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Published on: August 23, 2024
Tamoxifen improves cholinergically modulated cognitive performance in postmenopausal women
Paul Newhouse1, Kimberly Albert, Robert Astur
11] Vanderbilt Center for Cognitive Medicine, Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN, USA [2] Clinical Neuroscience Research Unit, Department of Psychiatry, University of Vermont College of Medicine, Burlington, VT, USA.
Summary
Tamoxifen (TMX) may improve cognitive function in older women by enhancing estrogen-like effects in the brain. This study found TMX attenuated drug-induced memory and spatial navigation impairments.
Area of Science:
- Neuroscience
- Pharmacology
- Gerontology
Background:
- Tamoxifen (TMX) is a selective estrogen receptor modulator used for breast cancer treatment.
- Its effects on cognitive function and brain activity are not well understood.
- Estrogen plays a role in cognitive processes, particularly memory.
Purpose of the Study:
- To investigate the impact of Tamoxifen (TMX) on cognitive performance in older women.
- To explore TMX's effects in a model of anticholinergic drug-induced cognitive dysfunction.
- To determine if TMX exhibits estrogen-like agonist activity in the human brain.
Main Methods:
- A double-blind, placebo-controlled, crossover study involving 21 postmenopausal women.
- Participants received 20 mg oral TMX or placebo for 3 months, followed by drug challenges with mecamylamine and scopolamine.
- Cognitive performance was assessed using tasks measuring attention, psychomotor function, verbal episodic memory, and spatial navigation.
Main Results:
- TMX significantly attenuated cognitive impairments induced by cholinergic blockade in verbal episodic memory and spatial navigation tasks.
- Effects on attention and psychomotor function were more variable.
- APOE ɛ4+ carriers showed a greater beneficial response to TMX compared to APOE ɛ4- individuals.
Conclusions:
- Tamoxifen (TMX) may act as an estrogen-like agonist in the brain, enhancing cholinergic system activity.
- TMX shows potential for improving hippocampally mediated learning and cognitive function in older women.
- APOE genotype may influence the cognitive benefits of TMX.
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