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Effects of valsartan compared with enalapril on blood pressure and cognitive function in elderly patients with essential hypertension.

OBJECTIVE: This prospective, randomised, open-label, blinded-endpoint study was to compare the effects of the angiotensin II (Ang II) AT1 receptor antagonist valsartan with those of the ACE inhibitor enalapril on blood pressure (BP) and cognitive functions in elderly hypertensive patients. METHODS: One hundred and forty-four patients aged 61-80 years with mild to moderate essential hypertension (DBP > or =95 mmHg and < or =110 mmHg at the end of a 2-week placebo run-in period) were randomly assigned to once daily (o.d.) treatment with valsartan 160 mg ( n=73) or enalapril 20 mg ( n=71) for 16 weeks. The patients were examined every 4 weeks during the study, with pre-dose BP (standard mercury sphygmomanometer, Korotkoff I and V) and heart rate (pulse palpation) being recorded at each visit. Cognitive function was evaluated at the end of the wash-out period and after 16 weeks of active treatment by means of five tests (verbal fluency, the Boston naming test, word list memory, word list recall and word list recognition). RESULTS: Both valsartan and enalapril had a clear antihypertensive effect, but the former led to a slightly greater reduction in SBP/DBP at 16 weeks (18.6+/-4.6/13.7+/-4.0 mmHg vs 15.6+/-5.1/10.9+/-3.9 mmHg; P<0.01). Enalapril did not induce any significant changes in any of the cognitive function test scores; valsartan significantly increased the word list memory score (+11.8%; P<0.05 vs baseline and P<0.01 vs enalapril) and the word list recall score (+18.7%; P<0.05 vs baseline and P<0.01 vs enalapril), but not those of the other tests. CONCLUSION: These findings indicate that, in elderly hypertensive patients, 16 weeks of treatment with valsartan 160 mg o.d. is more effective than enalapril 20 mg o.d. in reducing BP, and (unlike enalapril) improves some of the components of cognitive function, particularly episodic memory.

Aged↗

[Effects of one Chinese herbs on improving cognitive function and memory of Alzheimer's disease mouse models].

OBJECTIVE: To investigate Chinese herbs with the effect on significantly improving the cognitive function and retention of patients with Alzheimer's disease. METHOD: AD mouse models were established by injecting poly-beta-AP25-35 into the cerebral ventricle of mice. The curative effects of traditional Chinese herbs Dangguishaoyaosan, Chaihujialonggumulitang and two herbs (CHP I and CHP II) developed by the authors on improving the memory and cognitive function of AD mouse models were studied by the detection of behavioral and histochemical tests, with piracetam serving as control. RESULT: CHP II has profound curative effects on improving the memory and cognitive function of AD-like animal model. CONCLUSION: The present study indicates that it has a satisfactory prospect to seek new drugs from Chinese herbs to treat AD.

Acorus↗

Executive cognitive functioning in alcohol use disorders.

Executive cognitive functioning (ECF) has been identified as an important determinant in the etiology of alcoholism. ECF represents a "higher-order" cognitive construct involved in the self-regulation of goal-directed behavior. The prefrontal cortex and its subcortical connections represent the primary neurological substrate that subserves ECF. Both alcoholics and individuals at high risk for alcoholism exhibit a mild dysfunction in ECF. However, this deficit appears to be significantly stronger in alcoholics with a comorbid diagnosis of an antisocial personality disorder. Individuals with other disorders that are also highly comorbid with alcoholism, such as attention deficit hyperactivity disorder and conduct disorder, also demonstrate deficits in ECF. As such, compromised ECF may not be specific to alcoholism, but instead, might be a potential underlying etiologic substrate for a number of disorders of behavioral excess-disinhibition. Subsequent to reviewing the literature implicating ECF deficits in alcoholism and comorbid disorders, the authors present a heuristic cognitive-neurobehavioral model of alcoholism implicating the frontostriatal system. Finally, recommendations for the prevention and treatment of alcoholism, based on this model, are discussed.

Alcoholism↗

Cognitive function in relation with bone mass and nutrition: cross-sectional association in postmenopausal women.

BACKGROUND: It has been suggested that bone loss and cognitive decline are co-occurring conditions, possibly due to their relationship with estrogen. Cognitive decline has been associated with various nutritional deficiencies as well. The purpose of this study was to determine if cognitive function is related to bone mineral density of various skeletal sites as well as to various dietary components. METHODS: Cross-sectional study with 97 healthy, Caucasian, postmenopausal women (59.4-85.0 years) enrolled in a larger longitudinal study, investigating the effects of sodium on bone mass. The subjects were divided into two groups based on cognition scores. Group 1 represented lower and Group 2 higher scores on cognitive function. Bone mineral density from the whole body, lumbar spine, femur and forearm were measured with the Lunar DPX-MD instrument. Anthropometry was measured by standard methods. Cognition was assessed using the Mini Mental State Examination. Cumulative (over 2 years) dietary intake from 3-day records was analyzed by Food Processor(R) (ESHA Research, Salem, OR) and cumulative physical activity was assessed using Allied Dunbar National Fitness Survey for older adults. RESULTS: Subjects' cognition scores ranged from 22-30 (normal, 27-30), indicating all subjects had either mild or no cognitive impairment. Multiple Analysis of Covariance adjusted for age, height, weight, physical activity, alcohol, calcium, sodium and energy intake, showed a statistically significant association between cognition and bone mineral density of all measurable sites (eta2 = 0.21, P < 0.01). However, after Analysis of Covariance follow-up tests and Bonferroni correction, the differences for individual bone sites diminished, though Group 2 had higher adjusted means for all sites except for the femoral neck, Ward's triangle and trochanter. There was a positive significant association between cognition score and carbohydrate and potassium intake (eta2 = 0.07, P = 0.050). Group 2 did have a significantly higher potassium intake (P = 0.023). In multiple regression, saturated fat had a significant negative relationship with cognitive function. CONCLUSIONS: It appears mild degree of cognitive impairment may be a marker for lower bone mineral density as well as for a diet lower in carbohydrate and potassium intake, and higher in saturated fat. Consequently, older women with cognitive impairment may benefit of being screened for potential bone loss and poor nutrition.

Journal Article↗

[Effect of olanzapine treatment on cognitive functions in patients with schizophrenia].

AIM: The aim of this study was to assess whether olanzapine treatment results in an improvement of cognitive functions that became impaired by the schizophrenic process. METHOD: The correlation of the intensity of schizophrenic symptoms and duration of the disease with the level of cognitive functions were also examined. The schizophrenic patients were examined in three steps: before beginning of olanzapine treatment, after 6 weeks of treatment, and after approximately 12 months since the beginning of the olanzapine treatment, 36 patients were examined (9 female, 27 male) aged 20-53 (X = 25.4). The following tests were applied: Positive and Negative Syndromes Scale--PANSS, Squire's Memory Questionnaire, sub-scales: Digit span and Similarities of the Wechsler's Intelligence Scale, Long-term memory sub-test of the Choynowski's Memory Scale, Diagnosis of Brain Damages, Clock Completion Test, Decroly's Box. RESULTS: The olanzapine treatment of schizophrenia was characterised by significant antipsychotic efficacy including both positive and negative symptoms. The positive symptoms were associated with the attention range, the planning process context and the immediate memory with the tendency towards loosing remembrance in the process of non-verbal learning. The negative symptoms were associated with concrete conceptual thinking. Improvement of cognitive functions was noted for almost all of the examined functions. The effect of olanzapine therapy in schizophrenic patients may be regarded as personality integrating.

Adult↗

Estrogen and cognitive functioning in men with mild cognitive impairment.

Although men do not experience an abrupt cessation of gonadal hormone production at midlife as do women, levels of testosterone (T) decrease gradually with aging. Because estradiol (E2) arises mainly from the conversion of T in men, the availability of E2 also decreases with increasing age. In randomized clinical trials, E2 replacement therapy has been shown to maintain aspects of cognition in postmenopausal women, specifically with regard to verbal memory. The present prospective, randomized, cross-over trial is being undertaken in order to determine whether E2 will enhance verbal memory in men with Mild Cognitive Impairment (MCI). Men with MCI will randomly receive E2 or placebo for the first 3 mo of treatment and will then be crossed-over to the other treatment for an additional 3 mo. A battery of neuropsychological tests will be administered at pretreatment and, again, following each 3-mo treatment phase. It is hypothesized that elderly men with MCI will perform better on tests of explicit memory when they are being treated with E2 compared to their performance under placebo conditions.

Cognition Disorders↗

Cognitive functioning and symptomatology in chronic schizophrenia.

Chronic schizophrenic patients in a long stay hospital were found to have low levels of intelligence (mean IQ of 80), which was attributed to the effects of substantial intellectual deterioration on below average pre-morbid levels of functioning. Patients with the lowest IQ scores had the least severe positive symptoms but symptomatology was not related to age or extent of intellectual decline. Speed of functioning was relatively more impaired than level of intellectual functioning, with cognitive speed being more affected than motor speed. The severity of negative but not positive symptoms was significantly related to the severity of bradyphrenia (cognitive slowing), a result which would be consistent with the notion of a subcortical pathology in patients with Type II schizophrenia.

Adult↗

Effects of physical activity on cognitive functioning in middle age: evidence from the Whitehall II prospective cohort study.

OBJECTIVES: We examined the association between physical activity and cognitive functioning in middle age. METHODS: Data were derived from a prospective occupational cohort study of 10308 civil servants aged 35-55 years at baseline (phase 1; 1985-1988). Physical activity level, categorized as low, medium, or high, was assessed at phases 1, 3 (1991-1994), and 5 (1997-1999). Cognitive functioning was tested at phase 5, when respondents were 46-68 years old. RESULTS: In both prospective (odds ratio [OR] = 1.65; 95% confidence interval [CI]=1.30, 2.10) and cross-sectional (OR=1.79; 95% CI=1.38, 2.32) analyses, low levels of physical activity were a risk factor for poor performance on a measure of fluid intelligence. Analyses aimed at assessing cumulative effects (summary of physical activity levels at the 3 time points) showed a graded linear relationship with fluid intelligence, with persistently low levels of physical activity being particularly harmful (OR=2.21; 95% CI=1.37, 3.57). CONCLUSIONS: Low levels of physical activity are a risk factor for cognitive functioning in middle age, fluid intelligence in particular.

Adult↗

Estrogen's impact on cognitive functions in multiple sclerosis.

It has long been suspected that hormonal factors contribute directly and indirectly to the etiology and pathogenesis of multiple sclerosis (MS). The susceptibility of MS is higher in women than in men and women are even more susceptible to hormonal influences when onset occurs at an early or delayed age. Pregnancy has a short-term favorable effect on the course of the disease but there is an increased rate of relapse during the post-partum period. In addition, women often report premenstrual exacerbation of their symptoms with remission during menses. These findings suggest that in women estrogens may exert a stabilizing effect on the clinical manifestations of MS. The role of estrogens is supported also by observations of a higher incidence of cognitive impairment in women than men with MS. A 50 year old woman with a remitting progressive MS experienced profound deterioration in cognitive functions during withdrawal from estrogen therapy which was initiated for the treatment of amenorrhea. Improvement in cognitive functions occurred shortly after she restarted therapy with an estrogen/progesterone preparation and was maintained during long term therapy. Serotonin (5-HT) mechanisms have been implicated in memory functions and estrogens modulate these functions through an interaction with 5-HT2 receptors in the cerebral cortex and limbic system. It is suggested that estrogen withdrawal induces impairment in cognitive functions through dysregulation of 5-HT2 receptor activity and 5-HT neurotransmission. These findings suggest that estrogens have a beneficial influence on cognitive functions in MS patients and that hormonal supplementation might be advised in menopausal and postmenopausal MS patients for the prevention of cognitive deterioration.

Cognition↗

Cognition, functional status, education, and the diagnosis of dementia and mild cognitive impairment in Spanish-speaking elderly.

A group of 314 Spanish-speaking elders were classified in 55 participants with mild to moderate dementia, 74 participants with mild cognitive impairment (MCI), and 185 control participants, according to clinical evaluation derived. Sensitivity, specificity, and detection characteristics of frequently cognitive and functional tests were calculated in comparison with the clinical evaluation: Minimental State Examination, Brief Neuropsychological Test Battery, Short Blessed test, Pfeffer Functional Activities Questionnaire, and Blessed Dementia Scale. Influence of education on sensitivity and specificity values varied along the tests. For all the cognitive and functional measures, a great number of MCI participants who fulfilled Mayo's (Mayo's Clinical School) clinical criteria (Petersen et al., 1999) were misclassified as controls and a few were misclassified as demented. Level of education plays a very important role in both cognitive and functional assessment. The cognitive tests that are commonly used to screen demented patients may fail to detect MCI particularly in high-functioning individuals as well as those who are well educated.

Activities of Daily Living↗

Longitudinal changes in cognitive functioning in adult day care participants.

This study examines longitudinal changes in cognitive functioning over the course of 2 years in participants of adult day cae programs. Cognitive measures included the Brief Cognitive Rating Scale (BCRS) and the Mini-Mental State Examination (MMSE). Longitudinal data were available for five measurement points over 2 years for 82 participants (22 males and 60 females). Overall, results from this study suggest that there were significant cognitive declines on BCRS and MMSE, even after only 1 or 2 years in the study. The rates of impairment over the 2 years for BCRS and MMSE were highly correlated. Within each measure, the individual rates of decline were very heterogenous and were influenced by the presence, type, and prognosis of dementia. Participants with multi-infarct dementia had greater cognitive decline than did those with other types of dementias. Initial cognitive functioning and physician's prognosis of dementia trajectory were also significant predictors of change over time. Results suggest a floor effect in the BCRS.

Activities of Daily Living↗

Specialized cognitive function and reading achievement in hearing-impaired adolescents.

This study evaluated the performance of hearing-impaired adolescents on tests of specialized cognitive functioning and explored the linkage between cognitive profile and reading achievement. Other variables noted were mathematics achievement, speech production, etiology, and age of onset of hearing loss. Subjects were 62 severely-to-profoundly hearing-impaired students between 15 and 20 years of age, 31 "high readers" and 31 "low readers." Results indicated that, for this sample, cognitive function was below average for the verbal and sequential skills associated with the left hemisphere but above average for the "visuospatial" skills associated with the right hemisphere. Reading performance proved to be highly correlated with cognitive profile, as did mathematics performance and, to a lesser extent, speech and age of onset. Ramifications for instruction are discussed--in particular, development of strategies for using the right hemispheric cognitive strengths, as identified in this sample, to help overcome the deficits in "verbosequential" processing and reading achievement traditionally associated with hearing-impaired students.

Achievement↗

Cognitive function in myotonic dystrophy: a follow-up study.

Intellectual and cognitive function were studied in 35 patients with myotonic dystrophy (DM). All 5 patients with the congenital form showed moderate or mild mental retardation. The 30 adult-onset patients had normal intelligence and memory quotients. In this adult-onset group no differences in cognitive function were observed either with respect to sex or physical disability. The sex of the affected parent, mother vs. father, was also without effect in this group. A follow-up study was performed in 16 patients with a mean test interval of 12 years. There was no severe cognitive impairment over this time span or a significant correlation between the progression of physical and cognitive dysfunction.

Adolescent↗

The relationship of subcortical MRI hyperintensities and brain volume to cognitive function in vascular dementia.

The relationship between MRI findings (i.e., subcortical hyperintensities; SH, whole brain volume) and the cognitive dysfunction of vascular dementia (VaD) was examined. Participants included 24 persons that met NINDS-AIREN criteria for VaD (MMSE = 19.9 +/- 4.2) and underwent comprehensive neuropsychological assessment and MRI brain imaging. The volume of subcortical hyperintensities (SH) was strongly associated with executive-psychomotor performance, but not with performance across other cognitive domains or global cognitive functional level. Conversely, WBV was strongly associated with global cognitive functioning and performance across most cognitive domains (memory, language, visual integration), but not with executive-psychomotor functioning. The failure of SH to account for either the global dementia evident in these VaD patients or impairments across most cognitive domains suggests that deep subcortical white matter disease may only indirectly contribute to the global cognitive dysfunction of VaD. That WBV emerged as a stronger correlate of dementia raises further questions regarding the cerebral mechanisms that contribute to the development of VaD.

Aged↗

Regular use of nonsteroidal anti-inflammatory drugs and cognitive function in aging women.

OBJECTIVE: To examine the relationship of nonsteroidal anti-inflammatory drug (NSAID) use and cognitive decline in young-old women. METHODS: The authors prospectively studied 16,128 Nurses' Health Study participants, aged 70 to 81 years at baseline, who provided information on NSAID use and potential confounders in biennial questionnaires from 1976 through 1998. From 1995 through 2001, we administered, by telephone, six tests of cognitive function, including the Telephone Interview of Cognitive Status (TICS). Second interviews were begun 2 years later and completed on 13,255 women to date. The authors used multiple logistic regression to estimate relative risks (RR) of low baseline scores (defined as the bottom 10%) and substantial decline (worst 10%). RESULTS: Compared to never users, the RR was 0.75 (95% CI 0.59, 0.96) for a low baseline TICS score with current aspirin use of 15+ years duration, and 0.79 (95% CI 0.62, 1.02) for current use of NSAID (primarily ibuprofen) lasting 8+ years. Results for aspirin users were weaker on other tests, but long-term ibuprofen users had a RR of 0.75 (95% CI 0.56, 1.00) for a low baseline global score (combination of all six tests). The RR for substantial global cognitive decline was 0.93 (95% CI 0.68, 1.26) with long-term aspirin use, and 0.77 (95% CI 0.57, 1.05) with long-term ibuprofen use. CONCLUSIONS: In these young-old women, current, long-term NSAID users, especially of nonaspirin agents, showed reduced odds of low cognitive function and possibly lower rates of substantial cognitive decline over 2 years. Continued follow-up will help determine if associations differ at older ages.

Acetaminophen↗

Adjuvant breast cancer treatment and cognitive function: current knowledge and research directions.

Evidence is mounting that potentially curative systemic adjuvant therapy for early-stage breast cancer may result in cognitive impairment. Five published studies have investigated cognitive function in this setting, and the consistent results of all five studies suggest an adverse effect of adjuvant chemotherapy. These studies are reviewed with particular attention to their methodologic limitations. For example, all five studies used cross-sectional designs, none controlled for possible confounding hormonal factors, and three examined patients who had not received a uniform chemotherapy regimen. The potential roles of chemotherapy-induced menopause and of adjuvant hormonal therapy in cognitive impairment are also discussed. Priorities for future research include confirmation of an effect of adjuvant chemotherapy in a study with a longitudinal design, closer examination of the potential contribution of hormonal factors, and similar studies on the effect of adjuvant therapy on cognitive function in other cancer types. If an effect of systemic adjuvant therapy on cognitive function is confirmed, such an effect will have implications for informed consent. It may also result in incorporation of objective measures of cognition in clinical trials of adjuvant therapy and in the investigation of preventive interventions that might minimize the impact of cognitive dysfunction after cancer treatment.

Antineoplastic Agents, Hormonal↗

The relationship between impaired glucose tolerance, type 2 diabetes, and cognitive function.

The present review integrates findings of published studies that have evaluated the cognitive function of treated and untreated type 2 diabetic patients and provides a detailed overview of the neuropsychological assessments conducted. Cognitive deficits are observed in older people with glucose intolerance or untreated diabetes but these deficits appear to be attenuated by treatments that improve glycemic control. Cognitive decrements in treated type 2 diabetic patients are most consistently observed on measures of verbal memory (35% of the measures) and processing speed (45% of the measures) while preserved function is observed on measures of visuospatial, attention, semantic and language function. Some studies suggest that deficits in cognitive functions are associated with poorer glycemic control. A number of other factors, such as depression, cardiovascular and cerebrovascular disease, increase these deficits. We conclude that, in diabetic patients who achieve and maintain good glycemic control, type 2 diabetes only has a small impact on cognitive functions before the age of 70 years. However, early onset of type 2 diabetes, poor glycemic control and the presence of micro- and macrovascular disease may interact to produce early cognitive deficits. In older adults (70 years and over), diabetes likely interacts with other dementing processes such as vascular disease and Alzheimer's disease to hasten cognitive decline.

Cognition↗

Cognitive functioning and posttraumatic stress disorder.

OBJECTIVE: The authors examined the association of cognitive impairment with posttraumatic stress disorder (PTSD) and other psychiatric diagnoses known to affect cognitive functioning. METHOD: The results of standardized neuropsychological tests were compared in four groups of Vietnam veterans: veterans with both a lifetime history of PTSD and a current diagnosis of depression, anxiety, or substance abuse; veterans with only a PTSD diagnosis; veterans with only a current diagnosis of depression, anxiety, or substance abuse; and veterans with none of these diagnoses. RESULTS: Veterans with both PTSD and concurrent diagnoses. exhibited more impairment in cognitive functioning than did veterans without these diagnoses. CONCLUSIONS: Cognitive deficits seen among persons diagnosed with PTSD may be associated with their concomitant diagnoses.

Adult↗