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Association between Kidney Tubular Secretory Clearance with Cognitive Function among Adults with CKD in the Systolic Blood Pressure Intervention Trial.

BACKGROUND: Persons with CKD are disproportionally affected with cognitive impairment, yet the pathophysiology linking the two conditions is unclear. Because kidney tubule secretion is essential for clearance of medications, uremic toxins, and metabolites, we hypothesized that worse tubular secretion would be associated with reduced cognitive function in CKD. METHODS: The Systolic Blood Pressure Intervention Trial tested a systolic blood pressure target <120 mmHg vs. <140 mmHg in hypertensive individuals at high cardiovascular risk. In paired blood and urine specimens from 1,937 participants with eGFR <60 ml/min/1.73m2, we measured 10 endogenous tubule-secreted metabolites and calculated a urine/plasma ratio for each, then averaged these to generate a summary secretion score. We used unadjusted and multivariable-adjusted linear regression and mixed models to evaluate cross-sectional and longitudinal associations of the secretion score with the Montreal Cognitive Assessment, Digit Symbol Coding, and Logical Memory immediate and delayed tests-measured at baseline and months 24 and 48 of follow-up. Multivariable Cox regression evaluated associations with incident probable dementia and mild cognitive impairment, adjudicated by prespecified criteria. RESULTS: Mean age was 73 &#xb1; 9 years, 41% were women, mean eGFR was 48.2 &#xb1; 11.4 ml/min/1.73m2, median albuminuria was 14.8 [7.1-48.6] mg/g. Lower secretion score was associated with a 0.06 higher adjusted logical memory delayed score (95% CI: 0.02, 0.11) but not with other cognitive tests at baseline or longitudinal cognitive decline. After a median 4.1 years of follow-up, 118 developed probable dementia and 187 developed mild cognitive impairment. Each 1-SD lower secretion score was associated with lower risk of probable dementia (HR 0.78, 95% CI: 0.63, 0.98) but not mild cognitive impairment. CONCLUSIONS: Among Systolic Blood Pressure Intervention Trial participants with CKD, lower estimated tubular secretion was not associated with worse cognition at baseline or during longitudinal follow-up.

Journal Article↗

A latent growth curve analysis of late-life sensory and cognitive function over 8 years: evidence for specific and common factors underlying change.

Correlations among rates of change in sensory and cognitive functioning in adulthood were evaluated. Measures of Vision, Hearing, Memory, Speed and Verbal ability were obtained in 1992, 1994, and 2000 in the Australian Longitudinal Study of Aging (N = 2,087 at baseline). Data from 1,823 participants who undertook at least 1 clinical assessment were analyzed using latent growth curve models. A significant moderate-sized association between rates of change in Memory and Vision was found. This remained after statistically controlling for the effects of age, gender, education, self-rated health, medical conditions, and depressive symptoms. Rate of change in Hearing was weakly associated with rate of change in Memory. The results support a theory incorporating a major role for unique factors in addition to common factors underlying sensory and cognitive change in old age.

Aged↗

Compliance and cognitive function: a methodological approach to measuring unintentional errors in medication compliance in the elderly. McGill-Calgary Drug Research Team.

This study describes the development of a method for assessing the relationship between cognitive function, comprehension, and compliance with medication. We assessed multiple aspects of cognitive performance, medication planning ability, and medication compliance in a convenience sample of 20 outpatients. Using a test battery that measured mental status, attention/concentration, memory function, and motor strength and dexterity, we found that: (1) standard mental status assessment was poorly correlated with memory function; (2) attention/concentration and memory were related to medication planning accuracy; (3) motor dexterity and strength were related to the ability to access medications; and (4) visual perception and memory were the skills most strongly correlated with medication compliance. Findings suggest that aspects of attention/concentration, visual and verbal memory, and motor function which are untapped by simple mental status assessment are related to medication access, planning, and compliance in elderly patients.

Aged↗

The relationship between psychological dimensions of depressive symptoms and cognitive functioning in the elderly - the MEMO-Study.

Aim of this study was to examine the association of symptom dimensions of depressive symptoms and cognitive functioning in the elderly. In a population-based study with 365 participants 65-83 years of age, dimensions of depressive symptoms were assessed with the four subscales of the CES-D-score and standardized cognitive tests assessing attention, memory, cognitive speed, and motor speed were performed. Compared to men, women scored significantly higher on the subscales for depressed affect and somatic complaints. Older participants had a significantly higher score for interpersonal difficulties. Participants with lower education had higher scores on all four psychological dimensions of depressive symptoms than those with high education (only significant for depressive affect). Individuals scoring high on CES-D subscales for depressive affect and somatic complaints had statistically significant (after Bonferroni adjustment) lower scores in attention and motor function in multivariate analyses. No significant associations between the symptom dimensions of positive affect and interpersonal difficulties with any of the cognitive tests were found in univariate and multivariate analyses (after Bonferroni adjustment). Our findings suggest specific patterns in the relationships between symptom dimensions of depressive symptoms and cognitive dysfunction in the general elderly population. This novel approach might be useful in addressing the heterogeneity of cognitive impairment in depression and in predicting cognitive outcome in depression.

Age Factors↗

Cyclic estrogen replacement improves cognitive function in aged ovariectomized rhesus monkeys.

Among the identified risks and benefits of hormone-replacement therapy, the effects of treatment on cognitive function in postmenopausal women have proved difficult to define. Here we conducted a controlled, prospective analysis in a nonhuman primate model to test whether surgical menopause and estrogen replacement influence the cognitive outcome of normal aging. Sixteen aged rhesus monkeys were ovariectomized, and throughout the course of subsequent neuropsychological assessment, half received a regimen of low-dose, cyclic estradiol replacement. Hormone treatment substantially reversed the marked age-related impairment vehicle-injected monkeys exhibited on a delayed response test of spatial working memory. Modest improvement was also observed on a delayed nonmatching-to-sample recognition memory task. In contrast, ovariectomy exacerbated age-related deficits in object discrimination learning; the magnitude of this effect was equivalent among vehicle- and estrogen-treated monkeys. Together, these results demonstrate that ovarian hormone status can broadly influence normal cognitive aging in monkeys, affecting capacities mediated by multiple brain regions, including the prefrontal cortex and the medial temporal lobe memory system. The animal model established here should enable progress toward defining the neurobiological mechanisms that mediate the beneficial effects of estrogen on age-related cognitive decline in primates.

Aging↗

Self-reports are not related to objective assessments of cognitive function and sedation in patients with cancer pain admitted to a palliative care unit.

Cancer patients often report complaints of cognitive impairment and sedation. It is not well known if subjective complaints reflect objective assessments of cognitive function (CF) and sedation. We obtained self-reports of sedation and CF from 29 patients admitted to a palliative care unit and receiving morphine treatment. Sedation was reported on a verbal rating scale (VRS) and CF was reported using the EORTC QLQ-C30 health-related quality-of-life questionnaire CF scale. The self-reports were compared with objective assessments of sedation and CF by applying the Observer's Assessment of Alertness/Sedation (OAA/S) scale and Mini Mental State Examination (MMS), respectively. The assessments were repeated for seven patients who were readmitted to the palliative care unit. The patient self-reports of memory, concentration and sedation were dichotomized into noncomplainers and complainers. The percentages of complainers were 54%, 46% and 37% for memory, concentration and sedation, respectively. Patients who complained from difficulties with concentration or memory did not score differently from noncomplainers on objective assessments of CF (MMS score), but had a significantly higher level of fatigue. Patients complaining from sedation did not score differently from noncomplainers on objective assessments of sedation (OAA/S score). We observed no significant correlations between EORTC QLQ-C30 CF scale scores and MMS scores, or between VRS sedation scores and OAA/S scores. The study demonstrates a lack of relationship between patient self-reports and objective methods for assessing sedation and cognitive failure. This finding illustrates the importance of differentiating between observations and patient self-reports. The results also question the validity of patient self-reports for measurements of cognitive failure and sedation.

Adult↗

Decreased corpus callosum size in sickle cell disease: relationship with cerebral infarcts and cognitive functioning.

We assessed midsagittal corpus callosum size in sickle cell disease (SCD) and its relationship to lesion volume, lesion location, and cognitive functioning. Twenty-eight children with SCD and 16 demographic controls completed magnetic resonance imaging (MRI) and neuropsychological testing. Corpus callosum (CC) size was smaller for children with silent infarcts (n = 8) or overt stroke (n = 8) than for those without visible infarcts (n = 12) or control participants. Lesion volume was a robust predictor of IQ and other cognitive scores; total CC size did not typically add explanatory power for these measures. The size of the rostral body of the CC, however, independently predicted measures of distractibility, speeded production, and working memory. Posterior CC size was also decreased among many of the children with SCD, even in the absence of visible infarcts in this region. Brain morphology appears to provide additional information about SCD-related effects on the brain above and beyond visible infarcts.

Anemia, Sickle Cell↗

Correlates of cognitive function in middle-aged adults. Atherosclerosis Risk in Communities (ARIC) Study Investigators.

The Atherosclerosis Risk in Communities Study administered cognitive function tests to more than 14,000 middle-aged adults in 1990-1992. The battery included the Delayed Word Recall test, the Digit Symbol Subtest of the Wechsler Adult Intelligence Scale-Revised, and the Controlled Oral Word Association (Word Fluency) test. Test performance was correlated positively with education level, negatively with age, was better in women than in men, and better in managers/professionals compared with other occupations. After controlling for these factors, race and community, the findings most consistent for both sexes were that Delayed Word Recall was negatively associated with depressive symptoms, diabetes, and fibrinogen level; the Digit Symbol Subtest was associated with marital status, negatively associated with depressive symptoms, smoking status, fibrinogen level, and carotid intima-media thickness, and positively associated with alcohol drinking and FEV1; and the Word Fluency test was positively associated with marital status, alcohol drinking, sports participation, and FEV1. Most of these cross-sectional results were in the predicted direction and have biologic plausibility, but mean differences between extreme categories were small (generally on the order of 0.1 to 0.2 of a standard deviation). Longitudinal study is warranted to evaluate whether small differences in middle-age lead to larger, clinically meaningful deficits with aging.

Age Distribution↗

Type-2 diabetes and cognitive function in a non-demented population.

OBJECTIVES: To study if type-2 (non-insulin-dependent) diabetes mellitus (NIDDM) is associated with cognitive dysfunction independently of clinically diagnosed dementia in an elderly population. MATERIAL AND METHODS: Cognitive function was investigated with a brief neuropsychological test battery in a non-demented elderly population consisting of 183 NIDDM (World Health Organization, 1985) patients and 732 non-diabetic subjects. RESULTS: Patients with NIDDM were impaired in the Trail-Making Test parts A and C, which may be a reflection of mildly affected frontal lobe/executive functions. Women with NIDDM performed better than non-diabetic subjects in the Mini-Mental State Examination. CONCLUSIONS: We conclude that NIDDM per se is not associated with impaired memory in the elderly, and the minor defects observed in tests of frontal lobe/executive functions are unlikely to affect daily living. In the non-demented population aged 69 78 years, NIDDM does not carry a significant risk of cognitive dysfunction, when compared to the non-diabetic subjects.

Activities of Daily Living↗

The influence of both drinking and familial risk statuses on cognitive functioning of social drinkers.

Problem and nonproblem drinking, college student sons of alcoholics were compared to problem and nonproblem drinking college student sons of nonalcoholic fathers with respect to cognitive functioning. Problem drinkers performed more poorly on two of the four cognitive tasks, Group Embedded Figures and Symbol-Digit Paired Associates Learning Task, thus supporting earlier findings of cognitive deficits in problem drinking nonalcoholics. Additionally, sons of alcoholics tended to perform more poorly than sons of nonalcoholics on the Group Embedded Figures Test. Cognitive performance was not predicted by any of four measures of impulsive/antisocial personality and behavior-preadult antisocial behavior, childhood behavior problems, sensation seeking, and the MacAndrew Alcoholism Scale. The findings of the research pointed to the importance of considering both drinking and familial alcoholism risk statuses in studies of the cognitive performance of nonalcoholics. Further implications and limitations of the findings are discussed.

Adolescent↗

Selective impairment of frontal-executive cognitive function in african americans with cardiovascular risk factors.

OBJECTIVES: To determine whether a summary cardiovascular risk score is associated with an increased risk of frontal-executive cognitive impairment. DESIGN: Cross-sectional study. SETTING: Subjects were recruited from senior centers, senior housing complexes, and communities in the Boston metropolitan area. PARTICIPANTS: Forty-three predominantly female elderly African Americans. MEASUREMENTS: Cardiovascular risk factors were assessed during an interview and clinical examination. For each subject, the total number of cardiovascular (CV) risk factors was summed to compute a CV risk score. A battery of neuropsychological tests was administered that examined memory, visuospatial abilities, and frontal-executive functions. Cognitive test scores were transformed into domain-specific (memory, visuospatial, frontal-executive) composite z scores. Cognitive impairment for each composite z score was defined as performance less than the median for the study group. Multivariate logistic regression was used to examine the relationship between the CV risk score and the risk for cognitive impairment in the three cognitive domains of interest. RESULTS: After controlling for age and education, the CV risk score was associated only with frontal-executive cognitive impairment (odds ratio (OR)=2.44, 95% confidence interval (CI)=1.06-5.65). The CV risk score was not associated with the risk of memory (OR=1.30, 95% CI=0.64-2.67) or visuospatial impairment (OR=1.49, 95% CI=0.66-3.36). Greater CV risk scores were associated with an increased likelihood of having frontal-executive cognitive impairment. CONCLUSION: CV risk factors may exert a specific deleterious effect on frontal-executive cognitive abilities as opposed to memory or visuospatial functions. Associated executive dysfunction may compromise the ability of patients with CV risk factors to comply with recommendations for risk reduction.

Aged↗

Cognitive functions among Hong Kong Chinese people with schizophrenia.

Persons with schizophrenia show deficits in a variety of cognitive domains including executive function, attention, memory and language. Similar interest in studying the impact of cognitive deficits on the everyday functioning of people with schizophrenia has been documented. This study examined the cognitive functioning among Hong Kong Chinese schizophrenic patients compared with other patient groups, and its relationship with functional outcome, especially in the social aspect. Results indicated that schizophrenic patients presented with mild cognitive problems compared with neurosurgical and demented patients. Initial support was found in relating cognitive functions, as measured by Neurobehavioral Cognitive Status Examination, with functional outcome as measured by Functional Independence Measures. The implication for community rehabilitation is also discussed.

Aged↗

The contribution of alpha 2-noradrenergic mechanisms of prefrontal cortical cognitive function. Potential significance for attention-deficit hyperactivity disorder.

This article aims to review research in nonhuman primates demonstrating that norepinephrine can enhance the cognitive functioning of the prefrontal cortex through actions at alpha 2 A-adrenergic receptors postjunctional to noradrenergic terminals. As prefrontal cortex cognitive deficits are prominent in several psychiatric disorders, including attention-deficit hyperactivity disorder, these basic findings may have relevance for the development of novel pharmacotherapies.

Adrenergic alpha-Agonists↗

The influence of serum vitamin B12 and folate status on cognitive functioning in very old age.

This study examined the relationship between low levels of serum vitamin B12 and folic acid (FA) and cognitive functioning in very old age. The four subsamples of non-demented persons aged 75-96 years - normal B12/normal FA; low B12/normal FA; normal B12/low FA; and low B12/low FA, were matched for age and education. A battery of cognitive tests was administered including Clock Tests, Block Design, Trail Making Tests (TMT), Digit Span, and tests of verbal fluency. Subjects with low levels of vitamins showed deficits in Block Design, TMT-B, Digit Span Backward, and letter fluency, but not in the remaining tests. In general, the effects of FA exceeded those of B12. This pattern of results was interpreted to mean that elderly persons with low vitamin levels have difficulty when fast and accurate processing of novel information is required, but are quite efficient in utilizing pre-existing knowledge structures.

Aged↗

Cognitive functioning after common whiplash. A controlled follow-up study.

A random sample of 98 patients with common whiplash was examined early after trauma (mean +/- SD, 7.3 +/- 3.9 days) and again 6 months later. Cognitive functioning was assessed in conjunction with complaints, pain intensity, well-being, subjective cognitive impairment, neuroticism, and medication. At 6 months, 67 patients had fully recovered (asymptomatic group), while 31 were still symptomatic (symptomatic group). Symptomatic patients who were older at baseline, had a greater variety of symptoms, higher neck pain intensity, and greater subjective cognitive impairment. At baseline, both groups scored poorly on tests requiring complex attentional processing. All neuropsychological functions improved to normal at 6 months in both groups. This improvement cannot be explained by a practice effect, as shown by the results of normal volunteers. The symptomatic group showed delayed recovery regarding complex attentional functioning, which may be related to adverse effects of medication.

Adult↗

Impact of rapid weight loss on cognitive function in collegiate wrestlers.

PURPOSE: The purpose of this study was to examine the effects of rapid weight loss (RWL) on cognitive function in collegiate wrestlers. METHODS: Wrestlers (N = 14) and controls (N = 15) were college-aged males who were tested at three different times: baseline, RWL, and rehydration. Wrestlers practiced RWL in preparation for competition while controls maintained normal body weight and dietary practices throughout the study. At each test session, blood glucose, hemoglobin (Hgb), hematocrit (Hct), plasma volume (PV), and body weight were measured. Subjects also completed mood and hypoglycemic profiles as well as five short cognitive tests. RESULTS: Two-way ANOVA and post-hoc tests revealed poorer performance for wrestlers than controls in two recall tests as well as greater mood negativity for the wrestlers after RWL. With RWL, between group differences were also evident in hypoglycemic profile, blood glucose, PV, and body weight. All measures returned to near baseline values after rehydration, suggesting that all physiological and cognitive effects associated with RWL were reversible. It is possible that precompetition anxiety may partially explain the results. CONCLUSIONS: RWL in collegiate wrestlers before a competition appears to cause physiological effects that are accompanied by transient mood reduction and impairment of short-term memory. The potential negative impact of this practice on the student-athlete should be considered.

Adolescent↗

Influence of solvent exposure and aging on cognitive functioning: an 18 year follow up of formerly exposed floor layers and their controls.

OBJECTIVES: To extend our knowledge of how exposure to neurotoxic substances during working life affects cognitive functioning in the long term. Does long term occupational exposure to organic solvents lead to aggravated cognitive impairment later in life? METHODS: A follow up was conducted of floor layers exposed to solvents and their unexposed referents (carpenters) 18 years after the baseline assessment. The pattern of cognitive changes in the two groups was compared, with the same 10 neuropsychological tests from the test battery for investigating functional disorders (TUFF) that were used at baseline. The study included 41 floor layers and 40 carpenters. A medical examination focused on health at the present and during the past 18 years. An extensive exposure assessment made in the initial study included questionnaires, interviews, and measurements. Additional exposure during the follow up period was minor, as explored in interviews at follow up. RESULTS: The entire group of floor layers did not deteriorate significantly more over time than did the carpenters. However, among the oldest subjects (>60 years), only floor layers showed decline in visual memory. Moreover, the most highly exposed floor layers deteriorated significantly more than their referents in visual memory and perceptual speed, and they tended to display larger decrements in motor speed. Significant dose effect relations were found; higher cumulative exposure was associated with decrements in visual episodic memory, perceptual speed and attention, and visuospatial skill. CONCLUSIONS: The hypothesis that floor layers would deteriorate more in cognitive performance than their unexposed referents over a period of 18 years was partly supported by the results of this study. The results are consistent with the view that the negative effects of exposure to solvents may interact with the normal aging process, primarily at heavy exposure.

Adhesives↗

A controlled study of the effect of balanced general anaesthesia on cognitive functions in hypertensives on propranolol.

The aim of this study was to observe the effect of general anaesthesia (GA) on multiple dimensions of cognitive functioning in hypertensives on propranolol therapy (group A) in comparison to a control group (group B). Ten subjects in each group were administered a battery of six psychological cognitive tests pre- and post-intervention under GA. Both groups showed a significant decrement in memory scores on the 4th postoperative day which showed signs of recovery on seventh day (P < 0.05 for both groups). The group A patients were further compromised in one of the intelligence test scores (Standard progressive matrices) from the beginning (P < 0.05). Although this intergroup deficit persisted even on the 7th postoperative day (P < 0.05), no added effects of GA on this parameter was observed in group A (P > 0.05). In conclusion, GA induced transient memory deficit in both groups. This should be kept in mind while considering 'street fitness' following general anaesthesia.

Adult↗