Longitudinal changes in white matter disease and cognition in the first year of the Alzheimer disease neuroimaging initiative.

Carmichael O, Schwarz C, Drucker D, Fletcher E, Harvey D, Beckett L, Jack CR Jr,
Weiner M, DeCarli C; Alzheimer’s Disease Neuroimaging Initiative.

Collaborators: Abdi H, Abeliovich A, Abellan van Kan G, Abner E, Acharya D, Adams
N, Adler D, Agrusti A, Agyemang A, Ahdidan J, Ahn JE, Aisen P, Aksu Y, Al-Akhras
M, Alarcon M, Alberca R, Alexander G, Alexander D, Almeida F, Anand R, Anand S,
Andrew M, Anjum A, Aoyama E, Ard MC, Arfanakis K, Armor T, Arnold S, Asatryan A,
Ashe-McNalley C, Ashiga H, Assareh A, Aubry F, Avants B, Avinash G, Awasthi S,
Ayan-Oshodi M, Bagci U, Bai S, Baker J, Banks S, Bard J, Barnes J, Barret O,
Bartzokis G, Barua N, Bauer C, Becker J, Beckett L, Bednar M, Beg MF, Bek S,
Bernard C, Bertram L, Bhagwagar Z, Biffi A, Bilgic B, Bishnoi M, Bishop C, Bishop
C, Bittner D, Black R, Blennow K, Bogorodzki P, Bokde A, Bonner-Jackson A,
Boppana M, Bourgeat P, Bowes M, Bowman G, Bowman D, Braskie M, Brewer J, Brickman
A, Broadbent S, Brooks D, Browndyke J, Bruat V, Brunton S, Buchert R, Buchsbaum
M, Buchsbaum M, Buckley C, Burger C, Burns J, Burton D, Butman J, Cabeza R,
Cairns N, Cairns N, Callhoff J, Callhoff J, Calvini P, Campbell A, Cantillon M,
Capella H, Cardona-Sanclemente LE, Carle A, Carmasin J, Carranza-Ath F, Casanova
R, Cash D, Cella M, Celsis P, Chan LT, Chaney M, Chanu P, Chao L, Charil A,
Chemali Z, Chen B, Chen K, Chen T, Chen M, Chen G, Chen R, Cheng WC, Chertkow H,
Chiang G, Chiba K, Chisholm J, Cho Y, Choe J, Choubey S, Christensen AL, Clark C,
Clark D, Clarkson M, Clayton D, Clunie D, Coimbra A, Compton D, Crane P, Crans G,
Croop R, Crowther D, Crum W, Cui Y, Curry C, Curtis S, Cutter G, Daiello L, Dake
M, Dale A, Damato VD, Darby E, Darkner S, Darkner S, Davatzikos C, Dave J, David
R, Davidson J, de Bruijne M, De Meyer G, De Nunzio G, De Santi S, DeCarli C,
Dechairo B, DeDuck K, Dejkam A, Delfino M, Delpassand E, Deniz O, Denney D,
DeOrchis V, Depy Carron D, deToledo-Morrell L, Devanand D, Devanarayan V, Diaz G,
Diaz-Arrastia R, Dickerson B, Dinov I, Dodge H, Donohue M, Dowling M, Drzezga A,
Duan X, Duchesne S, Duff K, Dukart J, Durazzo T, Dykstra K, Earl N, Edula G, Ekin
A, Engelman C, Epstein N, Erten-Lyons D, Eskildsen S, Falcone G, Fan Y, Farnum M,
Farrer L, Farzan A, Feldman H, Feng Y, Fennema-Notestine C, Fernandes M,
Fernandez E, Ferrarini L, Ferreira L, Ferrer E, Figurski M, Filipovych R, Finch
S, Finlay D, Fiot JB, Flenniken D, Fletcher E, Fletcher PT, Flynn Longmire C,
Forman M, Forsythe A, 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, Gamst A, Gan K, Garcia
MT, Garcia-Linares A, Garg G, Gaser C, Gastineau E, Gavidia G, Gazdzinski S, Ge
Q, Gemme G, German D, Ghassabi Z, Gil JE, Gill R, Gitelman D, Gleason C, Godbey
M, Goghari V, Gold M, Goldberg T, Gomeni R, Gong S, Gonzales C, Gordon B, 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, Guo L, Guo H, Guo J, Habeck C,
Hai Y, Haight T, Hakansson K, Hammarstrom P, Hampel H, Han T, Han J, Hanif M,
Hanna Y, Hardy P, Harvey D, Harvey D, Hasan MK, Hazart A, Hazel J, He Y, He H,
Head D, Heckemann R, Heidebrink J, Henderson D, Henrard S, Herholz K, Hernandez
M, Hess C, Hobart J, Hoffman J, Holder D, Honigberg L, Horsfield M, Hsu WW, Hsu
A, Hu Z, Hu Z, Hu X, Hu Z, Hu W, Hu Z, Huang SP, Huang CJ, Huang F, Huang Y,
Huang J, Huang C, Hubbard R, Huentelman M, Hui S, Huppertz HJ, Hurko O, Hurt S,
Huyck S, Hwang S, Hyun J, Ifeachor E, Iglesias M, Ikari Y, Immermann F, Inoue L,
Insel P, Irizarry M, Irungu BM, Ishibashi T, Ishii K, Ismail S, Ito K, Ito M,
Iwatsubo T, Iyer M, Jacobson M, Jacobson A, Jafari A, Jafari-Khouzani K, Jaffe C,
Jagust W, Jagust W, Jara H, Jaros M, Jefferson A, Jiang T, Johnson DK, Juengling
F, Juh R, Julin P, Bhaskar U, Kadish B, Kahle-Wrobleski K, Kallam HR,
Kalpathy-Cramer J, Karageorgiou E, Karantzoulis S, Karasev P, Kauwe J, Kawakami
H, Kazimipoor B, Kelleher T, Kennedy R, Kerr D, Kerrouche N, Khalil I, Khalil A,
Khatry D, Kihel B, Killeen N, Killiany R, Kim H, Kim H, Kim Y, Kim JH, Kimberg D,
Kimura T, King R, Kirby J, Kita H, Klimas M, Klopfenstein E, Kobayashi D,
Koikkalainen J, Kokomoor A, Kolasny A, Kondo Y, Koppel J, Korolev I, Kotran N,
Kouassi A, Koutsouleris N, Kozma L, Kramer J, Kratzer M, Kuceyeski A, Kuhn FP,
Kulkarni M, Kumar S, Kuo HT, Kuo J, Kurosawa K, Kwon OH, Laforet G, Lai S,
Lakatos A, Landau S, Landen J, Lane R, Langbaum J, Lanius V, Lavault R, Laxamana
J, Le T, Leahy R, Lee N, Lee V, Lee JH, Lee JM, Lee D, Lee J, Lefkimmiatis S,
Lemaitre H, Lenz R, Lester G, Levey A, Li R, Li W, Li S, Li L, Li SJ, Li G, Li L,
Li Y, Li J, Li CS, Liang P, Liang L, Liao YL, Lin M, Lin L, Lin LC, Liu T, Liu M,
Liu Y, Liu D, Liu P, Liu S, Liu X, Liu T, Lo R, Logovinsky V, Lois A, Long X,
Long Z, Looi J, Lu Y, Lu PH, Lukic A, Lull JJ, Lynch J, Ma L, Mackin S, Magda S,
Maglio S, Mak HK, Malave V, Mandal P, Mangin JF, Manohar D, Mansouri C, Mantri N,
Manzour A, Marambaud P, Marchewka A, Marek K, Markind S, Marshall G, Martin J,
Mather M, Mathis C, Matoug S, Matsuo Y, Matthews D, Mayo A, McEvoy L, McGeown W,
McIntyre J, McQuail J, Meadowcroft M, Meda S, Mehta N, Mele V, Mendonca B,
Menendez M, Meredith J, Merrill D, Mesulam MM, Meyer C, Mez J, Mickael G,
Miftahof R, Mikhno A, Miller D, Min Y, Miri R, Mirza M, Mitsis E, Mohan A, Monno
L, Montana G, Moore D, Birgani PM, Moratal D, Morimoto B, Mortamet B, Motyl R,
Mueller N, Mukherjee S, Mulder E, Murphy M, Murray B, Musiek E, Myers A, Najafi
S, Nazeri A, Nettiksimmons J, Neu S, Neves S, Ng YB, Nguyen D, Nguyen N, Nguyen
Xuan T, Nielsen C, Nuneez Benjumea F, O’Neil A, Obisesan T, Oh DH, Oh J, Okonkwo
O, Olde Rikkert M, Ollesch J, Olmos S, Ostrowitzki S, Oswald A, Ott B, Ourselin
S, Ouyang G, Paiva R, Pan Z, Pande Y, Pardoe H, Park KH, Park H, Parsey R,
Parveen R, Paskavitz J, Patel Y, Patil M, Paul R, Pawlak M, Peavy G, Peng Y,
Pepin JL, Perea R, Perneczky R, Petitti D, Petrella J, Peyrat JM, Pezoa J, Pham
CT, Phillips N, Piovezan M, Podhorski A, Pollari M, Pontecorvo M, Poppenk J,
Posner H, Potkin S, Poulin S, Prasad G, Prenger K, Prieto E, Prince J,
Puchakayala SR, Puchakayala SR, Qin W, Qiu R, Qiu W, Qiu A, Qualls CD, Rabie H,
Rajeesh R, Rajeesh JR, Rallabandi VP, Ramage A, Randolph C, Raniga P, Rao D, Rao
A, Raubertas R, Ray D, Razak H, Redolfi A, Reid A, Reilhac A, Reinsberger C,
Restrepo L, Retico A, Rezaeitabar Y, Richards J, Richter M, Riddle W, Ries M,
Rincon M, Rischall M, Robieson W, Rocha-Rego V, Rogalski E, Rogers E, Rojas I,
Romero K, Rosand J, Rosen O, Rosen A, Rosenberg P, Ross D, Ross J, Rousseau F,
Rowe C, Rubin D, Ruiz A, Rusinek H, Ryan L, Saad A, Sabbagh M, Sabuncu M, Sachs
M, Sacuiu S, Sadeghi A, Said Y, Saint-Aubert L, Sakata M, Salat D, Salmon D,
Salomi S, Salter H, Samwald M, Sanchez L, Sanjo N, Sankaranarayanan P, Sato S,
Sato H, Saumier D, Savio A, Sawada I, Saykin A, Schaffer JD, Scharre D, Schlosser
G, Schmand B, Schmansky N, Schmidt M, 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, Sfikas G, Shahbaba B, Shams S, Shankle
W, Shattuck D, Shaw L, Shaw L, Sheela J, Shen W, Shera D, Sherman J, Sherman M,
Sherva R, Shimizu K, Shuler C, Shulman J, Siegel R, Siemers E, Silveira M, Silver
M, Silverman D, Simmons A, Simpson I, Singh SP, Singh N, Siuciak J, Sjogren N,
Skup M, Small G, Smith B, Smith M, Smith C, Smyth T, Snow S, Soares H, Soldea O,
Solomon P, Solomon A, Song M, Song C, Sorensen G, Soudah E, Spampinato MV,
Spenger C, Sperling R, Spiegel R, Spies L, Squarcia S, Squire L, Staff R, Stern
Y, Strittmatter S, Styren S, Sugishita M, Sugishita K, Sukkar R, Sun J, Sun Y,
Sundell K, Suri M, Swan M, Takagi T, Takahasi T, Takeuchi T, Tang S, Tanner W,
Tao W, Tao D, Tariot P, Tarjoman M, Tatsuoka C, Taylor-Reinwald L, Terlizzi R,
Thiele F, Thomas R, Thomas B, Thompson P, Thompson W, Thornton-Wells T, Thurfjell
L, Titeux L, Tolli T, Toma A, Tomita N, Toro R, Tosun D, Toussaint P, Toyoshiba
H, Tractenberg RE, Trittschuh E, Truran D, Tsechpenakis G, Tucker-Drob E, Tung J,
Uesugi H, Ullrich L, Umadevi Venkataraju K, Umar N, Uzunbas G, Valdivia F, Van
Horn J, Van Leemput K, Van Train K, Van Zeeland A, Vargas G, Vasanawala M, Vemuri
P, Verwaerde P, Videbaek C, Vidoni E, Vigneron V, Villanueva-Meyer J, Visser PJ,
Vitolo O, Vlassenko A, Volkau I, Vounou M, Wade S, Walhovd KB, Wallace D, Wan H,
Wang A, Wang LS, Wang YM, Wang Y, Wang A, Wang L, Wang Y, Wang T, Wang Y, Wang H,
Wang H, Ward M, Warfield S, Waring S, Webb D, Wei L, Weiner M, Wen SH, Wenjing L,
Wenzel F, Westlye LT, Whitcher B, Whitwell J, WilliamFaltaos D, Williams D,
Wilmot B, Wingo T, Winkler A, Wiste H, Wolfson T, Wolke I, Wolz R, Woo J, Woo E,
Woods L, Worth A, Worth E, Wouters H, Wu L, Wu X, Wu YG, Wu T, Wyman B,
Wyss-Coray T, Xiao L, Xu G, Xu J, Yamane T, Yamashita F, Yamazawa M, Yan Y, Yan
P, Yang QX, Yang Z, Ye BS, Ye J, Yee L, Yesavage J, Yip W, Yoo B, Yuan K,
Yushkevich P, Zagorodnov V, Zagorski M, Zawadzki R, Zeitzer J, Zhang L, Zhang L,
Zhang T, Zhang H, Zhang B, Zhang K, Zhang H, Zhao Q, Zhao P, Zhen X, Zhen X,
Zheng Y, Zhijun Y, Zhou S, Zhou B, Zhou L, Zhou B, Zhu W, Zhu H, Zou H.

OBJECTIVE: To evaluate relationships between magnetic resonance imaging
(MRI)-based measures of white matter hyperintensities (WMHs), measured at
baseline and longitudinally, and 1-year cognitive decline using a large
convenience sample in a clinical trial design with a relatively mild profile of
cardiovascular risk factors.
DESIGN: Convenience sample in a clinical trial design.
SUBJECTS: A total of 804 participants in the Alzheimer Disease Neuroimaging
Initiative who received MRI scans, cognitive testing, and clinical evaluations at
baseline, 6-month follow-up, and 12-month follow-up visits. For each scan, WMHs
were detected automatically on coregistered sets of T1, proton density, and T2
MRI images using a validated method. Mixed-effects regression models evaluated
relationships between risk factors for WMHs, WMH volume, and change in outcome
measures including Mini-Mental State Examination (MMSE), Alzheimer Disease
Assessment Scale-Cognitive Subscale (ADAS-Cog), and Clinical Dementia Rating
Scale sum of boxes scores. Covariates in these models included race, sex, years
of education, age, apolipoprotein E genotype, baseline clinical diagnosis
(cognitively normal, mild cognitive impairment, or Alzheimer disease),
cardiovascular risk score, and MRI-based hippocampal and brain volumes.
RESULTS: Higher baseline WMH volume was associated with greater subsequent 1-year
increase in ADAS-Cog and decrease in MMSE scores. Greater WMH volume at follow-up
was associated with greater ADAS-Cog and lower MMSE scores at follow-up. Higher
baseline age and cardiovascular risk score and more impaired baseline clinical
diagnosis were associated with higher baseline WMH volume.
CONCLUSIONS: White matter hyperintensity volume predicts 1-year cognitive decline
in a relatively healthy convenience sample that was similar to clinical trial
samples, and therefore should be considered as a covariate of interest at
baseline and longitudinally in future AD treatment trials.

 

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