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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. Differential Diagnosis of Normal Pressure Hydrocephalus by MRI Mean Diffusivity Histogram Analysis

Author

Ivkovic, M, Liu, B, Ahmed, F, Moore, D, Huang, C, Raj, A, Kovanlikaya, I, Heier, L, and Relkin, N

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Biomedical Imaging, Neurodegenerative, Neurosciences, Brain Disorders, Aging, Parkinson's Disease, Dementia, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Neurological, Aged, Aged, 80 and over, Alzheimer Disease, Brain, Diagnosis, Differential, Female, Humans, Hydrocephalus, Normal Pressure, Image Processing, Computer-Assisted, Lewy Body Disease, Magnetic Resonance Imaging, Male, Middle Aged, Models, Theoretical, Neurodegenerative Diseases, Parkinson Disease, Reproducibility of Results, Sensitivity and Specificity, Nuclear Medicine & Medical Imaging, Clinical sciences, Physical chemistry
Abstract

Background and purposeAccurate diagnosis of normal pressure hydrocephalus is challenging because the clinical symptoms and radiographic appearance of NPH often overlap those of other conditions, including age-related neurodegenerative disorders such as Alzheimer and Parkinson diseases. We hypothesized that radiologic differences between NPH and AD/PD can be characterized by a robust and objective MR imaging DTI technique that does not require intersubject image registration or operator-defined regions of interest, thus avoiding many pitfalls common in DTI methods.Materials and methodsWe collected 3T DTI data from 15 patients with probable NPH and 25 controls with AD, PD, or dementia with Lewy bodies. We developed a parametric model for the shape of intracranial mean diffusivity histograms that separates brain and ventricular components from a third component composed mostly of partial volume voxels. To accurately fit the shape of the third component, we constructed a parametric function named the generalized Voss-Dyke function. We then examined the use of the fitting parameters for the differential diagnosis of NPH from AD, PD, and DLB.ResultsUsing parameters for the MD histogram shape, we distinguished clinically probable NPH from the 3 other disorders with 86% sensitivity and 96% specificity. The technique yielded 86% sensitivity and 88% specificity when differentiating NPH from AD only.ConclusionsAn adequate parametric model for the shape of intracranial MD histograms can distinguish NPH from AD, PD, or DLB with high sensitivity and specificity.

Published
2013

5. Guidelines for management of idiopathic normal pressure hydrocephalus: progress to date

Author

International NPH Consultant Group, Marmarou, A., Black, P., Bergsneider, M., Klinge, P., Relkin, N., Steiger, H. -J., editor, Poon, Wai S., editor, Chan, Matthew T. V., editor, Goh, Keith Y. C., editor, Lam, Joseph M. K., editor, Ng, Stephanie C. P., editor, Marmarou, Anthony, editor, Avezaat, Cees J. J., editor, Pickard, John D., editor, Czosnyka, Marek, editor, Hutchinson, Peter J. A., editor, and Katayama, Yoichi, editor

Published
2005
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8. Latrepirdine improves cognition and arrests progression of neuropathology in an Alzheimer's mouse model

Author

Steele, J W, Lachenmayer, M L, Ju, S, Stock, A, Liken, J, Kim, S H, Delgado, L M, Alfaro, I E, Bernales, S, Verdile, G, Bharadwaj, P, Gupta, V, Barr, R, Friss, A, Dolios, G, Wang, R, Ringe, D, Fraser, P, Westaway, D, St George-Hyslop, P H, Szabo, P, Relkin, N R, Buxbaum, J D, Glabe, C G, Protter, A A, Martins, R N, Ehrlich, M E, Petsko, G A, Yue, Z, and Gandy, S

Published
2013
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13. 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

15. 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

17. Abstracts from Hydrocephalus 2016.

Author

Adam, A, Robison, J, Lu, J, Jose, R, Badran, N, Vivas-Buitrago, T, Rigamonti, D, Sattar, A, Omoush, O, Hammad, M, Dawood, M, Maghaslah, M, Belcher, T, Carson, K, Hoffberger, J, Jusué Torres, I, Foley, S, Yasar, S, Thai, Q A, Wemmer, J, Klinge, P, Al-Mutawa, L, Al-Ghamdi, H, Carson, K A, Asgari, M, de Zélicourt, D, Kurtcuoglu, V, Garnotel, S, Salmon, S, Balédent, O, Lokossou, A, Page, G, Balardy, L, Czosnyka, Z, Payoux, P, Schmidt, E A, Zitoun, M, Sevestre, M A, Alperin, N, Baudracco, I, Craven, C, Matloob, S, Thompson, S, Haylock Vize, P, Thorne, L, Watkins, L D, Toma, A K, Bechter, Karl, Pong, A C, Jugé, L, Bilston, L E, Cheng, S, Bradley, W, Hakim, F, Ramón, J F, Cárdenas, M F, Davidson, J S, García, C, González, D, Bermúdez, S, Useche, N, Mejía, J A, Mayorga, P, Cruz, F, Martinez, C, Matiz, M C, Vallejo, M, Ghotme, K, Soto, H A, Riveros, D, Buitrago, A, Mora, M, Murcia, L, Bermudez, S, Cohen, D, Dasgupta, D, Curtis, C, Domínguez, L, Remolina, A J, Grijalba, M A, Whitehouse, K J, Edwards, R J, Eleftheriou, A, Lundin, F, Fountas, K N, Kapsalaki, E Z, Smisson, H F, Robinson, J S, Fritsch, M J, Arouk, W, Garzon, M, Kang, M, Sandhu, K, Baghawatti, D, Aquilina, K, James, G, Thompson, D, Gehlen, M, Schmid Daners, M, Eklund, A, Malm, J, Gomez, D, Guerra, M, Jara, M, Flores, M, Vío, K, Moreno, I, Rodríguez, S, Ortega, E, Rodríguez, E M, McAllister, J P, Guerra, M M, Morales, D M, Sival, D, Jimenez, A, Limbrick, D D, Ishikawa, M, Yamada, S, Yamamoto, K, Junkkari, A, Häyrinen, A, Rauramaa, T, Sintonen, H, Nerg, O, Koivisto, A M, Roine, R P, Viinamäki, H, Soininen, H, Luikku, A, Jääskeläinen, J E, Leinonen, V, Kehler, U, Lilja-Lund, O, Kockum, K, Larsson, Elna-Marie, Riklund, K, Söderström, L, Hellström, P, Laurell, K, Kojoukhova, M, Sutela, A, Vanninen, R, Vanha, K I, Timonen, M, Rummukainen, J, Korhonen, V, Helisalmi, S, Solje, E, Remes, A M, Huovinen, J, Paananen, J, Hiltunen, M, Kurki, M, Martin, B, Loth, F, Luciano, M, Luikku, A J, Hall, A, Herukka, S K, Mattila, J, Lötjönen, J, Alafuzoff, Irina, Jurjević, I, Miyajima, M, Nakajima, M, Murai, H, Shin, T, Kawaguchi, D, Akiba, C, Ogino, I, Karagiozov, K, Arai, H, Reis, R C, Teixeira, M J, Valêncio, C G, da Vigua, D, Almeida-Lopes, L, Mancini, M W, Pinto, F C G, Maykot, R H, Calia, G, Tornai, J, Silvestre, S S S, Mendes, G, Sousa, V, Bezerra, B, Dutra, P, Modesto, P, Oliveira, M F, Petitto, C E, Pulhorn, H, Chandran, A, McMahon, C, Rao, A S, Jumaly, M, Solomon, D, Moghekar, A, Relkin, N, Hamilton, M, Katzen, H, Williams, M, Bach, T, Zuspan, S, Holubkov, R, Rigamonti, A, Clemens, G, Sharkey, P, Sanyal, A, Sankey, E, Rigamonti, K, Naqvi, S, Hung, A, Schmidt, E, Ory-Magne, F, Gantet, P, Guenego, A, Januel, A C, Tall, P, Fabre, N, Mahieu, L, Cognard, C, Gray, L, Buttner-Ennever, J A, Takagi, K, Onouchi, K, Thompson, S D, Thorne, L D, Tully, H M, Wenger, T L, Kukull, W A, Doherty, D, Dobyns, W B, Moran, D, Vakili, S, Patel, M A, Elder, B, Goodwin, C R, Crawford, J A, Pletnikov, M V, Xu, J, Blitz, A, Herzka, D A, Guerrero-Cazares, H, Quiñones-Hinojosa, A, Mori, S, Saavedra, P, Treviño, H, Maitani, K, Ziai, W C, Eslami, V, Nekoovaght-Tak, S, Dlugash, R, Yenokyan, G, McBee, N, Hanley, D F, Adam, A, Robison, J, Lu, J, Jose, R, Badran, N, Vivas-Buitrago, T, Rigamonti, D, Sattar, A, Omoush, O, Hammad, M, Dawood, M, Maghaslah, M, Belcher, T, Carson, K, Hoffberger, J, Jusué Torres, I, Foley, S, Yasar, S, Thai, Q A, Wemmer, J, Klinge, P, Al-Mutawa, L, Al-Ghamdi, H, Carson, K A, Asgari, M, de Zélicourt, D, Kurtcuoglu, V, Garnotel, S, Salmon, S, Balédent, O, Lokossou, A, Page, G, Balardy, L, Czosnyka, Z, Payoux, P, Schmidt, E A, Zitoun, M, Sevestre, M A, Alperin, N, Baudracco, I, Craven, C, Matloob, S, Thompson, S, Haylock Vize, P, Thorne, L, Watkins, L D, Toma, A K, Bechter, Karl, Pong, A C, Jugé, L, Bilston, L E, Cheng, S, Bradley, W, Hakim, F, Ramón, J F, Cárdenas, M F, Davidson, J S, García, C, González, D, Bermúdez, S, Useche, N, Mejía, J A, Mayorga, P, Cruz, F, Martinez, C, Matiz, M C, Vallejo, M, Ghotme, K, Soto, H A, Riveros, D, Buitrago, A, Mora, M, Murcia, L, Bermudez, S, Cohen, D, Dasgupta, D, Curtis, C, Domínguez, L, Remolina, A J, Grijalba, M A, Whitehouse, K J, Edwards, R J, Eleftheriou, A, Lundin, F, Fountas, K N, Kapsalaki, E Z, Smisson, H F, Robinson, J S, Fritsch, M J, Arouk, W, Garzon, M, Kang, M, Sandhu, K, Baghawatti, D, Aquilina, K, James, G, Thompson, D, Gehlen, M, Schmid Daners, M, Eklund, A, Malm, J, Gomez, D, Guerra, M, Jara, M, Flores, M, Vío, K, Moreno, I, Rodríguez, S, Ortega, E, Rodríguez, E M, McAllister, J P, Guerra, M M, Morales, D M, Sival, D, Jimenez, A, Limbrick, D D, Ishikawa, M, Yamada, S, Yamamoto, K, Junkkari, A, Häyrinen, A, Rauramaa, T, Sintonen, H, Nerg, O, Koivisto, A M, Roine, R P, Viinamäki, H, Soininen, H, Luikku, A, Jääskeläinen, J E, Leinonen, V, Kehler, U, Lilja-Lund, O, Kockum, K, Larsson, Elna-Marie, Riklund, K, Söderström, L, Hellström, P, Laurell, K, Kojoukhova, M, Sutela, A, Vanninen, R, Vanha, K I, Timonen, M, Rummukainen, J, Korhonen, V, Helisalmi, S, Solje, E, Remes, A M, Huovinen, J, Paananen, J, Hiltunen, M, Kurki, M, Martin, B, Loth, F, Luciano, M, Luikku, A J, Hall, A, Herukka, S K, Mattila, J, Lötjönen, J, Alafuzoff, Irina, Jurjević, I, Miyajima, M, Nakajima, M, Murai, H, Shin, T, Kawaguchi, D, Akiba, C, Ogino, I, Karagiozov, K, Arai, H, Reis, R C, Teixeira, M J, Valêncio, C G, da Vigua, D, Almeida-Lopes, L, Mancini, M W, Pinto, F C G, Maykot, R H, Calia, G, Tornai, J, Silvestre, S S S, Mendes, G, Sousa, V, Bezerra, B, Dutra, P, Modesto, P, Oliveira, M F, Petitto, C E, Pulhorn, H, Chandran, A, McMahon, C, Rao, A S, Jumaly, M, Solomon, D, Moghekar, A, Relkin, N, Hamilton, M, Katzen, H, Williams, M, Bach, T, Zuspan, S, Holubkov, R, Rigamonti, A, Clemens, G, Sharkey, P, Sanyal, A, Sankey, E, Rigamonti, K, Naqvi, S, Hung, A, Schmidt, E, Ory-Magne, F, Gantet, P, Guenego, A, Januel, A C, Tall, P, Fabre, N, Mahieu, L, Cognard, C, Gray, L, Buttner-Ennever, J A, Takagi, K, Onouchi, K, Thompson, S D, Thorne, L D, Tully, H M, Wenger, T L, Kukull, W A, Doherty, D, Dobyns, W B, Moran, D, Vakili, S, Patel, M A, Elder, B, Goodwin, C R, Crawford, J A, Pletnikov, M V, Xu, J, Blitz, A, Herzka, D A, Guerrero-Cazares, H, Quiñones-Hinojosa, A, Mori, S, Saavedra, P, Treviño, H, Maitani, K, Ziai, W C, Eslami, V, Nekoovaght-Tak, S, Dlugash, R, Yenokyan, G, McBee, N, and Hanley, D F

Published
2017
Full Text
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18. Abstracts from Hydrocephalus 2016

Author

Adam, A., primary, Robison, J., additional, Lu, J., additional, Jose, R., additional, Badran, N., additional, Vivas-Buitrago, T., additional, Rigamonti, D., additional, Sattar, A., additional, Omoush, O., additional, Hammad, M., additional, Dawood, M., additional, Maghaslah, M., additional, Belcher, T., additional, Carson, K., additional, Hoffberger, J., additional, Jusué Torres, I., additional, Foley, S., additional, Yasar, S., additional, Thai, Q. A., additional, Wemmer, J., additional, Klinge, P., additional, Al-Mutawa, L., additional, Al-Ghamdi, H., additional, Carson, K. A., additional, Asgari, M., additional, de Zélicourt, D., additional, Kurtcuoglu, V., additional, Garnotel, S., additional, Salmon, S., additional, Balédent, O., additional, Lokossou, A., additional, Page, G., additional, Balardy, L., additional, Czosnyka, Z., additional, Payoux, P., additional, Schmidt, E. A., additional, Zitoun, M., additional, Sevestre, M. A., additional, Alperin, N., additional, Baudracco, I., additional, Craven, C., additional, Matloob, S., additional, Thompson, S., additional, Haylock Vize, P., additional, Thorne, L., additional, Watkins, L. D., additional, Toma, A. K., additional, Bechter, Karl, additional, Pong, A. C., additional, Jugé, L., additional, Bilston, L. E., additional, Cheng, S., additional, Bradley, W., additional, Hakim, F., additional, Ramón, J. F., additional, Cárdenas, M. F., additional, Davidson, J. S., additional, García, C., additional, González, D., additional, Bermúdez, S., additional, Useche, N., additional, Mejía, J. A., additional, Mayorga, P., additional, Cruz, F., additional, Martinez, C., additional, Matiz, M. C., additional, Vallejo, M., additional, Ghotme, K., additional, Soto, H. A., additional, Riveros, D., additional, Buitrago, A., additional, Mora, M., additional, Murcia, L., additional, Bermudez, S., additional, Cohen, D., additional, Dasgupta, D., additional, Curtis, C., additional, Domínguez, L., additional, Remolina, A. J., additional, Grijalba, M. A., additional, Whitehouse, K. J., additional, Edwards, R. J., additional, Eleftheriou, A., additional, Lundin, F., additional, Fountas, K. N., additional, Kapsalaki, E. Z., additional, Smisson, H. F., additional, Robinson, J. S., additional, Fritsch, M. J., additional, Arouk, W., additional, Garzon, M., additional, Kang, M., additional, Sandhu, K., additional, Baghawatti, D., additional, Aquilina, K., additional, James, G., additional, Thompson, D., additional, Gehlen, M., additional, Schmid Daners, M., additional, Eklund, A., additional, Malm, J., additional, Gomez, D., additional, Guerra, M., additional, Jara, M., additional, Flores, M., additional, Vío, K., additional, Moreno, I., additional, Rodríguez, S., additional, Ortega, E., additional, Rodríguez, E. M., additional, McAllister, J. P., additional, Guerra, M. M., additional, Morales, D. M., additional, Sival, D., additional, Jimenez, A., additional, Limbrick, D. D., additional, Ishikawa, M., additional, Yamada, S., additional, Yamamoto, K., additional, Junkkari, A., additional, Häyrinen, A., additional, Rauramaa, T., additional, Sintonen, H., additional, Nerg, O., additional, Koivisto, A. M., additional, Roine, R. P., additional, Viinamäki, H., additional, Soininen, H., additional, Luikku, A., additional, Jääskeläinen, J. E., additional, Leinonen, V., additional, Kehler, U., additional, Lilja-Lund, O., additional, Kockum, K., additional, Larsson, E. M., additional, Riklund, K., additional, Söderström, L., additional, Hellström, P., additional, Laurell, K., additional, Kojoukhova, M., additional, Sutela, A., additional, Vanninen, R., additional, Vanha, K. I., additional, Timonen, M., additional, Rummukainen, J., additional, Korhonen, V., additional, Helisalmi, S., additional, Solje, E., additional, Remes, A. M., additional, Huovinen, J., additional, Paananen, J., additional, Hiltunen, M., additional, Kurki, M., additional, Martin, B., additional, Loth, F., additional, Luciano, M., additional, Luikku, A. J., additional, Hall, A., additional, Herukka, S. K., additional, Mattila, J., additional, Lötjönen, J., additional, Alafuzoff, I., additional, Jurjević, I., additional, Miyajima, M., additional, Nakajima, M., additional, Murai, H., additional, Shin, T., additional, Kawaguchi, D., additional, Akiba, C., additional, Ogino, I., additional, Karagiozov, K., additional, Arai, H, additional, Reis, R. C., additional, Teixeira, M. J., additional, Valêncio, C. G., additional, da Vigua, D., additional, Almeida-Lopes, L., additional, Mancini, M. W., additional, Pinto, F. C. G., additional, Maykot, R. H., additional, Calia, G., additional, Tornai, J., additional, Silvestre, S. S. S., additional, Mendes, G., additional, Sousa, V., additional, Bezerra, B., additional, Dutra, P., additional, Modesto, P., additional, Oliveira, M. F., additional, Petitto, C. E., additional, Pulhorn, H., additional, Chandran, A., additional, McMahon, C., additional, Rao, A. S., additional, Jumaly, M., additional, Solomon, D., additional, Moghekar, A., additional, Relkin, N., additional, Hamilton, M., additional, Katzen, H., additional, Williams, M., additional, Bach, T., additional, Zuspan, S., additional, Holubkov, R., additional, Rigamonti, A., additional, Clemens, G., additional, Sharkey, P., additional, Sanyal, A., additional, Sankey, E., additional, Rigamonti, K., additional, Naqvi, S., additional, Hung, A., additional, Schmidt, E., additional, Ory-Magne, F., additional, Gantet, P., additional, Guenego, A., additional, Januel, A. C., additional, Tall, P., additional, Fabre, N., additional, Mahieu, L., additional, Cognard, C., additional, Gray, L., additional, Buttner-Ennever, J. A., additional, Takagi, K., additional, Onouchi, K, additional, Thompson, S. D., additional, Thorne, L. D., additional, Tully, H. M., additional, Wenger, T. L., additional, Kukull, W. A., additional, Doherty, D., additional, Dobyns, W. B., additional, Moran, D., additional, Vakili, S., additional, Patel, M. A., additional, Elder, B., additional, Goodwin, C. R., additional, Crawford, J. A., additional, Pletnikov, M. V., additional, Xu, J., additional, Blitz, A., additional, Herzka, D. A., additional, Guerrero-Cazares, H., additional, Quiñones-Hinojosa, A., additional, Mori, S., additional, Saavedra, P., additional, Treviño, H., additional, Maitani, K., additional, Ziai, W. C., additional, Eslami, V., additional, Nekoovaght-Tak, S., additional, Dlugash, R., additional, Yenokyan, G., additional, McBee, N., additional, and Hanley, D. F., additional

Published
2017
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19. Preliminary findings from the REVEAL Study: Genetic risk assessment and counseling for Alzheimer's disease

Author

Brown, T., LaRusse, S., Barber, M., Relkin, N., Whitehouse, P., Farrer, L., Cupples, L., Post, S., Ravdin, L., Katzen, H., Cisewski, D., Sami, S., Davis, J., Sadovnick, A., Quaid, K., Woodard, J., and Green, R.

Subjects
Human genetics -- Research, Genetic disorders -- Risk factors, Alzheimer's disease -- Genetic aspects, Apolipoproteins -- Genetic aspects, Genotype -- Research, Biological sciences
Published
2001

21. Amyloid-beta-directed immunotherapy for Alzheimer's disease

Author

Lannfelt, Lars, Relkin, N. R., and Siemers, E. R.

Subjects
clinical trials, Medicin och hälsovetenskap, Geriatrics, Geriatrik, immunotherapy, Alzheimer's disease, Medical and Health Sciences, amyloid-beta
Abstract

Current treatment options for Alzheimer's disease (AD) are limited to medications that reduce dementia symptoms. Given the rapidly ageing populations in most areas of the world, new therapeutic interventions for AD are urgently needed. In recent years, a number of drug candidates targeting the amyloid-ss (A ss) peptide have advanced into clinical trials; however, most have failed because of safety issues or lack of efficacy. The A ss peptide is central to the pathogenesis, and immunotherapy against A ss has attracted considerable interest. It offers the possibility to reach the target with highly specific drugs. Active immunization and passive immunization have been the most widely studied approaches to immunotherapy of AD. A favourable aspect of active immunization is the capacity for a small number of vaccinations to generate a prolonged antibody response. A potential disadvantage is the variability in the antibody response across patients. The potential advantages of passive immunotherapy include the reproducible delivery of a known amount of therapeutic antibodies to the patient and rapid clearance of those antibodies if side effects develop. A disadvantage is the requirement for repeated infusions of antibodies over time. After more than a decade of research, anti-amyloid immunotherapy remains one of the most promising emerging strategies for developing disease-modifying treatments for AD. In this review, we examine the presently ongoing A ss-directed immunotherapies that have passed clinical development Phase IIa.

Published
2014

22. Brain structure and function in patients with ovarian cancer treated with first-line chemotherapy: a pilot study.

Author

Correa, D., Root, J., Kryza-Lacombe, M., Mehta, M., Karimi, S., Hensley, M., Relkin, N., Correa, D D, Root, J C, and Hensley, M L

Abstract

Women with ovarian cancer often undergo chemotherapy involving multiple agents. However, little is known about treatment-related central neurotoxicity in this population. The goal of this cross-sectional study was to assess brain structure and function and neurocognitive abilities in patients with ovarian cancer following first-line chemotherapy. Eighteen patients with ovarian, peritoneal and fallopian tube cancer and eighteen healthy controls matched for gender, age and education participated in the study. The patients were evaluated 1-4 months following completion of first-line taxane/platinum chemotherapy. All participants underwent structural and functional magnetic resonance imaging (MRI), and completed neuropsychological tests of attention, memory and executive functions. Neuroimaging assessments included voxel-based morphometry (VBM) for measuring gray matter (GM) volume, and functional MRI (fMRI) during the N-back working memory task. The results of VBM showed that patients had significantly reduced GM volume compared to healthy controls in the right middle/superior frontal gyrus, and in the left supramarginal gyrus and left inferior parietal lobule. fMRI results indicated significantly decreased activation in patients relative to healthy controls in the left middle frontal gyrus and left inferior parietal lobule during the N-back task (1/2/3-back >0-back). There were no statistically significant differences between the two groups on the neuropsychological tests. This is the first study showing structural and functional alterations involving frontal and parietal regions in patients with ovarian cancer treated with first-line chemotherapy. These findings are congruent with studies involving women with breast cancer, and provide additional supporting evidence for central neurotoxicity associated with taxane/platinum chemotherapy. [ABSTRACT FROM AUTHOR]

Published
2017
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26. Increased Diffusion in the Brain of Professional Boxers: A Preclinical Sign of Traumatic Brain Injury?

Author

Zhang, Lj, Ravdin, Ld, Relkin, N., Zimmerman, Rd, Jordan, B., Lathan, We, and Aziz M. Ulug

Subjects
Adult, Male, Diffusion Magnetic Resonance Imaging, Reference Values, Athletic Injuries, Brain Injury, Chronic, Brain, Humans, Atrophy, Boxing, Middle Aged, Dominance, Cerebral, human activities
Abstract

BACKGROUND AND PURPOSE: Professional boxing is associated with chronic, repetitive head blows that may cause brain injuries. Diffusion-weighted imaging is sensitive to microscopic changes and may be a useful tool to quantify the microstructural integrity of the brain. In this study, we sought to quantify microscopic alterations associated with chronic traumatic brain injury in professional boxers. METHODS: MR and diffusion-weighted imaging were performed in 24 boxers and in 14 age- and sex-matched control subjects with no history of head trauma. Using distribution analysis, the average diffusion constant of the entire brain (BD(av)) and diffusion distribution width (σ) were calculated for each subject; findings in professional boxers were compared with those of control subjects. In the boxer group, correlations between diffusion changes and boxing history and diffusion changes and MR imaging findings were assessed. RESULTS: The measured diffusion values in the boxer group were significantly higher than those measured in the control group (BD(av), P < .0001; σ, P < .01). In the boxer group, a robust correlation was found between increased BD(av) and frequency of hospitalization for boxing injuries (r = 0.654, P < .05). The most common MR finding in the boxer group was volume loss inappropriate to age followed by cavum septum pellucidum, subcortical white matter disease, and periventricular white matter disease. CONCLUSION: Boxers had higher diffusion constants than those in control subjects. Our data suggest that microstructural damage of the brain associated with chronic traumatic brain injury may elevate whole-brain diffusion. This global elevation can exist even when routine MR findings are normal.

Published
2003

27. Latrepirdine improves cognition and arrests progression of neuropathology in an Alzheimer's mouse model

Author

Steele, J, Lachenmayer, M, Ju, S, Stock, A, Liken, J, Kim, S, Delgado, L, Alfaro, I, Bernales, S, Verdile, G, Bharadwaj, P, Gupta, V, Barr, R, Friss, A, Dolios, G, Wang, R, Ringe, D, Fraser, P, Westaway, D, St George-Hyslop, P, Szabo, P, Relkin, N, Buxbaum, J, Glabe, C, Protter, A, Martins, R, Ehrlich, M, Petsko, G, Yue, Z, Gandy, S, Steele, J, Lachenmayer, M, Ju, S, Stock, A, Liken, J, Kim, S, Delgado, L, Alfaro, I, Bernales, S, Verdile, G, Bharadwaj, P, Gupta, V, Barr, R, Friss, A, Dolios, G, Wang, R, Ringe, D, Fraser, P, Westaway, D, St George-Hyslop, P, Szabo, P, Relkin, N, Buxbaum, J, Glabe, C, Protter, A, Martins, R, Ehrlich, M, Petsko, G, Yue, Z, and Gandy, S

Abstract

Latrepirdine (Dimebon) is a pro-neurogenic, antihistaminic compound that has yielded mixed results in clinical trials of mild to moderate Alzheimer's disease, with a dramatically positive outcome in a Russian clinical trial that was unconfirmed in a replication trial in the United States. We sought to determine whether latrepirdine (LAT)-stimulated amyloid precursor protein (APP) catabolism is at least partially attributable to regulation of macroautophagy, a highly conserved protein catabolism pathway that is known to be impaired in brains of patients with Alzheimer's disease (AD). We utilized several mammalian cellular models to determine whether LAT regulates mammalian target of rapamycin (mTOR) and Atg5-dependent autophagy. Male TgCRND8 mice were chronically administered LAT prior to behavior analysis in the cued and contextual fear conditioning paradigm, as well as immunohistological and biochemical analysis of AD-related neuropathology. Treatment of cultured mammalian cells with LAT led to enhanced mTOR- and Atg5-dependent autophagy. Latrepirdine treatment of TgCRND8 transgenic mice was associated with improved learning behavior and with a reduction in accumulation of Aβ42 and α-synuclein. We conclude that LAT possesses pro-autophagic properties in addition to the previously reported pro-neurogenic properties, both of which are potentially relevant to the treatment and/or prevention of neurodegenerative diseases. We suggest that elucidation of the molecular mechanism(s) underlying LAT effects on neurogenesis, autophagy and behavior might warranty the further study of LAT as a potentially viable lead compound that might yield more consistent clinical benefit following the optimization of its pro-neurogenic, pro-autophagic and/or pro-cognitive activities. © 2013 Macmillan Publishers Limited.

Published
2013

28. Latrepirdine improves cognition and arrests progression of neuropathology in an Alzheimer's mouse model

Author

Steele, J., Lachenmayer, M., Shulin, J., Stock, A., Liken, J., Kim, S., Delgado, L., Alfrao, I., Bernales, S., Verdile, Giuseppe, Bharadwaj, P., Gupta, V., Barr, R., Friss, A., Dolios, G., Wang, R., Ringe, D., Fraser, P., Westaway, D., St George-Hislop, P., Szabo, P., Relkin, N., Buxbaum, J., Glade, C., Protter, A., Martins, R., Ehrlich, M., Petsko, G., Yue, Z., Gandy, S., Steele, J., Lachenmayer, M., Shulin, J., Stock, A., Liken, J., Kim, S., Delgado, L., Alfrao, I., Bernales, S., Verdile, Giuseppe, Bharadwaj, P., Gupta, V., Barr, R., Friss, A., Dolios, G., Wang, R., Ringe, D., Fraser, P., Westaway, D., St George-Hislop, P., Szabo, P., Relkin, N., Buxbaum, J., Glade, C., Protter, A., Martins, R., Ehrlich, M., Petsko, G., Yue, Z., and Gandy, S.

Published
2013

32. Latrepirdine improves cognition and arrests progression of neuropathology in an Alzheimer's mouse model

Author

Steele, J W, primary, Lachenmayer, M L, additional, Ju, S, additional, Stock, A, additional, Liken, J, additional, Kim, S H, additional, Delgado, L M, additional, Alfaro, I E, additional, Bernales, S, additional, Verdile, G, additional, Bharadwaj, P, additional, Gupta, V, additional, Barr, R, additional, Friss, A, additional, Dolios, G, additional, Wang, R, additional, Ringe, D, additional, Fraser, P, additional, Westaway, D, additional, St George-Hyslop, P H, additional, Szabo, P, additional, Relkin, N R, additional, Buxbaum, J D, additional, Glabe, C G, additional, Protter, A A, additional, Martins, R N, additional, Ehrlich, M E, additional, Petsko, G A, additional, Yue, Z, additional, and Gandy, S, additional

Published
2012
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37. Psychiatric complications in a patient with complex partial seizures [clinical conference]

Author

Steven Mattis, Milton Viederman, Kanwal Gs, Hilary P. Blumberg, Makari Gj, and Relkin N

Subjects
medicine.medical_specialty, medicine.diagnostic_test, Complex partial seizures, Cognitive disorder, Cognition, Neuropsychological test, medicine.disease, Central nervous system disease, Psychiatry and Mental health, Personality changes, Seizure Disorders, medicine, Ictal, Psychiatry, Psychology
Abstract

This case highlights the complexities of evaluating and treating psychiatric symptoms that are concurrent with a seizure disorder. Interictal and postictal psychoses, affective disorders, personality changes, and cognitive deficits are common problems that require modified psychiatric treatments.

Published
1996

44. The Mattis Dementia Rating Scale in nursing home octogenarians and nonagenarians: effects of age and education.

Author

Bennett, Alexandre, Nadler, Jodi, Spigler, Melanie, Rafalson, Luba, Abraham, Susy, Relkin, Norman, Bennett, A, Nadler, J, Spigler, M, Rafalson, L, Abraham, S, and Relkin, N

Subjects
DIAGNOSIS of dementia, AGE distribution, GERIATRIC assessment, COMPARATIVE studies, NEUROPSYCHOLOGICAL tests, RESEARCH methodology, MEDICAL cooperation, PSYCHOLOGICAL tests, REFERENCE values, REGRESSION analysis, RESEARCH, STATISTICAL sampling, EVALUATION research, EDUCATIONAL attainment, CROSS-sectional method, STANDARDS
Abstract

Despite their increasing representation in the population, little is known about the neuropsychological test performance of the oldest old, particularly those who live in residential settings. Limited published data and clinical experience suggest that this group is more likely to perform in the impaired range on standardized tests when cutoffs developed with younger groups are used. We examined the Dementia Rating Scale (DRS) performance of 82 nondemented nursing home residents, aged 80 to 99, with a mean education level of 11 years. Using published norms and cutoffs, a large percentage of this sample performed in the impaired range, particularly on the initiation and conceptualization subtests and on the total score. Education, but not age, was significantly related to performance in this sample. Percentages of patients misclassified were substantial in all groups, but were higher in those with less than 13 years of education. Using a lower total-score cutoff of 110 reduced the percentage of misclassifications markedly. We recommend the development and use of revised cutoff scores for the evaluation of very elderly nursing home residents. (J Geriatr Psychiatry Neurol 1997; 10:114-118). [ABSTRACT FROM PUBLISHER]

Published
1997
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45. Mental status testing in the elderly nursing home population.

Author

Nadler, Jodi D., Relkin, Norman R., Cohen, Melanie S., Hodder, Richard A., Reingold, Jacob, Plum, Fred, Nadler, J D, Relkin, N R, Cohen, M S, Hodder, R A, Reingold, J, and Plum, F

Subjects
DIAGNOSIS of dementia, MENTAL depression, AGE distribution, GERIATRIC assessment, COMPARATIVE studies, GERIATRICS, NEUROPSYCHOLOGICAL tests, RESEARCH methodology, MEDICAL cooperation, NURSING care facilities, PSYCHOLOGICAL tests, QUESTIONNAIRES, RESEARCH, RESEARCH evaluation, EVALUATION research, EDUCATIONAL attainment
Abstract

The clinical utility of selected brief cognitive screening instruments in detecting dementia in an elderly nursing home population was examined. One hundred twenty nursing home residents (mean age 87.9) were administered the Mini-Mental State Exam (MMSE) and the Modified Mini-Mental State Exam (3MS). The majority of the subjects (75%) were also administered the Dementia Rating Scale (DRS). Both clinically diagnosed demented (n = 57) and non-demented (n = 63) subjects participated in the study. Dementia was diagnosed in accordance with DSM-III-R criteria by physicians specializing in geriatric medicine. Using standard cutoffs for impairment, the 3MS, MMSE, and DRS achieved high sensitivity (82% to 100%) but low specificity (33% to 52%) in the detection of dementia among nursing home residents. Positive predictive values ranged from 52% to 61%, and negative predictive values from 77% to 100%. Higher age, lower education, and history of depression were significantly associated with misclassification of non-demented elderly subjects. Receiver Operating Characteristic (ROC) curve analyses revealed optimal classification of dementia with cutoff values of 74 for the 3MS, 22 for the MMSE, and 110 for the DRS. The results suggest that the 3MS, MMSE, and DRS do not differ significantly with respect to classification accuracy of dementia in a nursing home population. Elderly individuals of advanced age (i.e., the oldest-old) with lower education and a history of depression appear at particular risk for dementia misclassification with these instruments. Revised cutoff values for impairment should be employed when these instruments are applied to elderly residents of nursing homes and the oldest-old. [ABSTRACT FROM AUTHOR]

Published
1995
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