Raloxifene exposure enhances brain activation during memory performance in healthy elderly males; its possible relevance to behavior

Goekoop, Rutger; Duschek, Erik J J; Knol, Dirk L.; Barkhof, Frederik; Netelenbos, Coen; Scheltens, Philip; Rombouts, Serge A.R.B.

doi:10.1016/j.neuroimage.2004.11.012

Cited by 33 publications

(21 citation statements)

References 78 publications

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“…Such effects are in line with findings from a large number of studies, suggesting that estrogens have a context-dependent effect on cortical arousal (Morgan et al, 2004;Cahill and Alkire, 2003). Based on the locations of treatment effects, we predicted small effects of raloxifene treatment on working memory performance, executive functions, and verbal skills (Goekoop et al, 2005).…”

Section: Introductionsupporting

confidence: 88%

“…Raloxifene globally enhanced brain activation during face encoding, with the exception of subcortical, medial temporal, and visual structures. This was interpreted as a global effect of raloxifene treatment on cortical arousal, rather than a specific influence on each of the cognitive domains represented by this pattern (Goekoop et al, 2005). Such effects are in line with findings from a large number of studies, suggesting that estrogens have a context-dependent effect on cortical arousal (Morgan et al, 2004;Cahill and Alkire, 2003).…”

Section: Introductionsupporting

confidence: 80%

“…Immediately after face encoding, which involved the presentation of four blocks of unfamiliar faces (24 in total), alternating with blocks of fixation (Goekoop et al, 2005), a recognition task was administered. Total scanning time was 6 min 12 s for the encoding task and 3 min 40 s for the recognition task.…”

Section: Face Recognition Taskmentioning

confidence: 99%

“…Treatment effects on brain function can be mapped to individual brain structures at high spatial resolution (Honey and Bullmore, 2004). The behavioral significance of such effects may be examined either by direct correlation of behavioral measures with such effects (Goekoop et al, 2005), or by examining brain function associated with distinct response types during memory performance (eg correct hits, correct rejections) (Buckner et al, 1998). This allows a detailed analysis of the effects of SERMs on memory function, which may eventually be relevant to the design and development of new SERMs that target specific aspects of memory performance, such as encoding and retrieval processes (Bernardi et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…In a previous fMRI study, we examined effects of raloxifene treatment vs placebo on brain function in healthy elderly males during encoding of new information (human faces) into memory (Goekoop et al, 2005). Raloxifene globally enhanced brain activation during face encoding, with the exception of subcortical, medial temporal, and visual structures.…”

Section: Introductionmentioning

confidence: 99%

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Raloxifene Treatment Enhances Brain Activation during Recognition of Familiar Items: a Pharmacological fMRI Study in Healthy Elderly Males

Goekoop

Barkhof

Duschek

et al. 2005

Neuropsychopharmacol

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Raloxifene is a selective estrogen receptor modulator that may delay the onset of mild cognitive impairment in elderly women. Effects of raloxifene treatment on mental performance in males remain to be investigated. In a previous functional magnetic resonance imaging (fMRI) study, we showed that raloxifene treatment enhanced brain activation in elderly males during encoding of new information (faces) into memory. The current study used fMRI in the same group of subjects to screen for effects of raloxifene treatment on brain function during face recognition. Healthy elderly males (n ¼ 28; mean age 63.6 years, SD 2.4) were scanned at baseline and after 3 months of treatment with either raloxifene 120 mg (n ¼ 14) or placebo (n ¼ 14) in a randomized, double-blind, placebo-controlled study design. Functional data were analyzed in an event-related fashion with respect to correct hits and correct rejections using FSL software. Performance data were analyzed with respect to recognition accuracy, latency, and response bias. Functional effects of treatment were found on brain activation related to correct hits only. When compared to placebo treatment, raloxifene treatment enhanced brain activation in the left posterior parahippocampal area (Z ¼ 3.9) and right inferior prefrontal cortex (Z ¼ 3.5). Recognition accuracy scores remained stable in the raloxifene group, whereas the placebo group showed a small but significant decrease in accuracy scores (p ¼ 0.02). No significant effects were found on response bias or latency. In conclusion, raloxifene treatment affects brain function during memory performance in a way that may reflect increased arousal during initial encoding, with downstream effects on brain function during retrieval of information. Behaviorally, such neurofunctional effects may actively block decreased memory performance as a result of contextdependency. The validity of these predictions can be tested in large-scale clinical trials.

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Section: Introductionsupporting

confidence: 88%

Section: Introductionsupporting

confidence: 80%

Section: Face Recognition Taskmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Raloxifene Treatment Enhances Brain Activation during Recognition of Familiar Items: a Pharmacological fMRI Study in Healthy Elderly Males

Goekoop

Barkhof

Duschek

et al. 2005

Neuropsychopharmacol

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Estrogen Receptor Modulators

Rosales

Gutgesell

Ratia

et al. 2021

Burger's Medicinal Chemistry and Drug Discovery

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The estrogen receptor (ER) has historically played and continues to play a prominent role in drug discovery as a target for medicinal chemists. The first targeted cancer therapy was directed at ERα and the first clinical drug that is a proteolysis targeting small molecule is also an ER ligand used to treat metastatic breast cancer. The last decade has been described as a renaissance in the medicinal chemistry of endocrine therapy, therefore, this article focuses on design of small molecule ERα ligands for treatment of hormone‐dependent breast cancer. As our understanding of the role of ER in resistance to endocrine therapy increases, further opportunities will be presented for medicinal chemists to design therapeutic agents for metastatic disease. Beyond breast cancer, ER, whether nuclear or extranuclear remains largely unexploited as a target for small molecule drug design, which is partly explained by the complexity of the underlying biology and partly by the cooling influence of the initial Women's Health Initiative outcomes on estrogen replacement therapy. Old and new concepts of ligand binding and signal transduction by ER are presented to stimulate the interests of medicinal chemists; accompanied by a catalogue of newer small molecule ligands reported in the literature and their interactions with ER.

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Current awareness in geriatric psychiatry

2005

Int J Geriat Psychiatry

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In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of geriatric psychiatry. Each bibliography is divided into 9 sections: 1 Books, Reviews & Symposia; 2 General; 3 Assessment; 4 Epidemiology; 5 Therapy; 6 Care; 7 Dementia; 8 Depression; 9 Psychology. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted

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Raloxifene exposure enhances brain activation during memory performance in healthy elderly males; its possible relevance to behavior

Cited by 33 publications

References 78 publications

Raloxifene Treatment Enhances Brain Activation during Recognition of Familiar Items: a Pharmacological fMRI Study in Healthy Elderly Males

Raloxifene Treatment Enhances Brain Activation during Recognition of Familiar Items: a Pharmacological fMRI Study in Healthy Elderly Males

Estrogen Receptor Modulators

Current awareness in geriatric psychiatry

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