Kidney disease as a determinant of cognitive decline and dementia

Chronic kidney disease (CKD) has evolved as a possible new determinant of cognitive decline and dementia. This review outlines the presumed pathophysiology of cognitive decline in CKD, which consists of traditional and new vascular risk factors as well as nonvascular risk factors and metabolic and biochemical abnormalities within the central nervous system caused by CKD. The recent major cross-sectional studies and longitudinal studies - including one meta-analysis that mostly suggest an association of cognitive decline and CKD are discussed. Finally, potential therapeutic strategies are presented

The effects of positive and negative retrieval cues on release from retroactive interference

The following study examined the effects of positive and negative retrieval cues within a release from retroactive interference design. Predictions based upon a modification to the cue-overloading hypothesis were evaluated. Subjects were 79 Introductory Psychology students. They learned two lists, each composed of four-legged animals, and were tested for recall of the originally-learned list. Informed subjects were supplied with a retrieval cue for the interpolated list to provide a release from retroactive interference. All subjects were further divided into those who were released by becoming aware during original learning and those who were not. Comparisons revealed a reliable and comparable degree of release for both postinformation groups as well as the uninformed-aware group. Further, released subjects who used semantically-based (positive) retrieval cues exhibited a lower rate of forgetting over the two-week retention interval than those who used episodically-based (negative) cues, though the difference was nonsignificant. Implications for future research within a proposed theoretical framework are discussed

The effects of positive and negative retrieval cues on release from retroactive interference

The following study examined the effects of positive and negative retrieval cues within a release from retroactive interference design. Predictions based upon a modification to the cue-overloading hypothesis were evaluated. Subjects were 79 Introductory Psychology students. They learned two lists, each composed of four-legged animals, and were tested for recall of the originally-learned list. Informed subjects were supplied with a retrieval cue for the interpolated list to provide a release from retroactive interference. All subjects were further divided into those who were released by becoming aware during original learning and those who were not. Comparisons revealed a reliable and comparable degree of release for both postinformation groups as well as the uninformed-aware group. Further, released subjects who used semantically-based (positive) retrieval cues exhibited a lower rate of forgetting over the two-week retention interval than those who used episodically-based (negative) cues, though the difference was nonsignificant. Implications for future research within a proposed theoretical framework are discussed

Coumestrol has neuroprotective effects before and after global cerebral ischemia in female rats

AbstractGlobal ischemia arising during cardiac arrest or cardiac surgery causes highly selective, delayed death of hippocampal CA1 neurons. Phytoestrogens are naturally occurring plant-derived compounds that are present in the human diet and are considered selective estrogen receptor (ER) modulators. The phytoestrogen coumestrol is a potent isoflavonoid, with binding affinities for both ER-α and ER-β that are comparable to those of 17b-estradiol. The present study examined the hypothesis that coumestrol protects hippocampal neurons in ovariectomized rats in a model of cerebral global ischemia. Ovariectomized rats were subjected to global ischemia (10min) or sham surgery and received a single intracerebroventricular or peripheral infusion of 20μg of coumestrol, 20μg of estradiol or vehicle 1h before ischemia or 0h, 3h, 6h or 24h after reperfusion. Estradiol and coumestrol afforded significant neuroprotection in all times of administration, with the exception of estradiol given 24h after the ischemic insult. Animals received icv infusion of the broad-spectrum ER antagonist ICI 182,780 (50μg) or vehicle into the lateral ventricle just before the E2 or coumestrol administration. The ER antagonist abolished estradiol protection, consistent with a role of classical ERs. In contrast, ICI 182,780 effected only partial reversal of the neuroprotective actions of coumestrol, suggesting that other cellular mediators in addition to classical ERs may be important. Additional research is needed to determine the molecular targets mediating the neuroprotective action of coumestrol and the therapeutic potential of this phytoestrogen in the mature nervous system

Predicting dementia in primary care patients with a cardiovascular health metric: a prospective population-based study

Background: Improving cardiovascular health possibly decreases the risk of dementia. Primary care practices offer a suitable setting for monitoring and controlling cardiovascular risk factors in the older population. The purpose of the study is to examine the association of a cardiovascular health metric including six behaviors and blood parameters with the risk of dementia in primary care patients. Methods: Participants (N = 3547) were insurants aged >= 55 of the largest German statutory health insurance company, who were enrolled in a six-year prospective population-based study. Smoking, physical activity, body mass index, blood pressure, total cholesterol, and fasting glucose were assessed by general practitioners at routine examinations. Using recommended cut-offs for each factor, the patients' cardiovascular health was classified as ideal, moderate, or poor. Behaviors and blood parameters sub-scores, as well as a total score, were calculated. Dementia diagnoses were retrieved from health insurance claims data. Results are presented as hazard ratios (HRs) and 95 % confidence intervals (95 % CIs). Results: Over the course of the study 296 new cases of dementia occurred. Adjusted for age, sex, and education, current smoking (HR = 1.77, 95 % CI 1.09-2.85), moderate (1.38, 1.05-1.81) or poor (1.81, 1.32-2.47) levels of physical activity, and poor fasting glucose levels (1.43, 1.02-2.02) were associated with an increased risk of dementia. Body mass index, blood pressure, and cholesterol were not associated with dementia. Separate summary scores for behaviors and blood values, as well as a total score showed no association with dementia. Sensitivity analyses with differently defined endpoints led to similar results. Conclusions: Due to complex relationships of body-mass index and blood pressure with dementia individual components cancelled each other out and rendered the sum-scores meaningless for the prediction of dementia

Acute Administration of Non-Classical Estrogen Receptor Agonists Attenuates Ischemia-Induced Hippocampal Neuron Loss in Middle-Aged Female Rats

Pretreatment with 17beta-estradiol (E2) is profoundly neuroprotective in young animals subjected to focal and global ischemia. However, whether E2 retains its neuroprotective efficacy in aging animals, especially when administered after brain insult, is largely unknown.We examined the neuroprotective effects of E2 and two agonists that bind to non-classical estrogen receptors, G1 and STX, when administered after ischemia in middle-aged rats after prolonged ovarian hormone withdrawal. Eight weeks after ovariectomy, middle-aged female rats underwent 10 minutes of global ischemia by four vessel occlusion. Immediately after reperfusion, animals received a single infusion of either E2 (2.25 microg), G1 (50 microg) or STX (50 microg) into the lateral ventricle (ICV) or a single systemic injection of E2 (100 microg/kg). Surviving pyramidal neurons in the hippocampal CA1 were quantified 1 week later. E2 and both agonists that target non-classical estrogen receptors (G1 and STX) administered ICV at the time of reperfusion provided significant levels of neuroprotection, with 55-60% of CA1 neurons surviving vs 15% survival in controls. A single systemic injection of a pharmacological dose of E2 also rescued approximately 50% of CA1 pyramidal neurons destined to die. To determine if E2 and G1 have similar mechanisms of action in hippocampal neurons, we compared the ability of E2 and G1 to modify CA1 pyramidal neuron responses to excitatory inputs from the Schaffer collaterals recorded in hippocampal slices derived from female rats not subjected to global ischemia. E2 and G1 (10 nM) significantly potentiated pyramidal neuron responses to excitatory inputs when applied to hippocampal slices.These findings suggest (1) that middle-aged female rats retain their responsiveness to E2 even after a long period of hormone withdrawal, (2) that non-classical estrogen receptors may mediate the neuroprotective actions of E2 when given after ischemia, and (3) that the neuroprotective efficacy of estrogens may be related to their modulation of synaptic activity in hippocampal slices