Increased working memory-related brain activity in middle-aged women with cognitive complaints

Dumas, Julie A.; Kutz, Amanda M.; McDonald, Brenna C.; Naylor, Magdalena R.; Pfaff, Ashley C.; Saykin, Andrew J.; Newhouse, Paul

doi:10.1016/j.neurobiolaging.2012.08.013

Cited by 56 publications

(63 citation statements)

References 11 publications

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“…Data showing objective cognitive impairments after menopause are inconsistent (see (Hogervorst and Bandelow, 2010) for a meta-analysis). Dumas, Newhouse, and colleagues have recently examined the cognitive and neural representation of cognitive complaints in postmenopausal women (Dumas et al, 2013). Middle-aged postmenopausal women with subjective cognitive complaints showed increased activation relative to women with no complaints in working memory-related brain regions as working memory load increased during an N-back task.…”

Section: Implications and Discussionmentioning

confidence: 99%

Estrogen–cholinergic interactions: Implications for cognitive aging

Newhouse

Dumas

2015

Hormones and Behavior

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While many studies in humans have investigated the effects of estrogen and hormone therapy on cognition, potential neurobiological correlates of these effects have been less well studied. An important site of action for estrogen in the brain is the cholinergic system. Several decades of research support the critical role of CNS cholinergic systems in cognition in humans, particularly in learning and memory formation and attention. In humans, the cholinergic system has been implicated in many aspects of cognition including the partitioning of attentional resources, working memory, inhibition of irrelevant information, and improved performance on effort-demanding tasks. Studies support the hypothesis that estradiol helps to maintain aspects of attention and verbal and visual memory. Such cognitive domains are exactly those modulated by cholinergic systems and extensive basic and preclinical work over the past several decades has clearly shown that basal forebrain cholinergic systems are dependent on estradiol support for adequate functioning. This paper will review recent human studies from our laboratories and others that have extended preclinical research examining estrogen-cholinergic interactions to humans. Studies examined include estradiol and cholinergic antagonist reversal studies in normal older women, examinations of the neural representations of estrogen-cholinergic interactions using functional brain imaging, and studies of the ability of selective estrogen receptor modulators such as tamoxifen to interact with cholinergic-mediated cognitive performance. We also discuss the implications of these studies for the underlying hypotheses of cholinergic-estrogen interactions and cognitive aging, and indications for prophylactic and therapeutic potential that may exploit these effects.

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Section: Implications and Discussionmentioning

confidence: 99%

Estrogen–cholinergic interactions: Implications for cognitive aging

Newhouse

Dumas

2015

Hormones and Behavior

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“…Twelve, healthy, lean or obese, but non-diabetic women aged 18 – 40 years were recruited (age range: 20–36 years, mean ± SEM = 26.5±1.3 years; body mass index >18<25, n=7, or >30, n=5). Exclusion criteria were similar to our previous studies 5,10,11 .…”

Section: Methodsmentioning

confidence: 99%

Dietary saturated fat and monounsaturated fat have reversible effects on brain function and the secretion of pro-inflammatory cytokines in young women

et al. 2016

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Background Previous literature suggests that a higher ratio of palmitic acid (PA)/oleic acid (OA) in the diet induces inflammation, which may result in deficient brain insulin signaling, and, secondarily, impaired physical activity, sleep efficiency, and cognitive functioning. Objective We hypothesized that lowering the typical dietary PA/OA would affect the activation of relevant brain networks during a working memory task and would also lower secretion of pro-inflammatory cytokines. Design In 12 female subjects participating in a randomized, cross-over trial comparing 3-week high PA diet (HPA) and low PA and a high OA diet (HOA), we evaluated functional magnetic resonance imaging (fMRI) using an N-back test of working memory, cytokine secretion by lipopolysaccharide(LPS)-stimulated peripheral blood mononuclear cells (PBMC), and plasma cytokine concentrations. Results Brain activation during the HPA diet compared to the HOA diet was increased in regions of the basal ganglia including the caudate and putamen (p<0.005). In addition, compared to the HOA diet, during the HPA diet, the plasma concentrations of IL-6 (p= 0.04) and IL-1β (p= 0.05) were higher, and there was a higher secretion of IL-18 (p=0.015) and a trend for higher IL-1β secretion (p=.066) from LPS-stimulated PBMCs. Conclusions The HPA diet resulted in increased brain activation in the basal ganglia compared to the HOA diet as well as increased secretion of pro-inflammatory cytokines. These data provide evidence that short-term (2 week) diet interventions impact brain network activation during a working memory task and that these effects are reversible since the order of the study diets was randomized. These data are consistent with the hypothesis that lowering the dietary PA content via substitution with OA also could affect cognition.

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“…Although severe cognitive deficits notably occur in dementia and neurodegenerative diseases, mild cognitive deficits are also prevalent in otherwise healthy older subjects in both humans and in rodent models (Aenlle et al, 2009;Dumas et al, 2013;Ennaceur et al, 2008;Gautam et al, 2011;Gunstad et al, 2006;Salthouse, 2010). Thus, in the following we focus on the physiology of age-related cognitive changes in otherwise healthy middle-aged subjects as such studies may elucidate early changes in mechanisms of age-related cognitive deficits.…”

Section: Introductionmentioning

confidence: 99%

Reversal of age-associated cognitive deficits is accompanied by increased plasticity-related gene expression after chronic antidepressant administration in middle-aged mice

Abdourahman

Tamm

et al. 2015

Pharmacology Biochemistry and Behavior

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Cognitive decline occurs during healthy aging, even in middle-aged subjects, via mechanisms that could include reduced stem cell proliferation, changed growth factor expression and/or reduced expression of synaptic plasticity genes. Although antidepressants alter these mechanisms in young rodents, their effects in older animals are unclear. In middle-aged mice, we examined the effects of a selective serotonin reuptake inhibitor (fluoxetine) and a multimodal antidepressant (vortioxetine) on cognitive and affective behaviors, brain stem cell proliferation, growth factor and gene expression. Twelve-month-old female C57BL/6 mice exhibited impaired visuospatial memory in the novel object placement (location) task associated with reduced expression of several plasticity-related genes. Chronic treatment with vortioxetine, but not fluoxetine, improved visuospatial memory and reduced depression-like behavior in the forced swim test in middle-aged mice. Vortioxetine, but not fluoxetine, increased hippocampal expression of several neuroplasticity-related genes in middle-aged mice (e.g., Nfkb1, Fos, Fmr1, Camk2a, Arc, Shank1, Nlgn2, and Rab3a). Neither drug reversed the age-associated decrease in stem cell proliferation. Hippocampal growth factor levels were not consistent with behavioral outcomes. Thus, a change in the expression of multiple genes involved in neuronal plasticity by antidepressant treatment was associated with improved cognitive function and a reduction in depression-like behavior in middle-aged mice.

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Increased working memory-related brain activity in middle-aged women with cognitive complaints

Cited by 56 publications

References 11 publications

Estrogen–cholinergic interactions: Implications for cognitive aging

Estrogen–cholinergic interactions: Implications for cognitive aging

Dietary saturated fat and monounsaturated fat have reversible effects on brain function and the secretion of pro-inflammatory cytokines in young women

Reversal of age-associated cognitive deficits is accompanied by increased plasticity-related gene expression after chronic antidepressant administration in middle-aged mice

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