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1. Prognostic relevance of gait-related cognitive functions for dementia conversion in amnestic mild cognitive impairment

Author

Tuena, C, Maestri, S, Serino, S, Pedroli, E, Stramba-Badiale, M, Riva, G, Silbert, L, Lind, B, Crissey, R, Kaye, J, Carter, R, Dolen, S, Quinn, J, Schneider, L, Pawluczyk, S, Becerra, M, Teodoro, L, Dagerman, K, Spann, B, Brewer, J, Fleisher, A, Vanderswag, H, Ziolkowski, J, Heidebrink, J, Zbizek-Nulph, L, Lord, J, Albers, C, Petersen, R, Mason, S, Knopman, D, Johnson, K, Villanueva-Meyer, J, Pavlik, V, Pacini, N, Lamb, A, Kass, J, Doody, R, Shibley, V, Chowdhury, M, Rountree, S, Dang, M, Stern, Y, Honig, L, Mintz, A, Ances, B, Morris, J, Winkfield, D, Carroll, M, Stobbs-Cucchi, G, Oliver, A, Creech, M, Mintun, M, Schneider, S, Geldmacher, D, Love, M, Griffith, R, Clark, D, Brockington, J, Marson, D, Grossman, H, Goldstein, M, Greenberg, J, Mitsis, E, Shah, R, Lamar, M, Samuels, P, Duara, R, Greig-Custo, M, Rodriguez, R, Albert, M, Onyike, C, Farrington, L, Rudow, S, Brichko, R, Kielb, S, Smith, A, Raj, B, Fargher, K, Sadowski, M, Wisniewski, T, Shulman, M, Faustin, A, Rao, J, Castro, K, Ulysse, A, Chen, S, Doraiswamy, P, Petrella, J, James, O, Wong, T, Borges-Neto, S, Karlawish, J, Wolk, D, Vaishnavi, S, Clark, C, Arnold, S, Smith, C, Jicha, G, Khouli, R, Raslau, F, Lopez, O, Oakley, M, Simpson, D, Porsteinsson, A, Martin, K, Kowalski, N, Keltz, M, Goldstein, B, Makino, K, Ismail, M, Brand, C, Thai, G, Pierce, A, Yanez, B, Sosa, E, Witbracht, M, Kelley, B, Nguyen, T, Womack, K, Mathews, D, Quiceno, M, Levey, A, Lah, J, Hajjar, I, Burns, J, Swerdlow, R, Brooks, W, Silverman, D, Kremen, S, Apostolova, L, Tingus, K, Lu, P, Bartzokis, G, Woo, E, Teng, E, Graff-Radford, N, Parfitt, F, Poki-Walker, K, Farlow, M, Hake, A, Matthews, B, Brosch, J, Herring, S, van Dyck, C, Mecca, A, Good, S, Macavoy, M, Carson, R, Varma, P, Chertkow, H, Vaitekunas, S, Hosein, C, Black, S, Stefanovic, B, Heyn, C, Hsiung, G, Kim, E, Mudge, B, Sossi, V, Feldman, H, Assaly, M, Finger, E, Pasternak, S, Rachinsky, I, Kertesz, A, Drost, D, Rogers, J, Grant, I, Muse, B, Rogalski, E, Robson, J, Mesulam, M, Kerwin, D, Wu, C, Johnson, N, Lipowski, K, Weintraub, S, Bonakdarpour, B, Pomara, N, Hernando, R, Sarrael, A, Rosen, H, Miller, B, Weiner, M, Perry, D, Turner, R, Reynolds, B, Mccann, K, Poe, J, Marshall, G, Sperling, R, Yesavage, J, Taylor, J, Chao, S, Coleman, J, White, J, Lane, B, Rosen, A, Tinklenberg, J, Belden, C, Atri, A, Clark, K, Zamrini, E, Sabbagh, M, Killiany, R, Stern, R, Mez, J, Kowall, N, Budson, A, Obisesan, T, Ntekim, O, Wolday, S, Khan, J, Nwulia, E, Nadarajah, S, Lerner, A, Ogrocki, P, Tatsuoka, C, Fatica, P, Fletcher, E, Maillard, P, Olichney, J, Decarli, C, Carmichael, O, Bates, V, Capote, H, Rainka, M, Borrie, M, Lee, T, Bartha, R, Johnson, S, Asthana, S, Carlsson, C, Perrin, A, Burke, A, Scharre, D, Kataki, M, Tarawneh, R, Hart, D, Zimmerman, E, Celmins, D, Miller, D, Ponto, L, Smith, K, Koleva, H, Shim, H, Nam, K, Schultz, S, Williamson, J, Craft, S, Cleveland, J, Yang, M, Sink, K, Ott, B, Drake, J, Tremont, G, Daiello, L, Ritter, A, Bernick, C, Munic, D, O'Connelll, A, Mintzer, J, Wiliams, A, Masdeu, J, Shi, J, Garcia, A, Newhouse, P, Potkin, S, Salloway, S, Malloy, P, Correia, S, Kittur, S, Pearlson, G, Blank, K, Anderson, K, Flashman, L, Seltzer, M, Hynes, M, Santulli, R, Relkin, N, Chiang, G, Lee, A, Lin, M, Ravdin, L, Tuena C., Maestri S., Serino S., Pedroli E., Stramba-Badiale M., Riva G., Silbert L. C., Lind B., Crissey R., Kaye J. A., Carter R., Dolen S., Quinn J., Schneider L. S., Pawluczyk S., Becerra M., Teodoro L., Dagerman K., Spann B. M., Brewer J., Fleisher A., Vanderswag H., Ziolkowski J., Heidebrink J. L., Zbizek-Nulph L., Lord J. L., Albers C. S., Petersen R., Mason S. S., Knopman D., Johnson K., Villanueva-Meyer J., Pavlik V., Pacini N., Lamb A., Kass J. S., Doody R. S., Shibley V., Chowdhury M., Rountree S., Dang M., Stern Y., Honig L. S., Mintz A., Ances B., Morris J. C., Winkfield D., Carroll M., Stobbs-Cucchi G., Oliver A., Creech M. L., Mintun M. A., Schneider S., Geldmacher D., Love M. N., Griffith R., Clark D., Brockington J., Marson D., Grossman H., Goldstein M. A., Greenberg J., Mitsis E., Shah R. C., Lamar M., Samuels P., Duara R., Greig-Custo M. T., Rodriguez R., Albert M., Onyike C., Farrington L., Rudow S., Brichko R., Kielb S., Smith A., Raj B. A., Fargher K., Sadowski M., Wisniewski T., Shulman M., Faustin A., Rao J., Castro K. M., Ulysse A., Chen S., Doraiswamy P. M., Petrella J. R., James O., Wong T. Z., Borges-Neto S., Karlawish J. H., Wolk D. A., Vaishnavi S., Clark C. M., Arnold S. E., Smith C. D., Jicha G. A., Khouli R. E., Raslau F. D., Lopez O. L., Oakley M. A., Simpson D. M., Porsteinsson A. P., Martin K., Kowalski N., Keltz M., Goldstein B. S., Makino K. M., Ismail M. S., Brand C., Thai G., Pierce A., Yanez B., Sosa E., Witbracht M., Kelley B., Nguyen T., Womack K., Mathews D., Quiceno M., Levey A. I., Lah J. J., Hajjar I., Burns J. M., Swerdlow R. H., Brooks W. M., Silverman D. H. S., Kremen S., Apostolova L., Tingus K., Lu P. H., Bartzokis G., Woo E., Teng E., Graff-Radford N. R., Parfitt F., Poki-Walker K., Farlow M. R., Hake A. M., Matthews B. R., Brosch J. R., Herring S., van Dyck C. H., Mecca A. P., Good S. P., MacAvoy M. G., Carson R. E., Varma P., Chertkow H., Vaitekunas S., Hosein C., Black S., Stefanovic B., Heyn C., Hsiung G. -Y. R., Kim E., Mudge B., Sossi V., Feldman H., Assaly M., Finger E., Pasternak S., Rachinsky I., Kertesz A., Drost D., Rogers J., Grant I., Muse B., Rogalski E., Robson J., Mesulam M. -M., Kerwin D., Wu C. -K., Johnson N., Lipowski K., Weintraub S., Bonakdarpour B., Pomara N., Hernando R., Sarrael A., Rosen H. J., Miller B. L., Weiner M. W., Perry D., Turner R. S., Reynolds B., MCCann K., Poe J., Marshall G. A., Sperling R. A., Johnson K. A., Yesavage J., Taylor J. L., Chao S., Coleman J., White J. D., Lane B., Rosen A., Tinklenberg J., Belden C. M., Atri A., Clark K. A., Zamrini E., Sabbagh M., Killiany R., Stern R., Mez J., Kowall N., Budson A. E., Obisesan T. O., Ntekim O. E., Wolday S., Khan J. I., Nwulia E., Nadarajah S., Lerner A., Ogrocki P., Tatsuoka C., Fatica P., Fletcher E., Maillard P., Olichney J., DeCarli C., Carmichael O., Bates V., Capote H., Rainka M., Borrie M., Lee T. -Y., Bartha R., Johnson S., Asthana S., Carlsson C. M., Perrin A., Burke A., Scharre D. W., Kataki M., Tarawneh R., Hart D., Zimmerman E. A., Celmins D., Miller D. D., Ponto L. L. B., Smith K. E., Koleva H., Shim H., Nam K. W., Schultz S. K., Williamson J. D., Craft S., Cleveland J., Yang M., Sink K. M., Ott B. R., Drake J., Tremont G., Daiello L. A., Drake J. D., Ritter A., Bernick C., Munic D., O'Connelll A., Mintzer J., Wiliams A., Masdeu J., Shi J., Garcia A., Newhouse P., Potkin S., Salloway S., Malloy P., Correia S., Kittur S., Pearlson G. D., Blank K., Anderson K., Flashman L. A., Seltzer M., Hynes M. L., Santulli R. B., Relkin N., Chiang G., Lee A., Lin M., Ravdin L., Tuena, C, Maestri, S, Serino, S, Pedroli, E, Stramba-Badiale, M, Riva, G, Silbert, L, Lind, B, Crissey, R, Kaye, J, Carter, R, Dolen, S, Quinn, J, Schneider, L, Pawluczyk, S, Becerra, M, Teodoro, L, Dagerman, K, Spann, B, Brewer, J, Fleisher, A, Vanderswag, H, Ziolkowski, J, Heidebrink, J, Zbizek-Nulph, L, Lord, J, Albers, C, Petersen, R, Mason, S, Knopman, D, Johnson, K, Villanueva-Meyer, J, Pavlik, V, Pacini, N, Lamb, A, Kass, J, Doody, R, Shibley, V, Chowdhury, M, Rountree, S, Dang, M, Stern, Y, Honig, L, Mintz, A, Ances, B, Morris, J, Winkfield, D, Carroll, M, Stobbs-Cucchi, G, Oliver, A, Creech, M, Mintun, M, Schneider, S, Geldmacher, D, Love, M, Griffith, R, Clark, D, Brockington, J, Marson, D, Grossman, H, Goldstein, M, Greenberg, J, Mitsis, E, Shah, R, Lamar, M, Samuels, P, Duara, R, Greig-Custo, M, Rodriguez, R, Albert, M, Onyike, C, Farrington, L, Rudow, S, Brichko, R, Kielb, S, Smith, A, Raj, B, Fargher, K, Sadowski, M, Wisniewski, T, Shulman, M, Faustin, A, Rao, J, Castro, K, Ulysse, A, Chen, S, Doraiswamy, P, Petrella, J, James, O, Wong, T, Borges-Neto, S, Karlawish, J, Wolk, D, Vaishnavi, S, Clark, C, Arnold, S, Smith, C, Jicha, G, Khouli, R, Raslau, F, Lopez, O, Oakley, M, Simpson, D, Porsteinsson, A, Martin, K, Kowalski, N, Keltz, M, Goldstein, B, Makino, K, Ismail, M, Brand, C, Thai, G, Pierce, A, Yanez, B, Sosa, E, Witbracht, M, Kelley, B, Nguyen, T, Womack, K, Mathews, D, Quiceno, M, Levey, A, Lah, J, Hajjar, I, Burns, J, Swerdlow, R, Brooks, W, Silverman, D, Kremen, S, Apostolova, L, Tingus, K, Lu, P, Bartzokis, G, Woo, E, Teng, E, Graff-Radford, N, Parfitt, F, Poki-Walker, K, Farlow, M, Hake, A, Matthews, B, Brosch, J, Herring, S, van Dyck, C, Mecca, A, Good, S, Macavoy, M, Carson, R, Varma, P, Chertkow, H, Vaitekunas, S, Hosein, C, Black, S, Stefanovic, B, Heyn, C, Hsiung, G, Kim, E, Mudge, B, Sossi, V, Feldman, H, Assaly, M, Finger, E, Pasternak, S, Rachinsky, I, Kertesz, A, Drost, D, Rogers, J, Grant, I, Muse, B, Rogalski, E, Robson, J, Mesulam, M, Kerwin, D, Wu, C, Johnson, N, Lipowski, K, Weintraub, S, Bonakdarpour, B, Pomara, N, Hernando, R, Sarrael, A, Rosen, H, Miller, B, Weiner, M, Perry, D, Turner, R, Reynolds, B, Mccann, K, Poe, J, Marshall, G, Sperling, R, Yesavage, J, Taylor, J, Chao, S, Coleman, J, White, J, Lane, B, Rosen, A, Tinklenberg, J, Belden, C, Atri, A, Clark, K, Zamrini, E, Sabbagh, M, Killiany, R, Stern, R, Mez, J, Kowall, N, Budson, A, Obisesan, T, Ntekim, O, Wolday, S, Khan, J, Nwulia, E, Nadarajah, S, Lerner, A, Ogrocki, P, Tatsuoka, C, Fatica, P, Fletcher, E, Maillard, P, Olichney, J, Decarli, C, Carmichael, O, Bates, V, Capote, H, Rainka, M, Borrie, M, Lee, T, Bartha, R, Johnson, S, Asthana, S, Carlsson, C, Perrin, A, Burke, A, Scharre, D, Kataki, M, Tarawneh, R, Hart, D, Zimmerman, E, Celmins, D, Miller, D, Ponto, L, Smith, K, Koleva, H, Shim, H, Nam, K, Schultz, S, Williamson, J, Craft, S, Cleveland, J, Yang, M, Sink, K, Ott, B, Drake, J, Tremont, G, Daiello, L, Ritter, A, Bernick, C, Munic, D, O'Connelll, A, Mintzer, J, Wiliams, A, Masdeu, J, Shi, J, Garcia, A, Newhouse, P, Potkin, S, Salloway, S, Malloy, P, Correia, S, Kittur, S, Pearlson, G, Blank, K, Anderson, K, Flashman, L, Seltzer, M, Hynes, M, Santulli, R, Relkin, N, Chiang, G, Lee, A, Lin, M, Ravdin, L, Tuena C., Maestri S., Serino S., Pedroli E., Stramba-Badiale M., Riva G., Silbert L. C., Lind B., Crissey R., Kaye J. A., Carter R., Dolen S., Quinn J., Schneider L. S., Pawluczyk S., Becerra M., Teodoro L., Dagerman K., Spann B. M., Brewer J., Fleisher A., Vanderswag H., Ziolkowski J., Heidebrink J. L., Zbizek-Nulph L., Lord J. L., Albers C. S., Petersen R., Mason S. S., Knopman D., Johnson K., Villanueva-Meyer J., Pavlik V., Pacini N., Lamb A., Kass J. S., Doody R. S., Shibley V., Chowdhury M., Rountree S., Dang M., Stern Y., Honig L. S., Mintz A., Ances B., Morris J. C., Winkfield D., Carroll M., Stobbs-Cucchi G., Oliver A., Creech M. L., Mintun M. A., Schneider S., Geldmacher D., Love M. N., Griffith R., Clark D., Brockington J., Marson D., Grossman H., Goldstein M. A., Greenberg J., Mitsis E., Shah R. C., Lamar M., Samuels P., Duara R., Greig-Custo M. T., Rodriguez R., Albert M., Onyike C., Farrington L., Rudow S., Brichko R., Kielb S., Smith A., Raj B. A., Fargher K., Sadowski M., Wisniewski T., Shulman M., Faustin A., Rao J., Castro K. M., Ulysse A., Chen S., Doraiswamy P. M., Petrella J. R., James O., Wong T. Z., Borges-Neto S., Karlawish J. H., Wolk D. A., Vaishnavi S., Clark C. M., Arnold S. E., Smith C. D., Jicha G. A., Khouli R. E., Raslau F. D., Lopez O. L., Oakley M. A., Simpson D. M., Porsteinsson A. P., Martin K., Kowalski N., Keltz M., Goldstein B. S., Makino K. M., Ismail M. S., Brand C., Thai G., Pierce A., Yanez B., Sosa E., Witbracht M., Kelley B., Nguyen T., Womack K., Mathews D., Quiceno M., Levey A. I., Lah J. J., Hajjar I., Burns J. M., Swerdlow R. H., Brooks W. M., Silverman D. H. S., Kremen S., Apostolova L., Tingus K., Lu P. H., Bartzokis G., Woo E., Teng E., Graff-Radford N. R., Parfitt F., Poki-Walker K., Farlow M. R., Hake A. M., Matthews B. R., Brosch J. R., Herring S., van Dyck C. H., Mecca A. P., Good S. P., MacAvoy M. G., Carson R. E., Varma P., Chertkow H., Vaitekunas S., Hosein C., Black S., Stefanovic B., Heyn C., Hsiung G. -Y. R., Kim E., Mudge B., Sossi V., Feldman H., Assaly M., Finger E., Pasternak S., Rachinsky I., Kertesz A., Drost D., Rogers J., Grant I., Muse B., Rogalski E., Robson J., Mesulam M. -M., Kerwin D., Wu C. -K., Johnson N., Lipowski K., Weintraub S., Bonakdarpour B., Pomara N., Hernando R., Sarrael A., Rosen H. J., Miller B. L., Weiner M. W., Perry D., Turner R. S., Reynolds B., MCCann K., Poe J., Marshall G. A., Sperling R. A., Johnson K. A., Yesavage J., Taylor J. L., Chao S., Coleman J., White J. D., Lane B., Rosen A., Tinklenberg J., Belden C. M., Atri A., Clark K. A., Zamrini E., Sabbagh M., Killiany R., Stern R., Mez J., Kowall N., Budson A. E., Obisesan T. O., Ntekim O. E., Wolday S., Khan J. I., Nwulia E., Nadarajah S., Lerner A., Ogrocki P., Tatsuoka C., Fatica P., Fletcher E., Maillard P., Olichney J., DeCarli C., Carmichael O., Bates V., Capote H., Rainka M., Borrie M., Lee T. -Y., Bartha R., Johnson S., Asthana S., Carlsson C. M., Perrin A., Burke A., Scharre D. W., Kataki M., Tarawneh R., Hart D., Zimmerman E. A., Celmins D., Miller D. D., Ponto L. L. B., Smith K. E., Koleva H., Shim H., Nam K. W., Schultz S. K., Williamson J. D., Craft S., Cleveland J., Yang M., Sink K. M., Ott B. R., Drake J., Tremont G., Daiello L. A., Drake J. D., Ritter A., Bernick C., Munic D., O'Connelll A., Mintzer J., Wiliams A., Masdeu J., Shi J., Garcia A., Newhouse P., Potkin S., Salloway S., Malloy P., Correia S., Kittur S., Pearlson G. D., Blank K., Anderson K., Flashman L. A., Seltzer M., Hynes M. L., Santulli R. B., Relkin N., Chiang G., Lee A., Lin M., and Ravdin L.

Abstract

Background: Increasing research suggests that gait abnormalities can be a risk factor for Alzheimer’s Disease (AD). Notably, there is growing evidence highlighting this risk factor in individuals with amnestic Mild Cognitive Impairment (aMCI), however further studies are needed. The aim of this study is to analyze cognitive tests results and brain-related measures over time in aMCI and examine how the presence of gait abnormalities (neurological or orthopedic) or normal gait affects these trends. Additionally, we sought to assess the significance of gait and gait-related measures as prognostic indicators for the progression from aMCI to AD dementia, comparing those who converted to AD with those who remained with a stable aMCI diagnosis during the follow-up. Methods: Four hundred two individuals with aMCI from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database were included. Robust linear mixed-effects models were used to study the impact of gait abnormalities on a comprehensive neuropsychological battery over 36 months while controlling for relevant medical variables at baseline. The impact of gait on brain measures was also investigated. Lastly, the Cox proportional-hazards model was used to explore the prognostic relevance of abnormal gait and neuropsychological associated tests. Results: While controlling for relevant covariates, we found that gait abnormalities led to a greater decline over time in attention (DSST) and global cognition (MMSE). Intriguingly, psychomotor speed (TMT-A) and divided attention (TMT-B) declined uniquely in the abnormal gait group. Conversely, specific AD global cognition tests (ADAS-13) and auditory-verbal memory (RAVLT immediate recall) declined over time independently of gait profile. All the other cognitive tests were not significantly affected by time or by gait profile. In addition, we found that ventricles size increased faster in the abnormal gait group compared to the normal gait group. In terms of prognosis, abno

Published
2023

2. A blood-based signature of cerebrospinal fluid A beta(1-42) status

Author

Goudey, B., Fung, B.J., Schieber, C., Faux, N.G., 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., Kaye, J., Quinn, J., Silbert, L., 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., Morris, J.C., Carroll, M., Creech, M.L., Franklin, E., Mintun, M.A., Schneider, S., Oliver, A., Marson, D., Griffth, R., Clark, D., Geldmacher, D., Brockington, J., Roberson, E., Natelson Love, M., Grossman, H., Mitsis, E., Shah, R.C., deToledo-Morrell, L., Duara, R., Varon, D., Greig, M.T., Roberts, P., Albert, M., Onyike, C., D'Agostino, D., Kielb, S., Galvin, J.E., Cerbone, B., Michel, C.A., Pogorelec, D.M., Rusinek, H., Leon, M.J. de, Glodzik, L., De Santi, S., Doraiswamy, P.M., Petrella, J.R., Borges-Neto, S., Wong, T.Z., Coleman, E., Smith, C.D., Jicha, G., Hardy, P., Sinha, P., Oates, E., Conrad, G., Porsteinsson, A.P., Goldstein, B.S., Martin, K., Makino, K.M., Ismail, M.S., Brand, C., Mulnard, R.A., Thai, G., McAdams-Ortiz, C., Womack, K., Mathews, D., Quiceno, M., Levey, A.I., Lah, J.J., Cellar, J.S., Burns, J.M., Swerdlow, R.H., Brooks, W.M., Apostolova, L., Tingus, K., Woo, E., Silverman, D.H.S., Lu, P.H., Bartzokis, G., Graff-Radford, N.R., Parftt, F., Kendall, T., Johnson, H., Farlow, M.R., Hake, A.M., Matthews, B.R., Brosch, J.R., Herring, S., Hunt, C., Dyck, .H. van, Carson, R.E., MacAvoy, M.G., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Caldwell, C., Hsiung, Ging-Yuek Robin, Feldman, H., Mudge, B., Assaly, M., Finger, E., Pasternack, S., Rachisky, I., Trost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M.-M., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C.-K., Johnson, N., Sadowsky, C., Villena, T., Turner, R.S., Reynolds, B., Sperling, R.A., Johnson, K.A., Marshall, G., Yesavage, J., Taylor, J.L., 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., Obisesan, T.O., Wolday, S., Allard, J., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., DeCarli, C., Carmichael, O., 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., Burke, A., Trncic, N., 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., Flashman, L.A., Seltzer, M., Hynes, M.L., Santulli, R.B., Sink, K.M., Gordineer, L., 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., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Pomara, N., Hernando, R., Sarrael, A., Relkin, N., Chaing, G., Lin, M., Ravdin, L., Smith, A., Raj, B.A., Fargher, K., Saykin, A., Nho, K., Kling, M., Toledo, J., Shaw, L., Trojanowski, J., Farrer, L., Kastsenmueller, G., Arnold, M., Wishart, D., Wurtz, P., Bhattcharyya, S., Duijin, C. van, Mangravite, L., Han, X., Hankemeier, T., Fiehn, O., Barupal, D., Thiele, I., Heinken, A., Meikle, P., Price, N., Funk, C., Jia, W., Kueider-Paisley, A., Tenebaum, J., Black, C., Moseley, A., Thompson, W., Mahmoudiandehkorki, S., Baillie, R., Welsh-Bohmer, K., Plassman, B., and Epidemiology

Subjects
Male, 0301 basic medicine, Apolipoprotein E, Oncology, medicine.medical_specialty, Amyloid, Amyloid beta, lcsh:Medicine, Article, 03 medical and health sciences, Apolipoproteins E, 0302 clinical medicine, Cerebrospinal fluid, Alzheimer Disease, Predictive Value of Tests, Internal medicine, medicine, Humans, Dementia, Cognitive decline, lcsh:Science, Aged, Aged, 80 and over, Amyloid beta-Peptides, Multidisciplinary, biology, Chemokine CCL26, business.industry, lcsh:R, Alzheimer’s Disease Metabolomics Consortium, Alzheimer’s Disease Neuroimaging Initiative, medicine.disease, Peptide Fragments, 3. Good health, 030104 developmental biology, biology.protein, Chromogranin A, Female, lcsh:Q, Alzheimer's disease, business, Biomarkers, 030217 neurology & neurosurgery, Alzheimer's Disease Neuroimaging Initiative
Abstract

It is increasingly recognized that Alzheimer’s disease (AD) exists before dementia is present and that shifts in amyloid beta occur long before clinical symptoms can be detected. Early detection of these molecular changes is a key aspect for the success of interventions aimed at slowing down rates of cognitive decline. Recent evidence indicates that of the two established methods for measuring amyloid, a decrease in cerebrospinal fluid (CSF) amyloid β1−42 (Aβ1−42) may be an earlier indicator of Alzheimer’s disease risk than measures of amyloid obtained from Positron Emission Tomography (PET). However, CSF collection is highly invasive and expensive. In contrast, blood collection is routinely performed, minimally invasive and cheap. In this work, we develop a blood-based signature that can provide a cheap and minimally invasive estimation of an individual’s CSF amyloid status using a machine learning approach. We show that a Random Forest model derived from plasma analytes can accurately predict subjects as having abnormal (low) CSF Aβ1−42 levels indicative of AD risk (0.84 AUC, 0.78 sensitivity, and 0.73 specificity). Refinement of the modeling indicates that only APOEε4 carrier status and four plasma analytes (CGA, Aβ1−42, Eotaxin 3, APOE) are required to achieve a high level of accuracy. Furthermore, we show across an independent validation cohort that individuals with predicted abnormal CSF Aβ1−42 levels transitioned to an AD diagnosis over 120 months significantly faster than those with predicted normal CSF Aβ1−42 levels and that the resulting model also validates reasonably across PET Aβ1−42 status (0.78 AUC). This is the first study to show that a machine learning approach, using plasma protein levels, age and APOEε4 carrier status, is able to predict CSF Aβ1−42 status, the earliest risk indicator for AD, with high accuracy.

Published
2019
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3. 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

4. Genome-wide scan of healthy human connectome discovers SPON1 gene variant influencing dementia severity

Author

Jahanshad, N., Rajagopalan, P., Hua, X., Hibar, D. P., Nir, T. M., Toga, A. W., Jack, C. R., Saykin, A. J., Green, R. C., Weiner, M. W., Medland, S. E., Montgomery, G. W., Hansell, N. K., McMahon, K. L., de Zubicaray, G. I., Martin, N. G., Wright, M. J., Thompson, P. M., the Alzheimer's Disease Neuroimaging Initiative, Weiner, M., Aisen, P., Petersen, R., Jagust, W., Trojanowski, J. Q., Beckett, L., Morris, J., Liu, E., Montine, T., Gamst, A., Thomas, R. G., Donohue, M., Walter, S., Gessert, D., Sather, T., Harvey, D., Kornak, J., Dale, A., Bernstein, M., Felmlee, J., Fox, N., Thompson, P., Schuff, N., Alexander, G., DeCarli, C., Bandy, D., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Cairns, N. J., Taylor-Reinwald, L., Trojanowki, J. Q., Shaw, L., Lee, V. M. Y., Korecka, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Khachaturian, Z., Frank, R., Snyder, P. J., Molchan, S., Kaye, J., Quinn, J., Lind, B., Dolen, S., Schneider, L. S., Pawluczyk, S., Spann, B. M., Brewer, J., Vanderswag, H., Heidebrink, J. L., Lord, J. L., Johnson, K., Doody, R. S., Villanueva-Meyer, J., Chowdhury, M., Stern, Yaakov, Honig, L. S., Bell, K. L., Morris, J. C., Ances, B., Carroll, M., Leon, S., Mintun, M. A., Schneider, S., Marson, D., Griffith, R., Clark, D., Grossman, H., Mitsis, E., Romirowsky, A., deToledo-Morrell, L., Shah, R. C., Duara, R., Varon, D., Roberts, P., Albert, M., Onyike, C., Kielb, S., Rusinek, H., de Leon, M. J., Glodzik, L., De Santi, S., Doraiswamy, P. M., Petrella, J. R., Coleman, R. E., Arnold, S. E., Karlawish, J. H., Wolk, D., Smith, C. D., Jicha, G., Hardy, P., Lopez, O. L., Oakley, M., 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., 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., Lu, P. H., Bartzokis, G., Silverman, D. H. S., Graff-Radford, N. R., Parfitt, F., Johnson, H., Farlow, M. R., Hake, A. M., Matthews, B. R., Herring, S., van Dyck, C. H., Carson, R. E., MacAvoy, M. G., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Caldwell, C., Hsiung, G.-Y. R., Feldman, H., Mudge, B., Assaly, M., Kertesz, A., Rogers, J., Trost, D., Bernick, C., Munic, D., Kerwin, D., Mesulam, M.-M., Lipowski, K., Wu, C.-K., Johnson, N., Sadowsky, C., Martinez, W., Villena, T., Turner, R. S., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Frey, M., Yesavage, J., Taylor, J. L., Lane, B., Rosen, A., Tinklenberg, J., Sabbagh, M., Belden, C., Jacobson, S., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P. L., Obisesan, T. O., Wolday, S., Bwayo, S. K., Lerner, A., Hudson, L., Ogrocki, P., Fletcher, E., Carmichael, O., Olichney, J., 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., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Zimmerman, E. A., Celmins, D., Brown, A. D., Pearlson, G. D., Blank, K., Anderson, K., Santulli, R. B., 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., Longmire, C. F., Spicer, K., Finger, E., Rachinsky, I., and Drost, D.

Published
2013
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5. Association of common genetic variants in GPCPD1 with scaling of visual cortical surface area in humans

Author

Bakken, TE, Roddey, JC, Djurovic, S, Akshoomoff, N, Amaral, DG, Bloss, CS, Casey, BJ, Chang, L, Ernst, TM, Gruen, JR, Jernigan, TL, Kaufmann, WE, Kenet, T, Kennedy, DN, Kuperman, JM, Murray, SS, Sowell, ER, Rimol, LM, Mattingsdal, M, Melle, I, Agartz, I, Andreassen, OA, Schork, NJ, Dale, AM, Alzheimer’s Disease Neuroimaging Initiative, Pediatric Imaging, Neurocognition, Genetics Study, Weiner, M, Aisen, P, Petersen, R, Jack, CR, Jr, Jagust, W, Trojanowki, JQ, Toga, AW, Beckett, L, Green, RC, Saykin, AJ, Morris, J, Liu, E, Montine, T, Gamst, A, Thomas, RG, Donohue, M, Walter, S, Gessert, D, Sather, T, Harvey, D, Kornak, J, Dale, A, Bernstein, M, Felmlee, J, Fox, N, Thompson, P, Schuff, N, Alexander, G, DeCarli, C, Bandy, D, Koeppe, RA, Foster, N, Reiman, EM, Chen, K, Mathis, C, Cairns, NJ, Taylor-Reinwald, L, Shaw, L, Lee, VM, Korecka, M, Crawford, K, Neu, S, Foroud, TM, Potkin, S, Shen, L, Kachaturian, Z, Frank, R, Snyder, PJ, Molchan, S, Kaye, J, Quinn, J, Lind, B, Dolen, S, Schneider, LS, Pawluczyk, S, Spann, BM, Brewer, J, Vanderswag, H, Heidebrink, JL, Lord, JL, Johnson, K, Doody, RS, Villanueva-Meyer, J, Chowdhury, M, Stern, Yaakov, Honig, LS, Bell, KL, Morris, JC, Ances, B, Carroll, M, Leon, S, Mintun, MA, Schneider, S, Marson, D, Griffith, R, Clark, D, Grossman, H, Mitsis, E, Romirowsky, A, deToledo-Morrell, L, Shah, RC, Duara, R, Varon, D, Roberts, P, Albert, M, Onyike, C, Kielb, S, Rusinek, H, de, Leon, MJ, Glodzik, L, De, Santi, S, Doraiswamy, PM, Petrella, JR, Coleman, RE, Arnold, SE, Karlawish, JH, Wolk, D, Smith, CD, Jicha, G, Hardy, P, Lopez, OL, Oakley, M, Simpson, DM, Porsteinsson, AP, Goldstein, BS, Martin, K, Makino, KM, Ismail, MS, Brand, C, Mulnard, RA, Thai, G, Mc-Adams-Ortiz, C, Womack, K, Mathews, D, Quiceno, M, Diaz-Arrastia, R, King, R, Martin-Cook, K, DeVous, M, Levey, AI, Lah, JJ, Cellar, JS, Burns, JM, Anderson, HS, Swerdlow, RH, Apostolova, L, Lu, PH, Bartzokis, G, Silverman, DH, Graff-Radford, NR, Parfitt, F, Johnson, H, Farlow, MR, Hake, AM, Matthews, BR, Herring, S, van, Dyck, CH, Carson, RE, MacAvoy, MG, Chertkow, H, Bergman, H, Hosein, C, Black, S, Stefanovic, B, Caldwell, C, Ging-Yuek, Hsiung, R, Feldman, H, Mudge, B, Assaly, M, Kertesz, A, Rogers, J, Trost, D, Bernick, C, Munic, D, Kerwin, D, Mesulam, MM, Lipowski, K, Wu, CK, Johnson, N, Sadowsky, C, Martinez, W, Villena, T, Turner, RS, Reynolds, B, Sperling, RA, Johnson, KA, Marshall, G, Frey, M, Yesavage, J, Taylor, JL, Lane, B, Rosen, A, Tinklenberg, J, Sabbagh, M, Belden, C, Jacobson, S, Kowall, N, Killiany, R, Budson, AE, Norbash, A, Johnson, PL, Obisesan, TO, Wolday, S, Bwayo, SK, Lerner, A, Hudson, L, Ogrocki, P, Fletcher, E, Carmichael, O, Olichney, J, Kittur, S, Borrie, M, Lee, TY, Bartha, R, Johnson, S, Asthana, S, Carlsson, CM, Potkin, SG, Preda, A, Nguyen, D, Tariot, P, Fleisher, A, Reeder, S, Bates, V, Capote, H, Rainka, M, Scharre, DW, Kataki, M, Zimmerman, EA, Celmins, D, Brown, AD, Pearlson, GD, Blank, K, Anderson, K, Santulli, RB, Schwartz, ES, Sink, KM, Williamson, JD, Garg, P, Watkins, F, Ott, BR, Querfurth, H, Tremont, G, Salloway, S, Malloy, P, Correia, S, Rosen, HJ, Miller, BL, Mintzer, J, Longmire, CF, Spicer, K, Finger, E, Rachinsky, I, Drost, D, Jernigan, T, McCabe, C, Grant, E, Ernst, T, Kuperman, J, Chung, Y, Murray, S, Bloss, C, Darst, B, Pritchett, L, Saito, A, Amaral, D, DiNino, M, Eyngorina, B, Sowell, E, Houston, S, Soderberg, L, Kaufmann, W, van, Zijl, P, Rizzo-Busack, H, Javid, M, Mehta, N, Ruberry, E, Powers, A, Rosen, B, Gebhard, N, Manigan, H, Frazier, J, Kennedy, D, Yakutis, L, Hill, M, Gruen, J, Bosson-Heenan, J, and Carlson, H

Subjects
anatomy & histology, pathology [Visual Cortex], Adult, Diagnostic Imaging, Male, Linkage disequilibrium, Visual perception, genetic structures, Adolescent, Genotype, Imaging genetics, methods [Diagnostic Imaging], Single-nucleotide polymorphism, Genome-wide association study, Saccharomyces cerevisiae, Biology, Polymorphism, Single Nucleotide, Cohort Studies, methods [Brain Mapping], pathology [Brain], Cortex (anatomy), Genetic variation, Medicine and Health Sciences, medicine, Humans, genetics [Phosphoric Diester Hydrolases], Aged, Visual Cortex, Genetics, Brain Mapping, Multidisciplinary, Models, Genetic, Phosphoric Diester Hydrolases, metabolism [Saccharomyces cerevisiae], Brain, Genetic Variation, Genomics, Middle Aged, Biological Sciences, Visual cortex, medicine.anatomical_structure, Female, Genome-Wide Association Study
Abstract

Visual cortical surface area varies two- to threefold between human individuals, is highly heritable, and has been correlated with visual acuity and visual perception. However, it is still largely unknown what specific genetic and environmental factors contribute to normal variation in the area of visual cortex. To identify SNPs associated with the proportional surface area of visual cortex, we performed a genome-wide association study followed by replication in two independent cohorts. We identified one SNP (rs6116869) that replicated in both cohorts and had genome-wide significant association ( P combined = 3.2 × 10 −8 ). Furthermore, a metaanalysis of imputed SNPs in this genomic region identified a more significantly associated SNP (rs238295; P = 6.5 × 10 −9 ) that was in strong linkage disequilibrium with rs6116869. These SNPs are located within 4 kb of the 5′ UTR of GPCPD1 , glycerophosphocholine phosphodiesterase GDE1 homolog ( Saccharomyces cerevisiae ), which in humans, is more highly expressed in occipital cortex compared with the remainder of cortex than 99.9% of genes genome-wide. Based on these findings, we conclude that this common genetic variation contributes to the proportional area of human visual cortex. We suggest that identifying genes that contribute to normal cortical architecture provides a first step to understanding genetic mechanisms that underlie visual perception.

Published
2012

6. Chronic traumatic encephalopathy: Clinical-biomarker correlations and current concepts in pathogenesis

Author

Gandy, S, Ikonomovic, MD, Mitsis, E, Elder, G, Ahlers, ST, Barth, J, Stone, JR, Dekosky, ST, Gandy, S, Ikonomovic, MD, Mitsis, E, Elder, G, Ahlers, ST, Barth, J, Stone, JR, and Dekosky, ST

Abstract

Background: Chronic traumatic encephalopathy (CTE) is a recently revived term used to describe a neurodegenerative process that occurs as a long term complication of repetitive mild traumatic brain injury (TBI). Corsellis provided one of the classic descriptions of CTE in boxers under the name "dementia pugilistica" (DP). Much recent attention has been drawn to the apparent association of CTE with contact sports (football, soccer, hockey) and with frequent battlefield exposure to blast waves generated by improvised explosive devices (IEDs). Recently, a promising serum biomarker has been identified by measurement of serum levels of the neuronal microtubule associated protein tau. New positron emission tomography (PET) ligands (e.g., [18F] T807) that identify brain tauopathy have been successfully deployed for the in vitro and in vivo detection of presumptive tauopathy in the brains of subjects with clinically probable CTE.

Published
2014

7. Tauopathy PET and amyloid PET in the diagnosis of chronic traumatic encephalopathies: studies of a retired NFL player and of a man with FTD and a severe head injury

Author

Mitsis, E M, primary, Riggio, S, additional, Kostakoglu, L, additional, Dickstein, D L, additional, Machac, J, additional, Delman, B, additional, Goldstein, M, additional, Jennings, D, additional, D’Antonio, E, additional, Martin, J, additional, Naidich, T P, additional, Aloysi, A, additional, Fernandez, C, additional, Seibyl, J, additional, DeKosky, S T, additional, Elder, G A, additional, Marek, K, additional, Gordon, W, additional, Hof, P R, additional, Sano, M, additional, and Gandy, S, additional

Published
2014
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8. Generative FDG-PET and MRI model of aging and disease progression in Alzheimer's disease.

Author

Alzheimer's Disease Neuroimaging Initiative, Weiner, M., Aisen, P., Petersen, R., Jack CR.<Suffix>Jr</Suffix>, Jagust, W., Trojanowki, JQ., Toga, AW., Beckett, L., Green, RC., Saykin, AJ., Morris, J., Liu, E., Montine, T., Gamst, A., Thomas, RG., Donohue, M., Walter, S., Gessert, D., Sather, T., Harvey, D., Kornak, J., Dale, A., Bernstein, M., Felmlee, J., Fox, N., Thompson, P., Schuff, N., DeCarli, C., Bandy, D., Koeppe, RA., Foster, N., Reiman, EM., Chen, K., Mathis, C., Cairns, NJ., Taylor-Reinwald, L., Shaw, L., Lee, VM., Korecka, M., Crawford, K., Neu, S., Foroud, TM., Potkin, S., Shen, L., Kachaturian, Z., Frank, R., Snyder, PJ., Molchan, S., Kaye, J., Quinn, J., Lind, B., Dolen, S., Schneider, LS., Pawluczyk, S., Spann, BM., Brewer, J., Vanderswag, H., Heidebrink, JL., Lord, JL., Johnson, K., Doody, RS., Villanueva-Meyer, J., Chowdhury, M., Stern, Y., Honig, LS., Bell, KL., Morris, JC., Ances, B., Carroll, M., Leon, S., Mintun, MA., Schneider, S., Marson, D., Griffith, R., Clark, D., Grossman, H., Mitsis, E., Romirowsky, A., deToledo-Morrell, L., Shah, RC., Duara, R., Varon, D., Roberts, P., Albert, M., Onyike, C., Kielb, S., Rusinek, H., de Leon MJ., Glodzik, L., De Santi, S., Doraiswamy, P., Petrella, JR., Coleman, R., Arnold, SE., Karlawish, JH., Wolk, D., Smith, CD., Jicha, G., Hardy, P., Lopez, OL., Oakley, M., Simpson, DM., Porsteinsson, AP., Goldstein, BS., Martin, K., Makino, KM., Ismail, M., Brand, C., Mulnard, RA., Thai, G., Mc-Adams-Ortiz, C., Womack, K., Mathews, D., Quiceno, M., Diaz-Arrastia, R., King, R., Martin-Cook, K., DeVous, M., Levey, AI., Lah, JJ., Cellar, JS., Burns, JM., Anderson, HS., Swerdlow, RH., Apostolova, L., Lu, PH., Bartzokis, G., Silverman, DH., Graff-Radford, NR., Parfitt, F., Johnson, H., Farlow, MR., Hake, AM., Matthews, BR., Herring, S., van Dyck CH., Carson, RE., MacAvoy, MG., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Caldwell, C., Hsiung, GY., Feldman, H., Mudge, B., Assaly, M., Kertesz, A., Rogers, J., Trost, D., Bernick, C., Munic, D., Kerwin, D., Mesulam, MM., Lipowski, K., Wu, CK., Johnson, N., Sadowsky, C., Martinez, W., Villena, T., Turner, RS., Reynolds, B., Sperling, RA., Johnson, KA., Marshall, G., Frey, M., Yesavage, J., Taylor, JL., Lane, B., Rosen, A., Tinklenberg, J., Sabbagh, M., Belden, C., Jacobson, S., Kowall, N., Killiany, R., Budson, AE., Norbash, A., Johnson, PL., Obisesan, TO., Wolday, S., Bwayo, SK., Lerner, A., Hudson, L., Ogrocki, P., Fletcher, E., Carmichael, O., Olichney, J., Kittur, S., Borrie, M., Lee, TY., Bartha, R., Johnson, S., Asthana, S., Carlsson, CM., Potkin, SG., Preda, A., Nguyen, D., Tariot, P., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, DW., Kataki, M., Zimmerman, EA., Celmins, D., Brown, AD., Pearlson, GD., Blank, K., Anderson, K., Santulli, RB., Schwartz, ES., Sink, KM., Williamson, JD., Garg, P., Watkins, F., Ott, BR., Querfurth, H., Tremont, G., Salloway, S., Malloy, P., Correia, S., Rosen, HJ., Miller, BL., Mintzer, J., Longmire, CF., Spicer, K., Finger, E., Rachinsky, I., Drost, D., Dukart, J., Kherif, F., Mueller, K., Adaszewski, S., Schroeter, M.L., Frackowiak, R.S., Draganski, B., Alzheimer's Disease Neuroimaging Initiative, Weiner, M., Aisen, P., Petersen, R., Jack CR.<Suffix>Jr</Suffix>, Jagust, W., Trojanowki, JQ., Toga, AW., Beckett, L., Green, RC., Saykin, AJ., Morris, J., Liu, E., Montine, T., Gamst, A., Thomas, RG., Donohue, M., Walter, S., Gessert, D., Sather, T., Harvey, D., Kornak, J., Dale, A., Bernstein, M., Felmlee, J., Fox, N., Thompson, P., Schuff, N., DeCarli, C., Bandy, D., Koeppe, RA., Foster, N., Reiman, EM., Chen, K., Mathis, C., Cairns, NJ., Taylor-Reinwald, L., Shaw, L., Lee, VM., Korecka, M., Crawford, K., Neu, S., Foroud, TM., Potkin, S., Shen, L., Kachaturian, Z., Frank, R., Snyder, PJ., Molchan, S., Kaye, J., Quinn, J., Lind, B., Dolen, S., Schneider, LS., Pawluczyk, S., Spann, BM., Brewer, J., Vanderswag, H., Heidebrink, JL., Lord, JL., Johnson, K., Doody, RS., Villanueva-Meyer, J., Chowdhury, M., Stern, Y., Honig, LS., Bell, KL., Morris, JC., Ances, B., Carroll, M., Leon, S., Mintun, MA., Schneider, S., Marson, D., Griffith, R., Clark, D., Grossman, H., Mitsis, E., Romirowsky, A., deToledo-Morrell, L., Shah, RC., Duara, R., Varon, D., Roberts, P., Albert, M., Onyike, C., Kielb, S., Rusinek, H., de Leon MJ., Glodzik, L., De Santi, S., Doraiswamy, P., Petrella, JR., Coleman, R., Arnold, SE., Karlawish, JH., Wolk, D., Smith, CD., Jicha, G., Hardy, P., Lopez, OL., Oakley, M., Simpson, DM., Porsteinsson, AP., Goldstein, BS., Martin, K., Makino, KM., Ismail, M., Brand, C., Mulnard, RA., Thai, G., Mc-Adams-Ortiz, C., Womack, K., Mathews, D., Quiceno, M., Diaz-Arrastia, R., King, R., Martin-Cook, K., DeVous, M., Levey, AI., Lah, JJ., Cellar, JS., Burns, JM., Anderson, HS., Swerdlow, RH., Apostolova, L., Lu, PH., Bartzokis, G., Silverman, DH., Graff-Radford, NR., Parfitt, F., Johnson, H., Farlow, MR., Hake, AM., Matthews, BR., Herring, S., van Dyck CH., Carson, RE., MacAvoy, MG., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Caldwell, C., Hsiung, GY., Feldman, H., Mudge, B., Assaly, M., Kertesz, A., Rogers, J., Trost, D., Bernick, C., Munic, D., Kerwin, D., Mesulam, MM., Lipowski, K., Wu, CK., Johnson, N., Sadowsky, C., Martinez, W., Villena, T., Turner, RS., Reynolds, B., Sperling, RA., Johnson, KA., Marshall, G., Frey, M., Yesavage, J., Taylor, JL., Lane, B., Rosen, A., Tinklenberg, J., Sabbagh, M., Belden, C., Jacobson, S., Kowall, N., Killiany, R., Budson, AE., Norbash, A., Johnson, PL., Obisesan, TO., Wolday, S., Bwayo, SK., Lerner, A., Hudson, L., Ogrocki, P., Fletcher, E., Carmichael, O., Olichney, J., Kittur, S., Borrie, M., Lee, TY., Bartha, R., Johnson, S., Asthana, S., Carlsson, CM., Potkin, SG., Preda, A., Nguyen, D., Tariot, P., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, DW., Kataki, M., Zimmerman, EA., Celmins, D., Brown, AD., Pearlson, GD., Blank, K., Anderson, K., Santulli, RB., Schwartz, ES., Sink, KM., Williamson, JD., Garg, P., Watkins, F., Ott, BR., Querfurth, H., Tremont, G., Salloway, S., Malloy, P., Correia, S., Rosen, HJ., Miller, BL., Mintzer, J., Longmire, CF., Spicer, K., Finger, E., Rachinsky, I., Drost, D., Dukart, J., Kherif, F., Mueller, K., Adaszewski, S., Schroeter, M.L., Frackowiak, R.S., and Draganski, B.

Abstract

The failure of current strategies to provide an explanation for controversial findings on the pattern of pathophysiological changes in Alzheimer's Disease (AD) motivates the necessity to develop new integrative approaches based on multi-modal neuroimaging data that captures various aspects of disease pathology. Previous studies using [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and structural magnetic resonance imaging (sMRI) report controversial results about time-line, spatial extent and magnitude of glucose hypometabolism and atrophy in AD that depend on clinical and demographic characteristics of the studied populations. Here, we provide and validate at a group level a generative anatomical model of glucose hypo-metabolism and atrophy progression in AD based on FDG-PET and sMRI data of 80 patients and 79 healthy controls to describe expected age and symptom severity related changes in AD relative to a baseline provided by healthy aging. We demonstrate a high level of anatomical accuracy for both modalities yielding strongly age- and symptom-severity- dependant glucose hypometabolism in temporal, parietal and precuneal regions and a more extensive network of atrophy in hippocampal, temporal, parietal, occipital and posterior caudate regions. The model suggests greater and more consistent changes in FDG-PET compared to sMRI at earlier and the inversion of this pattern at more advanced AD stages. Our model describes, integrates and predicts characteristic patterns of AD related pathology, uncontaminated by normal age effects, derived from multi-modal data. It further provides an integrative explanation for findings suggesting a dissociation between early- and late-onset AD. The generative model offers a basis for further development of individualized biomarkers allowing accurate early diagnosis and treatment evaluation.

Published
2013

9. 123I-5-IA-85380 SPECT Imaging of Nicotinic Acetylcholine Receptor Availability in Nonsmokers: Effects of Sex and Menstrual Phase

Author

Cosgrove, K. P., primary, Mitsis, E. M., additional, Bois, F., additional, Frohlich, E., additional, Tamagnan, G. D., additional, Krantzler, E., additional, Perry, E., additional, Maciejewski, P. K., additional, Epperson, C. N., additional, Allen, S., additional, O'Malley, S., additional, Mazure, C. M., additional, Seibyl, J. P., additional, van Dyck, C. H., additional, and Staley, J. K., additional

Published
2007
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11. Dynamic proportional loss of functional connectivity revealed change of left superior frontal gyrus in subjective cognitive decline: an explanatory study based on Chinese and Western cohorts.

Author

Wang L, Hu W, Dong F, Sheng C, Wu J, Han Y, Jiang J, Weiner MW, Aisen P, Petersen R, Jack CR, Jagust W, Trojanowski 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, 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 SG, 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, Rountree S, Dang M, Stern Y, Honig LS, Bell KL, Ances B, Carroll M, Leon S, Mintun MA, 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 RC, Duara R, Varon D, Greig MT, Roberts P, Onyike C, D'Agostino D, Kielb S, Galvin JE, Cerbone B, Michel CA, Rusinek H, de Leon MJ, Glodzik L, De Santi S, Doraiswamy P, Petrella JR, Wong TZ, Arnold SE, Karlawish JH, Wolk D, Smith CD, Jicha G, Hardy P, Sinha P, Oates E, Conrad G, Lopez OL, Oakley M, Simpson DM, Porsteinsson AP, Goldstein BS, Martin K, Makino KM, Ismail M, Brand C, Mulnard RA, Thai G, McAdams-Ortiz C, Womack K, Mathews D, Quiceno M, Diaz-Arrastia R, King R, Weiner M, Martin-Cook K, DeVous M, Levey AI, Lah JJ, Cellar JS, Burns JM, Anderson HS, Swerdlow RH, Apostolova L, Tingus K, Woo E, Silverman DHS, Lu PH, Bartzokis G, Graff-Radford NR, Parfitt F, Kendall T, Johnson H, Farlow MR, Hake AM, Matthews BR, Herring S, Hunt C, van Dyck CH, Carson RE, MacAvoy MG, Chertkow H, Bergman H, Hosein C, Hsiung GR, Feldman H, Mudge B, Assaly M, Bernick C, Munic D, Kertesz A, Rogers J, Trost D, Kerwin D, Lipowski K, Wu CK, Johnson N, Sadowsky C, Martinez W, Villena T, Turner RS, Johnson K, Reynolds B, Sperling RA, Johnson KA, Marshall G, Frey M, Lane B, Rosen A, Tinklenberg J, Sabbagh MN, Belden CM, Jacobson SA, Sirrel SA, Kowall N, Killiany R, Budson AE, Norbash A, Johnson PL, Allard J, Lerner A, Ogrocki P, Hudson L, Fletcher E, Carmichae O, Olichney J, DeCarli C, Kittur S, Borrie M, Lee TY, Bartha R, Johnson S, Asthana S, Carlsson CM, Preda A, Nguyen D, Tariot P, Reeder S, Bates V, Capote H, Rainka M, Scharre DW, Kataki M, Adeli A, Zimmerman EA, Celmins D, Brown AD, Pearlson GD, Blank K, Anderson K, Santulli RB, Kitzmiller TJ, Schwartz ES, Sink KM, Williamson JD, Garg P, Watkins F, Ott BR, Querfurth H, Tremont G, Salloway S, Malloy P, Correia S, Rosen HJ, Miller BL, Mintzer J, Spicer K, Bachman D, Pasternak S, Rachinsky I, Drost D, Pomara N, Hernando R, Sarrael A, Schultz SK, Ponto LLB, Shim H, Smith KE, Relkin N, Chaing G, Raudin L, Smith A, Fargher K, Raj BA, Neylan T, Grafman J, Davis M, Morrison R, Hayes J, Finley S, Friedl K, Fleischman D, Arfanakis K, James O, Massoglia D, Fruehling J, Harding S, Peskind ER, Petrie EC, Li G, Yesavage JA, Taylor JL, and Furst AJ

Abstract

Brain network dynamics have been extensively explored in patients with subjective cognitive decline (SCD). However, these studies are susceptible to individual differences, scanning parameters, and other confounding factors. Therefore, how to reveal subtle SCD-related subtle changes remains unclear. Cross-sectional and longitudinal resting-state functional magnetic resonance imaging data from both Chinese and Western populations were analyzed. We proposed a framework of dynamic proportional loss of functional connectivity (DPLFC). After its stability was validated, the optimal parameters were applied for the clinical diagnosis of SCD. DPLFC yielded a relatively high intraclass correlation coefficient. In particular, the DPLFC of the left superior frontal gyrus (SFG) progressively decreased along the Alzheimer's disease (AD) continuum. Compared with the traditional index, the DPLFC had better classification performance between cognitively normal controls and patients with SCD. Furthermore, DPLFC was related to Aβ deposition and scale scores. Patients with lower DPLFC values had a greater risk of cognitive decline. Decreased DPLFC in the left SFG may be a potential AD-related neuroimaging biomarker at an early stage., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to American Aging Association.)

Published
2025
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12. Chronic traumatic encephalopathy: clinical-biomarker correlations and current concepts in pathogenesis.

Author

Gandy S, Ikonomovic MD, Mitsis E, Elder G, Ahlers ST, Barth J, Stone JR, and DeKosky ST

Subjects
Humans, Biomarkers analysis, Brain Injury, Chronic diagnosis, Brain Injury, Chronic physiopathology
Abstract

Background: Chronic traumatic encephalopathy (CTE) is a recently revived term used to describe a neurodegenerative process that occurs as a long term complication of repetitive mild traumatic brain injury (TBI). Corsellis provided one of the classic descriptions of CTE in boxers under the name "dementia pugilistica" (DP). Much recent attention has been drawn to the apparent association of CTE with contact sports (football, soccer, hockey) and with frequent battlefield exposure to blast waves generated by improvised explosive devices (IEDs). Recently, a promising serum biomarker has been identified by measurement of serum levels of the neuronal microtubule associated protein tau. New positron emission tomography (PET) ligands (e.g., [18 F] T807) that identify brain tauopathy have been successfully deployed for the in vitro and in vivo detection of presumptive tauopathy in the brains of subjects with clinically probable CTE., Methods: Major academic and lay publications on DP/CTE were reviewed beginning with the 1928 paper describing the initial use of the term CTE by Martland., Results: The major current concepts in the neurological, psychiatric, neuropsychological, neuroimaging, and body fluid biomarker science of DP/CTE have been summarized. Newer achievements, such as serum tau and [18 F] T807 tauopathy imaging, are also introduced and their significance has been explained., Conclusion: Recent advances in the science of DP/CTE hold promise for elucidating a long sought accurate determination of the true prevalence of CTE. This information holds potentially important public health implications for estimating the risk of contact sports in inflicting permanent and/or progressive brain damage on children, adolescents, and adults.

Published
2014
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13. 123I-5-IA-85380 SPECT measurement of nicotinic acetylcholine receptors in human brain by the constant infusion paradigm: feasibility and reproducibility.

Author

Staley JK, van Dyck CH, Weinzimmer D, Brenner E, Baldwin RM, Tamagnan GD, Riccardi P, Mitsis E, and Seibyl JP

Subjects
Adult, Azetidines administration & dosage, Feasibility Studies, Female, Humans, Infusions, Intravenous, Male, Metabolic Clearance Rate, Middle Aged, Pyridines administration & dosage, Radiopharmaceuticals administration & dosage, Radiopharmaceuticals pharmacokinetics, Reproducibility of Results, Sensitivity and Specificity, Tissue Distribution, Azetidines pharmacokinetics, Brain diagnostic imaging, Brain metabolism, Pyridines pharmacokinetics, Receptors, Nicotinic metabolism, Tomography, Emission-Computed, Single-Photon methods
Abstract

Unlabelled: (123)I-5-IA-85380 ((123)I-5-IA; [(123)I]-5-iodo-3-[2(S)-azetidinylmethoxy]pyridine) is a promising SPECT radiotracer for imaging beta(2)-containing nicotinic acetylcholine receptors (beta(2)-nAChRs) in brain. Beta(2)-nAChRs are the initial site of action of nicotine and are implicated in various neuropsychiatric disorders. The feasibility and reproducibility of the bolus-plus-constant-infusion paradigm for equilibrium modeling of (123)I-5-IA using SPECT in healthy nonsmokers was studied., Methods: Ten healthy nonsmokers (mean age +/- SD, 43.7 +/- 9.9 y) underwent two (123)I-5-IA SPECT scans within 4 wk. (123)I-5-IA was administered as a bolus (125.8 +/- 14.6 MBq) plus constant infusion (18.1 +/- 1.5 MBq/h). SPECT acquisitions (30 min) and venous blood sampling were performed every 60 min throughout the infusion (10-14 h). The test-retest variability and reliability of plasma activity (kBq/mL), the regional brain activity reflected by units of kBq/mL and %ID/mL (injected dose/mL brain tissue), and the equilibrium outcome measures V(T)' (ratio of total uptake to total plasma parent concentration) and V(T) (ratio of total uptake to free plasma parent concentration) were evaluated in 4 brain areas, including thalamus, striatum, cortex, and cerebellum., Results: Linear regression analysis revealed that time-activity curves for both plasma and brain (123)I-5-IA activity stabilized by 5 h, with an average change of [2.5%/h between 6 and 8 h of infusion, permitting equilibrium modeling. The plasma free fraction (f(1)), total parent, and clearance demonstrated good test-retest variability (mean, 10.9%-12.5%), whereas the variability of free parent was greater (mean, 24.3%). Regional brain activity (kBq/mL) demonstrated good test-retest variability (11.1%-16.4%) that improved when corrected for infusion rate (mean, 8.2%-9.9%) or for injected dose (mean, 9.5%-13.3%). V(T)' demonstrated better test-retest variability (mean, 7.0%-8.9%) than V(T) (mean, 12.9%-14.6%). Reliability assessed by the intraclass correlation coefficient (ICC) was superior for kBq/mL (ICC = 0.83-0.90) and %ID/mL (ICC = 0.93-0.96) compared with V(T)' (ICC = 0.30-0.64) and V(T) (ICC = 0.28-0.60). The lower reliability of V(T) was attributed to the poor reliability of the free fraction (ICC = 0.35) and free parent (ICC = 0.68)., Conclusion: These results support the feasibility and reproducibility of equilibrium imaging with (123)I-5-IA for measurement of beta(2)-nAChRs in human brain.

Published
2005

14. Serotonin and aggression in children.

Author

Mitsis EM, Halperin JM, and Newcorn JH

Subjects
Adolescent, Attention Deficit Disorder with Hyperactivity cerebrospinal fluid, Attention Deficit Disorder with Hyperactivity genetics, Attention Deficit Disorder with Hyperactivity psychology, Child, Child Behavior Disorders genetics, Environment, Family psychology, Humans, Monoamine Oxidase cerebrospinal fluid, Social Behavior, Aggression psychology, Child Behavior Disorders cerebrospinal fluid, Child Behavior Disorders psychology, Hydroxyindoleacetic Acid cerebrospinal fluid
Abstract

Research consistently indicates that in animals and adults, reduced central serotonergic (5-HT) function is associated with increased aggression. This relationship has been elucidated via cerebrospinal fluid monoamine metabolite levels, hormonal responses to pharmacologic challenge using serotonergic probes, platelet receptor binding studies, and, more recently, through molecular genetic approaches. In contrast, studies examining the relationship of 5-HT to aggression in children have been characterized by inconsistent findings. The literature examining the relationship between central 5-HT function and aggression is reviewed. Several hypotheses that might account for the discrepancies in the child literature are examined.

Published
2000
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15. Parent-teacher concordance for DSM-IV attention-deficit/hyperactivity disorder in a clinic-referred sample.

Author

Mitsis EM, McKay KE, Schulz KP, Newcorn JH, and Halperin JM

Subjects
Attention Deficit Disorder with Hyperactivity psychology, Child, Female, Humans, Male, Observer Variation, Psychometrics, Social Environment, Attention Deficit Disorder with Hyperactivity diagnosis, Personality Assessment statistics & numerical data, Referral and Consultation statistics & numerical data
Abstract

Objective: To examine concordance between parent and teacher reports of DSM-IV attention-deficit/hyperactivity disorder (ADHD) and its symptoms., Method: Parents and teachers of 74 clinically referred children were interviewed using the ADHD module of the Diagnostic Interview Schedule for Children. Parent-teacher agreement for the diagnosis of ADHD and its subtypes, as defined in DSM-IV, as well as parent-teacher concordance of in-school ADHD symptoms, was examined., Results: Agreement between parents and teachers was found to be relatively poor, with virtually no agreement for individual ADHD subtypes. Diagnoses based on either parent or teacher report frequently yielded a diagnosis of either inattentive or hyperactive-impulsive subtype of ADHD. However, when cross-informant data were used to form diagnoses, these subtypes became relatively rare, with most cases meeting criteria for ADHD combined type. In addition, parent reports of in-school behavior were more highly correlated with their own reports of their child's behavior at home than with teacher reports of their child's behavior in school., Conclusions: These data suggest that the diagnosis of ADHD inattentive or hyperactive-impulsive subtype based on data from a single informant may be of questionable validity, and they point to the importance of using multiple informants when diagnosing this disorder in clinically referred samples.

Published
2000
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