A review of the etiology, associated comorbidities, and treatment of orthostatic hypotension.

The magnitude of increase in systolic blood pressure in response to the shift from supine to upright posture is considered to reflect the adequacy of orthostatic regulation. Orthostatic integrity is largely maintained by the interaction between the skeletal muscle pump, neurovascular compensation, neurohumoral effects, and cerebral blood flow regulation. Various physiological states and disease conditions may disrupt these mechanisms as seen in vasovagal syncope, dysautonomic orthostatic intolerance, and postural orthostatic tachycardia syndrome. Orthostatic hypotension (OH) and decreased cerebral blood flow are strongly related. Even subclinical OH has been associated to different degrees with impaired cognitive function, decreased effort, reduced motivation, increased hopelessness, and signs of attention-deficit hyperactivity disorder and dementia, diabetes mellitus, and Parkinson disease. Furthermore, subclinical levels of inadequate blood pressure regulation in response to orthostasis have been linked to increased depression and anxiety and intergenerational behavioral sequelae between mother and child. Identifying causes of subclinical and clinical OH is critical in improving quality of life for both children and older adults. A better understanding of the underlying causes responsible for the etiology of OH could lead to a rational design of novel effective therapeutic regimens for the treatment of this condition and associated comorbidities.

A review of orthostatic blood pressure regulation and its association with mood and cognition.

AIMS: This paper will review literature that examines the psychological and neuropsychological correlates of orthostatic blood pressure regulation. RESULTS: The pattern of change in systolic blood pressure in response to the shift from supine to upright posture reflects the adequacy of orthostatic regulation. Orthostatic integrity involves the skeletal muscle pump, neurovascular compensation, neurohumoral effects and cerebral flow regulation. Various physiological states and disease conditions may disrupt these mechanisms. Clinical and subclinical orthostatic hypotension has been associated with impaired cognitive function, decreased effort, reduced motivation and increased hopelessness as well as dementia, diabetes mellitus, and Parkinson's disease. Furthermore, inadequate blood pressure regulation in response to orthostasis has been linked to increased depression and anxiety as well as to intergenerational behavioral sequalae. CONCLUSIONS: Identifying possible causes and consequences of subclinical and clinical OH are critical in improving quality of life for both children and older adults.

A Study of Proton Pump Inhibitors and Other Risk Factors in Warfarin-Associated Gastrointestinal Bleeding.

Background Warfarin users are at increased risk for gastrointestinal bleeding (GIB). History of GIB, stroke, cardiovascular or chronic kidney disease, age greater than 65 years, and drug interaction with proton pump inhibitors (PPI) have previously been identified as risk factors for GIB in warfarin users. We hypothesized that concomitant use of warfarin and PPI would increase the incidence of GIB relative to warfarin use alone. Methods We did a retrospective review of medical records of 626 patients taking warfarin for at least two weeks. Parameters including age, concomitant medication use (non-steroidal anti-inflammatory drugs (NSAID), aspirin, selective serotonin reuptake inhibitors (SSRIs), PPI, and anti-platelet drug), history of GIB, chronic renal failure (CRF), and peptic ulcer disease (PUD) prior to warfarin use were analyzed. Results Variables that increase the likelihood of bleeding in warfarin users included aspirin, PPI, history of PUD, history of previous GIB, CRF, and elevated prothrombin time (PT)/international normalized ratio (INR) values. Concomitant antiplatelet use showed a slight increase in GIB but this was not statistically significant (p=0.082). NSAID use and SSRI use were not associated with a higher risk of GIB among warfarin users. Patients who are on PPI and warfarin simultaneously are more likely to be on acetylsalicylic acid (ASA) or have a history of PUD, GIB, or CRF, all of which are associated with increased incidences of GIB. Conclusions Although concomitant use of warfarin and PPI appears to be associated with an increased incidence of GIB, these patients are more likely to have other risk factors that also increase the risk of a GIB outcome. Therefore, the interaction between PPI and warfarin is clinically insignificant.

Etiology and risk factors for developing orthostatic hypotension.

Orthostatic hypotension (OH) is regarded as a decrease primarily in systolic blood pressure on changing position from supine to erect. Based on clinical criteria, it is characterized by a decrease in systolic pressure of 20 mmHg and diastolic pressure of 10 mmHg within 1 to 3 minutes of standing after being supine. It is most prevalent in, although not limited to, the elderly population and is characterized by a variety of problems, including diminished cognition and disturbed emotion along with gate problems, falls, and brain and cardiovascular difficulties. Although often seen as an age-related condition, occurrence of OH is also associated with a number of autonomic nervous system neurodegenerative disorders. Medications may play a direct role in the risk of triggering OH; these drugs include, but are not limited to, agents used in the treatment of hypertension, myocardial ischemia, psychosis and schizophrenia, depression, Alzheimer and Parkinson disease as well as a vaccine approved for the prevention of cervical cancer. Most of these agents increase the risk for triggering OH through varying vasodilative mechanisms or through sympathetic nervous system interruption; for other drugs, no mechanism of action has been identified. These factors should be considered when diagnosing OH and when prescribing remedies for both patients with OH and those without OH; medication's contributions to the severity and/or risk of developing OH could limit their use. However, their effects could be attenuated or even eliminated by modifying drug dosages.

Orthostatic blood pressure regulation predicts classroom effort in children.

The increase in orthostatic systolic blood pressure associated with the shift in posture from lying to standing requires several compensatory mechanisms to ensure adequate cerebral perfusion. Decreased efficiency in the various mechanisms controlling orthostatic blood pressure regulation can result in dizziness, lightheadedness, and syncope. The degree of effectiveness of orthostatic systolic blood pressure regulation (OBPR) serves as a marker for a variety of problems including fatigue, depression, anxiety, reduced attention, impulsive behavior and reduced volition. In normal children, an insufficient increase in systolic blood pressure in response to upright posture is predictive of mild cognitive and affective problems. The present study examined orthostatic systolic blood pressure regulation in relation to yearlong teachers' evaluations of academic grades and effort in 7-11 year old children. Poorer systolic blood pressure regulation in response to orthostasis was associated with reduced levels of classroom effort, while academic grades were spared. Converging evidence from clinical as well as experimental studies suggests that the linkage between (OBPR) and effort may be partially mediated by sympathetic dysfunction, altered release of neurotransmitters, or reduced cerebral blood flow.

Parents matter: intergenerational influences of diabetes mellitus on glycemic control and morbidity in older type 2 diabetic males.

In a cross-sectional study, the effects of disease duration of type 2 diabetes mellitus (DM) were examined along with parent history of DM on disease-related outcome variables. Specifically, the moderating role of parent history of DM on outcome variables was examined. Participants were 53 male veterans with DM. Chart reviews and self-reports were examined. Results showed that in those with a positive parent history of DM, hopelessness increased with diabetes duration. In the negative parent history group, glycemic control worsened with disease duration. These findings suggest parent history of DM should be considered in designing interventions to facilitate coping with type 2 diabetes.

Blood glucose levels before and after cognitive testing in diabetes mellitus.

The primary indices of diabetes mellitus (DM), including hemoglobin A1c (HbA1c) and fasting glucose, appear to be only moderately predictive of the cognitive impairments exhibited by patients with DM. There is evidence that in DM the ability to utilize glucose is compromised and the authors hypothesized that this difficulty might be relevant to the study of cognitive function in DM. Thus, the authors examined the relationship between cognitive performance and changes in peripheral glucose from the start to the conclusion of cognitive testing. Individuals who showed decreased glucose levels from the start to the conclusion of cognitive testing performed significantly better than those exhibiting moderate to slight increases in glucose levels from the start to the conclusion of testing. Apparently, the putative utilization of blood glucose rather than the glucose levels prior to or following a cognitive challenge is associated with better cognitive performance primarily on more complex cognitive tests. This brief and inexpensive test of changes in glucose levels has potential clinical implications for assessing cognitive status in DM.

Light to moderate alcohol drinking is associated with higher cognitive function in males with type 2 diabetes.

This study examined cognitive function in males with type 2 diabetes who drank light to moderate levels of alcohol in comparison to abstainers. Patients who abstained from alcohol use (Abstainer; N = 99) were compared to patients who were current drinkers (Drinker; N = 20) with respect to demographic, clinical, and cognitive variables. There were no significant differences between the Drinker and Abstainer groups in demographic and general clinical variables (p values > .05). After controlling for various potential confounding variables including age, education level, number of years diagnosed with diabetes, hemoglobin A1c (HbA1c), hypertension status, and depression, multivariate analysis of covariance (MANCOVA) showed that the Drinker group performed significantly better than the Abstainer group, specifically on three of five cognitive tests - Digit Span Backward, Digit Symbol, and Trail Making B (p values < .05). Our findings suggest that light to moderate alcohol consumption, up to two drinks per day, is associated with relatively higher cognitive function in males with type 2 diabetes.

Race moderates age-related cognitive decline in type 2 diabetes.

The age-related rate of cognitive decline in patients with diabetes mellitus has received relatively little attention. In this cross-sectional study, Caucasian (N = 145) and African American (N = 25) males with diabetes mellitus were recruited to examine age-related changes in cognitive performance. It is known that African Americans with diabetes mellitus are at increased risk for more frequent and more severe diabetes-related complications. It was hypothesized that such complications may accelerate age-related cognitive decline in African Americans. Three timed tests varying in complexity assessed attention, mental flexibility, and learning. Advancing age was uniformly associated with decreasing cognitive performance but only on more complex tasks did race moderate this relationship. A steeper age-related decline was observed in African Americans on more complex cognitive tests. Diabetes may be an accelerated form of aging that impacts cognition and race appears to differentially moderate this relationship.

Improving glycemic control: the role of leisure activities and intrinsic motivation in older type 2 diabetic men.

Greater frequency of involvement with sedentary leisure activities may be associated with better disease outcomes. In this study, the frequency of engagement in sedentary leisure activities served as a construct employed to reflect the possible association between motivation and adherence with diabetic regimen. Up to a point, the higher frequency of leisure behaviors correlated with improved glycemic control and triglyceride levels in older type 2 diabetic male veterans (N = 49). Moreover, as the number of comorbidities increased, the positive association between the frequency of leisure behavior and long-term glucose control grew even stronger. Possibly, individuals with more comorbidities, who nevertheless have the resources to engage in a greater number of leisure activities, are also predisposed to adhere more effectively to medical regimen as reflected in more positive biomedical markers. Especially, those with more advanced disease-related complications benefit more from leisure activities in glycemic control.

Non-CNS pathogenic origin of Parkinson's disease.

The gut with its variety of microbiota may serve as an etiological origin of diseases. Gut microbes may also play a role in the pathogenesis of diseases beyond their simple nutritional maintenance and support. For example, gut protein aggregation, possibly aided by microbes as well as nasal influences, might be linked to disease that may move to the brain through the vagus nerve. To this end, Braak has offered a "dual-hit" hypothesis that proposes a novel etiology for Parkinson's disease (PD). The hypothesis places the initial origin of the disease in the nose and the gastrointestinal tract (GI) after infection by an unknown pathogen that could aggregate in the gut and then eventually spread to the brain via the autonomic plexuses. Gut health functioning, therefore, may affect brain status and behavior. A protein known as alpha-synuclein accumulates in brains of people with Parkinson's disease that is also present in the GI before the onset of motor symptoms. Therefore, the stomach, previously thought to be a stable mechanism throughout life, might explain some etiological origins of disease. Finally, the vagus nerve of the autonomic system that extends from the brain to the abdomen and exercises both sympathetic and parasympathetic roles might be associated with PD diagnosis along with Lewy body influences.

Effects of choice on performance in two cultures.

Research in Japan and the United States has demonstrated that learning and memory may be improved when individuals are permitted to choose materials to be learned. In Japanese studies, the effects appear to be limited to the specific materials actually chosen, whereas in the United States, choice enhances recall of chosen as well as other materials that are later assigned. In the United States, personal choice has been hypothesized to affect both the learner's relationship to the chosen materials as well as motivation; in Japan personal choice affects the relationship between the learner and the chosen materials. Apparently the consequences of choice may vary in these cultures.

Personal control and disordered eating in female adolescents with type 1 diabetes.

OBJECTIVE: The onset and subsequent management of diabetes can challenge one's sense of control. Sense of control can also be affected by the biological changes accompanying normal pubertal development. The negative impact on one's sense of control may be further exacerbated when both events (i.e., diabetes and puberty) occur in relatively close temporal proximity. RESEARCH DESIGN AND METHODS: This study examined the relationship between sense of control and disordered eating and glycemic control in 45 female adolescents with type 1 diabetes. RESULTS: A lower sense of overall control and a lower sense of bodily control were both directly related to more severe eating-disordered symptoms. However, a lower sense of overall control and lower bodily control were related to poorer metabolic control primarily when the diagnosis of diabetes occurred closer to the onset of puberty. CONCLUSIONS: Clinicians should assess and monitor perceptions of control and also consider the temporal proximity of disease onset and onset of puberty when managing type 1 diabetes in female adolescents.

Perception of difficulty and glucose control: Effects on academic performance in youth with type†I†diabetes.

AIM: To investigate whether perceptions of task difficulty on neuropsychological tests predicted academic achievement after controlling for glucose levels and depression. METHODS: Participants were type 1 diabetic adolescents, with a mean age = 12.5 years (23 females and 16 males), seen at a northwest suburban Chicago hospital. The sample population was free of co-morbid clinical health conditions. Subjects completed a three-part neuropsychological battery including the Digit Symbol Task, Trail Making Test, and Controlled Oral Word Association test. Following each task, individuals rated task difficulty and then completed a depression inventory. Performance on these three tests is reflective of neuropsychological status in relation to glucose control. Blood glucose levels were measured immediately prior to and after completing the neuropsychological battery using a glucose meter. HbA1c levels were obtained from medical records. Academic performance was based on self-reported grades in Math, Science, and English. Data was analyzed using multiple regression models to evaluate the associations between academic performance, perception of task difficulty, and glucose control. RESULTS: Perceptions of difficulty on a neuropsychological battery significantly predicted academic performance after accounting for glucose control and depression. Perceptions of difficulty on the neuropsychological tests were inversely correlated with academic performance (r = -0.48), while acute (blood glucose) and long-term glucose levels increased along with perceptions of task difficulty (r = 0.47). Additionally, higher depression scores were associated with poorer academic performance (r = -0.43). With the first regression analysis, perception of difficulty on the neuropsychological tasks contributed to 8% of the variance in academic performance after controlling for peripheral blood glucose and depression. In the second regression analysis, perception of difficulty accounted for 11% of the variance after accounting for academic performance and depression. The final regression analysis indicated that perception of difficulty increased with peripheral blood glucose, contributing to 22% of the variance. Most importantly, after controlling for perceptions of task difficulty, academic performance no longer predicted glucose levels. Finally, subjects who found the cognitive battery difficult were likely to have poor academic grades. CONCLUSION: Perceptions of difficulty on neurological tests exhibited a significant association with academic achievement, indicating that deficits in this skill may lead to academic disadvantage in diabetic patients.

Estrogen replacement therapy, subsyndromal depression, and orthostatic blood pressure regulation.

Although estrogen replacement therapy (ERT) alleviates depressed moods in postmenopausal women, it is not known whether ERT is equally effective in reducing affective and somatic depressive complaints. One of the authors' goals in this study was to examine possible differences between women receiving and not receiving ERT. The authors studied a group of postmenopausal women. Somatic symptoms in the ERT group were significantly lower than in the Non-ERT group. Affective scores were only marginally lower in the ERT group (p = .06). After controlling for affective depression, the advantage of ERT remained significant with respect to somatic levels, but control for somatic levels essentially eliminated the effects of ERT on affective depression values. Second, in response to orthostatic challenge, the change in systolic blood pressure was significantly smaller in the ERT group. Apparently ERT is associated with more effective blood pressure regulation. Thus there are several potential benefits of ERT, despite recent evidence finding several untoward effects of long-term treatment.

Subclinical orthostatic pulse pressure confirms mothers' ratings of ADHD in preschoolers.

Subclinical levels of orthostatic hypotension (OH) have been linked to a variety of emotional and behavioral outcomes across the life span. These connections are not surprising, given the multitude of correlated conditions, including autonomic control, cardiovascular functioning, baroreceptor activity, and dopamine and serotonin. The current study assessed blood pressure regulation in healthy preschool children ages 3-5 (n = 61). The Conner's Parent Rating Scale Revised was used to assess indexes of attention deficit hyperactivity disorder (ADHD). With the difference between standing and supine pulse pressure as the index of orthostatic blood pressure regulation, the results indicated that efficient pulse pressure regulation was significantly correlated with lower ADHD scores. Poorer orthostatic pulse pressure regulation in response to an orthostatic challenge may be a risk for symptoms of ADHD.

Gender differences in orthostatic hypotension.

Orthostatic hypotension is a decrease in systolic blood pressure of more than 20 mm Hg or a decrease in diastolic blood pressure of at least 10 mm Hg, within 3 minutes of changing from a supine to an upright position. The typical clinical presentation of orthostatic hypotension includes dizziness, syncope, blurry vision and loss of balance. Symptoms may be more frequent in women, but the complicating roles played by comorbid factors and the estrogen mechanisms are not well understood. Women have a more active parasympathetic system, higher estrogen levels and a lower center of gravity. Thus, women less effectively compensate for the drop of blood pressure in response to positional change. An understanding of these mechanisms contributing to orthostatic hypotension may improve diagnosis and treatment of the problem.

The negative association of BMI with classroom effort in elementary school children.

This study was designed to evaluate the association between BMI and classroom effort in third to fifth grade, ages seven through 12. Teachers, completely blinded and unaware of the study at the time of their classroom evaluations, provided reports of academic performance and effort. Boys and girls (n = 45), which are members of an ethnically diverse community, participated. In addition to classroom measures, height, weight, and percentage body fat were evaluated. A multiple regression model controlling for ethnicity, gender, and age revealed that increasing BMI scores had little association with academic performance but effort scores decreased significantly as BMI increased. This is the first study to show that elevations in BMI in children are associated with decreasing effort in an academic setting. Thus, BMI associated reductions in effort may result in suboptimal levels of performance in the academic setting as well as in other aspects of life.

Cognition and hopelessness in association with subsyndromal orthostatic hypotension.

BACKGROUND: The move from lying to standing is typically associated with a variety of physiological and neurohumoral changes, most especially a slight increase in systolic blood pressure (SBP). Decreased efficacy of the various mechanisms that control orthostatic blood pressure (BP) regulation may result in lightheadedness, dizziness, syncope, and cerebral hypoperfusion. The lack of effective orthostatic BP regulation is a symptom for various problems, including fatigue, depression, anxiety, and reduced attention. METHODS: This study examined men and women (N = 74) who were aged 30-75 years and asymptomatic for clinical orthostatic hypotension. RESULTS: Relatively poor BP regulation in response to orthostasis was associated with decreased verbal memory, decreased concentration, and higher hopelessness scores. CONCLUSIONS: Individuals who exhibited less effective SBP regulation even to a subsyndromal degree in response to an orthostatic challenge may be at increased risk for cognitive and affective problems. The relationship between orthostatic BP regulation is best described as curvilinear.

Subsyndromal orthostatic blood pressure regulation correlates with motor skills in head start children.

The purpose of this study was to investigate the functional relationship between subsyndromal orthostatic blood pressure regulation and motor skills in 3-5 year old children. It is known that the efficiency of orthostatic blood pressure regulation is affected by a variety of processes, most especially neurohumoral as well as sympathetic nervous system function. Using the DIAL-3 to evaluate gross motor (jump, hop, skip), fine motor (building) and copying abilities, we found a significant curvilinear association between the difference in systolic blood pressure following an orthostatic challenge and the DIAL-3 composite motor skills score. This relationship indicated that up to a point an increase in systolic blood pressure upon standing was associated with the highest composite motor score; further, the association was stronger in females (R(2)=0.12). This study illustrates that in response to an orthostatic challenge, a moderate increase in orthostatic systolic blood pressure serves as a marker for those processes such as dopamine and sympathetic nervous system function that provide the resources for orthostatic blood pressure regulation and cognition in young children. Thus, by identifying individuals with orthostatic systolic dysregulation early, one may attenuate problematic physiological and psychological effects associated with subsyndromal orthostatic blood pressure regulation.