgic, B., Allan, L.M., Archer, J., Attems, J., Bayer, A., Blackburn, D., Brayne, C., Bullock, R., Connelly, P.J., Farrant, A., Fish, M., Harkness, K., Ince, P.G., Langhorne, P., Mann, J., Matthews, F.E., Mayer, P., Pendlebury, S.T., Perneczky, R., Peters, R., Smithard, D., Stephan, B.C., Swartz, J.E., Todd, S., Werring, D.J., Wijayasiri, S.N., Wilcock, G., Zamboni, G., Au, R., Borson, S., Bozoki, A., Browndyke, J.N., Corrada, M.M., Crane, P.K., Diniz, B.S., Etcher, L., Fillit, H., Greenberg, S.M., Grinberg, L.T., Hurt, S.W., Lamar, M., Mielke, M., Ott, B.R., Perry, G., Powers, W.J., Ramos-Estebanez, C., Reed, B., Roberts, R.O., Romero, J.R., Saykin, A.J., Seshadri, S., Silbert, L., Stern, Y., Zarow, C., Skrobot, Olivia A., O'Brien, John, Black, Sandra, Chen, Christopher, DeCarli, Charles, Erkinjuntti, Timo, Ford, Gary A., Kalaria, Rajesh N., Pantoni, Leonardo, Pasquier, Florence, Roman, Gustavo C., Wallin, Anders, Sachdev, Perminder, Skoog, Ingmar, Ben-Shlomo, Yoav, Passmore, Anthony P., Love, Seth, and Kehoe, Patrick G.

Published
2017
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11. Using Digital Tools to Advance Alzheimer's Drug Trials During a Pandemic: The EU/US CTAD Task Force

Author

Kaye, J, Aisen, P, Amariglio, R, Au, R, Ballard, C, Carrillo, M, Fillit, H, Iwatsubo, T, Jimenez-Maggiora, G, Lovestone, S, Natanegara, F, Papp, K, Soto, ME, Weiner, M, and Vellas, B

Subjects
Clinical Trials as Topic, Digital Technology, Aging, Biomedical Research, Advisory Committees, Clinical Trials and Supportive Activities, Neurosciences, COVID-19, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, Alzheimer's Disease, remote assessments, United States, clinical outcomes, Brain Disorders, Good Health and Well Being, Alzheimer Disease, Clinical Research, Neurological, Acquired Cognitive Impairment, Humans, Dementia, European Union, Alzheimer’s disease, digital tools
Abstract

The 2020 COVID-19 pandemic has disrupted Alzheimer's disease (AD) clinical studies worldwide. Digital technologies may help minimize disruptions by enabling remote assessment of subtle cognitive and functional changes over the course of the disease. The EU/US Clinical Trials in Alzheimer's Disease (CTAD) Task Force met virtually in November 2020 to explore the opportunities and challenges associated with the use of digital technologies in AD clinical research. While recognizing the potential of digital tools to accelerate clinical trials, improve the engagement of diverse populations, capture clinically meaningful data, and lower costs, questions remain regarding the stability, validity, generalizability, and reproducibility of digital data. Substantial concerns also exist regarding regulatory acceptance and privacy. Nonetheless, the Task Force supported further exploration of digital technologies through collaboration and data sharing, noting the need for standardization of digital readouts. They also concluded that while it may be premature to employ remote assessments for trials of novel experimental medications, remote studies of non-invasive, multi-domain approaches may be feasible at this time.

Published
2021

14. 1st Conference Clinical Trials on Alzheimer’s Disease September 17-18-19, 2008 School of Medecine Montpellier, France

Author

Gabelle, A., Roche, S., Gény, C., Portet, F., Touchon, J., Lehmann, S., De Meyer, G., Shapiro, F., Vanderstichele, H., Vanmechelen, E., Engelborghs, S., De Deyn, P. P., Shaw, L., Trojanowski, J., Nestor, S. M., Rupsingh, R., Borrie, M., Smith, M., Wells, J. L., Bartha, R., Blennow, K., De Meyer, G., Hansson, O., Minthon, L., Wallin, A., Zetterberg, H., Lewezuk, P., Vandertischele, H., Kornhuber, J., Wiltfang, J., Iqbal, K., Chalbot, S., Grundke-Iqbal, I., Gertz, H. J., Berwig, M., Leicht, H., Zhu, C. W., Leibman, C., Townsend, R., Mclaughlin, T., Scarmeas, N., Albert, M., Brandt, J., Blacker, D., Sano, M., Stern, Y., Bravo, G., Dubois, M. F., Hansel, S., Duguet, A. M., Robert, P. H., Deudon, A., Ake, N., Gervais, X., Leone, E., Lavallart, B., Amato, D., Zavitz, K., Green, R. C., Schneider, L. S., Swabb, E., Van Kan, G. Abellan, Carrie, I., Gillette, S., Soto, M. E., Gardette, J., Przybylski, C., Andrieu, S., Vellas, B., Dangour, A. D., Allen, E., Elbourne, D., Fletcher, A., Richards, M., Uauy, R., Green, R. C., Schneider, L. S., Zavitz, K. H., Wurtman, R. J., Peters, O., Lorenz, D., Möller, H. J., Frölich, L., Heuser, I., Vandenberghe, R., Thurfjell, L., Owenius, R., Brooks, D. J., Nelissen, N., Koole, M., Bormans, G., Van Laere, K., Boada, M., Muñoz, J., Tárraga, L., Ortiz, P., Hernández, I., Becker, J., López, O., Buendia, M., Pla, R., Grifols, J. R., Paez, A., Núñez, L., Ferrer, I., Lachno, D. R., De Groote, G., Kostanjevecki, V., Siemers, E. R., Willey, M. B., Ruiz, A., Ramírez-Lorca, R., Sáez, M. E., Mauleón, A., Rosende-Roca, M., Martínez-Lage, P., Gutiérrez, M., Real, L. Miguel, López-arrieta, J., Gayán, J., Antúnez, C., González-Pérez, A., Hugonot-Diener, L., Bchiri, J. El, Fraisse, M. L., Von Raison, F., Bone, M., Duron, E., Husson, J. M., Meeuwsen, E. J., Melis, R. J. F., Adang, E. M., Krabbe, P. F., Schölzel-Dorenbos, C. J. M., Ruckert, M. G. M. Olde, Truemner, J., Best, S., Lozanski, M., Nsiah, C., Wells, J., Tractenberg, R. E., Tractenberg, R. E., Chu, L. W., Yik, P. Y., Mok, W., Chung, C. P., Gauthier, S., Douillet, P., Doody, R., Fox, N. C., Orgogozo, J. M., Ingenbleek, Y., Bienvenu, J., Molloy, D. W., Standish, T., Cowan, D., Almeida, E., Diloreto, P., Woolmore-Goodwin, S., Clarke, J., Berardi, P., Smith, M., Purcell, T., Woolmore-Goodwin, S., Gutmanis, I., Borrie, M., Robert, P. H., Reynish, E., Cantet, C., Erder, M. H., Fillit, H., Hofbauer, R. K., Setyawan, J., Tourkodimitris, S., Fridman, M., Lyketsos, C., Unzeta, M., Valente, T., Hidalgo, J., Ramirez, B., Anglés, N., Morelló, J. R., Reguant, J., Boada, M., Claassen, J. A., Van Beek, A. H., Olde Rikkert, M. G., Roca, I., Cuberas, G., Castell, J., Buendia, M., Pla, R., Núñez, L., Ferrer, I., Latger, C., Tramoni, E., Elkhoury, C., Aubert-Khalfa, S., Ceccaldi, M., Schneeberger, A., Mandler, M., Otava, O., Mattner, F., Schmidt, W., Gatignol, P., David, C., Guitton, C., Plaza, M., Szaniszlo, P., German, P., Hajas, G., Kruzel, M., Boldogh, I., Wesnes, K., Satek, S., Turk, P., Satek, S., Vinay, M., Wetten, S., Li, H., Galwey, N., Gibson, R. A., Irizarry, M. C., Nourhashémi, F., Gillette-Guyonnet, S., Andrieu, S., Rolland, Y., Ousset, P. J., Verwey, N. A., Blennow, K., Clark, C., Cole, G. M., De Deyn, P. P., Galasko, D., Hampel, H., Hartmann, T., Kapaki, E., Lannfelt, L., Mehta, P. D., Parnetti, L., Petzold, A., Pirttila, T., Saleh, L., Skinningsrud, A., Swieten, J. C. V., Verbeek, M. M., Wiltfang, J., Younkin, S., Blankenstein, M. A., Ishihara-Paul, L., Viswanathan, A., Allen, J. K., Hyman, B. T., Betensky, R., Weil, J., The Alzheimer’s Disease Neuroimaging Initiative, The MAPT Study Investigators, The Xaliproden Ad Study Team, and the PLASA Group

Published
2008
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15. Practical recommendations for timely, accurate diagnosis of symptomatic Alzheimer’s disease (MCI and dementia) in primary care: a review and synthesis

Author

Liss, J. L., primary, Seleri Assunção, S., additional, Cummings, J., additional, Atri, A., additional, Geldmacher, D. S., additional, Candela, S. F., additional, Devanand, D. P., additional, Fillit, H. M., additional, Susman, J., additional, Mintzer, J., additional, Bittner, T., additional, Brunton, S. A., additional, Kerwin, D. R., additional, Jackson, W. C., additional, Small, G. W., additional, Grossberg, G. T., additional, Clevenger, C. K., additional, Cotter, V., additional, Stefanacci, R., additional, Wise‐Brown, A., additional, and Sabbagh, M. N., additional

Published
2021
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16. Progress toward standardized diagnosis of vascular cognitive impairment

Author

Skrobot, Olivia A., Black, Sandra E., Chen, Christopher, DeCarli, Charles, Erkinjuntti, Timo, Ford, Gary A., Kalaria, Rajesh N., O'Brien, John, Pantoni, Leonardo, Pasquier, Florence, Roman, Gustavo C., Wallin, Anders, Sachdev, Perminder, Skoog, Ingmar, Ben-Shlomo, Yoav, Passmore, Anthony P., Love, Seth, Kehoe, Patrick G., Taragano, F.E., Kril, J., Cavalieri, M., Jellinger, K.A., Kovacs, G.G., Engelborghs, S., Lafosse, C., Bertolucci, P.H., Brucki, S., Caramelli, P., de Toledo Ferraz Alves, T.C., Bocti, C., Fulop, T., Hogan, D.B., Hsiung, G.R., Kirk, A., Leach, L., Robillard, A., Sahlas, D.J., Guo, Q., Tian, J., Hokkanen, L., Jokinen, H., Benisty, S., Deramecourt, V., Hauw, J., Lenoir, H., Tsatali, M., Tsolaki, M., Sundar, U., Coen, R.F., Korczyn, A.D., Altieri, M., Baldereschi, M., Caltagirone, C., Caravaglios, G., Di Carlo, A., Di Piero, V., Gainotti, G., Galluzzi, S., Logroscino, G., Mecocci, P., Moretti, D.V., Padovani, A., Fukui, T., Ihara, M., Mizuno, T., Kim, S.Y., Akinyemi, R., Baiyewu, O., Ogunniyi, A., Szczudlik, A., Bastos-Leite, A.J., Firmino, H., Massano, J., Verdelho, A., Kruglov, L.S., Ikram, M.K., Kandiah, N., Arana, E., Barroso-Ribal, J., Calatayud, T., Cruz-Jentoft, A.J., López-Pousa, S., Martinez-Lage, P., Mataro, M., Börjesson-Hanson, A., Englund, E., Laukka, E.J., Qiu, C., Viitanen, M., Biessels, G.J., de Leeuw, F.-E., den Heijer, T., Exalto, L.G., Kappelle, L.J., Prins, N.D., Richard, E., Schmand, B., van den Berg, E., van der Flier, W.M., Bilgic, B., Allan, L.M., Archer, J., Attems, J., Bayer, A., Blackburn, D., Brayne, C., Bullock, R., Connelly, P.J., Farrant, A., Fish, M., Harkness, K., Ince, P.G., Langhorne, Peter, Mann, J., Matthews, F.E., Mayer, P., Pendlebury, S.T., Perneczky, R., Peters, R., Smithard, D., Stephan, B.C., Swartz, J.E., Todd, S., Werring, D.J., Wijayasiri, S.N., Wilcock, G., Zamboni, G., Au, R., Borson, S., Bozoki, A., Browndyke, J.N., Corrada, M.M., Crane, P.K., Diniz, B.S., Etcher, L., Fillit, H., Greenberg, S.M., Grinberg, L.T., Hurt, S.W., Lamar, M., Mielke, M., Ott, B.R., Perry, G., Powers, W.J., Ramos-Estebanez, C., Reed, B., Roberts, R.O., Romero, J.R., Saykin, A.J., Seshadri, S., Silbert, L., Stern, Y., Zarow, C., Epidemiology, Neurology, General Practice, VICCCS Grp, Clinicum, Neurologian yksikkö, Department of Neurosciences, University of Helsinki, Department of Physics, HUS Neurocenter, Amsterdam Neuroscience - Neurodegeneration, APH - Personalized Medicine, and APH - Methodology

Subjects
0301 basic medicine, Neurology, Delphi Technique, Epidemiology, Delphi method, Delphi, Vascular dementia, 3124 Neurology and psychiatry, 0302 clinical medicine, SMALL VESSEL DISEASE, Neuropsychological assessment, Stroke, medicine.diagnostic_test, Health Policy, Neuropsychology, CLINICAL-CRITERIA, Brain, Cognition, 3. Good health, ALZHEIMERS-DISEASE, Settore MED/26 - NEUROLOGIA, Psychiatry and Mental health, Vascular cognitive impairment, NINDS-AIREN, ACUTE STROKE, STROKE, Clinical psychology, medicine.medical_specialty, Clinical Neurology, MINI-MENTAL-STATE, Guidelines, ATROPHY, 03 medical and health sciences, Cellular and Molecular Neuroscience, WHITE-MATTER CHANGES, Developmental Neuroscience, Vascular, medicine, Journal Article, Dementia, Humans, Intensive care medicine, business.industry, Dementia, Vascular, 3112 Neurosciences, medicine.disease, Criteria, 030104 developmental biology, consensus, Consensus, Neurology (clinical), Geriatrics and Gerontology, Psychiatry and Mental Health, CEREBRAL-BLOOD-FLOW, Human medicine, business, 030217 neurology & neurosurgery
Abstract

Hanna Jokinen tutkimusryhmän jäsenenä (VICCCS Grp) Introduction: Progress in understanding and management of vascular cognitive impairment (VCI) has been hampered by lack of consensus on diagnosis, reflecting the use of multiple different assessment protocols. A large multinational group of clinicians and researchers participated in a two-phase Vascular Impairment of Cognition Classification Consensus Study (VICCCS) to agree on principles (VICCCS-1) and protocols (VICCCS-2) for diagnosis of VCI. We present VICCCS-2. Methods: We used VICCCS-1 principles and published diagnostic guidelines as points of reference for an online Delphi survey aimed at achieving consensus on clinical diagnosis of VCI. Results: Six survey rounds comprising 65-79 participants agreed guidelines for diagnosis of VICCCS-revised mild and major forms of VCI and endorsed the National Institute of Neurological Disorders-Canadian Stroke Network neuropsychological assessment protocols and recommendations for imaging. Discussion: The VICCCS-2 suggests standardized use of the National Institute of Neurological Disorders-Canadian Stroke Network recommendations on neuropsychological and imaging assessment for diagnosis of VCI so as to promote research collaboration. (C) 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Published
2018

23. Progress toward standardized diagnosis of vascular cognitive impairment: Guidelines from the Vascular Impairment of Cognition Classification Consensus Study

Author

Skrobot, Olivia A., Black, Sandra E., Chen, Christopher, DeCarli, Charles, Erkinjuntti, Timo, Ford, Gary A., Kalaria, Rajesh N., O'Brien, John, Pantoni, Leonardo, Pasquier, Florence, Roman, Gustavo C., Wallin, Anders, Sachdev, Perminder, Skoog, Ingmar, VICCCS Group, Taragano, F. E., Kril, J., Cavalieri, M., Jellinger, K. A., Kovacs, G. G., Engelborghs, S., Lafosse, C., Bertolucci, P. H., Brucki, S., Caramelli, P., De Toledo Ferraz Alves, T. C., Bocti, C., Fulop, T., Hogan, D. B., Hsiung, G. R., Kirk, A., Leach, L., Robillard, A., Sahlas, D. J., Guo, Q., Tian, J., Hokkanen, L., Jokinen, H., Benisty, S., Deramecourt, V., Hauw, J., Lenoir, H., Tsatali, M., Tsolaki, M., Sundar, U., Coen, R. F., Korczyn, A. D., Altieri, M., Baldereschi, M., Caltagirone, C., Caravaglios, G., Di Carlo, A., Di Piero, V., Gainotti, G., Galluzzi, S., Logroscino, G., Mecocci, P., Moretti, D. V., Padovani, A., Fukui, T., Ihara, M., Mizuno, T., Kim, S. Y., Akinyemi, R., Baiyewu, O., Ogunniyi, A., Szczudlik, A., Bastos-Leite, A. J., Firmino, H., Massano, J., Verdelho, A., Kruglov, L. S., Ikram, M. K., Kandiah, N., Arana, E., Barroso-Ribal, J., Calatayud, T., Cruz-Jentoft, A. J., López-Pousa, S., Martinez-Lage, P., Mataro, M., Börjesson-Hanson, A., Englund, E., Laukka, E. J., Qiu, C., Viitanen, M., Biessels, G. J., De Leeuw, F.-E., Den Heijer, T., Exalto, L. G., Kappelle, L. J., Prins, N. D., Richard, E., Schmand, B., Van Den Berg, E., Van Der Flier, W. M., Bilgic, B., Allan, L. M., Archer, J., Attems, J., Bayer, A., Blackburn, D., Brayne, C., Bullock, R., Connelly, P. J., Farrant, A., Fish, M., Harkness, K., Ince, P. G., Langhorne, P., Mann, J., Matthews, F. E., Mayer, P., Pendlebury, S. T., Perneczky, R., Peters, R., Smithard, D., Stephan, B. C., Swartz, J. E., Todd, S., Werring, D. J., Wijayasiri, S. N., Wilcock, G., Zamboni, G., Au, R., Borson, S., Bozoki, A., Browndyke, J. N., Corrada, M. M., Crane, P. K., Diniz, B. S., Etcher, L., Fillit, H., Greenberg, S. M., Grinberg, L. T., Hurt, S. W., Lamar, M., Mielke, M., Ott, B. R., Perry, G., Powers, W. J., Ramos-Estebanez, C., Reed, B., Roberts, R. O., Romero, J. R., Saykin, A. J., Seshadri, S., Silbert, L., Stern, Yaakov, Zarow, C., Ben-Shlomo, Yoav, Passmore, Anthony P., Love, Seth, and Kehoe, Patrick G.

Subjects
Cognition disorders, Cognition disorders--Diagnosis, FOS: Clinical medicine, Neurosciences
Abstract

Introduction: Progress in understanding and management of vascular cognitive impairment (VCI) has been hampered by lack of consensus on diagnosis, reflecting the use of multiple different assessment protocols. A large multinational group of clinicians and researchers participated in a two-phase Vascular Impairment of Cognition Classification Consensus Study (VICCCS) to agree on principles (VICCCS-1) and protocols (VICCCS-2) for diagnosis of VCI. We present VICCCS-2. Methods: We used VICCCS-1 principles and published diagnostic guidelines as points of reference for an online Delphi survey aimed at achieving consensus on clinical diagnosis of VCI. Results: Six survey rounds comprising 65–79 participants agreed guidelines for diagnosis of VICCCS-revised mild and major forms of VCI and endorsed the National Institute of Neurological Disorders–Canadian Stroke Network neuropsychological assessment protocols and recommendations for imaging. Discussion: The VICCCS-2 suggests standardized use of the National Institute of Neurological Disorders–Canadian Stroke Network recommendations on neuropsychological and imaging assessment for diagnosis of VCI so as to promote research collaboration.

Published
2018
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24. Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference

Author

Young, A. L., Marinescu, R. V., Oxtoby, N. P., Bocchetta, M., Yong, K., Firth, N. C., Cash, D. M., Thomas, D. L., Dick, K. M., Cardoso, J., van Swieten, J., Borroni, B., Galimberti, D., Masellis, M., Tartaglia, M. C., Rowe, J. B., Graff, C., Tagliavini, F., Frisoni, G. B., Laforce, R., Finger, E., de Mendonca, A., Sorbi, S., Warren, J. D., Crutch, S., Fox, N. C., Ourselin, S., Schott, J. M., Rohrer, J. D., Alexander, D. C., Andersson, C., Archetti, S., Arighi, A., Benussi, L., Binetti, G., Black, S., Cosseddu, M., Fallstrom, M., Ferreira, C., Fenoglio, C., Freedman, M., Fumagalli, G. G., Gazzina, S., Ghidoni, R., Grisoli, M., Jelic, V., Jiskoot, L., Keren, R., Lombardi, G., Maruta, C., Meeter, L., Mead, S., van Minkelen, R., Nacmias, B., Oijerstedt, L., Padovani, A., Panman, J., Pievani, M., Polito, C., Premi, E., Prioni, S., Rademakers, R., Redaelli, V., Rogaeva, E., Rossi, G., Rossor, M., Scarpini, E., Tang-Wai, D., Thonberg, H., Tiraboschi, P., Verdelho, A., Weiner, M. W., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M. M., Potter, W., Snyder, P., Schwartz, A., Montine, T., Thomas, R. G., Donohue, M., Walter, S., Gessert, D., Sather, T., Jiminez, G., Harvey, D., Bernstein, M., Thompson, P., Schuff, N., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Cairns, N. J., Householder, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., Buckholtz, N., Albert, M., Frank, R., Hsiao, J., Kaye, J., Quinn, J., Lind, B., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Beccera, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Doody, R. S., Villanueva-Meyer, J., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Ances, B., Carroll, M., Leon, S., Mintun, M. A., Schneider, S., Oliver, A., Marson, D., Griffith, R., Clark, D., Geldmacher, D., Brockington, J., Roberson, E., Grossman, H., Mitsis, E., de Toledo-Morrell, L., Shah, R. C., Duara, R., Varon, D., Greig, M. T., Roberts, P., Onyike, C., D'Agostino, D., Kielb, S., Galvin, J. E., Cerbone, B., Michel, C. A., Rusinek, H., de Leon, M. J., Glodzik, L., De Santi, S., Doraiswamy, P. M., Petrella, J. R., Wong, T. Z., Arnold, S. E., Karlawish, J. H., Wolk, D., Smith, C. D., Jicha, G., Hardy, P., Sinha, P., Oates, E., Conrad, G., Lopez, O. L., Oakley, M. A., Simpson, D. M., Porsteinsson, A. P., Goldstein, B. S., Martin, K., Makino, K. M., Ismail, M. S., Brand, C., Mulnard, R. A., Thai, G., Mc-Adams-Ortiz, C., Womack, K., Mathews, D., Quiceno, M., Diaz-Arrastia, R., King, R., Weiner, M., Martin-Cook, K., Devous, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Anderson, H. S., Swerdlow, R. H., Apostolova, L., Tingus, K., Woo, E., Silverman, D. H., P. H., Lu, Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Kendall, T., Johnson, H., Farlow, M. R., Hake, A. M., Matthews, B. R., Herring, S., Hunt, C., van Dyck, C. H., Carson, R. E., Macavoy, M. G., Chertkow, H., Bergman, H., Hosein, C., Stefanovic, B., Caldwell, C., Hsiung, G. -Y. R., Feldman, H., Mudge, B., Assaly, M., Kertesz, A., Rogers, J., Bernick, C., Munic, D., Kerwin, D., Mesulam, M. -M., Lipowski, K., C. -K., Wu, Johnson, N., Sadowsky, C., Martinez, W., Villena, T., Turner, R. S., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Frey, M., Lane, B., Rosen, A., Tinklenberg, J., Sabbagh, M. N., Belden, C. M., Jacobson, S. A., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P. L., Allard, J., Lerner, A., Ogrocki, P., Hudson, L., Fletcher, E., Carmichael, O., Olichney, J., Decarli, C., Kittur, S., Borrie, M., Lee, T. -Y., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Potkin, S. G., Preda, A., Nguyen, D., Tariot, P., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Adeli, A., Zimmerman, E. A., Celmins, D., Brown, A. D., Pearlson, G. D., Blank, K., Anderson, K., Santulli, R. B., Kitzmiller, T. J., Schwartz, E. S., Sink, K. M., Williamson, J. D., Garg, P., Watkins, F., Ott, B. R., Querfurth, H., Tremont, G., Salloway, S., Malloy, P., Correia, S., Rosen, H. J., Miller, B. L., Mintzer, J., Spicer, K., Bachman, D., Pasternak, S., Rachinsky, I., Drost, D., Pomara, N., Hernando, R., Sarrael, A., Schultz, S. K., Ponto, L. L. B., Shim, H., Smith, K. E., Relkin, N., Chaing, G., Raudin, L., Smith, A., Fargher, K., Raj, B. A., Neylan, T., Grafman, J., Davis, M., Morrison, R., Hayes, J., Finley, S., Friedl, K., Fleischman, D., Arfanakis, K., James, O., Massoglia, D., Fruehling, J. J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Taylor, J. L., and Furst, A. J.

Published
2018

25. Vascular dementia: stroke prevention takes on new urgency

Author

Butler, R.N., Ahronheim, J., Fillit, H., Rapaport, S.I., and Tatemichi, T.K.

Subjects
Hypertension -- Care and treatment, Health, Seniors
Abstract

Studies have shown that vascular dementia may be more common than strokes in causing dementia. Alzheimer's disease is the most common cause. Vascular dementia may be more amenable to treatment than Alzheimer's, and prompt treatment may prevent a later stroke. A panel of physicians held a discussion about diagnosis, the factors leading to risk and the likely prognosis., Vascular dementia is a clinical syndrome of acquired intellectual impairment resulting from brain injury due to a cerebrovascular disorder. It is a complex diagnosis, and diagnostic criteria vary. In community [...]

Published
1993

26. DESIGNING TRIALS OF DISEASE MODIFYING AGENTS FOR EARLY AND PRECLINICAL ALZHEIMER’S DISEASE INTERVENTION: WHAT EVIDENCE IS MEANINGFUL TO PATIENTS, PROVIDERS, AND PAYERS?

Author

Messner, D.A., primary, Rabins, P., additional, Downing, A.C., additional, Irizarry, M., additional, Foster, N.L., additional, Al Naber, J., additional, Dabbous, O., additional, Fillit, H., additional, Gabler, S., additional, Krakauer, R., additional, Lotz, D., additional, Payzant, E., additional, Schneider, L., additional, Tyrone, J., additional, Van Amerongen, D., additional, and Wuest, D., additional

Published
2018
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28. Association between anticholinergic medication use and cognition, brain metabolism, and brain atrophy in cognitively normal older adults

Author

Risacher, SL, McDonald, BC, Tallman, EF, West, JD, Farlow, MR, Unverzagt, FW, Gao, S, Boustani, M, Crane, PK, Petersen, RC, Jack, CR, Jagust, WJ, Aisen, PS, Weiner, MW, Saykin, AJ, Trojanowki, JQ, Toga, AW, Beckett, L, Green, RC, Morris, J, Shaw, LM, Khachaturian, Z, Sorensen, G, Carrillo, M, Kuller, L, Raichle, M, Paul, S, Davies, P, Fillit, H, Hefti, F, Holtzman, D, Mesulam, MM, Potter, W, Snyder, PJ, Schwartz, A, Montine, T, Thomas, RG, Donohue, M, Walter, S, Gessert, D, Sather, T, Jiminez, G, Balasubramanian, AB, Mason, J, Sim, I, Harvey, D, Bernstein, M, Fox, N, Thompson, P, Schuff, N, DeCarli, C, Borowski, B, Gunter, J, Senjem, M, Vemuri, P, Jones, D, Kantarci, K, Ward, C, Koeppe, RA, Foster, N, Reiman, EM, Chen, K, Mathis, C, Landau, S, Cairns, NJ, Householder, E, Taylor-Reinwald, L, Lee, V, Korecka, M, Figurski, M, Crawford, K, and Neu, S

Abstract

Copyright 2016 American Medical Association. All rights reserved. IMPORTANCE The use of anticholinergic (AC) medication is linked to cognitive impairment and an increased risk of dementia. To our knowledge, this is the first study to investigate the association between AC medication use and neuroimaging biomarkers of brain metabolism and atrophy as a proxy for understanding the underlying biology of the clinical effects of AC medications. OBJECTIVE To assess the association between AC medication use and cognition, glucose metabolism, and brain atrophy in cognitively normal older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Indiana Memory and Aging Study (IMAS). DESIGN, SETTING, AND PARTICIPANTS The ADNI and IMAS are longitudinal studies with cognitive, neuroimaging, and other data collected at regular intervals in clinical and academic research settings. For the participants in the ADNI, visits are repeated 3, 6, and 12 months after the baseline visit and then annually. For the participants in the IMAS, visits are repeated every 18 months after the baseline visit (402 cognitively normal older adults in the ADNI and 49 cognitively normal older adults in the IMAS were included in the present analysis). Participants were either taking (hereafter referred to as the AC+ participants [52 from the ADNI and 8 from the IMAS]) or not taking (hereafter referred to as the AC- participants [350 from the ADNI and 41 from the IMAS]) at least 1 medication with medium or high AC activity. Data analysis for this study was performed in November 2015. MAIN OUTCOMES AND MEASURES Cognitive scores, mean fludeoxyglucose F 18 standardized uptake value ratio (participants from the ADNI only), and brain atrophy measures from structural magnetic resonance imaging were compared between AC+ participants and AC- participants after adjusting for potential confounders. The total AC burden score was calculated and was related to target measures. The association of AC use and longitudinal clinical decline (mean [SD] follow-up period, 32.1 [24.7] months [range, 6-108 months]) was examined using Cox regression. RESULTS The 52 AC+ participants (mean [SD] age, 73.3 [6.6] years) from the ADNI showed lower mean scores onWeschler Memory Scale-Revised Logical Memory Immediate Recall (raw mean scores: 13.27 for AC+ participants and 14.16 for AC- participants; P = .04) and the Trail Making Test Part B (raw mean scores: 97.85 seconds for AC+ participants and 82.61 seconds for AC- participants; P = .04) and a lower executive function composite score (raw mean scores: 0.58 for AC+ participants and 0.78 for AC- participants; P = .04) than the 350 AC- participants (mean [SD] age, 73.3 [5.8] years) from the ADNI. Reduced total cortical volume and temporal lobe cortical thickness and greater lateral ventricle and inferior lateral ventricle volumes were seen in the AC+ participants relative to the AC- participants. CONCLUSIONS AND RELEVANCE The use of AC medication was associated with increased brain atrophy and dysfunction and clinical decline. Thus, use of AC medication among older adults should likely be discouraged if alternative therapies are available.

Published
2016

30. The Vascular Impairment of Cognition Classification Consensus Study

Author

Skrobot, Olivia A., primary, O'Brien, John, additional, Black, Sandra, additional, Chen, Christopher, additional, DeCarli, Charles, additional, Erkinjuntti, Timo, additional, Ford, Gary A., additional, Kalaria, Rajesh N., additional, Pantoni, Leonardo, additional, Pasquier, Florence, additional, Roman, Gustavo C., additional, Wallin, Anders, additional, Sachdev, Perminder, additional, Skoog, Ingmar, additional, Taragano, F.E., additional, Kril, J., additional, Cavalieri, M., additional, Jellinger, K.A., additional, Kovacs, G.G., additional, Engelborghs, S., additional, Lafosse, C., additional, Bertolucci, P.H., additional, Brucki, S., additional, Caramelli, P., additional, Toledo Ferraz Alves, T.C., additional, Bocti, C., additional, Fulop, T., additional, Hogan, D.B., additional, Hsiung, G.R., additional, Kirk, A., additional, Leach, L., additional, Robillard, A., additional, Sahlas, D.J., additional, Guo, Q., additional, Tian, J., additional, Hokkanen, L., additional, Jokinen, H., additional, Benisty, S., additional, Deramecourt, V., additional, Hauw, J., additional, Lenoir, H., additional, Tsatali, M., additional, Tsolaki, M., additional, Sundar, U., additional, Coen, R.F., additional, Korczyn, A.D., additional, Altieri, M., additional, Baldereschi, M., additional, Caltagirone, C., additional, Caravaglios, G., additional, Di Carlo, A., additional, DI Piero, V., additional, Gainotti, G., additional, Galluzzi, S., additional, Logroscino, G., additional, Mecocci, P., additional, Moretti, D.V., additional, Padovani, A., additional, Fukui, T., additional, Ihara, M., additional, Mizuno, T., additional, Kim, S.Y., additional, Akinyemi, R., additional, Baiyewu, O., additional, Ogunniyi, A., additional, Szczudlik, A., additional, Bastos‐Leite, A.J., additional, Firmino, H., additional, Massano, J., additional, Verdelho, A., additional, Kruglov, L.S., additional, Ikram, M.K., additional, Kandiah, N., additional, Arana, E., additional, Barroso‐Ribal, J., additional, Calatayud, T., additional, Cruz‐Jentoft, A.J., additional, López‐Pousa, S., additional, Martinez‐Lage, P., additional, Mataro, M., additional, Börjesson‐Hanson, A., additional, Englund, E., additional, Laukka, E.J., additional, Qiu, C., additional, Viitanen, M., additional, Biessels, G.J., additional, Leeuw, F.‐E., additional, Heijer, T., additional, Exalto, L.G., additional, Kappelle, L.J., additional, Prins, N.D., additional, Richard, E., additional, Schmand, B., additional, Berg, E., additional, Flier, W.M., additional, Bilgic, B., additional, Allan, L.M., additional, Archer, J., additional, Attems, J., additional, Bayer, A., additional, Blackburn, D., additional, Brayne, C., additional, Bullock, R., additional, Connelly, P.J., additional, Farrant, A., additional, Fish, M., additional, Harkness, K., additional, Ince, P.G., additional, Langhorne, P., additional, Mann, J., additional, Matthews, F.E., additional, Mayer, P., additional, Pendlebury, S.T., additional, Perneczky, R., additional, Peters, R., additional, Smithard, D., additional, Stephan, B.C., additional, Swartz, J.E., additional, Todd, S., additional, Werring, D.J., additional, Wijayasiri, S.N., additional, Wilcock, G., additional, Zamboni, G., additional, Au, R., additional, Borson, S., additional, Bozoki, A., additional, Browndyke, J.N., additional, Corrada, M.M., additional, Crane, P.K., additional, Diniz, B.S., additional, Etcher, L., additional, Fillit, H., additional, Greenberg, S.M., additional, Grinberg, L.T., additional, Hurt, S.W., additional, Lamar, M., additional, Mielke, M., additional, Ott, B.R., additional, Perry, G., additional, Powers, W.J., additional, Ramos‐Estebanez, C., additional, Reed, B., additional, Roberts, R.O., additional, Romero, J.R., additional, Saykin, A.J., additional, Seshadri, S., additional, Silbert, L., additional, Stern, Y., additional, Zarow, C., additional, Ben‐Shlomo, Yoav, additional, Passmore, Anthony P., additional, Love, Seth, additional, and Kehoe, Patrick G., additional

Published
2016
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31. Large-scale genomics unveil polygenic architecture of human cortical surface area

Author

Chen, CH, Peng, Q, Schork, AJ, Lo, MT, Fan, CC, Wang, Y, Desikan, RS, Bettella, F, Hagler, DJ, Westlye, LT, Kremen, WS, Jernigan, TL, Le Hellard, S, Steen, VM, Espeseth, T, Huentelman, M, Håberg, AK, Agartz, I, Djurovic, S, Andreassen, OA, Schork, N, Dale, AM, McCabe, C, Chang, L, Akshoomoff, N, Newman, E, Ernst, T, Van Zijl, P, Kuperman, J, Murray, S, Bloss, C, Appelbaum, M, Gamst, A, Thompson, W, Bartsch, H, Weiner, M, Aisen, P, Petersen, R, Jack, CR, Jagust, W, Trojanowki, JQ, Toga, AW, Beckett, L, Green, RC, Saykin, AJ, Morris, J, Shaw, LM, Khachaturian, Z, Sorensen, G, Carrillo, M, Kuller, L, Raichle, M, Paul, S, Davies, P, Fillit, H, Hefti, F, Holtzman, D, Mesulman, MM, Potter, W, Snyder, PJ, Schwartz, A, Montine, T, Thomas, RG, Donohue, M, Walter, S, Gessert, D, Sather, T, Jiminez, G, Harvey, D, Bernstein, M, Fox, N, Thompson, P, Schuff, N, DeCarli, C, Borowski, B, Gunter, J, Senjem, M, Vemuri, P, Jones, D, Kantarci, K, Ward, C, Koeppe, RA, Foster, N, and Reiman, EM

Abstract

© 2015 Macmillan Publishers Limited. All rights reserved. Little is known about how genetic variation contributes to neuroanatomical variability, and whether particular genomic regions comprising genes or evolutionarily conserved elements are enriched for effects that influence brain morphology. Here, we examine brain imaging and single-nucleotide polymorphisms (SNPs) data from ∼ 2,700 individuals. We show that a substantial proportion of variation in cortical surface area is explained by additive effects of SNPs dispersed throughout the genome, with a larger heritable effect for visual and auditory sensory and insular cortices (h2 ∼ 0.45). Genome-wide SNPs collectively account for, on average, about half of twin heritability across cortical regions (N = 466 twins). We find enriched genetic effects in or near genes. We also observe that SNPs in evolutionarily more conserved regions contributed significantly to the heritability of cortical surface area, particularly, for medial and temporal cortical regions. SNPs in less conserved regions contributed more to occipital and dorsolateral prefrontal cortices.

Published
2015

32. Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE

Author

Ayton, S, Faux, NG, Bush, AI, Weiner, MW, Aisen, P, Petersen, R, Jack, CR, Jagust, W, Trojanowki, JQ, Toga, AW, Beckett, L, Green, RC, Saykin, AJ, Morris, J, Shaw, LM, Khachaturian, Z, Sorensen, G, Kuller, L, Raichle, M, Paul, S, Davies, P, Fillit, H, Hefti, F, Holtzman, D, Mesulam, MM, Potter, W, Snyder, P, Schwartz, A, Montine, T, Thomas, RG, Donohue, M, Walter, S, Gessert, D, Sather, T, Jiminez, G, Harvey, D, Bernstein, M, Fox, N, Thompson, P, Schuff, N, Borowski, B, Gunter, J, Senjem, M, Vemuri, P, Jones, D, Kantarci, K, Ward, C, Koeppe, RA, Foster, N, Reiman, EM, Chen, K, Mathis, C, Landau, S, Cairns, NJ, Householder, E, Taylor-Reinwald, L, Lee, V, Korecka, M, Figurski, M, Crawford, K, Neu, S, Foroud, TM, Potkin, S, Shen, L, Faber, K, Kim, S, Nho, K, Thal, L, Buckholtz, N, Albert, M, Frank, R, Hsiao, J, Kaye, J, Quinn, J, Lind, B, Carter, R, Dolen, S, Schneider, LS, Pawluczyk, S, Beccera, M, Teodoro, L, Spann, BM, Brewer, J, Vanderswag, H, Fleisher, A, Heidebrink, JL, Lord, JL, Mason, SS, Albers, CS, Knopman, D, Johnson, K, Doody, RS, Villanueva-Meyer, J, Chowdhury, M, and Rountree, S

Abstract

© 2015 Macmillan Publishers Limited. All rights reserved. Brain iron elevation is implicated in Alzheimer's disease (AD) pathogenesis, but the impact of iron on disease outcomes has not been previously explored in a longitudinal study. Ferritin is the major iron storage protein of the body; by using cerebrospinal fluid (CSF) levels of ferritin as an index, we explored whether brain iron status impacts longitudinal outcomes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF ferritin levels were negatively associated with cognitive performance over 7 years in 91 cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and predicted MCI conversion to AD. Ferritin was strongly associated with CSF apolipoprotein E levels and was elevated by the Alzheimer's risk allele, APOE-ε4. These findings reveal that elevated brain iron adversely impacts on AD progression, and introduce brain iron elevation as a possible mechanism for APOE-ε4 being the major genetic risk factor for AD.

Published
2015

40. Immunohistochemical identification of thrombospondin in normal human brain and in Alzheimer's disease

Author

Buée, L., Hof, P. R., Roberts, D. D., Delacourte, A., Morrison, J. H., and Fillit, H. M.

Subjects
Cerebral Cortex, Alzheimer Disease, Lectins, Pyramidal Tracts, Brain, Humans, Platelet Membrane Glycoproteins, Thrombospondins, Immunohistochemistry, Research Article, Aged
Abstract

Thrombospondin is part of a family of adhesive glycoproteins and is involved in a number of physiologic processes such as angiogenesis and neurite outgrowth. Immunohistochemical localization of thrombospondin in normal human brains was investigated in the hippocampus and inferior temporal cortex. Two antibodies (one polyclonal and one monoclonal) against thrombospondin-labeled microvessels, glial cells, and a subpopulation of pyramidal neurons. The distribution of thrombospondin staining in patients with Alzheimer's disease was found to be comparable to control subjects. However, in patients with Alzheimer's disease a subset of pyramidal neurons that may be vulnerable in Alzheimer's disease exhibited decreased staining. This decrease in the intensity of labeling might constitute a marker for a neuronal population prone to early degeneration. In addition, thrombospondin staining was demonstrated in senile plaques in Alzheimer's disease. These results suggest that thrombospondin may be involved in the process of neuronal degeneration and senile plaque formation.

Published
1992

42. Aging: The Reality: Biomarkers of Aging: From Primitive Organisms to Humans

Author

Butler, R. N., primary, Sprott, R., additional, Warner, H., additional, Bland, J., additional, Feuers, R., additional, Forster, M., additional, Fillit, H., additional, Harman, S. M., additional, Hewitt, M., additional, Hyman, M., additional, Johnson, K., additional, Kligman, E., additional, McClearn, G., additional, Nelson, J., additional, Richardson, A., additional, Sonntag, W., additional, Weindruch, R., additional, and Wolf, N., additional

Published
2004
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44. Rivastigmine reduces caregiver burden in Alzheimer's disease

Author

Hill, J., Fillit, H., and Chang, S.

Subjects
Health, Seniors
Abstract

Alzheimer's disease (AD) reduces quality of life, impairs health, and lowers productivity of caregivers. Rivastigmine has been shown to be effective in improving cognition and functioning on activities of daily living of AD patients. This study estimated the impact of rivastigmine therapy on caregiver burden. Study data were derived from a survey of unpaid caregivers of community-dwelling patients classified as mild to moderate AD. Caregivers of 51 patients receiving rivastigmine and with no history of using other cholinesterase inhibitors were compared to caregivers of 578 patients who had never received a cholinesterase inhibitor. Analyses controlled for patient severity, and income, relationship, age, and gender of the caregiver. Caregivers of patients receiving rivastigmine experienced significantly less burden as measured by the frequency of performing 15 caregiver tasks (p=.03), difficulty of performing 15 tasks (p=.05), and likelihood of using paid caregivers (p=.03). Rivastigmine therapy reduces caregiver burden for patients newly initiating therapy.

Published
2002

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