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REPLY

The Importance of Measuring Executive Function When Studying the Effects of Cognition-Enhancing Agents

right arrow Parminder Raina, PhD; Pasqualina L. Santaguida, PhD; and Christopher Patterson, MD

2 September 2008 | Volume 149 Issue 5 | Pages 359-360


IN RESPONSE:

We thank Dr. Rockwood for his thoughtful and perceptive response to our review. We completely agree that aggregate scores on instruments that do not measure executive function may fail to capture useful improvements in individuals receiving cholinesterase inhibitors or other cognition-enhancing agents. Of the many attempts to isolate meaningful individual responses to treatment, goal attainment scaling is among the most sensitive and robust. Although "listening to patients" is not always a means of determining outcome and is rarely quantified in as rigorous a manner as advocated by Dr. Rockwood, we share his enthusiasm for it, the most basic and satisfying element of clinical care.

Dr. Rockwood also cites 2 related publications that demonstrate this point. One of these studies was eligible for our review (1). Inclusion of this study does not alter the effect size for the mean difference in the Alzheimer Disease Assessment Scale cognitive subscale (ADAS-cog) score (–2.39 [95% CI, –3.32 to 1.46]) in the meta-analysis of treatment effects of galantamine for Alzheimer disease, and the heterogeneity is not improved either (chi-square P = 0.003; I= 70.3%). The other study was published after completion of our review (2).

It was also brought to our attention that there was an error in Raskind and colleagues' study of galantamine (3). The mean change for the ADAS-cog score was –1.9 for the treatment group rather than 1.9 as stated in the original publication. Corrections or corrigenda for previously published articles are uniformly considered by the National Library of Medicine to be errata. In this case, searching in MEDLINE by the author's name does not return the correction; neither does the citation listed within PubMed or Ovid indicate that a correction was issued. In short, detection of such corrections is problematic because of the manner in which they are indexed; uniformity among journals and consistency in indexing is required. Nonetheless, the effect size of the ADAS-cog summary estimate is still not clinically significant and does not change our interpretation of the evidence report. The Figure shows both the addition of Rockwood and colleagues' study (2) and the effect of this correction on the meta-analysis for galantamine. It shows a slight increase in the effect size (–3.06 [CI, –3.53 to 2.58]), and the tests for heterogeneity are no longer significant (chi-square P = 0.715; I= 0.0%). The effect size for galantamine is statistically, but not clinically, significant.


Figure 1
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Figure. Summary estimates for the change in Alzheimer's Disease Assessment Scale–cognitive subscale scores.

The Figure includes Rockwood and colleagues' study (1) and the correction in Raskind and colleagues' study (3).

 


Author and Article Information
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From McMaster University, Hamilton L8S 4M1, Ontario, Canada.

Potential Financial Conflicts of Interest: Honoraria: P. Santaguida (American College of Physicians).


References
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1. Rockwood K, Fay S, Song X, MacKnight C, Gorman M, Video-Imaging Synthesis of Treating Alzheimer's Disease (VISTA) Investigators. Attainment of treatment goals by people with Alzheimer's disease receiving galantamine: a randomized controlled trial. CMAJ. 2006;174:1099-105. [PMID: 16554498].[Abstract/Free Full Text]

2. Rockwood K, Fay S, Jarrett P, Asp E. Effect of galantamine on verbal repetition in AD: a secondary analysis of the VISTA trial. Neurology. 2007;68:1116-21. [PMID: 17404193].[Abstract/Free Full Text]

3. Raskind MA, Peskind ER, Wessel T, Yuan W. Galantamine in AD: A 6-month randomized, placebo-controlled trial with a 6-month extension. The Galantamine USA-1 Study Group. Neurology. 2000;54:2261-8. [PMID: 10881250].[Abstract/Free Full Text]

4. Brodaty H, Corey-Bloom J, Potocnik FC, Truyen L, Gold M, Damaraju CR. Galantamine prolonged-release formulation in the treatment of mild to moderate Alzheimer's disease. Dement Geriatr Cogn Disord. 2005;20:120-32. [PMID: 15990426].[Medline]

5. Bullock R, Erkinjuntti T, Lilienfeld S, GAL-INT-6 Study Group. Management of patients with Alzheimer's disease plus cerebrovascular disease: 12-month treatment with galantamine. Dement Geriatr Cogn Disord. 2004;17:29-34. [PMID: 14560062].[Medline]

6. Tariot PN, Solomon PR, Morris JC, Kershaw P, Lilienfeld S, Ding C. A 5-month, randomized, placebo-controlled trial of galantamine in AD. The Galantamine USA-10 Study Group. Neurology. 2000;54:2269-76. [PMID: 10881251].[Abstract/Free Full Text]

7. Wilcock GK, Lilienfeld S, Gaens E. Efficacy and safety of galantamine in patients with mild to moderate Alzheimer's disease: multicentre randomised controlled trial. Galantamine International-1 Study Group. BMJ. 2000;321:1445-9. [PMID: 11110737].[Abstract/Free Full Text]

8. Wilkinson D, Murray J. Galantamine: a randomized, double-blind, dose comparison in patients with Alzheimer's disease. Int J Geriatr Psychiatry. 2001;16:852-7. [PMID: 11571763].[Medline]


Related articles in Annals:

Clinical Guidelines
Effectiveness of Cholinesterase Inhibitors and Memantine for Treating Dementia: Evidence Review for a Clinical Practice Guideline
Parminder Raina, Pasqualina Santaguida, Afisi Ismaila, Christopher Patterson, David Cowan, Mitchell Levine, Lynda Booker, AND Mark Oremus
Annals 2008 148: 379-397. [ABSTRACT][SUMMARY][Full Text]  

Letters
The Importance of Measuring Executive Function When Studying the Effects of Cognition-Enhancing Agents
Kenneth Rockwood
Annals 2008 149: 358-359. [Full Text]  




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