Cognitive function over time in the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT): results of a randomized, controlled trial of naproxen and celecoxib

ADAPT Research Group, Barbara K Martin, Christine Szekely, Jason Brandt, Steven Piantadosi, John C S Breitner, Suzanne Craft, Denis Evans, Robert Green, Michael Mullan, Breitner, Neil Buckholtz, Susan Molchan, Evans, Martin, Curtis Meinert, Craft, Green, Constantine Lyketsos, Mullan, Marwan Sabbagh, Pierre N Tariot, Saleem Ismail, Brandt, Piantadosi, Janette Negele, Melissa Montero, Bonnie Piantadosi, Themistocles Dassopoulos, Claudia Kawas, Leon Thal, Kathleen Welsh-Bohmer, Andrew Whelton, Breitner, Negele, Montero, Elizabeth Aigbe, Jill Dorje, Brenna Cholerton, Meinert, Martin, Piantadosi, Robert Casper, Michele Donithan, Hsu-Tai Liu, Piantadosi, Anne V Shanklin, Paul Smith, Buckholtz, Susan Molchan, Constantine G Lyketsos, Martin Steinberg, Brandt, Julia J Pedroso, Alyssa Bergey, Themos Dassopoulos, Melanie Dieter, Carol Gogel, Chiadi Onyike, Lynn Smith, Veronica Wilson-Sturdivant, Nadine Yoritomo, Green, Sanford Auerbach, Robert Stern, Patricia Boyle, Dawn Cisewski, Jane Mwicigi, Mary-Tara Roth, Lorraine Baldwin, Margaret Brickley, Patrick Compton, Debra Hanna, Sylvia Lambrechts, Janet Nafissi, Andreja Packard, Mayuri Thakuria, Saleem Ismail, Tariot, Anton Porsteinsson, J Michael Ryan, Robin Henderson-Logan, Colleen McCallum, Suzanne Decker, Laura Jakimovick, Kara Jones, Arlene Pustalka, Susan Salem-Spencer, Asa Widman, Craft, Mark Fishel, Laura Baker, Deborah Dahl, Kathleen Nelson, Susan Bigda, Yoshie Biro, Ruth Boucher, Nickolas Dasher, Edward DeVita, Grace Garrett, Austin Hamm, Jeff Lindsey, Laura Sissons-Ross, Marwan Sabbagh, Joseph Rogers, Donald Connor, Carolyn Liebsack, Nancy Thompson, Joanne Ciemo, Kathryn Davis, Theresa Hicksenhiser, Sherry Johnson-Traver, Healther Kolody, Lisa Royer, Nina Silverberg, Deborah Tweedy, Mullan, Cheryl Luis, Timothy Crowell, Julia Parrish, Laila Abdullah, Theavy Chea, Scott Creamer, Melody Brooks Jayne, Antoinette Oliver, Summer Price, Joseph Zolton, C Morton Hawkins, Bernard Carroll, Dallas M High, Ronald Petersen, Thomas Schnitzer, Buckholtz, Evans, Meinert, ADAPT Research Group, Barbara K Martin, Christine Szekely, Jason Brandt, Steven Piantadosi, John C S Breitner, Suzanne Craft, Denis Evans, Robert Green, Michael Mullan, Breitner, Neil Buckholtz, Susan Molchan, Evans, Martin, Curtis Meinert, Craft, Green, Constantine Lyketsos, Mullan, Marwan Sabbagh, Pierre N Tariot, Saleem Ismail, Brandt, Piantadosi, Janette Negele, Melissa Montero, Bonnie Piantadosi, Themistocles Dassopoulos, Claudia Kawas, Leon Thal, Kathleen Welsh-Bohmer, Andrew Whelton, Breitner, Negele, Montero, Elizabeth Aigbe, Jill Dorje, Brenna Cholerton, Meinert, Martin, Piantadosi, Robert Casper, Michele Donithan, Hsu-Tai Liu, Piantadosi, Anne V Shanklin, Paul Smith, Buckholtz, Susan Molchan, Constantine G Lyketsos, Martin Steinberg, Brandt, Julia J Pedroso, Alyssa Bergey, Themos Dassopoulos, Melanie Dieter, Carol Gogel, Chiadi Onyike, Lynn Smith, Veronica Wilson-Sturdivant, Nadine Yoritomo, Green, Sanford Auerbach, Robert Stern, Patricia Boyle, Dawn Cisewski, Jane Mwicigi, Mary-Tara Roth, Lorraine Baldwin, Margaret Brickley, Patrick Compton, Debra Hanna, Sylvia Lambrechts, Janet Nafissi, Andreja Packard, Mayuri Thakuria, Saleem Ismail, Tariot, Anton Porsteinsson, J Michael Ryan, Robin Henderson-Logan, Colleen McCallum, Suzanne Decker, Laura Jakimovick, Kara Jones, Arlene Pustalka, Susan Salem-Spencer, Asa Widman, Craft, Mark Fishel, Laura Baker, Deborah Dahl, Kathleen Nelson, Susan Bigda, Yoshie Biro, Ruth Boucher, Nickolas Dasher, Edward DeVita, Grace Garrett, Austin Hamm, Jeff Lindsey, Laura Sissons-Ross, Marwan Sabbagh, Joseph Rogers, Donald Connor, Carolyn Liebsack, Nancy Thompson, Joanne Ciemo, Kathryn Davis, Theresa Hicksenhiser, Sherry Johnson-Traver, Healther Kolody, Lisa Royer, Nina Silverberg, Deborah Tweedy, Mullan, Cheryl Luis, Timothy Crowell, Julia Parrish, Laila Abdullah, Theavy Chea, Scott Creamer, Melody Brooks Jayne, Antoinette Oliver, Summer Price, Joseph Zolton, C Morton Hawkins, Bernard Carroll, Dallas M High, Ronald Petersen, Thomas Schnitzer, Buckholtz, Evans, Meinert

Abstract

Background: Observational studies have shown reduced risk of Alzheimer dementia in users of nonsteroidal anti-inflammatory drugs.

Objective: To evaluate the effects of naproxen sodium and celecoxib on cognitive function in older adults.

Design: Randomized, double-masked chemoprevention trial.

Setting: Six US memory clinics.

Participants: Men and women aged 70 years and older with a family history of Alzheimer disease; 2117 of 2528 enrolled had follow-up cognitive assessment.

Interventions: Celecoxib (200 mg twice daily), naproxen sodium (220 mg twice daily), or placebo, randomly allocated in a ratio of 1:1:1.5, respectively.

Main outcome measures: Seven tests of cognitive function and a global summary score measured annually.

Results: Longitudinal analyses showed lower global summary scores over time for naproxen compared with placebo (- 0.05 SDs; P = .02) and lower scores on the Modified Mini-Mental State Examination over time for both treatment groups compared with placebo (- 0.33 points for celecoxib [P = .04] and - 0.36 points for naproxen [P = .02]). Restriction of analyses to measures collected from persons without dementia attenuated the treatment group differences. Analyses limited to measures obtained while participants were being issued study drugs produced results similar to the intention-to-treat analyses.

Conclusions: Use of naproxen or celecoxib did not improve cognitive function. There was weak evidence for a detrimental effect of naproxen.

Trial registration: ClinicalTrials.gov NCT00007189.

Figures

Figure 1
Figure 1
Flowchart of the Alzheimer's Disease Anti-inflammatory Prevention Trial. * Indicates numbers available only for those randomized, not those screened for eligibility; †, participants considered to have terminated study drug if study drugs had been started but were no longer being issued at scheduled visits before December 17, 2004 (does not include temporary interruptions); ‡, participants considered administratively censored if their 1-year visit window had not closed by June 17, 2005; §, participants considered lost to cognitive assessment after 1 or more years if they did not have cognitive assessment data in the 1.5 years before June 17, 2005 (losses include death).
Figure 2
Figure 2
Raw scores for each of the 7 tests of cognitive function and the global summary over time by treatment group (baseline, N=2528; year 1, n=2088; year 2, n=1485; year 3, n=700). BVMT-R indicates Brief Visuospatial Memory Test–Revised; HVLT-R, Hopkins Verbal Learning Test–Revised; RBMT, Rivermead Behavioral Memory Test; and 3MS-E, Modified Mini-Mental State Examination.
Figure 3
Figure 3
Odds ratios (ORs) comparing treatment groups with placebo for magnitudes of decline from baseline in global summary (A) and Modified Mini-Mental State Examination (3MS-E) (B) scores. CI indicates confidence interval.

Source: PubMed

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