NEUROLOGY 1996;47:166-177
© 1996 American Academy of Neurology
Long-term tacrine (Cognex) treatmentEffects on nursing home placement and mortality
D. Knopman, MD,
L. Schneider, MD,
K. Davis, MD,
S. Talwalker, PhD,
F. Smith, PhD,
T. Hoover, PhD and
S. Gracon, DVM
the Tacrine Study Group*; *See Appendix 1 *Table 7* on page 174 for participating institutions and principal investigators.
From the Department of Neurology (Dr. Knopman), University of Minnesota, Minneapolis, MN; Department of Psychiatry (Dr. Schneider), University of Southern California, Los Angeles, CA; Department of Psychiatry (Dr. Davis), Mt. Sinai School of Medicine, New York, NY; and Pharmaceutical Research (Drs. Talwalker, Smith, Hoover, and Gracon), Parke-Davis, Ann Arbor, MI.
Drs. Knopman, Schneider, and Davis served as paid consultants to Parke-Davis but own neither stock nor equity in Warner-Lambert Company. Drs. Talwalker, Smith, Hoover, and Gracon are employees of Parke-Davis and own stock or options in Warner-Lambert Co.
Supported by Parke-Davis Pharmaceutical Research.
Presented in part at the 4th International Springfield-Nice Conference on Alzheimer's Disease, Nice, France, April 16, 1996, and the Lancet Conference on Alzheimer's Disease, Edinburgh, Scotland, April 24, 1996.
Received November 21, 1995. Accepted in final form January 9, 1996.
Address correspondence and reprint requests to Dr. David Knopman, Department of Neurology, Box 295, University of Minnesota, Minneapolis, MN 55455.
Objective: To assess the possible association between tacrine (Cognex, manufactured by Parke-Davis, Morris Plains, NJ) dose and likelihood of nursing home placement (NHP) or death in patients with AD. Design: A 30-week, randomized, double-blind, placebo-controlled, parallel-group multicenter clinical trial involving 663 patients, after which patients were treated openly and followed up a minimum of 2 years later. Patients: At baseline, outpatients were at least 50 years of age, met criteria for probable AD, with baseline Mini-Mental State Examination scores between 10 and 26 (inclusive), were otherwise healthy, and had a caregiver who could provide assessments and ensure medication compliance. Interventions: Randomized assignment to placebo or one of three ascending dosage regimens of tacrine over 30 weeks, followed by open label treatment for all patients who began the double-blind trial. Outcome Measures: NHP and death were examined using logistic regression. Results: Patients who remained on tacrine and were receiving doses > 80 mg/d or > 120 mg/d were less likely to have entered a nursing home than patients on lower doses (odds ratios > 2.7, 2.8, respectively.) There was a trend for lower mortality for patients receiving > 120 mg/d (p = 0.063). Conclusions: Treatment with tacrine at doses > 80 mg/d was associated with a reduced likelihood of NHP. These data demonstrate that tacrine's 30-week effects on cognitive function and clinicians' global ratings may generalize to effects on a major milestone of AD. Future studies should attempt to replicate these findings prospectively.
NEUROLOGY 1996;47: 166-177
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|
|
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|
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|
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|
|
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|
|
|
|
|
|
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280(20):
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[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Cummings, C. E. Coffey, J. D. Duffy, E. C. Lauterbach, M. Lovell, P. F. Malloy, D. R. Royall, T. A. Rummans, and S. Salloway
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[Abstract]
[Full Text]
|
|
|
|
|
|
|
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54(11):
1406 - 1409.
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|
|
|
|
|
|
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G. W. Small, P. V. Rabins, P. P. Barry, N. S. Buckholtz, S. T. DeKosky, S. H. Ferris, S. I. Finkel, L. P. Gwyther, Z. S. Khachaturian, B. D. Lebowitz, et al.
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October 22, 1997;
278(16):
1363 - 1371.
[Abstract]
[PDF]
|
|
|
|
|
|
|
W. B. Applegate and M. Pahor
Geriatric Medicine
JAMA,
June 18, 1997;
277(23):
1863 - 1864.
[PDF]
|
|
|
|
|
|
|
J. C. Beck and A. Stuck
Preventing Disability: Beyond the Black Box
JAMA,
December 4, 1996;
276(21):
1756 - 1757.
[Abstract]
[PDF]
|
|
|
|
|
|
|
G. W. Small, L. M. Ercoli, D. H. S. Silverman, S.-C. Huang, S. Komo, S. Y. Bookheimer, H. Lavretsky, K. Miller, P. Siddarth, N. L. Rasgon, et al.
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97(11):
6037 - 6042.
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|
|
|
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