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Atenolol Compared with Nifedipine: Effect on Cognitive Function and Mood in Elderly Hypertensive Patients

Michael H. Skinner, MD; Andrew Futterman, PhD; Diane Morrissette, PhD; Larry W. Thompson, PhD; Brian B. Hoffman, MD; and Terrence F. Blaschke, MD
[+] Article and Author Information

Affiliations: From Stanford University Medical Center, Stanford, California; and Veterans Affairs Medical Center, Palo Alto, California.

Grant Support: By NIH grant AG05627 and a grant from the American Federation for Aging Research. Dr. Skinner was supported by a Substance Abuse Fellowship through the Veterans Affairs Hospital, Palo Alto, California.

Requests for Reprints: Michael H. Skinner, MD, Division of Clinical Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78284-6205.

Current Author Addresses: Dr. Skinner: Division of Clinical Pharmacology, University of Texas Health Science Center, San Antonio, TX 78284-6205.

Dr. Futterman: Department of Psychology, College of the Holy Cross, Worcester, MA 01610.

Dr. Morrissette: Department of Molecular and Cellular Physiology, Stanford University Medical Center, Stanford, CA 94305.

Drs. Thompson and Blaschke: Department of Medicine, Stanford University Medical Center, Stanford, CA 94305.

Dr. Hoffman: Geriatric Research and Education Center, Veterans Affairs Medical Center, 3801 Miranda Avenue, Palo Alto, CA 94304.


Ann Intern Med. 1992;116(8):615-623. doi:10.7326/0003-4819-116-8-615
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Objective: To compare the effects of atenolol and nifedipine on mood and cognitive function in elderly hypertensive patients.

Design: Randomized, double-blind, crossover trial.

Patients: Thirty-one elderly volunteers (7 women and 24 men) 60 to 81 years of age with mild to moderate hypertension were recruited from the general community and a Veterans Affairs hospital hypertension clinic. Six volunteers withdrew at early phases of the study for reasons unrelated to adverse drug effects.

Interventions: Participants had 2 weeks of placebo, 2 to 6 weeks of titration with atenolol or nifedipine, and 4 weeks of treatment followed by similar periods with the other drug.

Measurements: Psychometric tests designed to assess mood and cognitive function.

Results: In the group first treated with nifedipine, the summed recall score on the Buschke selective reminding test (a test of verbal learning and memory) decreased by 9.3 words (95% Cl, 2.8 to 15.6 words), or 9%, during nifedipine treatment compared with placebo (P = 0.031). The group first treated with atenolol showed no improvement in summed recall scores when results seen during atenolol therapy and placebo administration were compared (P = 0.10); however, this group had an improvement of 16.1 words (Cl, 5.6 to 26.5 words), or of 16%, when the atenolol score was compared with the nifedipine score (P = 0.026). In the group first treated with nifedipine, 6 of 11 patients (55%) showed a decrease of 5 words or more during nifedipine therapy compared with placebo, whereas only 1 of the 14 patients (7%) in the group first treated with atenolol showed a similar decrease (P < 0.01). On the digit symbol test (a psychomotor test), patients treated first with atenolol tended to improve, whereas patients treated first with nifedipine tended to decline. The difference between nifedipine and atenolol, in terms of the change from the score seen during placebo, was 4.3 codings (Cl, 0.7 to 7.9 codings) or 10% (P = 0.043). No statistically significant differences were seen between nifedipine and atenolol therapy regarding the other measures of psychomotor ability, sustained attention, motor performance, verbal fluency, or abstract reasoning, and no effects of either drug on mood or PsychopathologicPsychopathologic symptoms were noted.

Conclusions: Although atenolol and nifedipine are generally free of gross effects on cognition or mood, nifedipine may subtly impair learning and memory in some elderly hypertensive patients.

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