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Estrogen use and verbal memory in healthy postmenopausal women.

OBJECTIVE: To assess whether differences in verbal memory might be related to estrogen use in a group of healthy, well-functioning, postmenopausal community-residing women from a broad socioeconomic range. METHODS: Healthy postmenopausal women drawn from the general population were given tests of verbal and spatial memory, language, attention, and general spatial skills. The performance of women taking estrogen was compared to that of women from the same population who were not taking any form of estrogen replacement therapy. RESULTS: There were no differences between the estrogen users and non-users on any sociodemographic variables. However, the scores of women taking estrogen were significantly higher on tests of immediate and delayed paragraph recall compared to the scores of non-users. No differences were apparent on other tests of cognitive functioning, including tests of spatial memory. CONCLUSION: Estrogen appears to have a specific effect on verbal memory skills in healthy postmenopausal women. The clinical relevance of these findings for healthy older women remains to be determined.

Estrogen Replacement Therapy↗

Central nervous effects of leptin and insulin on hippocampal leptin and insulin receptor expression following a learning task in Wistar rats.

Insulin and leptin are well known to be involved in the regulation of food intake and body weight. Recent studies have suggested that both hormones may also affect memory and learning processes. We explored whether the intrahippocampal administration of insulin or leptin improved spatial memory formation in rats following a radial maze task and whether the insulin and leptin receptor expression in different areas of the hippocampus was affected. Animals without a learning task were also investigated in order to differentiate between the influence of spatial learning and hormone application on receptor expression. Spatial memory formation was found unaltered following the different applications. The application of insulin increased the expression of the long form of the leptin receptor in the Ammon's horn and dentate gyrus region of the hippocampus in the learning group only. These data clearly show that learning is a prerequisite for the effect of insulin on leptin receptor expression.

Animals↗

Cognitive impairments in patients with seasonal affective disorder.

Eleven patients with seasonal affective disorder (SAD) and ten controls matched for age, IQ, and education were tested on a number of computerised tests designed to assess attention, memory, and learning. When depressed, patients showed no deficit in attention but were impaired on spatial memory and learning. They were also significantly slower to respond than controls, with a pattern that suggested slowed information processing centrally, rather than simple sensory or motor slowing. On recovery from depression, improvement was seen in most tests, although impairment remained in latency to respond on a test of spatial memory. This continuing impairment correlated with residual depressive symptoms but not with ventricular brain ratio (VBR).

Adult↗

Posttraumatic stress disorder: cerebellar regulation of psychological, interpersonal, and biological responses to trauma?

Alteration in the sense of time is the most commonly reported peritraumatic dissociative symptom. A case report of a trauma victim illustrates the posttraumatic alteration in the sense of time as well as loss of spatial memory. Recent studies of cerebellar function indicate the cerebellum may be critical to both spatial memory and the sense of time. Identifying regulators of psychological, interpersonal, and biological responses to traumatic events is important in advancing our understanding of the effects of trauma. The cerebellum may be part of the initial posttraumatic response.

Adaptation, Psychological↗

Neuropsychological characteristics of children with the 22q11 Deletion Syndrome: a descriptive analysis.

Previous reports of cognitive functioning in children with the 22q11 Deletion Syndrome have reported marked variability in IQ and achievement subtest scores. Studies have begun to explore neuropsychological function in 22q11 DS however results are inconsistent and the profile incomplete. We assessed 40 children ages 5-12 with 22q11 DS. Consistent with past results, visual-spatial memory was significantly lower than verbal memory. Differentially lowered scores were found only in visual attention, working memory and motor function. Contrary with some past results quantitative, verbal ability, and visual spatial memory scores were within 1 SD from the standardization sample mean. Motor behavior, not typically discussed with regard to 22q11 DS school-age children, may be critical to incorporate in neurocognitive studies of children with 22q11 DS. Implications of these findings are considered with regard to past results.

Brain↗

The effects of combined androgen blockade on cognitive function during the first cycle of intermittent androgen suppression in patients with prostate cancer.

PURPOSE: Men with prostate specific antigen (PSA) only relapse of prostate cancer after primary therapy are generally fully functional and asymptomatic with a life expectancy of up to 10 or more years. These patients are often treated with androgen suppression. We evaluate the effects of androgen suppression on cognitive function. MATERIALS AND METHODS: Hormone naïve patients without evidence of metastases with an increasing PSA were treated with intermittent androgen suppression consisting of 9 months of leuprolide and flutamide followed by an off treatment period determined by the increase in PSA. Cognitive function tests were administered at baseline, after 9 months of androgen suppression and after 3 months off treatment. Cognitive tests measured spatial abilities, spatial memory, verbal fluency, verbal memory and selective attention. A total of 19 patients 52 to 76 years old completed the intermittent androgen suppression study along with 15 healthy community dwelling control participants. RESULTS: Combined androgen blockade reduced PSA and testosterone in all patients compared to baseline. Patients did not significantly change on measures of verbal and spatial memory, executive functions or language. Patients declined on a measure of spatial rotation and improved on a measure of verbal memory during treatment which continued during the off treatment period. CONCLUSIONS: Although preliminary, these findings demonstrate that 9 months of combined androgen blockade resulted in a beneficial effect on verbal memory but adversely affected a measure of spatial ability. Intermittent androgen suppression for a period of 9 months in otherwise healthy men with prostate cancer may have beneficial and adverse effects on cognition that are selective.

Aged↗

Effects of spatial and nonspatial cognitive activity on postural stability.

Is postural stability controlled automatically, or is it affected by concurrent cognitive activity? Are the effects influenced by the nature of the cognitive activity required, and do they increase in old age? To address these questions, 70 participants aged 20-79 years were asked to stand as still as possible on a force platform (postural control task) while performing (a) no cognitive task, (b) a spatial memory task, and (c) a nonspatial memory task. The memory tasks were also performed while seated as a comparison condition. Both spatial and nonspatial memory recall declined with increasing age but were unaffected by position (standing vs. seated). Postural stability declined with age; moreover, there was support for an earlier finding that age decline was greatest when performing the spatial memory task. Each recording period was split into two phases which, for the spatial and nonspatial memory tasks, corresponded to encoding and maintaining the stimuli. In comparison with no task, participants were more stable when encoding stimuli (particularly in the spatial task), but they were less stable when maintaining stimuli (particularly in the nonspatial task). The results suggest that postural stability can be affected by cognitive activity in complex ways, depending on the age of participants, the type of cognitive task (spatial vs. nonspatial), and the cognitive processing required (encoding vs. maintenance).

Adult↗

Effects of motor activity on children's intentional and incidental memory for spatial locations.

Kindergartners (means = 57) and third graders (means = 8-7) encountered a large model town in 1 of 3 conditions of motor involvement with the environment: standing, riding, or walking. Half the children in each motor condition were instructed to remember the location of the buildings (international memory), while the remaining children were not given specific memory instructions (incidental memory). Only the kindergartners' accuracy increased as a function of the amount of motor activity. There was no difference between intentional and incidental memory conditions. It was concluded that: (1) Kindergartners depend on motor activity more than third graders to learn about the location of objects in an unfamiliar environment; and (2) the complexity of the spatial task was primarily responsible for equivalent performance in the intentional and incidental memory conditions.

Age Factors↗

Developmental analysis of the Wechsler Memory Scale.

Memory functions commonly decline with age. All dimensions of memory functioning may not change equally with age. Some studies have shown declines in visual-spatial memory tasks, others in remembering stories, and another in learning pairs of associated words. The purpose of this study was to determine which dimensions deteriorate with increasing age. In addition, this study examines the construct validity of the Wechsler Memory Scale (WMS), for which previous reports note two-, three- and four-factor solutions. WMS data from 1264 males and 1141 females at six age intervals, 20-29, 30-39, 40-49, 50-59, 60-69 and 70-79 years, were compared on seven subtests to assess age trends. Visual-spatial memory tasks, remembering stories, and learning pairs of associated words proved more difficult with advanced age. Using theoretical, psychometric and statistical criteria, a one-factor (cluster) solution in both sexes across all age groups shows that the WMS measures only one construct, memory. This was shown by using principal component analyses, hierarchical cluster analyses, and very simple structure.

Adult↗

Effects of spatial and nonspatial cognitive activity on postural stability.

Is postural stability controlled automatically, or is it affected by concurrent cognitive activity? Are the effects influenced by the nature of the cognitive activity required, and do they increase in old age? To address these questions, 70 participants aged 20-79 years were asked to stand as still as possible on a force platform (postural control task) while performing (a) no cognitive task, (b) a spatial memory task, and (c) a nonspatial memory task. The memory tasks were also performed while seated as a comparison condition. Both spatial and nonspatial memory recall declined with increasing age but were unaffected by position (standing vs. seated). Postural stability declined with age; moreover, there was support for an earlier finding that age decline was greatest when performing the spatial memory task. Each recording period was split into two phases which, for the spatial and nonspatial memory tasks, corresponded to encoding and maintaining the stimuli. In comparison with no task, participants were more stable when encoding stimuli (particularly in the spatial task), but they were less stable when maintaining stimuli (particularly in the nonspatial task). The results suggest that postural stability can be affected by cognitive activity in complex ways, depending on the age of participants, the type of cognitive task (spatial vs. nonspatial), and the cognitive processing required (encoding vs. maintenance).

Journal Article↗

Circulating corticosterone alters the rate of neuropathological and behavioral changes induced by trimethyltin in rats.

When trimethyltin (TMT) is administered to rats, the plasma corticosterone concentration rises transiently 3 to 4 days later. We examined whether plasma corticosterone plays a causative role in the TMT-induced impairment of the hippocampus as assessed by pathological and behavioral tests. TMT-administered rats were supplementally treated with either adrenalectomy or metyrapone (twice daily for the first 7 days after TMT) in order to permanently deplete or transiently suppress circulating corticosterone. Loss of pyramidal cells in the CA1 and CA3 fields, mossy fiber sprouting, and impairment of spatial memory were observed after TMT intoxication. Adrenalectomy apparently aggravated both the hippocampal damage and the spatial memory impairment induced by TMT treatment. The TMT+metyrapone treatment groups exhibited a significant reduction in pyramidal cells in both the CA1 and the CA3 regions. However, the neuronal damage in CA1 was significantly different between the TMT and the TMT+metyrapone groups. Metyrapone significantly reduced the TMT-induced damage to pyramidal cells in CA1, but not CA3, and it also abolished mossy fiber sprouting. TMT-induced learning impairment and hyperactivity were alleviated by metyrapone treatment. It is thus concluded that both the high levels of corticosterone induced by TMT and the pathologically low levels of corticosterone induced by adrenalectomy will worsen the consequences of TMT.

Adrenalectomy↗

Intra-septal injections of glucose and glibenclamide attenuate galanin-induced spontaneous alternation performance deficits in the rat.

Injection of the neuroactive peptide galanin into the rat hippocampus and medial septal area impairs spatial memory and cholinergic system activity. Conversely, injection of glucose into these same brain regions enhances spatial memory and cholinergic system activity. Glucose and galanin may both modulate neuronal activity via opposing actions at ATP-sensitive K+ (K-ATP) channels. The experiments described in this report tested the ability of glucose and the direct K-ATP channel blocker glibenclamide to attenuate galanin-induced impairments in spontaneous alternation performance in the rat. Intra-septal injection of galanin (2.5 microgram), 30 min prior to plus-maze spontaneous alternation performance, significantly decreased alternation scores compared to those of rats receiving injections of vehicle solution. Co-injection of glucose (20 nmol) or the K-ATP channel blocker glibenclamide (5 nmol) attenuated the galanin-induced performance deficits. Glibenclamide produced an inverted-U dose-response curve in its interaction with galanin, with doses of 0.5 and 10 nmol having no effect on galanin-induced spontaneous alternation deficits. Drug treatments did not alter motor activity, as measured by overall number of arm entries during spontaneous alternation testing, relative to vehicle injected controls. These findings support the hypothesis that, in the septal region, galanin and glucose act via K-ATP channels to modulate neural function and behavior.

Animals↗

Intervention with environmental enrichment after experimental brain trauma enhances cognitive recovery in male but not female rats.

Environmental enrichment (EE) has been repeatedly shown to affect multiple aspects of brain function, and is known to enhance cognitive recovery after experimental traumatic brain injury (TBI) in males. However, the impact of gender on how EE affects behavioral performance after experimental TBI have not been studied. Male and normally cycling female Sprague-Dawley rats underwent controlled cortical impact injury or sham surgery and then were placed in either a standard or enriched housing environment. Motor function was assessed both pre-injury and for the first 5 days after injury. Spatial memory was assessed beginning 14 days after injury. Placement in an EE after TBI enhanced spatial memory performance in male but not female rats. EE did not impact motor performance in this setting. These findings have gender specific implications for how to approach and evaluate treatments and interventions after TBI.

Animals↗

Subchronic benzo[a]pyrene exposure disrupts APOE4-regulated lipid metabolism to induce Tau hyperphosphorylation and cognitive deficits.

BACKGROUND: Benzo[a]pyrene (B[a]P) is both a carcinogen and a potent neurotoxic pollutant. Despite growing evidence linking B[a]P to neurological dysfunction, the responsible mechanisms have not been elucidated. METHODS: Here, we employed human apolipoprotein E4 (hAPOE4) transgenic mice and APOE knockout (APOE-KO) mice to evaluate the influence of APOE on B[a]P-mediated neurotoxicity. hAPOE4 mice overexpress the human APOE4 isoform, whereas APOE-KO mice lack APOE expression; wild-type C57BL/6 J mice served as controls. Animals received intraperitoneal injections of B[a]P at 0, 2.5, or 6.25 mg/kg on alternate days for 3 months. Spatial memory and learning were examined via Morris Water Maze (MWM). Neuronal morphology, including dendritic branching and spine density in the CA1 region of the hippocampus and dentate gyrus (DG), was assessed using Golgi-Cox staining. Neurofibrillary tangles were detected by silver glycine staining. Tau, phosphorylated Tau (Ser199 and Ser396), and LRP1 were evaluated using Western blot and immunohistochemical analyses. Chromatin immunoprecipitation PCR (ChIP-PCR) was undertaken to examine the regulation of APOE4 expression by the aryl hydrocarbon receptor (AHR). In addition, both untargeted metabolomics and lipidomics analyses were conducted following B[a]P exposure. RESULTS: B[a]P led to pronounced impairments in mouse spatial memory and learning, shown by greater escape latency, less time in the target quadrant, and a decreased number of platform crossings in MWM tests. Structural analyses revealed a significant reduction in dendritic branching within the hippocampal CA1 and DG regions. These neurobehavioral and morphological deficits were most severe in hAPOE4 mice, which displayed greater cognitive impairment and more extensive dendritic loss than B[a]P-treated wild-type mice, indicating that APOE4 amplifies B[a]P-induced neurotoxicity. ChIP assays demonstrated that B[a]P modulates APOE4 transcription through AHR-dependent mechanisms. Additionally, metabolomics and lipidomics analyses revealed widespread B[a]P-induced metabolic remodeling, suggesting that disrupted lipid metabolism and altered neuronal membrane integrity may contribute to the observed neurotoxicity and cognitive dysfunction. CONCLUSION: Collectively, the results indicate that B[a]P-mediated neurotoxicity may be facilitated, at least in part, by APOE4-dependent dysregulation of lipid metabolic pathways.

Animals↗

Evolutionary psychology of spatial representations in the hominidae.

Comparatively little is known about the inherited primate background underlying human cognition, the human cognitive "wild-type." Yet it is possible to trace the evolution of human cognitive abilities and tendencies by contrasting the skills of our nearest cousins, not just chimpanzees, but all the extant great apes, thus showing what we are likely to have inherited from the common ancestor. By looking at human infants early in cognitive development, we can also obtain insights into native cognitive biases in our species. Here, we focus on spatial memory, a central cognitive domain. We show, first, that all nonhuman great apes and 1-year-old human infants exhibit a preference for place over feature strategies for spatial memory. This suggests the common ancestor of all great apes had the same preference. We then examine 3-year-old human children and find that this preference reverses. Thus, the continuity between our species and the other great apes is masked early in human ontogeny. These findings, based on both phylogenetic and ontogenetic contrasts, open up the prospect of a systematic evolutionary psychology resting upon the cladistics of cognitive preferences.

Animals↗

Ovarian hormones and cognition in the aged female rat: I. Long-term, but not short-term, ovariectomy enhances spatial performance.

Although research suggests that ovariectomy (ovx) is detrimental to spatial cognition in young rats, little work has evaluated the cognitive effects of ovx in aged rats. The authors investigated the effects of ovx in aged rats using the water radial-arm maze. In Study 1, young rats and aged rats receiving ovx 1.5 months before testing outperformed aged rats receiving sham surgery or ovx 21 days before testing. In Study 2, young rats and aged rats receiving ovx 2.0 or 6.0 months before testing outperformed aged sham rats. Aged rats exhibited estradiol and elevated progesterone levels comparable to those of young rats. The findings suggest that 1.5-6.0 months, but not 21 days, of ovx improves spatial memory in aged rats. The hypothesis that long-term ovarian hormone loss is detrimental to spatial memory in aged rats was not supported. The authors hypothesize that removal of elevated progesterone levels is related to the ovx-induced cognitive enhancement.

Aging↗

Perirhinal cortex and anterior thalamic lesions: comparative effects on learning and memory.

Three learning and memory tasks were used to compare the effects of neurotoxic anterior thalamic nuclei (ATN) and perirhinal cortex (PRC) lesions in rats. Rats with ATN lesions showed impaired spatial memory in a 12-arm radial maze, whereas rats with PRC lesions showed intact spatial memory, despite the use of minimal pretraining and extensive within-session delays (to 40 rain). PRC, but not ATN, lesions produced impairments on a configural learning task using complex visual-tactile cues in the radial maze. Neither ATN nor PRC lesions consistently affected spontaneous object recognition across extended sample-test delays (to 40 min). These findings confirm the differential involvement of the ATN and PRC in learning and memory.

Animals↗