Association of raloxifene and tamoxifen therapy with cognitive performance, odds of mild cognitive impairment, and brain MRI markers of neurodegeneration

Abstract

The aim of this cross‐sectional study was to examine whether a history of selective estrogen receptor modifiers (SERMs), tamoxifen and raloxifene, use was associated with cognitive performance, odds of mild cognitive impairment (MCI), or magnetic resonance imaging (MRI) markers of neurodegeneration associated with Alzheimer's disease. We included women with prior history of breast cancer or no prior history of any cancer at enrollment in the Mayo Clinic Study of Aging (MCSA). This information was abstracted using the Rochester Epidemiology Project medical‐linkage system. Logistic regression was used to examine associations of SERMs with odds of MCI. Linear regression models were used to examine associations of SERMs with cognitive z‐scores (Memory, Executive Function, Language, Visuospatial Skills, Global Cognition), and MRI markers. Among 2840 women aged 50 and older in the MCSA, 151 had a history of breast cancer, and 42 (28%) of these had a history of tamoxifen treatment. A total of 2235 women had no prior history of any cancer, and 76 (3%) of these had a history of raloxifene use. No significant associations between tamoxifen use and cognition, or odds of MCI were observed among women with a history of breast cancer after adjusting for confounders. Similarly, raloxifene use was not significantly associated with cognition, or odds of MCI in women without a history of cancer after adjusting for confounders. We did not find significant associations between the use of either SERM and MRI markers. Use of tamoxifen or raloxifene was not significantly associated with cognition in postmenopausal women.

Hormonal Therapies in Multiple Sclerosis: a Review of Clinical Data

“…Among these SERMs, tamoxifen, commonly used for adjuvant therapy for early breast cancer treatment, is able to cross the blood–brain barrier, and with its well-documented safety profile, has been of interest for clinical use in remyelination. However, studies on cognition and tamoxifen in the non-MS population have shown inconsistent results; this heterogeneity may be partially attributed to differing age groups, bucketing of hormonal therapies, and uses of non-breast cancer controls vs. breast cancer controls [ 65 •]. Some studies indicate associations with tamoxifen and impaired verbal learning and memory [ 66 ] and higher risk of Alzheimer’s disease [ 67 ], while others, including a large retrospective cohort study of 57,843 women aged 45 to 90 with breast cancer, reported lower risk of Alzheimer’s disease and dementia after tamoxifen use [ 68 ].…”

“…Some studies indicate associations with tamoxifen and impaired verbal learning and memory [ 66 ] and higher risk of Alzheimer’s disease [ 67 ], while others, including a large retrospective cohort study of 57,843 women aged 45 to 90 with breast cancer, reported lower risk of Alzheimer’s disease and dementia after tamoxifen use [ 68 ]. Yet, others show no association between tamoxifen and cognition [ 65 •].…”

Neuroprotective Potential of Raloxifene via G-Protein-Coupled Estrogen Receptors in Aβ-Oligomer-Induced Neuronal Injury

“…However, there are scattered reports from retrospective studies regarding the oral administration of raloxifene and its impact on cognitive function. Some studies suggest that it preserves cognitive function [ 16 ], while others indicate that it has no effect [ 17 ]. Recently, large-scale clinical trials were conducted in patients with mild cognitive impairment and AD, and the results demonstrated that raloxifene was not effective in preventing the onset of AD [ 18 ].…”