 |
|
Cholinesterase Inhibition for Alzheimer Disease
A Meta-analysis of the Tacrine Trials
Nawab Qizilbash, MRCP, DPhil;
Anne Whitehead, MSc;
Julian Higgins, PhD;
Gordon Wilcock, FRCP, DM;
Lon Schneider, MD;
Martin Farlow, MD;
for the Dementia Trialists' Collaboration
JAMA. 1998;280:1777-1782.
Objectives.— To determine the effects of cholinesterase inhibition with tacrine hydrochloride for the symptoms of Alzheimer disease in terms of cognitive performance, clinical global impression, behavior, and functional autonomy.
Data Sources.— The Cochrane Dementia Group registry of trials.
Study Selection.— Unconfounded, randomized, double-blind, placebo-controlled trials in which tacrine had been given for more than 1 day and that were completed before January 1, 1996.
Data Extraction.— Two reviewers independently selected trials for inclusion and individual patient data were sought.
Data Synthesis.— Data were analyzed from 12 trials that included 1984 patients with Alzheimer disease. At 12 weeks, cognitive performance, as measured by the Mini-Mental State Examination (score range, 0-30), was better in patients receiving tacrine than in patients receiving placebo by 0.62 points (95% confidence interval [CI], 0.23-1.00; P=.002). Compared with similar untreated patients who would be expected to deteriorate by 0.50 to 1.00 points on the Mini-Mental State Examination during 12 weeks, the progress of patients receiving tacrine would be expected to range between an improvement of 0.12 and a deterioration of 0.38 points. The odds ratio for improvement on the Clinical Global Impression of Change scale (range, 1-7) for patients receiving tacrine compared with those receiving placebo was 1.58 (95% CI, 1.18-2.11; P=.002). The behavioral noncognitive subscale of the Alzheimer's Disease Assessment Scale (range, 0-50) showed a difference in favor of tacrine of 0.58 points (95% CI, 0.17-1.00; P=.006). Improvement on the Progressive Deterioration Scale, largely an index of functional activities, was not significant (0.75; 95% CI, -0.43 to 1.93; P=.21). Age, severity of dementia, and exposure to tacrine prior to randomization had no clear influence on the treatment effect. There was a nonsignificant trend toward increasing effect with increasing dose for cognitive function and the Clinical Global Impression of Change. For patients without prior exposure to tacrine, the odds of patients' withdrawing during the study while they were receiving tacrine compared with placebo was 3.63 (95% CI, 2.80-4.71; P<.001). Eleven (95% CI, 7-31) patients would need to be treated to achieve any improvement on the Clinical Global Impression scale, and 42 (95% CI, 23-125) to achieve a moderate or marked improvement. One patient would be expected to withdraw for every 4 (95% CI, 3-5) patients treated.
Conclusions.— Cholinesterase inhibition with tacrine appears to reduce deterioration in cognitive performance during the first 3 months and increase the odds of global clinical improvement. Effects observed on measures of behavioral disturbance were of questionable clinical significance, and functional autonomy was not significantly affected. The clinical relevance of the benefits of cholinesterase inhibition remains controversial, and long-term trials with clinically relevant end points are required.
From the Dementia Trialists' Collaboration, Cochrane Dementia Group, Department of Clinical Geratology, University of Oxford, Radcliffe Infirmary, Oxford, England (Dr Qizilbash); MPS Research Unit, University of Reading, England (Ms Whitehead); Systematic Reviews Training Unit, Institute of Child Health, London, England (Dr Higgins); Department of Care of the Elderly, Frenchay Hospital, Bristol, England (Dr Wilcock); Department of Psychiatry, University of Southern California School of Medicine, Los Angeles (Dr Schneider); and Department of Neurology, Indiana University School of Medicine, Indianapolis (Dr Farlow).
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Size of the treatment effect on cognition of cholinesterase inhibition in Alzheimer's disease
Rockwood
J. Neurol. Neurosurg. Psychiatry 2004;75:677-685.
ABSTRACT
| FULL TEXT
Evidence-Based Practices in Geriatric Mental Health Care
Bartels et al.
Focus 2004;2:268-281.
ABSTRACT
| FULL TEXT
Screening for Dementia in Primary Care: A Summary of the Evidence for the U.S. Preventive Services Task Force
Boustani et al.
ANN INTERN MED 2003;138:927-937.
ABSTRACT
| FULL TEXT
Efficacy of Cholinesterase Inhibitors in the Treatment of Neuropsychiatric Symptoms and Functional Impairment in Alzheimer Disease: A Meta-analysis
Trinh et al.
JAMA 2003;289:210-216.
ABSTRACT
| FULL TEXT
Evidence-Based Practices in Geriatric Mental Health Care
Bartels et al.
Psychiatr. Serv. 2002;53:1419-1431.
ABSTRACT
| FULL TEXT
Cholinesterase inhibitor treatment alters the natural history of Alzheimer's disease
Lopez et al.
J. Neurol. Neurosurg. Psychiatry 2002;72:310-314.
ABSTRACT
| FULL TEXT
To IPD or not to IPD?: Advantages and Disadvantages of Systematic Reviews Using Individual Patient Data
Stewart and Tierney
Eval Health Prof 2002;25:76-97.
ABSTRACT
A videotaped CIBIC for dementia patients: Validity and reliability in a simulated clinical trial
Quinn et al.
Neurology 2002;58:433-437.
ABSTRACT
| FULL TEXT
Cholinergic Enhancement and Increased Selectivity of Perceptual Processing During Working Memory
Furey et al.
Science 2000;290:2315-2319.
ABSTRACT
| FULL TEXT
Further Evidence for a Dissociation Between Different Forms of Mnemonic Expressions in a Mouse Model of Age-related Cognitive Decline: Effects of Tacrine and S 17092, a Novel Prolyl Endopeptidase Inhibitor
Marighetto et al.
Learn. Mem. 2000;7:159-169.
ABSTRACT
| FULL TEXT
Donepezil Therapy in Clinical Practice: A Randomized Crossover Study
Greenberg et al.
Arch Neurol 2000;57:94-99.
ABSTRACT
| FULL TEXT
Meta-analysis of Tacrine for Alzheimer Disease: The Influence of Industry Sponsors
Koepp et al.
JAMA 1999;281:2287-2288.
FULL TEXT
Other articles noted
Evid. Based Ment. Health 1999;2:40-40.
FULL TEXT
Acetylcholinesterase inhibitors for Alzheimer's disease
Flicker
BMJ 1999;318:615-616.
FULL TEXT
|
