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Beta amyloid, tau, neuroimaging, and cognition: sequence modeling of biomarkers for Alzheimer's Disease.

Alzheimer's disease (AD) is associated with a cascade of pathological events involving formation of amyloid-based neuritic plaques and tau-based neurofibrillary tangles, changes in brain structure and function, and eventually, cognitive impairment and functional disability. The precise sequence of w... Full description

Journal Title: Brain imaging and behavior December 2012, Vol.6(4), pp.610-620
Main Author: Han, S Duke
Other Authors: Gruhl, Jonathan , Beckett, Laurel , Dodge, Hiroko H , Stricker, Nikki H , Farias, Sarah , Mungas, Dan , Han, S Duke
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1931-7565 ; DOI: 10.1007/s11682-012-9177-0
Link: http://search.proquest.com/docview/1285464754/?pq-origsite=primo
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title: Beta amyloid, tau, neuroimaging, and cognition: sequence modeling of biomarkers for Alzheimer's Disease.
format: Article
creator:
  • Han, S Duke
  • Gruhl, Jonathan
  • Beckett, Laurel
  • Dodge, Hiroko H
  • Stricker, Nikki H
  • Farias, Sarah
  • Mungas, Dan
  • Han, S Duke
subjects:
  • Aged–Cerebrospinal Fluid
  • Aged, 80 and Over–Diagnosis
  • Alzheimer Disease–Cerebrospinal Fluid
  • Amyloid Beta-Peptides–Blood
  • Biomarkers–Methods
  • Diagnosis, Computer-Assisted–Cerebrospinal Fluid
  • Female–Cerebrospinal Fluid
  • Humans–Cerebrospinal Fluid
  • Male–Cerebrospinal Fluid
  • Middle Aged–Cerebrospinal Fluid
  • Neuroimaging–Cerebrospinal Fluid
  • Neuropsychological Tests–Cerebrospinal Fluid
  • Proportional Hazards Models–Cerebrospinal Fluid
  • Reproducibility of Results–Cerebrospinal Fluid
  • Sensitivity and Specificity–Cerebrospinal Fluid
  • Tau Proteins–Cerebrospinal Fluid
  • Amyloid Beta-Peptides
  • Biomarkers
  • Tau Proteins
ispartof: Brain imaging and behavior, December 2012, Vol.6(4), pp.610-620
description: Alzheimer's disease (AD) is associated with a cascade of pathological events involving formation of amyloid-based neuritic plaques and tau-based neurofibrillary tangles, changes in brain structure and function, and eventually, cognitive impairment and functional disability. The precise sequence of when each of these disease markers becomes abnormal is not yet clearly understood. The present study systematically tested the relationship between classes of biomarkers according to a proposed model of temporal sequence by Jack et al. (Lancet Neurology 9:119-128, 2010). We examined temporal relations among four classes of biomarkers: CSF Aβ, CSF tau, neuroimaging variables (hippocampal volume, ventricular volume, FDG PET), and cognitive variables (memory and executive function). Random effects modeling of longitudinal data obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) was used to test hypotheses that putative earlier markers of AD predicted change in later markers, and that intervening markers reduced effects of earlier on later markers. Specifically, we hypothesized that CSF tau would explain CSF Aβ's relation to neuroimaging and cognitive variables, and neuroimaging variables would explain tau's relation to cognitive variables. Consistent with hypotheses, results indicated that CSF Aβ effects on cognition change were substantially attenuated by CSF tau and measures of brain structure and function, and CSF tau effects on cognitive change were attenuated by neuroimaging variables. Contrary to hypotheses, CSF Aβ and CSF tau were observed to have independent effects on neuroimaging and CSF tau had a direct effect on baseline cognition independent of brain structure and function. These results have implications for clarifying the temporal sequence of AD changes and corresponding biomarkers.
language: eng
source:
identifier: E-ISSN: 1931-7565 ; DOI: 10.1007/s11682-012-9177-0
fulltext: fulltext
issn:
  • 19317565
  • 1931-7565
url: Link


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titleBeta amyloid, tau, neuroimaging, and cognition: sequence modeling of biomarkers for Alzheimer's Disease.
creatorHan, S Duke ; Gruhl, Jonathan ; Beckett, Laurel ; Dodge, Hiroko H ; Stricker, Nikki H ; Farias, Sarah ; Mungas, Dan ; Han, S Duke
contributorWeiner, Michael (correspondence author) ; Aisen, Paul (record owner) ; Weiner, Michael ; Aisen, Paul ; Petersen, Ronald ; Jack, Clifford R ; Jagust, William ; Trojanowki, John Q ; Toga, Arthur W ; Beckett, Laurel ; Green, Robert C ; Saykin, Andrew J ; Morris, John ; Liu, Enchi ; Green, Robert C ; Montine, Tom ; Petersen, Ronald ; Aisen, Paul ; Gamst, Anthony ; Thomas, Ronald G ; Donohue, Michael ; Walter, Sarah ; Gessert, Devon ; Sather, Tamie ; Beckett, Laurel ; Harvey, Danielle ; Gamst, Anthony ; Donohue, Michael ; Kornak, John ; Jack, Clifford R ; Dale, Anders ; Bernstein, Matthew ; Felmlee, Joel ; Fox, Nick ; Thompson, Paul ; Schuff, Norbert ; Alexander, Gene ; Decarli, Charles ; Jagust, William ; Bandy, Dan ; Koeppe, Robert A ; Foster, Norm ; Reiman, Eric M ; Chen, Kewei ; Mathis, Chet ; Morris, John ; Cairns, Nigel J ; Taylor-Reinwald, Lisa ; Trojanowki, J Q ; Shaw, Les ; Lee, Virginia M Y ; Korecka, Magdalena ; Toga, Arthur W ; Crawford, Karen ; Neu, Scott ; Saykin, Andrew J ; Foroud, Tatiana M ; Potkin, Steven ; Shen, Li ; Kachaturian, Zaven ; Frank, Richard ; Snyder, Peter J ; Molchan, Susan ; Kaye, Jeffrey ; Quinn, Joseph ; Lind, Betty ; Dolen, Sara ; Schneider, Lon S ; Pawluczyk, Sonia ; Spann, Bryan M ; Brewer, James ; Vanderswag, Helen ; Heidebrink, Judith L ; Lord, Joanne L ; Petersen, Ronald ; Johnson, Kris ; Doody, Rachelle S ; Villanueva-Meyer, Javier ; Chowdhury, Munir ; Stern, Yaakov ; Honig, Lawrence S ; Bell, Karen L ; Morris, John C ; Ances, Beau ; Carroll, Maria ; Leon, Sue ; Mintun, Mark A ; Schneider, Stacy ; Marson, Daniel ; Griffith, Randall ; Clark, David ; Grossman, Hillel ; Mitsis, Effie ; Romirowsky, Aliza ; Detoledo-Morrell, Leyla ; Shah, Raj C ; Duara, Ranjan ; Varon, Daniel ; Roberts, Peggy ; Albert, Marilyn ; Onyike, Chiadi ; Kielb, Stephanie ; Rusinek, Henry ; de Leon, Mony J ; Glodzik, Lidia ; De Santi, Susan ; Doraiswamy, P Murali ; Petrella, Jeffrey R ; Coleman, R Edward ; Arnold, Steven E ; Karlawish, Jason H ; Wolk, David ; Smith, Charles D ; Jicha, Greg ; Hardy, Peter ; Lopez, Oscar L ; Oakley, Maryann ; Simpson, Donna M ; Porsteinsson, Anton P ; Goldstein, Bonnie S ; Martin, Kim ; Makino, Kelly M ; Ismail, M Saleem ; Brand, Connie ; Mulnard, Ruth A ; Thai, Gaby ; Mc-Adams-Ortiz, Catherine ; Womack, Kyle ; Mathews, Dana ; Quiceno, Mary ; Diaz-Arrastia, Ramon ; King, Richard ; Weiner, Myron ; Martin-Cook, Kristen ; Devous, Michael ; Levey, Allan I ; Lah, James J ; Cellar, Janet S ; Burns, Jeffrey M ; Anderson, Heather S ; Swerdlow, Russell H ; Apostolova, Liana ; Lu, Po H ; Bartzokis, George ; Silverman, Daniel H S ; Graff-Radford, Neill R ; Parfitt, Francine ; Johnson, Heather ; Farlow, Martin R ; Hake, Ann Marie ; Matthews, Brandy R ; Herring, Scott ; van Dyck, Christopher H ; Carson, Richard E ; Macavoy, Martha G ; Chertkow, Howard ; Bergman, Howard ; Hosein, Chris ; Black, Sandra ; Stefanovic, Bojana ; Caldwell, Curtis ; Hsiung, Ging-Yuek Robin ; Feldman, Howard ; Mudge, Benita ; Assaly, Michele ; Kertesz, Andrew ; Rogers, John ; Trost, Dick ; Bernick, Charles ; Munic, Donna ; Kerwin, Diana ; Mesulam, Marek-Marsel ; Lipowski, Kristina ; Wu, Chuang-Kuo ; Johnson, Nancy ; Sadowsky, Carl ; Martinez, Walter ; Villena, Teresa ; Turner, Raymond Scott ; Johnson, Kathleen ; Reynolds, Brigid ; Sperling, Reisa A ; Johnson, Keith A ; Marshall, Gad ; Frey, Meghan ; Yesavage, Jerome ; Taylor, Joy L ; Lane, Barton ; Rosen, Allyson ; Tinklenberg, Jared ; Sabbagh, Marwan ; Belden, Christine ; Jacobson, Sandra ; Kowall, Neil ; Killiany, Ronald ; Budson, Andrew E ; Norbash, Alexander ; Johnson, Patricia Lynn ; Obisesan, Thomas O ; Wolday, Saba ; Bwayo, Salome K ; Lerner, Alan ; Hudson, Leon ; Ogrocki, Paula ; Fletcher, Evan ; Carmichael, Owen ; Olichney, John ; Decarli, Charles ; Kittur, Smita ; Borrie, Michael ; Lee, T-Y ; Bartha, Rob ; Johnson, Sterling ; Asthana, Sanjay ; Carlsson, Cynthia M ; Potkin, Steven G ; Preda, Adrian ; Nguyen, Dana ; Tariot, Pierre ; Fleisher, Adam ; Reeder, Stephanie ; Bates, Vernice ; Capote, Horacio ; Rainka, Michelle ; Scharre, Douglas W ; Kataki, Maria ; Zimmerman, Earl A ; Celmins, Dzintra ; Brown, Alice D ; Pearlson, Godfrey D ; Blank, Karen ; Anderson, Karen ; Saykin, Andrew J ; Santulli, Robert B ; Schwartz, Eben S ; Sink, Kaycee M ; Williamson, Jeff D ; Garg, Pradeep ; Watkins, Franklin ; Ott, Brian R ; Querfurth, Henry ; Tremont, Geoffrey
ispartofBrain imaging and behavior, December 2012, Vol.6(4), pp.610-620
identifierE-ISSN: 1931-7565 ; DOI: 10.1007/s11682-012-9177-0
subjectAged–Cerebrospinal Fluid ; Aged, 80 and Over–Diagnosis ; Alzheimer Disease–Cerebrospinal Fluid ; Amyloid Beta-Peptides–Blood ; Biomarkers–Methods ; Diagnosis, Computer-Assisted–Cerebrospinal Fluid ; Female–Cerebrospinal Fluid ; Humans–Cerebrospinal Fluid ; Male–Cerebrospinal Fluid ; Middle Aged–Cerebrospinal Fluid ; Neuroimaging–Cerebrospinal Fluid ; Neuropsychological Tests–Cerebrospinal Fluid ; Proportional Hazards Models–Cerebrospinal Fluid ; Reproducibility of Results–Cerebrospinal Fluid ; Sensitivity and Specificity–Cerebrospinal Fluid ; Tau Proteins–Cerebrospinal Fluid ; Amyloid Beta-Peptides ; Biomarkers ; Tau Proteins
languageeng
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descriptionAlzheimer's disease (AD) is associated with a cascade of pathological events involving formation of amyloid-based neuritic plaques and tau-based neurofibrillary tangles, changes in brain structure and function, and eventually, cognitive impairment and functional disability. The precise sequence of when each of these disease markers becomes abnormal is not yet clearly understood. The present study systematically tested the relationship between classes of biomarkers according to a proposed model of temporal sequence by Jack et al. (Lancet Neurology 9:119-128, 2010). We examined temporal relations among four classes of biomarkers: CSF Aβ, CSF tau, neuroimaging variables (hippocampal volume, ventricular volume, FDG PET), and cognitive variables (memory and executive function). Random effects modeling of longitudinal data obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) was used to test hypotheses that putative earlier markers of AD predicted change in later markers, and that intervening markers reduced effects of earlier on later markers. Specifically, we hypothesized that CSF tau would explain CSF Aβ's relation to neuroimaging and cognitive variables, and neuroimaging variables would explain tau's relation to cognitive variables. Consistent with hypotheses, results indicated that CSF Aβ effects on cognition change were substantially attenuated by CSF tau and measures of brain structure and function, and CSF tau effects on cognitive change were attenuated by neuroimaging variables. Contrary to hypotheses, CSF Aβ and CSF tau were observed to have independent effects on neuroimaging and CSF tau had a direct effect on baseline cognition independent of brain structure and function. These results have implications for clarifying the temporal sequence of AD changes and corresponding biomarkers.
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6Mungas, Dan
titleBeta amyloid, tau, neuroimaging, and cognition: sequence modeling of biomarkers for Alzheimer's Disease.
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1Aged, 80 and Over–Diagnosis
2Alzheimer Disease–Cerebrospinal Fluid
3Amyloid Beta-Peptides–Blood
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6Toga, Arthur W
7Beckett, Laurel
8Green, Robert C
9Saykin, Andrew J
10Morris, John
11Liu, Enchi
12Montine, Tom
13Gamst, Anthony
14Thomas, Ronald G
15Donohue, Michael
16Walter, Sarah
17Gessert, Devon
18Sather, Tamie
19Harvey, Danielle
20Kornak, John
21Dale, Anders
22Bernstein, Matthew
23Felmlee, Joel
24Fox, Nick
25Thompson, Paul
26Schuff, Norbert
27Alexander, Gene
28Decarli, Charles
29Bandy, Dan
30Koeppe, Robert A
31Foster, Norm
32Reiman, Eric M
33Chen, Kewei
34Mathis, Chet
35Cairns, Nigel J
36Taylor-Reinwald, Lisa
37Trojanowki, J Q
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39Lee, Virginia M Y
40Korecka, Magdalena
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42Neu, Scott
43Foroud, Tatiana M
44Potkin, Steven
45Shen, Li
46Kachaturian, Zaven
47Frank, Richard
48Snyder, Peter J
49Molchan, Susan
50Kaye, Jeffrey
51Quinn, Joseph
52Lind, Betty
53Dolen, Sara
54Schneider, Lon S
55Pawluczyk, Sonia
56Spann, Bryan M
57Brewer, James
58Vanderswag, Helen
59Heidebrink, Judith L
60Lord, Joanne L
61Johnson, Kris
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68Morris, John C
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titleBeta amyloid, tau, neuroimaging, and cognition: sequence modeling of biomarkers for Alzheimer's Disease.
authorHan, S Duke ; Gruhl, Jonathan ; Beckett, Laurel ; Dodge, Hiroko H ; Stricker, Nikki H ; Farias, Sarah ; Mungas, Dan ; Han, S Duke
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2Alzheimer Disease–Cerebrospinal Fluid
3Amyloid Beta-Peptides–Blood
4Biomarkers–Methods
5Diagnosis, Computer-Assisted–Cerebrospinal Fluid
6Female–Cerebrospinal Fluid
7Humans–Cerebrospinal Fluid
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1Gruhl, Jonathan
2Beckett, Laurel
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5Farias, Sarah
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7Weiner, Michael
8Aisen, Paul
9Petersen, Ronald
10Jack, Clifford R
11Jagust, William
12Trojanowki, John Q
13Toga, Arthur W
14Green, Robert C
15Saykin, Andrew J
16Morris, John
17Liu, Enchi
18Montine, Tom
19Gamst, Anthony
20Thomas, Ronald G
21Donohue, Michael
22Walter, Sarah
23Gessert, Devon
24Sather, Tamie
25Harvey, Danielle
26Kornak, John
27Dale, Anders
28Bernstein, Matthew
29Felmlee, Joel
30Fox, Nick
31Thompson, Paul
32Schuff, Norbert
33Alexander, Gene
34Decarli, Charles
35Bandy, Dan
36Koeppe, Robert A
37Foster, Norm
38Reiman, Eric M
39Chen, Kewei
40Mathis, Chet
41Cairns, Nigel J
42Taylor-Reinwald, Lisa
43Trojanowki, J Q
44Shaw, Les
45Lee, Virginia M Y
46Korecka, Magdalena
47Crawford, Karen
48Neu, Scott
49Foroud, Tatiana M
50Potkin, Steven
51Shen, Li
52Kachaturian, Zaven
53Frank, Richard
54Snyder, Peter J
55Molchan, Susan
56Kaye, Jeffrey
57Quinn, Joseph
58Lind, Betty
59Dolen, Sara
60Schneider, Lon S
61Pawluczyk, Sonia
62Spann, Bryan M
63Brewer, James
64Vanderswag, Helen
65Heidebrink, Judith L
66Lord, Joanne L
67Johnson, Kris
68Doody, Rachelle S
69Villanueva-Meyer, Javier
70Chowdhury, Munir
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76Clark, David
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atitleBeta amyloid, tau, neuroimaging, and cognition: sequence modeling of biomarkers for Alzheimer's Disease.
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date2012-12-01