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Neurology. 2009 Jun 16;72(24):2115-21. doi: 10.1212/WNL.0b013e3181aa52d3.

Donepezil delays progression to AD in MCI subjects with depressive symptoms.

Collaborators (252)

Merideth CH, Milbrand TA, Mende S, Ahern G, Kells C, Burton K, Schwartz A, Echols C, Zomok M, Dawson L, Baumel B, Crasto J, Radzivill R, Eisner L, Riveros J, Johnson A, Baumel B, Crasto J, Alonso D, Torres A, Doody RS, Sims J, Robinson N, Ott B, Clemens M, Grace J, Blass J, Cirio R, Schneider A, Adler L, Margolin R, Kent D, Roffman M, Marritt I, Kertesz A, Morlog D, Sano M, Dominguez E, Raganuth A, Santiago R, Weber C, Meyers B, Burke J, Wyne SV, McCart M, Guzman DA, Gravelle C, Bedirian I, Levey A, Cellar J, Gauchman N, Valia S, Newhouse PA, Gay E, Aisen P, Cechola MA, Johnson K, Reynolds B, Siegal A, Darvesh S, Cross J, Sherwood G, McCracken P, Aloisio S, Duban S, McKelvey C, Farlow M, Nurnberger P, Fleming K, Jessup N, Pearson J, Riley E, Chertkow H, Hosein C, Brandt J, Munro C, Kilada S, O'Donnell S, Lopez GJ, Switzer P, Miller A, La Rocca T, Freimark S, Growdon J, Tennis M, Graff-Radford N, Parfitt F, Makarov LM, Knopman DS, Boeve B, Haukom N, Mandarino M, Mullinax D, Petersen R, Gauthier S, Amyot D, Lippa C, Wilson AM, Petrucci R, Bagwell D, Mintzer JE, Stuckey M, Green RC, Shua-Haim J, Shua-Haim V, Wall S, Hovick A, Davis K, Mohs RC, Swedish K, Casadiego M, Negroni L, Ware K, Knox B, Pomara N, de la Pena C, Brenner R, Ferris S, Vlassopoulos M, Kastelan J, Lam J, Mesulam MM, Herzog L, Kaye J, Lear J, Berman S, Wild K, Thein S Jr, Cipriani D, Sadowsky C, Ramirez-Rojas Y, Sugerman AA, Cole-Kady JP, Alvarez K, Soika R, DeLaGandara J, Aggarwal N, Bennett D, Ferraro RM, Aldridge C, Li M, Nance RM, Vicari S, Schaefer F, Solomon P, Hathaway BJ, Crowe L, Robinson M, Grossberg G, Yesavage JA, Levy M, Sabbagh M, Hatton K, Black S, Lawrence J, Evans M, Krupp L, Madigan DM, Au WJ, Poff DN, Mulligan M, Orengo I, Feldman H, O'Neill V, Gilchrist K, Hogan D, Mueller P, Geldmacher D, Santillan C, Talea P, Sanders M, DeCarli C, Coleman J, Cotman C, Mulnard R, McAdams-Ortiz C, Kim H, Cummings J, Masterman DL, Carter MF, Bennett N, Berndt L, Grundman M, Olichney JM, Johnson SM, Jenkins CW, Yaffe K, Gearhart R, Smith V, Schmitt F, Cox J, Anderson S, Dearth CS, Rivero J, Ownby R, Williams J, Foster N, Lord J, Johnson N, Hochhalter A, Bernick C, Vranesh G, Munic D, LeBlanc P, Adair J, McClelland S, Clark C, Gravanda K, Cotter V, Nuñez J, Ryan-Ripp E, DeKosky S, Smith-Macedonia L, Baumgartner T, Kane AL, Tariot P, Goldstein B, Terwilliger L, Pfeiffer E, Luhn B, Baxter D, Hunter J, Schneider L, Taggart N, Stevens-Dagerman K, Weiner M, Martin-Cook K, Ninman T, Pierce S, Peskind E, Raskind M, Wood R, Brown N, O'Connell J, Pham N, Nichols ME, Bailie C, Hillesland D, Margolin R, Kent D, McFarland L, Morris JC, Stiening S, Dromerick A, Dyer C, Duara R, Roberts PD, Van Dyck C, MacAvoy M, Cretella L, Rightmer T, Zeiser L.

Author information

  • 1Departments of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. plu@mednet.ucla.edu

Abstract

OBJECTIVE:

To determine whether the presence of depression predicts higher rate of progression to Alzheimer disease (AD) in patients with amnestic mild cognitive impairment (aMCI) and whether donepezil treatment beneficially affect this relationship.

METHODS:

The study sample was composed of 756 participants with aMCI from the 3-year, double-blind, placebo-controlled Alzheimer's Disease Cooperative Study drug trial of donepezil and vitamin E. Beck Depression Inventory (BDI) was used to assess depressive symptoms at baseline and participants were followed either to the end of study or to the primary endpoint of progression to probable or possible AD.

RESULTS:

Cox proportional hazards regression, adjusted for age at baseline, gender, apolipoprotein genotype, and NYU paragraph delayed recall score, showed that higher BDI scores were associated with progression to AD (p = 0.03). The sample was stratified into depressed (BDI score > or =10; n = 208) and nondepressed (BDI <10; n = 548) groups. Kaplan-Meier analysis showed that among the depressed subjects, the proportion progressing to AD was lower for the donepezil group than the combined vitamin E and placebo groups at 1.7 years (p = 0.023), at 2.2 years (p = 0.025), and remained marginally lower at 2.7 years (p = 0.070). The survival curves among the three treatment groups did not differ within the nondepressed participants.

CONCLUSIONS:

Results suggest that depression is predictive of progression from amnestic mild cognitive impairment (aMCI) to Alzheimer disease (AD) and treatment with donepezil delayed progression to AD among depressed subjects with aMCI. Donepezil appears to modulate the increased risk of AD conferred by the presence of depressive symptoms.

PMID:
19528519
[PubMed - indexed for MEDLINE]
PMCID:
PMC2697965
Free PMC Article

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