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Vascular burden and Alzheimer disease pathologic progression

OBJECTIVE:: To investigate the vascular contribution to longitudinal changes in Alzheimer disease (AD) biomarkers. METHODS:: The Alzheimerʼs Disease Neuroimaging Initiative is a clinic based, longitudinal study with CSF, PET, and MRI biomarkers repeatedly measured in participants with normal cogniti... Full description

Journal Title: Neurology 2012, Vol.79(13), pp.1349-1355
Main Author: Lo, Y., Raymond
Other Authors: Jagust, J., William , Weiner, R., Michael , Aisen, Q., Paul , Weiner, W., Michael , Aisen, C., Paul , Petersen, J., Ronald , Jack, C., Clifford , Jagust, G., William , Trojanowki, R., John , Toga, A., Arthur , Beckett, M., Laurel , Green, J., Robert , Saykin, M.Y., Andrew , Morris, W., John , Liu, J., Enchi , Green, M., Robert , Montine, J., Tom , Petersen, S., Ronald , Aisen, M., Paul , Gamst, L., Anthony , Thomas, L., Ronald , Donohue, S., Michael , Walter, S., Sarah , Gessert, L., Devon , Sather, C., Tamie , Beckett, A., Laurel , Harvey, C., Danielle , Gamst, J, Anthony , Donohue, Murali, Michael , Kornak, R., John , Jack, Edward, Clifford , Dale, E., Anders , Bernstein, H., Matthew , Felmlee, D., Joel , Fox, L., Nick , Thompson, M., Paul , Schuff, P., Norbert , Alexander, S., Gene , Decarli, M., Charles , Jagust, Saleem, William , Bandy, A., Dan , Koeppe, I., Robert , Foster, J., Norm , Reiman, S., Eric , Chen, M., Kewei , Mathis, S., Chet , Morris, H., John , Cairns, H., Nigel , Taylor-Reinwald, H.S., Lisa , Trojanowki, R, J.Q. , Shaw, R., Les , Lee, Marie, Virginia , Korecka, R., Magdalena , Toga, H., Arthur , Crawford, E., Karen , Neu, G., Scott , Saykin, Bojana, Andrew , Foroud, Robin, Tatiana , Potkin, Scott, Steven , Shen, A., Li , Kachaturian, A., Zaven , Frank, L., Richard , Snyder, E., Peter , Molchan, Lynn, Susan , Kaye, O., Jeffrey , Quinn, K., Joseph , Lind, Rob, Betty , Dolen, M., Sara , Schneider, G., Lon , Pawluczyk, W., Sonia , Spann, A., Bryan , Brewer, D., James , Vanderswag, D., Helen , Heidebrink, J., Judith , Lord, B., Joanne , Petersen, S., Ronald , Johnson, M., Kris , Doody, D., Rachelle , Villanueva-Meyer, R., Javier , Chowdhury, J., Munir , Stern, L., Yaakov , Honig, Flynn, Lawrence , Bell, Flynn, Karen , Morris, Flynn, John , Ances, Flynn, Beau , Carroll, Flynn, Maria , Leon, Flynn, Sue , Mintun, Flynn, Mark , Schneider, Flynn, Stacy , Marson, Flynn, Daniel , Griffith, Flynn, Randall , Clark, Flynn, David , Grossman, Flynn, Hillel , Mitsis, Flynn, Effie , Romirowsky, Flynn, Aliza , Detoledo-Morrell, Flynn, Leyla , Shah, Flynn, Raj , Duara, Flynn, Ranjan , Varon, Flynn, Daniel , Roberts, Flynn, Peggy , Albert, Flynn, Marilyn , Onyike, Flynn, Chiadi , Kielb, Flynn, Stephanie , Rusinek, Flynn, Henry , De Leon, Flynn, Mony , Glodzik, Flynn, Lidia , De Santi, Flynn, Susan , Doraiswamy, Flynn, P. , Petrella, Flynn, Jeffrey , Coleman, Flynn, R. , Arnold, Flynn, Steven , Karlawish, Flynn, Jason , Wolk, Flynn, David , Smith, Flynn, Charles , Jicha, Flynn, Greg , Hardy, Flynn, Peter , Lopez, Flynn, Oscar , Oakley, Flynn, Maryann , Simpson, Flynn, Donna , Porsteinsson, Flynn, Anton , Goldstein, Flynn, Bonnie , Martin, Flynn, Kim , Makino, Flynn, Kelly , Ismail, Flynn, M. , Brand, Flynn, Connie , Mulnard, Flynn, Ruth , Thai, Flynn, Gaby , Mc-Adams-Ortiz, Flynn, Catherine , Womack, Flynn, Kyle , Mathews, Flynn, Dana , Quiceno, Flynn, Mary , Diaz-Arrastia, Flynn, Ramon , King, Flynn, Richard , Weiner, Flynn, Myron , Martin-Cook, Flynn, Kristen , Devous, Flynn, Michael , Levey, Flynn, Allan , Lah, Flynn, James , Cellar, Flynn, Janet , Burns, Flynn, Jeffrey , Anderson, Flynn, Heather , Swerdlow, Flynn, Russell , Apostolova, Flynn, Liana , Lu, Flynn, Po , Bartzokis, Flynn, George , Silverman, Flynn, Daniel , Graff-Radford, Flynn, Neill , Parfitt, Flynn, Francine , Johnson, Flynn, Heather , Farlow, Flynn, Martin , Hake, Flynn, Ann , Matthews, Flynn, Brandy , Herring, Flynn, Scott , Van Dyck, Flynn, Christopher , Carson, Flynn, Richard , Macavoy, Flynn, Martha , Chertkow, Flynn, Howard , Bergman, Flynn, Howard , Hosein, Flynn, Chris , Black, Flynn, Sandra , Stefanovic, Flynn, Dr , Caldwell, Flynn, Curtis , Hsiung, Flynn, Ging-Yuek , Feldman, Flynn, Howard , Mudge, Flynn, Benita , Assaly, Flynn, Michele , Kertesz, Flynn, Andrew , Rogers, Flynn, John , Trost, Flynn, Dick , Bernick, Flynn, Charles , Munic, Flynn, Donna , Kerwin, Flynn, Diana , Mesulam, Flynn, Marek-Marsel , Lipowski, Flynn, Kristina , Wu, Flynn, Chuang-Kuo , Johnson, Flynn, Nancy , Sadowsky, Flynn, Carl , Martinez, Flynn, Walter , Villena, Flynn, Teresa , Turner, Flynn, Raymond , Johnson, Flynn, Kathleen , Reynolds, Flynn, Brigid , Sperling, Flynn, Reisa , Johnson, Flynn, Keith , Marshall, Flynn, Gad , Frey, Flynn, Meghan , Yesavage, Flynn, Jerome , Taylor, Flynn, Joy , Lane, Flynn, Barton , Rosen, Flynn, Allyson , Tinklenberg, Flynn, Jared , Sabbagh, Flynn, Marwan , Belden, Flynn, Christine , Jacobson, Flynn, Sandra , Kowall, Flynn, Neil , Killiany, Flynn, Ronald , Budson, Flynn, Andrew , Norbash, Flynn, Alexander , Johnson, Flynn, Patricia , Obisesan, Flynn, Thomas , Wolday, Flynn, Saba , Bwayo, Flynn, Salome , Lerner, Flynn, Alan , Hudson, Flynn, Leon , Ogrocki, Flynn, Paula , Fletcher, Flynn, Evan , Carmichael, Flynn, Owen , Olichney, Flynn, John , Decarli, Flynn, Charles , Kittur, Flynn, Smita , Borrie, Flynn, Michael , Lee, Flynn, T-Y , Bartha, Flynn, Dr , Johnson, Flynn, Sterling , Asthana, Flynn, Sanjay , Carlsson, Flynn, Cynthia , Potkin, Flynn, Steven , Preda, Flynn, Adrian , Nguyen, Flynn, Dana , Tariot, Flynn, Pierre , Fleisher, Flynn, Adam , Reeder, Flynn, Stephanie , Bates, Flynn, Vernice , Capote, Flynn, Horacio , Rainka, Flynn, Michelle , Scharre, Flynn, Douglas , Kataki, Flynn, Maria , Zimmerman, Flynn, Earl , Celmins, Flynn, Dzintra , Brown, Flynn, Alice , Pearlson, Flynn, Godfrey , Blank, Flynn, Karen , Anderson, Flynn, Karen , Saykin, Flynn, Andrew , Santulli, Flynn, Robert , Schwartz, Flynn, Eben , Sink, Flynn, Kaycee , Williamson, Flynn, Jeff , Garg, Flynn, Pradeep , Watkins, Flynn, Franklin , Ott, Flynn, Brian , Querfurth, Flynn, Henry , Tremont, Flynn, Geoffrey , Salloway, Flynn, Stephen , Malloy, Flynn, Paul , Correia, Flynn, Stephen , Rosen, Flynn, Howard , Miller, Flynn, Bruce , Mintzer, Flynn, Jacobo
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ID: ISSN: 0028-3878 ; DOI: 10.1212/WNL.0b013e31826c1b9d
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recordid: ovid10.1212/WNL.0b013e31826c1b9d
title: Vascular burden and Alzheimer disease pathologic progression
format: Article
creator:
  • Lo, Y., Raymond
  • Jagust, J., William
  • Weiner, R., Michael
  • Aisen, Q., Paul
  • Weiner, W., Michael
  • Aisen, C., Paul
  • Petersen, J., Ronald
  • Jack, C., Clifford
  • Jagust, G., William
  • Trojanowki, R., John
  • Toga, A., Arthur
  • Beckett, M., Laurel
  • Green, J., Robert
  • Saykin, M.Y., Andrew
  • Morris, W., John
  • Liu, J., Enchi
  • Green, M., Robert
  • Montine, J., Tom
  • Petersen, S., Ronald
  • Aisen, M., Paul
  • Gamst, L., Anthony
  • Thomas, L., Ronald
  • Donohue, S., Michael
  • Walter, S., Sarah
  • Gessert, L., Devon
  • Sather, C., Tamie
  • Beckett, A., Laurel
  • Harvey, C., Danielle
  • Gamst, J, Anthony
  • Donohue, Murali, Michael
  • Kornak, R., John
  • Jack, Edward, Clifford
  • Dale, E., Anders
  • Bernstein, H., Matthew
  • Felmlee, D., Joel
  • Fox, L., Nick
  • Thompson, M., Paul
  • Schuff, P., Norbert
  • Alexander, S., Gene
  • Decarli, M., Charles
  • Jagust, Saleem, William
  • Bandy, A., Dan
  • Koeppe, I., Robert
  • Foster, J., Norm
  • Reiman, S., Eric
  • Chen, M., Kewei
  • Mathis, S., Chet
  • Morris, H., John
  • Cairns, H., Nigel
  • Taylor-Reinwald, H.S., Lisa
  • Trojanowki, R, J.Q.
  • Shaw, R., Les
  • Lee, Marie, Virginia
  • Korecka, R., Magdalena
  • Toga, H., Arthur
  • Crawford, E., Karen
  • Neu, G., Scott
  • Saykin, Bojana, Andrew
  • Foroud, Robin, Tatiana
  • Potkin, Scott, Steven
  • Shen, A., Li
  • Kachaturian, A., Zaven
  • Frank, L., Richard
  • Snyder, E., Peter
  • Molchan, Lynn, Susan
  • Kaye, O., Jeffrey
  • Quinn, K., Joseph
  • Lind, Rob, Betty
  • Dolen, M., Sara
  • Schneider, G., Lon
  • Pawluczyk, W., Sonia
  • Spann, A., Bryan
  • Brewer, D., James
  • Vanderswag, D., Helen
  • Heidebrink, J., Judith
  • Lord, B., Joanne
  • Petersen, S., Ronald
  • Johnson, M., Kris
  • Doody, D., Rachelle
  • Villanueva-Meyer, R., Javier
  • Chowdhury, J., Munir
  • Stern, L., Yaakov
  • Honig, Flynn, Lawrence
  • Bell, Flynn, Karen
  • Morris, Flynn, John
  • Ances, Flynn, Beau
  • Carroll, Flynn, Maria
  • Leon, Flynn, Sue
  • Mintun, Flynn, Mark
  • Schneider, Flynn, Stacy
  • Marson, Flynn, Daniel
  • Griffith, Flynn, Randall
  • Clark, Flynn, David
  • Grossman, Flynn, Hillel
  • Mitsis, Flynn, Effie
  • Romirowsky, Flynn, Aliza
  • Detoledo-Morrell, Flynn, Leyla
  • Shah, Flynn, Raj
  • Duara, Flynn, Ranjan
  • Varon, Flynn, Daniel
  • Roberts, Flynn, Peggy
  • Albert, Flynn, Marilyn
  • Onyike, Flynn, Chiadi
  • Kielb, Flynn, Stephanie
  • Rusinek, Flynn, Henry
  • De Leon, Flynn, Mony
  • Glodzik, Flynn, Lidia
  • De Santi, Flynn, Susan
  • Doraiswamy, Flynn, P.
  • Petrella, Flynn, Jeffrey
  • Coleman, Flynn, R.
  • Arnold, Flynn, Steven
  • Karlawish, Flynn, Jason
  • Wolk, Flynn, David
  • Smith, Flynn, Charles
  • Jicha, Flynn, Greg
  • Hardy, Flynn, Peter
  • Lopez, Flynn, Oscar
  • Oakley, Flynn, Maryann
  • Simpson, Flynn, Donna
  • Porsteinsson, Flynn, Anton
  • Goldstein, Flynn, Bonnie
  • Martin, Flynn, Kim
  • Makino, Flynn, Kelly
  • Ismail, Flynn, M.
  • Brand, Flynn, Connie
  • Mulnard, Flynn, Ruth
  • Thai, Flynn, Gaby
  • Mc-Adams-Ortiz, Flynn, Catherine
  • Womack, Flynn, Kyle
  • Mathews, Flynn, Dana
  • Quiceno, Flynn, Mary
  • Diaz-Arrastia, Flynn, Ramon
  • King, Flynn, Richard
  • Weiner, Flynn, Myron
  • Martin-Cook, Flynn, Kristen
  • Devous, Flynn, Michael
  • Levey, Flynn, Allan
  • Lah, Flynn, James
  • Cellar, Flynn, Janet
  • Burns, Flynn, Jeffrey
  • Anderson, Flynn, Heather
  • Swerdlow, Flynn, Russell
  • Apostolova, Flynn, Liana
  • Lu, Flynn, Po
  • Bartzokis, Flynn, George
  • Silverman, Flynn, Daniel
  • Graff-Radford, Flynn, Neill
  • Parfitt, Flynn, Francine
  • Johnson, Flynn, Heather
  • Farlow, Flynn, Martin
  • Hake, Flynn, Ann
  • Matthews, Flynn, Brandy
  • Herring, Flynn, Scott
  • Van Dyck, Flynn, Christopher
  • Carson, Flynn, Richard
  • Macavoy, Flynn, Martha
  • Chertkow, Flynn, Howard
  • Bergman, Flynn, Howard
  • Hosein, Flynn, Chris
  • Black, Flynn, Sandra
  • Stefanovic, Flynn, Dr
  • Caldwell, Flynn, Curtis
  • Hsiung, Flynn, Ging-Yuek
  • Feldman, Flynn, Howard
  • Mudge, Flynn, Benita
  • Assaly, Flynn, Michele
  • Kertesz, Flynn, Andrew
  • Rogers, Flynn, John
  • Trost, Flynn, Dick
  • Bernick, Flynn, Charles
  • Munic, Flynn, Donna
  • Kerwin, Flynn, Diana
  • Mesulam, Flynn, Marek-Marsel
  • Lipowski, Flynn, Kristina
  • Wu, Flynn, Chuang-Kuo
  • Johnson, Flynn, Nancy
  • Sadowsky, Flynn, Carl
  • Martinez, Flynn, Walter
  • Villena, Flynn, Teresa
  • Turner, Flynn, Raymond
  • Johnson, Flynn, Kathleen
  • Reynolds, Flynn, Brigid
  • Sperling, Flynn, Reisa
  • Johnson, Flynn, Keith
  • Marshall, Flynn, Gad
  • Frey, Flynn, Meghan
  • Yesavage, Flynn, Jerome
  • Taylor, Flynn, Joy
  • Lane, Flynn, Barton
  • Rosen, Flynn, Allyson
  • Tinklenberg, Flynn, Jared
  • Sabbagh, Flynn, Marwan
  • Belden, Flynn, Christine
  • Jacobson, Flynn, Sandra
  • Kowall, Flynn, Neil
  • Killiany, Flynn, Ronald
  • Budson, Flynn, Andrew
  • Norbash, Flynn, Alexander
  • Johnson, Flynn, Patricia
  • Obisesan, Flynn, Thomas
  • Wolday, Flynn, Saba
  • Bwayo, Flynn, Salome
  • Lerner, Flynn, Alan
  • Hudson, Flynn, Leon
  • Ogrocki, Flynn, Paula
  • Fletcher, Flynn, Evan
  • Carmichael, Flynn, Owen
  • Olichney, Flynn, John
  • Decarli, Flynn, Charles
  • Kittur, Flynn, Smita
  • Borrie, Flynn, Michael
  • Lee, Flynn, T-Y
  • Bartha, Flynn, Dr
  • Johnson, Flynn, Sterling
  • Asthana, Flynn, Sanjay
  • Carlsson, Flynn, Cynthia
  • Potkin, Flynn, Steven
  • Preda, Flynn, Adrian
  • Nguyen, Flynn, Dana
  • Tariot, Flynn, Pierre
  • Fleisher, Flynn, Adam
  • Reeder, Flynn, Stephanie
  • Bates, Flynn, Vernice
  • Capote, Flynn, Horacio
  • Rainka, Flynn, Michelle
  • Scharre, Flynn, Douglas
  • Kataki, Flynn, Maria
  • Zimmerman, Flynn, Earl
  • Celmins, Flynn, Dzintra
  • Brown, Flynn, Alice
  • Pearlson, Flynn, Godfrey
  • Blank, Flynn, Karen
  • Anderson, Flynn, Karen
  • Saykin, Flynn, Andrew
  • Santulli, Flynn, Robert
  • Schwartz, Flynn, Eben
  • Sink, Flynn, Kaycee
  • Williamson, Flynn, Jeff
  • Garg, Flynn, Pradeep
  • Watkins, Flynn, Franklin
  • Ott, Flynn, Brian
  • Querfurth, Flynn, Henry
  • Tremont, Flynn, Geoffrey
  • Salloway, Flynn, Stephen
  • Malloy, Flynn, Paul
  • Correia, Flynn, Stephen
  • Rosen, Flynn, Howard
  • Miller, Flynn, Bruce
  • Mintzer, Flynn, Jacobo
subjects:
  • Neuroimaging
  • Mathematical Models
  • Alzheimer'S Disease
  • Magnetic Resonance Imaging
  • Substantia Alba
  • Glucose Metabolism
  • Biomarkers
  • Vascular Dementia
  • Executive Function
  • Neurodegenerative Diseases
  • Cerebrospinal Fluid
  • Apolipoprotein E4
  • Cognitive Ability
  • Dementia Disorders
  • Regression Analysis
  • Positron Emission Tomography
  • Atrophy
  • Cardiovascular Diseases
  • Amyloid
  • Neurology & Neuropathology
ispartof: Neurology, 2012, Vol.79(13), pp.1349-1355
description: OBJECTIVE:: To investigate the vascular contribution to longitudinal changes in Alzheimer disease (AD) biomarkers. METHODS:: The Alzheimerʼs Disease Neuroimaging Initiative is a clinic based, longitudinal study with CSF, PET, and MRI biomarkers repeatedly measured in participants with normal cognition (NC), mild cognitive impairment (MCI), and mild AD. Participants with severe cerebrovascular risks were excluded. Cardiovascular risk scores and MRI white matter hyperintensities (WMHs) were treated as surrogate markers for vascular burden. Generalized estimating equations were applied, and both vascular burden and its interaction with time (vascular burden × time) or time-varying WMHs were entered into regression models to assess whether biomarker rates of change were modified by vascular burden. RESULTS:: Cardiovascular risk profiles were not predictive of progression in CSF β42-amyloid, [F]fluorodeoxyglucose (FDG) PET uptake, and MRI hippocampal atrophy. Greater baseline cardiovascular risks or WMHs were generally associated with cognitive impairment, particularly poor executive function. WMHs increased over time with a faster rate in MCI and AD than in NC. Increased time-varying WMH was associated with faster decline in executive function and lower FDG uptake in NC. Otherwise, WMH was not associated with CSF and MRI biomarkers in the 3 groups. These findings remained unchanged after accounting for APOE4. CONCLUSION:: Increased WMHs are associated with aging, decreased glucose metabolism, and decline in executive function but do not affect AD-specific pathologic progression, suggesting that the vascular contribution to dementia is probably additive although not necessarily independent of the amyloid pathway. GLOSSARY: Aβ: β-amyloidAD: Alzheimer diseaseADNI: Alzheimerʼs Disease Neuroimaging InitiativeASAD-cog: Alzheimerʼs Disease Assessment Scale–Cognitive SubscaleFDG: [18F]fluorodeoxyglucoseGEE: generalized estimating equationMCI: mild cognitive impairmentMMSE: Mini-Mental State ExaminationNC: normal cognitionWMH: white matter hyperintensity
language:
source:
identifier: ISSN: 0028-3878 ; DOI: 10.1212/WNL.0b013e31826c1b9d
fulltext: fulltext
issn:
  • 0028-3878
  • 00283878
url: Link


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titleVascular burden and Alzheimer disease pathologic progression
creatorLo, Y., Raymond ; Jagust, J., William ; Weiner, R., Michael ; Aisen, Q., Paul ; Weiner, W., Michael ; Aisen, C., Paul ; Petersen, J., Ronald ; Jack, C., Clifford ; Jagust, G., William ; Trojanowki, R., John ; Toga, A., Arthur ; Beckett, M., Laurel ; Green, J., Robert ; Saykin, M.Y., Andrew ; Morris, W., John ; Liu, J., Enchi ; Green, M., Robert ; Montine, J., Tom ; Petersen, S., Ronald ; Aisen, M., Paul ; Gamst, L., Anthony ; Thomas, L., Ronald ; Donohue, S., Michael ; Walter, S., Sarah ; Gessert, L., Devon ; Sather, C., Tamie ; Beckett, A., Laurel ; Harvey, C., Danielle ; Gamst, J, Anthony ; Donohue, Murali, Michael ; Kornak, R., John ; Jack, Edward, Clifford ; Dale, E., Anders ; Bernstein, H., Matthew ; Felmlee, D., Joel ; Fox, L., Nick ; Thompson, M., Paul ; Schuff, P., Norbert ; Alexander, S., Gene ; Decarli, M., Charles ; Jagust, Saleem, William ; Bandy, A., Dan ; Koeppe, I., Robert ; Foster, J., Norm ; Reiman, S., Eric ; Chen, M., Kewei ; Mathis, S., Chet ; Morris, H., John ; Cairns, H., Nigel ; Taylor-Reinwald, H.S., Lisa ; Trojanowki, R, J.Q. ; Shaw, R., Les ; Lee, Marie, Virginia ; Korecka, R., Magdalena ; Toga, H., Arthur ; Crawford, E., Karen ; Neu, G., Scott ; Saykin, Bojana, Andrew ; Foroud, Robin, Tatiana ; Potkin, Scott, Steven ; Shen, A., Li ; Kachaturian, A., Zaven ; Frank, L., Richard ; Snyder, E., Peter ; Molchan, Lynn, Susan ; Kaye, O., Jeffrey ; Quinn, K., Joseph ; Lind, Rob, Betty ; Dolen, M., Sara ; Schneider, G., Lon ; Pawluczyk, W., Sonia ; Spann, A., Bryan ; Brewer, D., James ; Vanderswag, D., Helen ; Heidebrink, J., Judith ; Lord, B., Joanne ; Petersen, S., Ronald ; Johnson, M., Kris ; Doody, D., Rachelle ; Villanueva-Meyer, R., Javier ; Chowdhury, J., Munir ; Stern, L., Yaakov ; Honig, Flynn, Lawrence ; Bell, Flynn, Karen ; Morris, Flynn, John ; Ances, Flynn, Beau ; Carroll, Flynn, Maria ; Leon, Flynn, Sue ; Mintun, Flynn, Mark ; Schneider, Flynn, Stacy ; Marson, Flynn, Daniel ; Griffith, Flynn, Randall ; Clark, Flynn, David ; Grossman, Flynn, Hillel ; Mitsis, Flynn, Effie ; Romirowsky, Flynn, Aliza ; Detoledo-Morrell, Flynn, Leyla ; Shah, Flynn, Raj ; Duara, Flynn, Ranjan ; Varon, Flynn, Daniel ; Roberts, Flynn, Peggy ; Albert, Flynn, Marilyn ; Onyike, Flynn, Chiadi ; Kielb, Flynn, Stephanie ; Rusinek, Flynn, Henry ; De Leon, Flynn, Mony ; Glodzik, Flynn, Lidia ; De Santi, Flynn, Susan ; Doraiswamy, Flynn, P. ; Petrella, Flynn, Jeffrey ; Coleman, Flynn, R. ; Arnold, Flynn, Steven ; Karlawish, Flynn, Jason ; Wolk, Flynn, David ; Smith, Flynn, Charles ; Jicha, Flynn, Greg ; Hardy, Flynn, Peter ; Lopez, Flynn, Oscar ; Oakley, Flynn, Maryann ; Simpson, Flynn, Donna ; Porsteinsson, Flynn, Anton ; Goldstein, Flynn, Bonnie ; Martin, Flynn, Kim ; Makino, Flynn, Kelly ; Ismail, Flynn, M. ; Brand, Flynn, Connie ; Mulnard, Flynn, Ruth ; Thai, Flynn, Gaby ; Mc-Adams-Ortiz, Flynn, Catherine ; Womack, Flynn, Kyle ; Mathews, Flynn, Dana ; Quiceno, Flynn, Mary ; Diaz-Arrastia, Flynn, Ramon ; King, Flynn, Richard ; Weiner, Flynn, Myron ; Martin-Cook, Flynn, Kristen ; Devous, Flynn, Michael ; Levey, Flynn, Allan ; Lah, Flynn, James ; Cellar, Flynn, Janet ; Burns, Flynn, Jeffrey ; Anderson, Flynn, Heather ; Swerdlow, Flynn, Russell ; Apostolova, Flynn, Liana ; Lu, Flynn, Po ; Bartzokis, Flynn, George ; Silverman, Flynn, Daniel ; Graff-Radford, Flynn, Neill ; Parfitt, Flynn, Francine ; Johnson, Flynn, Heather ; Farlow, Flynn, Martin ; Hake, Flynn, Ann ; Matthews, Flynn, Brandy ; Herring, Flynn, Scott ; Van Dyck, Flynn, Christopher ; Carson, Flynn, Richard ; Macavoy, Flynn, Martha ; Chertkow, Flynn, Howard ; Bergman, Flynn, Howard ; Hosein, Flynn, Chris ; Black, Flynn, Sandra ; Stefanovic, Flynn, Dr ; Caldwell, Flynn, Curtis ; Hsiung, Flynn, Ging-Yuek ; Feldman, Flynn, Howard ; Mudge, Flynn, Benita ; Assaly, Flynn, Michele ; Kertesz, Flynn, Andrew ; Rogers, Flynn, John ; Trost, Flynn, Dick ; Bernick, Flynn, Charles ; Munic, Flynn, Donna ; Kerwin, Flynn, Diana ; Mesulam, Flynn, Marek-Marsel ; Lipowski, Flynn, Kristina ; Wu, Flynn, Chuang-Kuo ; Johnson, Flynn, Nancy ; Sadowsky, Flynn, Carl ; Martinez, Flynn, Walter ; Villena, Flynn, Teresa ; Turner, Flynn, Raymond ; Johnson, Flynn, Kathleen ; Reynolds, Flynn, Brigid ; Sperling, Flynn, Reisa ; Johnson, Flynn, Keith ; Marshall, Flynn, Gad ; Frey, Flynn, Meghan ; Yesavage, Flynn, Jerome ; Taylor, Flynn, Joy ; Lane, Flynn, Barton ; Rosen, Flynn, Allyson ; Tinklenberg, Flynn, Jared ; Sabbagh, Flynn, Marwan ; Belden, Flynn, Christine ; Jacobson, Flynn, Sandra ; Kowall, Flynn, Neil ; Killiany, Flynn, Ronald ; Budson, Flynn, Andrew ; Norbash, Flynn, Alexander ; Johnson, Flynn, Patricia ; Obisesan, Flynn, Thomas ; Wolday, Flynn, Saba ; Bwayo, Flynn, Salome ; Lerner, Flynn, Alan ; Hudson, Flynn, Leon ; Ogrocki, Flynn, Paula ; Fletcher, Flynn, Evan ; Carmichael, Flynn, Owen ; Olichney, Flynn, John ; Decarli, Flynn, Charles ; Kittur, Flynn, Smita ; Borrie, Flynn, Michael ; Lee, Flynn, T-Y ; Bartha, Flynn, Dr ; Johnson, Flynn, Sterling ; Asthana, Flynn, Sanjay ; Carlsson, Flynn, Cynthia ; Potkin, Flynn, Steven ; Preda, Flynn, Adrian ; Nguyen, Flynn, Dana ; Tariot, Flynn, Pierre ; Fleisher, Flynn, Adam ; Reeder, Flynn, Stephanie ; Bates, Flynn, Vernice ; Capote, Flynn, Horacio ; Rainka, Flynn, Michelle ; Scharre, Flynn, Douglas ; Kataki, Flynn, Maria ; Zimmerman, Flynn, Earl ; Celmins, Flynn, Dzintra ; Brown, Flynn, Alice ; Pearlson, Flynn, Godfrey ; Blank, Flynn, Karen ; Anderson, Flynn, Karen ; Saykin, Flynn, Andrew ; Santulli, Flynn, Robert ; Schwartz, Flynn, Eben ; Sink, Flynn, Kaycee ; Williamson, Flynn, Jeff ; Garg, Flynn, Pradeep ; Watkins, Flynn, Franklin ; Ott, Flynn, Brian ; Querfurth, Flynn, Henry ; Tremont, Flynn, Geoffrey ; Salloway, Flynn, Stephen ; Malloy, Flynn, Paul ; Correia, Flynn, Stephen ; Rosen, Flynn, Howard ; Miller, Flynn, Bruce ; Mintzer, Flynn, Jacobo
ispartofNeurology, 2012, Vol.79(13), pp.1349-1355
identifierISSN: 0028-3878 ; DOI: 10.1212/WNL.0b013e31826c1b9d
descriptionOBJECTIVE:: To investigate the vascular contribution to longitudinal changes in Alzheimer disease (AD) biomarkers. METHODS:: The Alzheimerʼs Disease Neuroimaging Initiative is a clinic based, longitudinal study with CSF, PET, and MRI biomarkers repeatedly measured in participants with normal cognition (NC), mild cognitive impairment (MCI), and mild AD. Participants with severe cerebrovascular risks were excluded. Cardiovascular risk scores and MRI white matter hyperintensities (WMHs) were treated as surrogate markers for vascular burden. Generalized estimating equations were applied, and both vascular burden and its interaction with time (vascular burden × time) or time-varying WMHs were entered into regression models to assess whether biomarker rates of change were modified by vascular burden. RESULTS:: Cardiovascular risk profiles were not predictive of progression in CSF β42-amyloid, [F]fluorodeoxyglucose (FDG) PET uptake, and MRI hippocampal atrophy. Greater baseline cardiovascular risks or WMHs were generally associated with cognitive impairment, particularly poor executive function. WMHs increased over time with a faster rate in MCI and AD than in NC. Increased time-varying WMH was associated with faster decline in executive function and lower FDG uptake in NC. Otherwise, WMH was not associated with CSF and MRI biomarkers in the 3 groups. These findings remained unchanged after accounting for APOE4. CONCLUSION:: Increased WMHs are associated with aging, decreased glucose metabolism, and decline in executive function but do not affect AD-specific pathologic progression, suggesting that the vascular contribution to dementia is probably additive although not necessarily independent of the amyloid pathway. GLOSSARY: Aβ: β-amyloidAD: Alzheimer diseaseADNI: Alzheimerʼs Disease Neuroimaging InitiativeASAD-cog: Alzheimerʼs Disease Assessment Scale–Cognitive SubscaleFDG: [18F]fluorodeoxyglucoseGEE: generalized estimating equationMCI: mild cognitive impairmentMMSE: Mini-Mental State ExaminationNC: normal cognitionWMH: white matter hyperintensity
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subjectNeuroimaging ; Mathematical Models ; Alzheimer'S Disease ; Magnetic Resonance Imaging ; Substantia Alba ; Glucose Metabolism ; Biomarkers ; Vascular Dementia ; Executive Function ; Neurodegenerative Diseases ; Cerebrospinal Fluid ; Apolipoprotein E4 ; Cognitive Ability ; Dementia Disorders ; Regression Analysis ; Positron Emission Tomography ; Atrophy ; Cardiovascular Diseases ; Amyloid ; Neurology & Neuropathology;
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0Lo, Y, Raymond
1Jagust, J, William
2Weiner, R, Michael
3Aisen, Q, Paul
4Weiner, W, Michael
5Aisen, C, Paul
6Petersen, J, Ronald
7Jack, C, Clifford
8Jagust, G, William
9Trojanowki, R, John
10Toga, A, Arthur
11Beckett, M, Laurel
12Green, J, Robert
13Saykin, M.Y, Andrew
14Morris, W, John
15Liu, J, Enchi
16Green, M, Robert
17Montine, J, Tom
18Petersen, S, Ronald
19Aisen, M, Paul
20Gamst, L, Anthony
21Thomas, L, Ronald
22Donohue, S, Michael
23Walter, S, Sarah
24Gessert, L, Devon
25Sather, C, Tamie
26Beckett, A, Laurel
27Harvey, C, Danielle
28Gamst, J, Anthony
29Donohue, Murali, Michael
30Kornak, R, John
31Jack, Edward, Clifford
32Dale, E, Anders
33Bernstein, H, Matthew
34Felmlee, D, Joel
35Fox, L, Nick
36Thompson, M, Paul
37Schuff, P, Norbert
38Alexander, S, Gene
39DeCarli, M, Charles
40Jagust, Saleem, William
41Bandy, A, Dan
42Koeppe, I, Robert
43Foster, J, Norm
44Reiman, S, Eric
45Chen, M, Kewei
46Mathis, S, Chet
47Morris, H, John
48Cairns, H, Nigel
49Taylor-Reinwald, H.S, Lisa
50Trojanowki, R, J.Q
51Shaw, R, Les
52Lee, Marie, Virginia
53Korecka, R, Magdalena
54Toga, H, Arthur
55Crawford, E, Karen
56Neu, G, Scott
57Saykin, Bojana, Andrew
58Foroud, Robin, Tatiana
59Potkin, Scott, Steven
60Shen, A, Li
61Kachaturian, A, Zaven
62Frank, L, Richard
63Snyder, E, Peter
64Molchan, Lynn, Susan
65Kaye, O, Jeffrey
66Quinn, K, Joseph
67Lind, Rob, Betty
68Dolen, M, Sara
69Schneider, G, Lon
70Pawluczyk, W, Sonia
71Spann, A, Bryan
72Brewer, D, James
73Vanderswag, D, Helen
74Heidebrink, J, Judith
75Lord, B, Joanne
76Johnson, M, Kris
77Doody, D, Rachelle
78Villanueva-Meyer, R, Javier
79Chowdhury, J, Munir
80Stern, L, Yaakov
81Honig, Flynn, Lawrence
82Bell, Flynn, Karen
83Morris, Flynn, John
84Ances, Flynn, Beau
85Carroll, Flynn, Maria
86Leon, Flynn, Sue
87Mintun, Flynn, Mark
88Schneider, Flynn, Stacy
89Marson, Flynn, Daniel
90Griffith, Flynn, Randall
91Clark, Flynn, David
92Grossman, Flynn, Hillel
93Mitsis, Flynn, Effie
94Romirowsky, Flynn, Aliza
95deToledo-Morrell, Flynn, Leyla
96Shah, Flynn, Raj
97Duara, Flynn, Ranjan
98Varon, Flynn, Daniel
99Roberts, Flynn, Peggy
100...
titleVascular burden and Alzheimer disease pathologic progression
descriptionOBJECTIVE:: To investigate the vascular contribution to longitudinal changes in Alzheimer disease (AD) biomarkers. METHODS:: The Alzheimerʼs Disease Neuroimaging Initiative is a clinic based, longitudinal study with CSF, PET, and MRI biomarkers repeatedly measured in participants with normal cognition (NC), mild cognitive impairment (MCI), and mild AD. Participants with severe cerebrovascular risks were excluded. Cardiovascular risk scores and MRI white matter hyperintensities (WMHs) were treated as surrogate markers for vascular burden. Generalized estimating equations were applied, and both vascular burden and its interaction with time (vascular burden × time) or time-varying WMHs were entered into regression models to assess whether biomarker rates of change were modified by vascular burden. RESULTS:: Cardiovascular risk profiles were not predictive of progression in CSF β42-amyloid, [F]fluorodeoxyglucose (FDG) PET uptake, and MRI hippocampal atrophy. Greater baseline cardiovascular risks or WMHs were generally associated with cognitive impairment, particularly poor executive function. WMHs increased over time with a faster rate in MCI and AD than in NC. Increased time-varying WMH was associated with faster decline in executive function and lower FDG uptake in NC. Otherwise, WMH was not associated with CSF and MRI biomarkers in the 3 groups. These findings remained unchanged after accounting for APOE4. CONCLUSION:: Increased WMHs are associated with aging, decreased glucose metabolism, and decline in executive function but do not affect AD-specific pathologic progression, suggesting that the vascular contribution to dementia is probably additive although not necessarily independent of the amyloid pathway. GLOSSARY: Aβ: β-amyloidAD: Alzheimer diseaseADNI: Alzheimerʼs Disease Neuroimaging InitiativeASAD-cog: Alzheimerʼs Disease Assessment Scale–Cognitive SubscaleFDG: [18F]fluorodeoxyglucoseGEE: generalized estimating equationMCI: mild cognitive impairmentMMSE: Mini-Mental State ExaminationNC: normal cognitionWMH: white matter hyperintensity
general
010.1212/WNL.0b013e31826c1b9d
1© 2012 American Academy of Neurology
2Lippincott Williams & Wilkins - Journals
sourceidovid
recordidovid10.1212/WNL.0b013e31826c1b9d
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00028-3878
100283878
rsrctypearticle
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addtitleNeurology
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scopeovid
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sort
titleVascular burden and Alzheimer disease pathologic progression
authorLo, Y., Raymond ; Jagust, J., William ; Weiner, R., Michael ; Aisen, Q., Paul ; Weiner, W., Michael ; Aisen, C., Paul ; Petersen, J., Ronald ; Jack, C., Clifford ; Jagust, G., William ; Trojanowki, R., John ; Toga, A., Arthur ; Beckett, M., Laurel ; Green, J., Robert ; Saykin, M.Y., Andrew ; Morris, W., John ; Liu, J., Enchi ; Green, M., Robert ; Montine, J., Tom ; Petersen, S., Ronald ; Aisen, M., Paul ; Gamst, L., Anthony ; Thomas, L., Ronald ; Donohue, S., Michael ; Walter, S., Sarah ; Gessert, L., Devon ; Sather, C., Tamie ; Beckett, A., Laurel ; Harvey, C., Danielle ; Gamst, J, Anthony ; Donohue, Murali, Michael ; Kornak, R., John ; Jack, Edward, Clifford ; Dale, E., Anders ; Bernstein, H., Matthew ; Felmlee, D., Joel ; Fox, L., Nick ; Thompson, M., Paul ; Schuff, P., Norbert ; Alexander, S., Gene ; Decarli, M., Charles ; Jagust, Saleem, William ; Bandy, A., Dan ; Koeppe, I., Robert ; Foster, J., Norm ; Reiman, S., Eric ; Chen, M., Kewei ; Mathis, S., Chet ; Morris, H., John ; Cairns, H., Nigel ; Taylor-Reinwald, H.S., Lisa ; Trojanowki, R, J.Q. ; Shaw, R., Les ; Lee, Marie, Virginia ; Korecka, R., Magdalena ; Toga, H., Arthur ; Crawford, E., Karen ; Neu, G., Scott ; Saykin, Bojana, Andrew ; Foroud, Robin, Tatiana ; Potkin, Scott, Steven ; Shen, A., Li ; Kachaturian, A., Zaven ; Frank, L., Richard ; Snyder, E., Peter ; Molchan, Lynn, Susan ; Kaye, O., Jeffrey ; Quinn, K., Joseph ; Lind, Rob, Betty ; Dolen, M., Sara ; Schneider, G., Lon ; Pawluczyk, W., Sonia ; Spann, A., Bryan ; Brewer, D., James ; Vanderswag, D., Helen ; Heidebrink, J., Judith ; Lord, B., Joanne ; Petersen, S., Ronald ; Johnson, M., Kris ; Doody, D., Rachelle ; Villanueva-Meyer, R., Javier ; Chowdhury, J., Munir ; Stern, L., Yaakov ; Honig, Flynn, Lawrence ; Bell, Flynn, Karen ; Morris, Flynn, John ; Ances, Flynn, Beau ; Carroll, Flynn, Maria ; Leon, Flynn, Sue ; Mintun, Flynn, Mark ; Schneider, Flynn, Stacy ; Marson, Flynn, Daniel ; Griffith, Flynn, Randall ; Clark, Flynn, David ; Grossman, Flynn, Hillel ; Mitsis, Flynn, Effie ; Romirowsky, Flynn, Aliza ; Detoledo-Morrell, Flynn, Leyla ; Shah, Flynn, Raj ; Duara, Flynn, Ranjan ; Varon, Flynn, Daniel ; Roberts, Flynn, Peggy ; Albert, Flynn, Marilyn ; Onyike, Flynn, Chiadi ; Kielb, Flynn, Stephanie ; Rusinek, Flynn, Henry ; De Leon, Flynn, Mony ; Glodzik, Flynn, Lidia ; De Santi, Flynn, Susan ; Doraiswamy, Flynn, P. ; Petrella, Flynn, Jeffrey ; Coleman, Flynn, R. ; Arnold, Flynn, Steven ; Karlawish, Flynn, Jason ; Wolk, Flynn, David ; Smith, Flynn, Charles ; Jicha, Flynn, Greg ; Hardy, Flynn, Peter ; Lopez, Flynn, Oscar ; Oakley, Flynn, Maryann ; Simpson, Flynn, Donna ; Porsteinsson, Flynn, Anton ; Goldstein, Flynn, Bonnie ; Martin, Flynn, Kim ; Makino, Flynn, Kelly ; Ismail, Flynn, M. ; Brand, Flynn, Connie ; Mulnard, Flynn, Ruth ; Thai, Flynn, Gaby ; Mc-Adams-Ortiz, Flynn, Catherine ; Womack, Flynn, Kyle ; Mathews, Flynn, Dana ; Quiceno, Flynn, Mary ; Diaz-Arrastia, Flynn, Ramon ; King, Flynn, Richard ; Weiner, Flynn, Myron ; Martin-Cook, Flynn, Kristen ; Devous, Flynn, Michael ; Levey, Flynn, Allan ; Lah, Flynn, James ; Cellar, Flynn, Janet ; Burns, Flynn, Jeffrey ; Anderson, Flynn, Heather ; Swerdlow, Flynn, Russell ; Apostolova, Flynn, Liana ; Lu, Flynn, Po ; Bartzokis, Flynn, George ; Silverman, Flynn, Daniel ; Graff-Radford, Flynn, Neill ; Parfitt, Flynn, Francine ; Johnson, Flynn, Heather ; Farlow, Flynn, Martin ; Hake, Flynn, Ann ; Matthews, Flynn, Brandy ; Herring, Flynn, Scott ; Van Dyck, Flynn, Christopher ; Carson, Flynn, Richard ; Macavoy, Flynn, Martha ; Chertkow, Flynn, Howard ; Bergman, Flynn, Howard ; Hosein, Flynn, Chris ; Black, Flynn, Sandra ; Stefanovic, Flynn, Dr ; Caldwell, Flynn, Curtis ; Hsiung, Flynn, Ging-Yuek ; Feldman, Flynn, Howard ; Mudge, Flynn, Benita ; Assaly, Flynn, Michele ; Kertesz, Flynn, Andrew ; Rogers, Flynn, John ; Trost, Flynn, Dick ; Bernick, Flynn, Charles ; Munic, Flynn, Donna ; Kerwin, Flynn, Diana ; Mesulam, Flynn, Marek-Marsel ; Lipowski, Flynn, Kristina ; Wu, Flynn, Chuang-Kuo ; Johnson, Flynn, Nancy ; Sadowsky, Flynn, Carl ; Martinez, Flynn, Walter ; Villena, Flynn, Teresa ; Turner, Flynn, Raymond ; Johnson, Flynn, Kathleen ; Reynolds, Flynn, Brigid ; Sperling, Flynn, Reisa ; Johnson, Flynn, Keith ; Marshall, Flynn, Gad ; Frey, Flynn, Meghan ; Yesavage, Flynn, Jerome ; Taylor, Flynn, Joy ; Lane, Flynn, Barton ; Rosen, Flynn, Allyson ; Tinklenberg, Flynn, Jared ; Sabbagh, Flynn, Marwan ; Belden, Flynn, Christine ; Jacobson, Flynn, Sandra ; Kowall, Flynn, Neil ; Killiany, Flynn, Ronald ; Budson, Flynn, Andrew ; Norbash, Flynn, Alexander ; Johnson, Flynn, Patricia ; Obisesan, Flynn, Thomas ; Wolday, Flynn, Saba ; Bwayo, Flynn, Salome ; Lerner, Flynn, Alan ; Hudson, Flynn, Leon ; Ogrocki, Flynn, Paula ; Fletcher, Flynn, Evan ; Carmichael, Flynn, Owen ; Olichney, Flynn, John ; Decarli, Flynn, Charles ; Kittur, Flynn, Smita ; Borrie, Flynn, Michael ; Lee, Flynn, T-Y ; Bartha, Flynn, Dr ; Johnson, Flynn, Sterling ; Asthana, Flynn, Sanjay ; Carlsson, Flynn, Cynthia ; Potkin, Flynn, Steven ; Preda, Flynn, Adrian ; Nguyen, Flynn, Dana ; Tariot, Flynn, Pierre ; Fleisher, Flynn, Adam ; Reeder, Flynn, Stephanie ; Bates, Flynn, Vernice ; Capote, Flynn, Horacio ; Rainka, Flynn, Michelle ; Scharre, Flynn, Douglas ; Kataki, Flynn, Maria ; Zimmerman, Flynn, Earl ; Celmins, Flynn, Dzintra ; Brown, Flynn, Alice ; Pearlson, Flynn, Godfrey ; Blank, Flynn, Karen ; Anderson, Flynn, Karen ; Saykin, Flynn, Andrew ; Santulli, Flynn, Robert ; Schwartz, Flynn, Eben ; Sink, Flynn, Kaycee ; Williamson, Flynn, Jeff ; Garg, Flynn, Pradeep ; Watkins, Flynn, Franklin ; Ott, Flynn, Brian ; Querfurth, Flynn, Henry ; Tremont, Flynn, Geoffrey ; Salloway, Flynn, Stephen ; Malloy, Flynn, Paul ; Correia, Flynn, Stephen ; Rosen, Flynn, Howard ; Miller, Flynn, Bruce ; Mintzer, Flynn, Jacobo
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0Lo, Y., Raymond
1Jagust, J., William
2Weiner, R., Michael
3Aisen, Q., Paul
4Weiner, W., Michael
5Aisen, C., Paul
6Petersen, J., Ronald
7Jack, C., Clifford
8Jagust, G., William
9Trojanowki, R., John
10Toga, A., Arthur
11Beckett, M., Laurel
12Green, J., Robert
13Saykin, M.Y., Andrew
14Morris, W., John
15Liu, J., Enchi
16Green, M., Robert
17Montine, J., Tom
18Petersen, S., Ronald
19Aisen, M., Paul
20Gamst, L., Anthony
21Thomas, L., Ronald
22Donohue, S., Michael
23Walter, S., Sarah
24Gessert, L., Devon
25Sather, C., Tamie
26Beckett, A., Laurel
27Harvey, C., Danielle
28Gamst, J, Anthony
29Donohue, Murali, Michael
30Kornak, R., John
31Jack, Edward, Clifford
32Dale, E., Anders
33Bernstein, H., Matthew
34Felmlee, D., Joel
35Fox, L., Nick
36Thompson, M., Paul
37Schuff, P., Norbert
38Alexander, S., Gene
39Decarli, M., Charles
40Jagust, Saleem, William
41Bandy, A., Dan
42Koeppe, I., Robert
43Foster, J., Norm
44Reiman, S., Eric
45Chen, M., Kewei
46Mathis, S., Chet
47Morris, H., John
48Cairns, H., Nigel
49Taylor-Reinwald, H.S., Lisa
50Trojanowki, R, J.Q.
51Shaw, R., Les
52Lee, Marie, Virginia
53Korecka, R., Magdalena
54Toga, H., Arthur
55Crawford, E., Karen
56Neu, G., Scott
57Saykin, Bojana, Andrew
58Foroud, Robin, Tatiana
59Potkin, Scott, Steven
60Shen, A., Li
61Kachaturian, A., Zaven
62Frank, L., Richard
63Snyder, E., Peter
64Molchan, Lynn, Susan
65Kaye, O., Jeffrey
66Quinn, K., Joseph
67Lind, Rob, Betty
68Dolen, M., Sara
69Schneider, G., Lon
70Pawluczyk, W., Sonia
71Spann, A., Bryan
72Brewer, D., James
73Vanderswag, D., Helen
74Heidebrink, J., Judith
75Lord, B., Joanne
76Johnson, M., Kris
77Doody, D., Rachelle
78Villanueva-Meyer, R., Javier
79Chowdhury, J., Munir
80Stern, L., Yaakov
81Honig, Flynn, Lawrence
82Bell, Flynn, Karen
83Morris, Flynn, John
84Ances, Flynn, Beau
85Carroll, Flynn, Maria
86Leon, Flynn, Sue
87Mintun, Flynn, Mark
88Schneider, Flynn, Stacy
89Marson, Flynn, Daniel
90Griffith, Flynn, Randall
91Clark, Flynn, David
92Grossman, Flynn, Hillel
93Mitsis, Flynn, Effie
94Romirowsky, Flynn, Aliza
95Detoledo-Morrell, Flynn, Leyla
96Shah, Flynn, Raj
97Duara, Flynn, Ranjan
98Varon, Flynn, Daniel
99Roberts, Flynn, Peggy
100...
jtitleNeurology
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0Lo
1Jagust
2Weiner
3Aisen
4Petersen
5Jack
6Trojanowki
7Toga
8Beckett
9Green
10Saykin
11Morris
12Liu
13Montine
14Gamst
15Thomas
16Donohue
17Walter
18Gessert
19Sather
20Harvey
21Kornak
22Dale
23Bernstein
24Felmlee
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26Thompson
27Schuff
28Alexander
29DeCarli
30Bandy
31Koeppe
32Foster
33Reiman
34Chen
35Mathis
36Cairns
37Taylor-Reinwald
38Shaw
39Lee
40Korecka
41Crawford
42Neu
43Foroud
44Potkin
45Shen
46Kachaturian
47Frank
48Snyder
49Molchan
50Kaye
51Quinn
52Lind
53Dolen
54Schneider
55Pawluczyk
56Spann
57Brewer
58Vanderswag
59Heidebrink
60Lord
61Johnson
62Doody
63Villanueva-Meyer
64Chowdhury
65Stern
66Honig
67Bell
68Ances
69Carroll
70Leon
71Mintun
72Marson
73Griffith
74Clark
75Grossman
76Mitsis
77Romirowsky
78deToledo-Morrell
79Shah
80Duara
81Varon
82Roberts
83Albert
84Onyike
85Kielb
86Rusinek
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89De Santi
90Doraiswamy
91Petrella
92Coleman
93Arnold
94Karlawish
95Wolk
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99Lopez
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4Ronald
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15Devon
16Tamie
17Danielle
18Anders
19Matthew
20Joel
21Nick
22Norbert
23Gene
24Charles
25Dan
26Norm
27Eric
28Kewei
29Chet
30Nigel
31Lisa
32J.Q.
33Les
34Virginia
35Magdalena
36Karen
37Scott
38Tatiana
39Steven
40Li
41Zaven
42Richard
43Peter
44Susan
45Jeffrey
46Joseph
47Betty
48Sara
49Lon
50Sonia
51Bryan
52James
53Helen
54Judith
55Joanne
56Kris
57Rachelle
58Javier
59Munir
60Yaakov
61Lawrence
62Beau
63Maria
64Sue
65Mark
66Stacy
67Daniel
68Randall
69David
70Hillel
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73Leyla
74Raj
75Ranjan
76Peggy
77Marilyn
78Chiadi
79Stephanie
80Henry
81Mony
82Lidia
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87Oscar
88MaryAnn
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91Bonnie
92Kim
93Kelly
94M.
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96Ruth
97Gaby
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99Kyle
100...
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1J.
2R.
3Q.
4W.
5C.
6G.
7A.
8M.
9M.Y.
10S.
11L.
12J
13Murali
14Edward
15E.
16H.
17D.
18P.
19Saleem
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24Bojana
25Robin
26Scott
27Lynn
28O.
29K.
30Rob
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au
0Lo, Y., Raymond
1Jagust, J., William
2Weiner, R., Michael
3Aisen, Q., Paul
4Weiner, W., Michael
5Aisen, C., Paul
6Petersen, J., Ronald
7Jack, C., Clifford
8Jagust, G., William
9Trojanowki, R., John
10Toga, A., Arthur
11Beckett, M., Laurel
12Green, J., Robert
13Saykin, M.Y., Andrew
14Morris, W., John
15Liu, J., Enchi
16Green, M., Robert
17Montine, J., Tom
18Petersen, S., Ronald
19Aisen, M., Paul
20Gamst, L., Anthony
21Thomas, L., Ronald
22Donohue, S., Michael
23Walter, S., Sarah
24Gessert, L., Devon
25Sather, C., Tamie
26Beckett, A., Laurel
27Harvey, C., Danielle
28Gamst, J, Anthony
29Donohue, Murali, Michael
30Kornak, R., John
31Jack, Edward, Clifford
32Dale, E., Anders
33Bernstein, H., Matthew
34Felmlee, D., Joel
35Fox, L., Nick
36Thompson, M., Paul
37Schuff, P., Norbert
38Alexander, S., Gene
39Decarli, M., Charles
40Jagust, Saleem, William
41Bandy, A., Dan
42Koeppe, I., Robert
43Foster, J., Norm
44Reiman, S., Eric
45Chen, M., Kewei
46Mathis, S., Chet
47Morris, H., John
48Cairns, H., Nigel
49Taylor-Reinwald, H.S., Lisa
50Trojanowki, R, J.Q.
51Shaw, R., Les
52Lee, Marie, Virginia
53Korecka, R., Magdalena
54Toga, H., Arthur
55Crawford, E., Karen
56Neu, G., Scott
57Saykin, Bojana, Andrew
58Foroud, Robin, Tatiana
59Potkin, Scott, Steven
60Shen, A., Li
61Kachaturian, A., Zaven
62Frank, L., Richard
63Snyder, E., Peter
64Molchan, Lynn, Susan
65Kaye, O., Jeffrey
66Quinn, K., Joseph
67Lind, Rob, Betty
68Dolen, M., Sara
69Schneider, G., Lon
70Pawluczyk, W., Sonia
71Spann, A., Bryan
72Brewer, D., James
73Vanderswag, D., Helen
74Heidebrink, J., Judith
75Lord, B., Joanne
76Johnson, M., Kris
77Doody, D., Rachelle
78Villanueva-Meyer, R., Javier
79Chowdhury, J., Munir
80Stern, L., Yaakov
81Honig, Flynn, Lawrence
82Bell, Flynn, Karen
83Morris, Flynn, John
84Ances, Flynn, Beau
85Carroll, Flynn, Maria
86Leon, Flynn, Sue
87Mintun, Flynn, Mark
88Schneider, Flynn, Stacy
89Marson, Flynn, Daniel
90Griffith, Flynn, Randall
91Clark, Flynn, David
92Grossman, Flynn, Hillel
93Mitsis, Flynn, Effie
94Romirowsky, Flynn, Aliza
95Detoledo-Morrell, Flynn, Leyla
96Shah, Flynn, Raj
97Duara, Flynn, Ranjan
98Varon, Flynn, Daniel
99Roberts, Flynn, Peggy
100...
atitleVascular burden and Alzheimer disease pathologic progression
jtitleNeurology
risdate201209
volume79
issue13
spage1349
epage1355
pages1349-1355
issn0028-3878
formatjournal
genrearticle
ristypeJOUR
abstractOBJECTIVE:: To investigate the vascular contribution to longitudinal changes in Alzheimer disease (AD) biomarkers. METHODS:: The Alzheimerʼs Disease Neuroimaging Initiative is a clinic based, longitudinal study with CSF, PET, and MRI biomarkers repeatedly measured in participants with normal cognition (NC), mild cognitive impairment (MCI), and mild AD. Participants with severe cerebrovascular risks were excluded. Cardiovascular risk scores and MRI white matter hyperintensities (WMHs) were treated as surrogate markers for vascular burden. Generalized estimating equations were applied, and both vascular burden and its interaction with time (vascular burden × time) or time-varying WMHs were entered into regression models to assess whether biomarker rates of change were modified by vascular burden. RESULTS:: Cardiovascular risk profiles were not predictive of progression in CSF β42-amyloid, [F]fluorodeoxyglucose (FDG) PET uptake, and MRI hippocampal atrophy. Greater baseline cardiovascular risks or WMHs were generally associated with cognitive impairment, particularly poor executive function. WMHs increased over time with a faster rate in MCI and AD than in NC. Increased time-varying WMH was associated with faster decline in executive function and lower FDG uptake in NC. Otherwise, WMH was not associated with CSF and MRI biomarkers in the 3 groups. These findings remained unchanged after accounting for APOE4. CONCLUSION:: Increased WMHs are associated with aging, decreased glucose metabolism, and decline in executive function but do not affect AD-specific pathologic progression, suggesting that the vascular contribution to dementia is probably additive although not necessarily independent of the amyloid pathway. GLOSSARY: Aβ: β-amyloidAD: Alzheimer diseaseADNI: Alzheimerʼs Disease Neuroimaging InitiativeASAD-cog: Alzheimerʼs Disease Assessment Scale–Cognitive SubscaleFDG: [18F]fluorodeoxyglucoseGEE: generalized estimating equationMCI: mild cognitive impairmentMMSE: Mini-Mental State ExaminationNC: normal cognitionWMH: white matter hyperintensity
pub© 2012 American Academy of Neurology
doi10.1212/WNL.0b013e31826c1b9d
eissn1526632X
date2012-09-25