Spatial patterns of brain amyloid-beta burden and atrophy rate associations in mild cognitive impairment.
Brain. 2011-03-22; 134(4): 1077-1088
DOI: 10.1093/brain/awr044
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Tosun D, Schuff N, Mathis CA, Jagust W, Weiner MW; Alzheimer’s Disease NeuroImaging Initiative.
Collaborators: Saradha A, Abdi H, Abdulkadir A, Abeliovich A, Abellan van Kan G,
Abner E, Acharya D, Agrusti A, Agyemang A, Ahdidan J, Ahmed S, Ahn JE, Aisen P,
Aksu Y, Al-Akhras M, Alarcon M, Alberca R, Alexander G, Alexander D, Alin A,
Almeida F, Amlien I, Anand S, Anderson D, Andrew M, Angersbach S, Anjum A, Aoyama
E, Arfanakis K, Armor T, Arnold S, Arunagiri V, Asatryan A, Ashe-McNalley C,
Ashiga H, Assareh A, Le Page A, Avants B, Avinash G, Aviv R, Awasthi S,
Ayan-Oshodi M, Babic T, Baek Y, Bagci U, Bai S, Baird G, Baker J, Banks S, Bard
J, Barnes J, Bartlett J, Bartzokis G, Barua N, Bauer C, Bayley P, Beck I, Becker
J, Becker JA, Beckett L, Bednar M, Beg MF, Bek S, Belaroussi B, Belmokhtar N,
Bernard C, Bertram L, Bhaskar U, Biffi A, Bigler E, Bilgic B, Bishop C, Bishop C,
Bittner D, Black R, Bogorodzki P, Bokde A, Bonner-Jackson A, Boppana M, Bourgeat
P, Bowes M, Bowman D, Bowman G, Braskie M, Braunewell K, Breitner J, Bresell A,
Brewer J, Brickman A, Britschgi M, Broadbent S, Brogren J, Brooks D, Browndyke J,
Brunton S, Buchert R, Buchsbaum M, Buckley C, Buerger K, Burger C, Burnham S,
Burns J, Burton D, Butman J, Cabeza R, Cairns N, Callhoff J, Callhoff J, Calvini
P, Cantillon M, Capella H, Carbotti A, Cardona-Sanclemente LE, Carle A, Carmasin
J, Carranza-Ath F, Casabianca J, Casanova R, Cash D, Cedarbaum J, Cella M, Celsis
P, Chanu P, Chao L, Charil A, Chemali Z, Chen R, Chen J, Chen G, Chen W, Chen K,
Chen S, Chen M, Cheng WC, Cherkas Y, Chertkow H, Cheung C, Cheung V, Chiang G,
Chiba K, Chin S, Chisholm J, Cho Y, Choe J, Choubey S, Chowbina S, Christensen
AL, Clark D, Clark C, Clarkson M, Clayton D, Clunie D, Coen M, Coimbra A, Coimbra
A, Compton D, Coppola G, Coulin S, Cover KS, Crane P, Crans G, Croop R, Crowther
D, Crum W, Cui Y, Curry C, Curtis S, Cutter G, Daiello L, Dake M, Dale A, Daliri
MR, Damato VD, Darby E, Darkner S, Darkner S, Davatzikos C, Dave J, David R,
DavidPrakash B, Davidson J, de Bruijne M, De Meyer G, De Nunzio G, DeCarli C,
Dechairo B, DeDuck K, Dehghan H, Dejkam A, Delfino M, Della Rosa PA, Dellavedova
L, Delpassand E, Delrieu J, DeOrchis V, Depy Carron D, deToledo-Morrell L,
Devanand D, Devanarayan V, Devous M, Diaz-Arrastia R, Bradford D, Ding X, Dinov
I, Dobson H, Dodge H, Donohue M, Dore V, Dorflinger E, Dowling M, Dowling M, Duan
X, Dubal D, Duchesne S, Duff K, Dukart J, Durazzo T, Dykstra K, Earl N, Edula G,
Ekin A, Elcoroaristizabal X, Emahazion T, Emahazion T, Engelman C, Epstein N,
Erten-Lyons D, Eskildsen S, Falcone G, Fan L, Fan Y, Farahibozorg S, Farb N,
Farnum M, Farrer L, Farzan A, Faux N, Feldman B, Feldman H, Feldman S,
Fennema-Notestine C, Fernandes M, Fernandez E, Ferrarini L, Ferreira MJ, Ferrer
E, Figurski M, Filipovych R, Fillit H, Finch S, Finlay D, Fiot JB, Flenniken D,
Fletcher PT, Fletcher E, Flynn Longmire C, Focke N, Forman M, Forsythe A, Fox S,
Fox-Bosetti S, Francis AL, Franco-Villalobos C, Franko E, Freeman S, Friedrich
CM, Friesenhahn M, Frings L, Frisoni G, Fritzsche K, Fujimoto Y, Fujiwara K,
Fullerton T, Furney S, Gallins P, Galvin B, Gamst A, Gan K, Garcia MT, Garg G,
Gaser C, Gastineau E, Gauthier S, Gavett B, Gavidia G, Gazdzinski S, Ge Q, Ge T,
Gemme G, Geraci J, Ghassabi Z, Gieschke R, Gil JE, Gill R, Gitelman D, Gleason C,
Glymour MM, Godbey M, Goghari V, Gold M, Goldberg T, Goldman J, Gomeni R, Gong S,
Gonzales C, Goodro R, Gordon B, Gore C, Gorriz JM, Grachev I, Grandey E, Grasela
T, Gratt J, Gray K, Greenberg B, Gregg K, Gregory E, Greicius M, Greve D, Grill
J, Gross A, Gross A, Guignot I, Guo J, Guo Q, Guo H, Guo L, Habeck C, Hai Y,
Haight T, Hammarstrom P, Hampel H, Han D, Han J, Han T, Hanif M, Hanna Y, Hardy
P, Harvey D, Hasan MK, Hayashi T, Hazart A, He H, He Y, Head D, Head D, Heckemann
R, Heidebrink J, Henderson D, Henrard S, Herholz K, Hernandez M, Herskovits AZ,
Hess C, Hildenbrand M, Hobart J, Hoffman J, Holder D, Hollingworth P, Holmes R,
Honigberg L, Hoppin J, Hou Y, Hsu A, Hsu WW, Hu X, Hu Z, Hu W, Huang J, Huang CC,
Huang C, Huang S, Huang Y, Huang F, Huang CJ, Huang SP, Hubbard R, Huentelman M,
Hui S, Huppertz HJ, Hurko O, Hurt S, Huyck S, Hwang S, Hyun J, Ifeachor E,
Iglesias M, Ikari Y, Ikonomidou V, Imani F, Immermann F, Inlow M, Inoue L, Insel
P, Irizarry M, Irungu Bm, Ishibashi T, Ishii K, Ismail S, Ismail S, Ito K,
Iturria-Medina Y, Iwatsubo T, Jacobson M, Jacqmin P, Jafari A, Jafari-Khouzani K,
Jaffe C, Jagust W, Jagust W, Jara H, Jasperse B, Jedynak B, Jefferson A, Jennings
JR, Jessen W, Jia F, Jiang T, Jing H, Johnson J, Johnson S, Johnson DK, Jones R,
Juengling F, Juh R, Julin P, Bhaskar U, Kadish B, Kahle-Wrobleski K, Kallam HR,
Kamboh MI, Kaneko T, Kaneta T, Kang JH, Karageorgiou E, Karantzoulis S, Karlawish
J, Katz E, Kaushik SS, Kauwe J, Kauwe J, Kawakami H, Kazimipoor B, Kelleher T,
Kennedy R, Kerchner G, Kerrouche N, Khalil I, Khalil A, Killeen N, Killiany R,
Kim JH, Kim H, Kim A, Kim Y, Kim H, Kim S, Kim H, Kim A, Kimberg D, Kimura T,
King R, Kirby J, Kirsch W, Klimas M, Kline R, Kling M, Klopfenstein E,
Koikkalainen J, Kokomoor A, Kolasny A, Koppel J, Korolev I, Kotran N, Kouassi A,
Kowalczyk A, Kozma L, Krams M, Kratzer M, Kuceyeski A, Kuhn FP, Kumar S, Kuo HT,
Kuo J, Kurosawa K, Kwon OH, Labrish C, Laforet G, Lai S, Lakatos A, Lam OK,
Lampron A, Landau S, Landen J, Lane R, Langbaum J, Langford D, Lanius V, Laxamana
J, Le T, Leahy R, Lee JM, Lee V, Lee JH, Lee G, Lee D, Lee N, Lefkimmiatis S,
Lemaitre H, Lenfant P, Lenz R, Leoutsakos JM, Lester G, Levey A, Li SJ, Li S, Li
W, Li CS, Li X, Li R, Li M, Li L, Li J, Li Y, Li Q, Li G, Liang K, Liang P, Liang
L, Liao YL, Lin LC, Lin L, Lin M, Lin AL, Liu S, Liu Y, Liu T, Liu M, Liu X, Liu
L, Liu H, Liu P, Liu T, Liu S, Liu D, Lo R, Lobanov V, Loewenstein D, Logovinsky
V, Long X, Long Z, Looi J, Lu PH, Lukic A, Lull JJ, Luo X, Lynch J, Ma L, Mackin
S, Mada M, Magda S, Maglio S, Maikusa N, Mak HK, Malave V, Maldjian J, Mandal P,
Mangin JF, Manjon J, Mantri N, Manzour A, Marambaud P, Marchewka A, Marek K,
Markind S, Marshall G, Martinez Torteya A, Mather M, Mathis C, Matoug S, Matsuo
Y, Mattei P, Matthews D, McArdle J, McCarroll S, McEvoy L, McGeown W, McGonigle
J, McIntyre J, McLaren D, McQuail J, Meadowcroft M, Meda S, Mehta N, Melie-Garcia
L, Melrose R, Mendonca B, Menendez M, Meredith J, Merrill D, Mesulam MM, Metti A,
Meyer C, Mez J, Mickael G, Miftahof R, Mikhno A, Miller D, Millikin C, Min Y,
Mirza M, Mistridis P, Mitchell M, Mitsis E, Mohan A, Moore D, Moradi Birgani P,
Moratal D, Morimoto B, Mormino E, Mortamet B, Moscato P, Mueller K, Mueller S,
Mueller N, Mukherjee S, Mulder E, Murayama S, Murphy M, Murray B, Musiek E, Myers
A, Najafi S, Nazarparvar B, Nazeri A, Nettiksimmons J, Neu S, Ng YB, Nguyen N,
Nguyen Xuan T, Nichols T, Nicodemus K, Niecko T, Nielsen C, Notomi K, Nutakki GC,
O’Bryant S, O’Neil A, Obisesan T, Oh DH, Oh J, Okonkwo O, Olde Rikkert M, Olmos
S, Ortner M, Ostrowitzki S, Oswald A, Ott B, Ourselin S, Ouyang G, Paiva R, Pan
Z, Pande Y, Pardo J, Pardoe H, Park H, Park L, Park MH, Park Sh, Park KH, Park S,
Parsey R, Parveen R, Paskavitz J, Patel Y, Patil M, Pawlak M, Payoux P, Pearson
J, Peavy G, Pell G, Peng Y, Pennec X, Pepin Jl, Perea R, Perneczky R, Petitti D,
Petrella J, Peyrat JM, Pezoa J, Pham CT, Phillips J, Phillips N, Pierson R,
Piovezan M, Podhorski A, Pollari M, Pontecorvo M, Poppenk J, Posner H, Potkin S,
Potter G, Potter E, Poulin S, Prasad G, Prenger K, Prince J, Priya A, Puchakayala
SR, Puchakayala SR, Qiu R, Qiu A, Qiu W, Qualls CD, Rabie H, Rajeesh R,
Rallabandi VP, Ramage A, Randolph C, Rao A, Rao D, Raubertas R, Ray D, Razak H,
Redolfi A, Reed B, Reid A, Reilhac A, Reinsberger C, Restrepo L, Retico A,
Richards J, Riddle W, Ries M, Rincon M, Rischall M, Rizk-Jackson A, Robieson W,
Rocha-Rego V, Rogalski E, Rogers E, Rojas I, Rojas Balderrama J, Romero K, Rorden
C, Rosand J, Rosen A, Rosen O, Rosenberg P, Ross D, Roubini E, Rousseau F, Rowe
C, Rubin D, Rubright J, Ruiz A, Rusinek H, Ryan L, Saad A, Sabbagh M, Sabuncu M,
Sachs M, Sadeghi A, Said Y, Saint-Aubert L, Sakata M, Salat D, Salmon D, Salter
H, Samwald M, Sanchez L, Sanders E, Sanders E, Sanjo N, Sarnel H, Sato H, Sato S,
Saumier D, Savio A, Sawada I, Saykin A, Schaffer JD, Scharre D, Schegerin M,
Schlosser G, Schmand B, Schmansky N, Schmidt M, Schmidt-Wilcke T, Schneider L,
Schramm H, Schuerch M, Schwartz E, Schwartz C, Schwarz A, Seethamraju R, Seixas
F, Selnes P, Senjem M, Senlin W, Seo SW, Sethuraman G, Sevigny J, Sevigny J,
Sfikas G, Sghedoni R, Shah SK, Shahbaba B, Shams S, Shattuck D, Shaw L, Shaw L,
Sheela J, Shen W, Shen Q, Shera D, Sherman J, Sherva R, Shi F, Shukla V, Shuler
C, Shulman J, Siegel R, Siemers E, Silveira M, Silver M, Silverman D, Sim I,
Simmons A, Simmons A, Simoes R, Simon M, Simpson I, Singh SP, Singh N, Siuciak J,
Sjogren N, Skinner J, Skup M, Small G, Smith M, Smith B, Smith C, Smyth T, Snow
S, Soares H, Soldea O, Solomon P, Solomon A, Som S, Song C, Song M, Sosova I,
Soudah E, Soydemir M, Spampinato MV, Spenger C, Sperling R, Spiegel R, Spies L,
Squarcia S, Squire L, Staff R, Stern Y, Straw J, Stricker N, Strittmatter S,
Stühler E, Styren S, Subramanian V, Sugishita M, Sukkar R, Sun J, Sun Y, Sun Y,
Sun J, Sundell K, Suri M, Suzuki A, Svetnik V, Swan M, Takahasi T, Takeuchi T,
Tanaka S, Tanchi C, Tancredi D, Tao W, Tao D, Taylor-Reinwald L, Teng E, Terlizzi
R, Thames A, Thiele F, Thomas B, Thomas R, Thompson P, Thompson W, Thornton-Wells
T, Thorvaldsson V, Thurfjell L, Titeux L, Tokuda T, Toledo JB, Tolli T, Toma A,
Tomita N, Toro R, Torrealdea P, Tosun D, Tousian M, Toussaint P, Toyoshiba H,
Tractenberg RE, Trittschuh E, Trojanowski J, Truran D, Tsechpenakis G,
Tucker-Drob E, Tufail A, Tung J, Turken A, Ueda Y, Ullrich L, Umadevi Venkataraju
K, Umar N, Uzunbas G, Van de Nes J, van der Brug M, Van Horn J, Van Leemput K,
Van Train K, Van Zeeland A, Vasanawala M, Vemuri P, Verwaerde P, Videbaek C,
Vidoni E, Villanueva-Meyer J, Visser PJ, Vitolo O, Vounou M, Wade S, Walhovd KB,
Wan H, Wang H, Wang YM, Wang Y, Wang A, Wang L, Wang Y, Wang X, Wang Z, Wang Y,
Wang T, Wang A, Wang H, Wang LS, Wang W, Wang L, Ward M, Warfield S, Waring S,
Watanabe T, Webb D, Wei L, Weiner M, Wen SH, Wenjing L, Wenzel F, Westlye LT,
Whitcher B, Whitlow C, Whitwell J, Wilhelmsen K, Williams D, Wilmot B, Wimsatt M,
Wingo T, Wiste H, Wolfson T, Wolke I, Wolz R, Woo J, Woo E, Woods L, Worth A,
Worth E, Wouters H, Wu T, Wu YG, Wu L, Wu X, Wyman B, Wyss-Coray T, Xiao G, Xiao
L, Xie S, Xu S, Xu Y, Xu YZ, Xu G, Xu J, Yamane T, Yamashita F, Yan Y, Yan Y, Yan
P, Yang E, Yang J, Yang QX, Yang Z, Yang G, Yang Z, Yang W, Ye L, Ye BS, Ye J, Ye
J, Yee L, Yesavage J, Ying S, Yoo B, Young J, Yu S, Yu D, Yuan G, Yuan K,
Yushkevich P, Zaborszky L, Zagorodnov V, Zagorski M, Zawadzki R, Zeitzer J,
Zelinski E, Zhang K, Zhang H, Zhang T, Zhang H, Zhang X, Zhang P, Zhang B, Zhang
J, Zhang L, Zhang L, Zhang Z, Zhao Q, Zhao J, Zhao P, Zhen X, Zhen X, Zheng Y,
Zhijun Y, Zhou B, Zhou S, Zhu W, Zhu H, Zhu W, Zilka S, Zito G, Zou H.
Amyloid-β accumulation in the brain is thought to be one of the earliest events
in Alzheimer’s disease, possibly leading to synaptic dysfunction,
neurodegeneration and cognitive/functional decline. The earliest detectable
changes seen with neuroimaging appear to be amyloid-β accumulation detected by
(11)C-labelled Pittsburgh compound B positron emission tomography imaging.
However, some individuals tolerate high brain amyloid-β loads without developing
symptoms, while others progressively decline, suggesting that events in the brain
downstream from amyloid-β deposition, such as regional brain atrophy rates, play
an important role. The main purpose of this study was to understand the
relationship between the regional distributions of increased amyloid-β and the
regional distribution of increased brain atrophy rates in patients with mild
cognitive impairment. To simultaneously capture the spatial distributions of
amyloid-β and brain atrophy rates, we employed the statistical concept of
parallel independent component analysis, an effective method for joint analysis
of multimodal imaging data. Parallel independent component analysis identified
significant relationships between two patterns of amyloid-β deposition and
atrophy rates: (i) increased amyloid-β burden in the left precuneus/cuneus and
medial-temporal regions was associated with increased brain atrophy rates in the
left medial-temporal and parietal regions; and (ii) in contrast, increased
amyloid-β burden in bilateral precuneus/cuneus and parietal regions was
associated with increased brain atrophy rates in the right medial temporal
regions. The spatial distribution of increased amyloid-β and the associated
spatial distribution of increased brain atrophy rates embrace a characteristic
pattern of brain structures known for a high vulnerability to Alzheimer’s disease
pathology, encouraging for the use of (11)C-labelled Pittsburgh compound B
positron emission tomography measures as early indicators of Alzheimer’s disease.
These results may begin to shed light on the mechanisms by which amyloid-β
deposition leads to neurodegeneration and cognitive decline and the development
of a more specific Alzheimer’s disease-specific imaging signature for diagnosis
and use of this knowledge in the development of new anti-therapies for
Alzheimer’s disease.
DOI: 10.1093/brain/awr044
PMCID: PMC3069703
PMID: 21429865 [Indexed for MEDLINE]