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Arch Neurol. 2011 Oct;68(10):1257-66. doi: 10.1001/archneurol.2011.123. Epub 2011 Jun 13.

Longitudinal change of biomarkers in cognitive decline.

Collaborators (196)

Aisen P, Jack CR Jr, Toga AW, Beckett L, Soares A, Green RC, Montine T, Thomas RG, Donohue M, Walter S, Dale A, Bernstein M, Felmlee J, Fox N, Thompson P, Schuff N, Alexander G, DeCarli C, Bandy D, Chen K, Morris J, Lee VM, Korecka M, Crawford K, Neu S, Harvey D, Kornak J, Saykin AJ, Foroud TM, Potkin S, Shen L, Buckholtz N, Kaye J, Dolen S, Quinn J, Schneider L, Pawluczyk S, Spann BM, Brewer J, Vanderswag H, Heidebrink JL, Lord JL, Petersen R, Johnson K, Doody RS, Villanueva-Meyer J, Chowdhury M, Stern Y, Honig LS, Bell KL, Morris JC, Mintun MA, Schneider S, Marson D, Griffith R, Clark D, Grossman H, Tang C, Marzloff G, deToledo-Morrell L, Shah RC, Duara R, Varon D, Roberts P, Albert MS, Pedroso J, Toroney J, Rusinek H, de Leon MJ, De Santi SM, Doraiswamy PM, Petrella JR, Aiello M, Clark CM, Pham C, Nunez J, Smith CD, Given CA 2nd, Hardy P, Lopez OL, Oakley M, Simpson DM, Ismail MS, Brand C, Richard J, Mulnard RA, Thai G, McAdams-Ortiz C, Diaz-Arrastia R, Martin-Cook K, DeVous M, Levey AI, Lah JJ, Cellar JS, Burns JM, Anderson HS, Laubinger MM, Bartzokis G, Silverman DH, Lu PH, Graff-Radford NR, Parfitt F, Johnson H, Farlow M, Herring S, Hake A, van Dyck CH, MacAvoy MG, Benincasa AL, Chertkow H, Bergman H, Hosein C, Black S, Graham S, Caldwell C, Hsiung GY, Feldman H, Assaly M, Kertesz A, Rogers J, Trost D, Bernick C, Health B, Wu C, Johnson N, Mesulam M, Sadowsky C, Martinez W, Villena T, Turner S, Johnson KB, Behan KE, Sperling RA, Rentz DM, Johnson KA, Rosen A, Tinklenberg J, Ashford W, Sabbagh M, Connor D, Jacobson S, Killiany R, Norbash A, Nair A, Obisesan TO, Jayam-Trouth A, Wang P, Lerner A, Hudson L, Fletcher E, Carmichael O, Kittur S, Mirje S, Borrie M, Lee T-, Bartha R, Johnson S, Asthana S, Carlsson CM, Potkin SG, Preda A, Nguyen D, Tariot P, Fleisher A, Reeder S, Bates V, Capote H, Rainka M, Hendin BA, Scharre DW, Kataki M, Zimmerman EA, Celmins D, Brown AD, Gandy S, Marenberg ME, Rovner BW, Pearlson G, Blank K, Anderson K, Saykin AJ, Hampshire N, Santulli RB, Englert J, Williamson JD, Sink K, Watkins F, Ott BR, Wu C, Cohen R, Salloway S, Malloy P, Correia S, Rosen HJ, Miller BL, Mintzer J.

Author information

  • 1Division of Epidemiology, University of California, Berkeley, 94720-3190, USA. rlo@berkeley.edu



To delineate the trajectories of Aβ42 level in cerebrospinal fluid (CSF), fludeoxyglucose F18 (FDG) uptake using positron emission tomography, and hippocampal volume using magnetic resonance imaging and their relative associations with cognitive change at different stages in aging and Alzheimer disease (AD).


Cohort study.


The 59 study sites for the Alzheimer's Disease Neuroimaging Initiative.


A total of 819 participants 55 to 90 years of age with normal cognition, mild cognitive impairment, and AD who were followed up during the period from 2005 to 2007.


Rates of change in level of Aβ42 in CSF, FDG uptake, hippocampal volume, and the Alzheimer Disease's Assessment Scale-cognitive subscale score during up to 36 months of follow-up by diagnostic group as well as prediction of cognitive change by each biomarker.


Reductions in the level of Aβ42 in CSF were numerically greater in participants with normal cognition than in participants with mild cognitive impairment or AD; whereas both glucose metabolic decline and hippocampal atrophy were significantly slower in participants with normal cognition than in participants with mild cognitive impairment or AD. Positive APOE4 status accelerated hippocampal atrophic changes in participants with mild cognitive impairment or AD, but did not modify rates of change in level of Aβ42 in CSF or FDG uptake. The Alzheimer Disease's Assessment Scale-cognitive subscale scores were related only to the baseline level of Aβ42 in CSF and the baseline FDG uptake in participants with normal cognition, which were about equally associated with change in FDG uptake and hippocampal volume in participants with mild cognitive impairment and best modeled by change in FDG uptake in participants with AD.


Trajectories of Aβ42 level in CSF, FDG uptake, and hippocampal volume vary across different cognitive stages. The longitudinal patterns support a hypothetical sequence of AD pathology in which amyloid deposition is an early event before hypometabolism or hippocampal atrophy, suggesting that biomarker prediction for cognitive change is stage dependent.

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[PubMed - indexed for MEDLINE]
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