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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. Sex-dependent association of common variants of microcephaly genes with brain structure

Author

Rimol, L. M., Agartz, I., Djurovic, S., Brown, A. A., Roddey, J. C., Kahler, A. K., Mattingsdal, M., Athanasiu, L., Joyner, A. H., Schork, N. J., Halgren, E., Sundet, K., Melle, I., Dale, A. M., Andreassen, O. A., Weiner, M., Thal, L., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J., Toga, A. W., Beckett, L., Green, R. C., Gamst, A., Potter, W. Z., Montine, T., Anders, D., Bernstein, M., Felmlee, J., Fox, N., Thompson, P., Schuff, N., Alexander, G., Bandy, D., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Shaw, L., Lee, V. M.- Y., Korecka, M., Crawford, K., Neu, S., Harvey, D., Kornak, J., Kachaturian, Z., Frank, R., Snyder, P. J., Molchan, S., Kaye, J., Vorobik, R., Quinn, J., Schneider, L., Pawluczyk, S., Spann, B., Fleisher, A. S., 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., Mintun, M. A., Schneider, S., Marson, D., Griffith, R., Badger, B., Grossman, H., Tang, C., Stern, J., deToledo-Morrell, L., Shah, R. C., Bach, J., Duara, R., Isaacson, R., Strauman, S., Albert, M. S., Pedroso, J., Toroney, J., Rusinek, H., de Leon, M. J., De Santi, S. M., Doraiswamy, P. M., Petrella, J. R., Aiello, M., Clark, C. M., Pham, C., Nunez, J., Smith, C. D., Given II, C. A., Hardy, P., DeKosky, S. T., Oakley, M., Simpson, D. M., Ismail, M. S., Porsteinsson, A., McCallum, C., Cramer, S. C., Mulnard, R. A., McAdams-Ortiz, C., Diaz-Arrastia, R., Martin-Cook, K., DeVous, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Anderson, H. S., Laubinger, M. M., Bartzokis, G., Silverman, D. H. S., Lu, P. H., Fletcher, R., Parfitt, F., Johnson, H., Farlow, M., Herring, S., Hake, A. M., van Dyck, C. H., MacAvoy, M. G., Bifano, L. A., Chertkow, H., Bergman, H., Hosein, C., Black, S., Graham, S., Caldwell, C., Feldman, H., Assaly, M., Hsiung, G.-Y. R., Kertesz, A., Rogers, J., Trost, D., Bernick, C., Gitelman, D., Johnson, N., Mesulam, M., Sadowsky, C., Villena, T., Mesner, S., Aisen, P. S., Johnson, K. B., Behan, K. E., Sperling, R. A., Rentz, D. M., Johnson, K. A., Rosen, A., Tinklenberg, J., Ashford, W., Sabbagh, M., Connor, D., Obradov, S., Killiany, R., Norbash, A., Obisesan, T. O., Jayam-Trouth, A., Wang, P., Auchus, A. P., Huang, J., Friedland, R. P., DeCarli, C., Fletcher, E., Carmichael, O., Kittur, S., Mirje, S., Johnson, S. C., Borrie, M., Lee, T.-Y., Asthana, S., Carlsson, C. M., Potkin, S. G., Highum, D., Preda, A., Nguyen, D., Tariot, P. N., Hendin, B. A., Scharre, D. W., Kataki, M., Beversdorf, D. Q., Zimmerman, E. A., Celmins, D., Brown, A. D., Gandy, S., Marenberg, M. E., Rovner, B. W., Pearlson, G., Blank, K., Anderson, K., Saykin, A. J., Santulli, R. B., Pare, N., Williamson, J. D., Sink, K. M., Potter, H., Ashok Raj, B., Giordano, A., Ott, B. R., Wu, C.-K., Cohen, R., Wilks, K. L., and Alzheimer's Disease Neuroimaging Initiative

Subjects
Adult, Male, Microcephaly, Molecular Sequence Data, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Brain mapping, ASPM, Sex Factors, medicine, Animals, Humans, SNP, Genetic Predisposition to Disease, Genetics, Brain Mapping, Multidisciplinary, CDK5RAP2, Brain morphometry, Brain, Middle Aged, Biological Sciences, medicine.disease, Magnetic Resonance Imaging, Phenotype, Brain size, Female
Abstract

Loss-of-function mutations in the genes associated with primary microcephaly (MCPH) reduce human brain size by about two-thirds, without producing gross abnormalities in brain organization or physiology and leaving other organs largely unaffected [Woods CG, et al. (2005) Am J Hum Genet 76:717–728]. There is also evidence suggesting that MCPH genes have evolved rapidly in primates and humans and have been subjected to selection in recent human evolution [Vallender EJ, et al. (2008) Trends Neurosci 31:637–644]. Here, we show that common variants of MCPH genes account for some of the common variation in brain structure in humans, independently of disease status. We investigated the correlations of SNPs from four MCPH genes with brain morphometry phenotypes obtained with MRI. We found significant, sex-specific associations between common, nonexonic, SNPs of the genes CDK5RAP2 , MCPH1 , and ASPM , with brain volume or cortical surface area in an ethnically homogenous Norwegian discovery sample ( n = 287), including patients with mental illness. The most strongly associated SNP findings were replicated in an independent North American sample ( n = 656), which included patients with dementia. These results are consistent with the view that common variation in brain structure is associated with genetic variants located in nonexonic, presumably regulatory, regions.

Published
2009
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3. Assessment of dementia risk in aging adults using both FDG-PET and FDDNP-PET imaging

Author

Ercoli, L. M., Small, G. W, Siddarth, P., Kepe, V., Huang, S-C., Miller, K. J., Lavretsky, H., Bookheimer, S. Y., Barrio, J. R., and Silverman, D. H. S.

Subjects
Aged, 80 and over, Male, Neurofibrillary Tangles, Plaque, Amyloid, Middle Aged, Risk Assessment, Article, Fluorodeoxyglucose F18, Risk Factors, Cerebellum, Positron-Emission Tomography, Nitriles, Cluster Analysis, Humans, Cognitive Dysfunction, Dementia, Female, Radiopharmaceuticals, Aged
Abstract

In a previous study, positron emission tomography (PET) with 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP), a molecule that binds to plaques and tangles in vitro, identified three subgroups of non-demented subjects according to FDDNP binding patterns: low global (LG) binding; high frontal, parietal, medial temporal binding (HF/PA); and high medial and lateral temporal and posterior cingulate (HT/PC) binding. In this follow-up investigation, we compared 2-deoxy-2-[F-18]fluoro- d-glucose (FDG)-PET cerebral metabolic patterns in the three FDDNP-PET binding subgroups.Fifty-four subjects with normal aging (N = 28) or amnestic forms of mild cognitive impairment (N = 26) underwent FDDNP-PET and FDG-PET scanning. Subjects in the LG, HF/PA, and HT/PC FDDNP subgroups were compared according to visual ratings, statistical parametric mapping, and automated region of interest analyses of their FDG-PET data.The FDDNP-PET subgroups demonstrated different glucose metabolic patterns according to visual ratings, region of interest, and statistical parametric mapping analyses of FDG-PET data. The LG FDDNP subgroup showed no areas of significant hypometabolism relative to the other subgroups and had low Alzheimer's disease risk by FDG-PET standards. The HF/PA FDDNP subgroup demonstrated hypometabolism in bilateral inferior parietal/parietotemporal, bilateral posterior cingulate, perisylvian, mid-temporal gyrus, and dorsolateral prefrontal regions, which is a pattern suggestive of high Alzheimer's disease risk. The HT/PC FDDNP subgroup demonstrated heterogeneous FDG-PET patterns with predominant anterior frontal and anterior temporal hypometabolism, suggestive of mixed etiologies, including fronto-temporal dementia risk.The FDG-PET data provided independent validation that different patterns of FDDNP-PET binding in non-demented individuals may be associated with differential dementia risk.

Published
2012

4. Visual-statistical interpretation of (18)F-FDG-PET images for characteristic Alzheimer patterns in a multicenter study: inter-rater concordance and relationship to automated quantitative evaluation.

Author

Yamane T, Ikari Y, Nishio T, Ishii K, Ishii K, Kato T, Ito K, Silverman DH, Senda M, Asada T, Arai H, Sugishita M, and Iwatsubo T

Subjects
Alzheimer Disease complications, Artificial Intelligence, Cognitive Dysfunction complications, Data Interpretation, Statistical, Female, Humans, Image Enhancement methods, Japan, Male, Middle Aged, Observer Variation, Radiopharmaceuticals, Reproducibility of Results, Sensitivity and Specificity, Algorithms, Alzheimer Disease diagnostic imaging, Cognitive Dysfunction diagnostic imaging, Fluorodeoxyglucose F18, Image Interpretation, Computer-Assisted methods, Pattern Recognition, Automated methods, Positron-Emission Tomography methods
Abstract

Background and Purpose: The role of (18)F-FDG-PET in the diagnosis of Alzheimer disease is increasing and should be validated. The aim of this study was to assess the inter-rater variability in the interpretation of (18)F-FDG-PET images obtained in the Japanese Alzheimer's Disease Neuroimaging Initiative, a multicenter clinical research project., Materials and Methods: This study analyzed 274 (18)F-FDG-PET scans (67 mild Alzheimer disease, 100 mild cognitive impairment, and 107 normal cognitive) as baseline scans for the Japanese Alzheimer's Disease Neuroimaging Initiative, which were acquired with various types of PET or PET/CT scanners in 23 facilities. Three independent raters interpreted all PET images by using a combined visual-statistical method. The images were classified into 7 (FDG-7) patterns by the criteria of Silverman et al and further into 2 (FDG-2) patterns., Results: Agreement among the 7 visual-statistical categories by at least 2 of the 3 readers occurred in >94% of cases for all groups: Alzheimer disease, mild cognitive impairment, and normal cognitive. Perfect matches by all 3 raters were observed for 62% of the cases by FDG-7 and 76 by FDG-2. Inter-rater concordance was moderate by FDG-7 (κ = 0.57) and substantial in FDG-2 (κ = 0.67) on average. The FDG-PET score, an automated quantitative index developed by Herholz et al, increased as the number of raters who voted for the AD pattern increased (ρ = 0.59, P < .0001), and the FDG-PET score decreased as those for normal pattern increased (ρ = -0.64, P < .0001)., Conclusions: Inter-rater agreement was moderate to substantial for the combined visual-statistical interpretation of (18)F-FDG-PET and was also significantly associated with automated quantitative assessment.

Published
2014
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