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The effect of improved glycemic control on cognitive functions in the elderly patient with diabetes.

BACKGROUND: A number of studies have found that cognitive function is impaired in elderly patients with non-insulin dependent diabetes mellitus (NIDDM) when compared with age-matched non-diabetic controls. In addition, it has been reported that elderly NIDDM patients who have poor glycemic control have a greater impairment in cognition that elderly NIDDM patients with good control. We conducted the following prospective study to determine if improved glycemic control would result in an improvement in cognitive function in elderly patients with NIDDM: METHODS: Sixteen untreated elderly patients with NIDDM underwent a battery of neuropsychologic tests on two occasions, separated by at least two weeks. They were then started on an oral hypoglycemic agent. After they had been on a stable dose of medication for 6 months the neuropsychologic tests were repeated. RESULTS: Fasting glucose decreased significantly after treatment (before: 13.8 +/- 1.2 mmol/l; after 8.4 +/- 0.4 mmol/l, p < .01). After 6 months of treatment patients had improvement in their scores on the Grooved Pegboard, Trail Making-Part A, Stroop-Word Naming, Cued Recall and Picture Arrangement tests (all p < .05). CONCLUSIONS: Improved glycemic control in the elderly patient with NIDDM may have beneficial effects on selective areas of cognition.

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Alzheimer's neurofibrillary pathology and the spectrum of cognitive function: findings from the Nun Study.

The development of interventions designed to delay the onset of dementia highlights the need to determine the neuropathologic characteristics of individuals whose cognitive function ranges from intact to demented, including those with mild cognitive impairments. We used the Braak method of staging Alzheimer's disease pathology in 130 women ages 76-102 years who were participants in the Nun Study, a longitudinal study of aging and Alzheimer's disease. All participants had complete autopsy data and were free from neuropathologic conditions other than Alzheimer's disease lesions that could affect cognitive function. Findings showed a strong relationship between Braak stage and cognitive state. The presence of memory impairment was associated with more severe Alzheimer's disease pathology and higher incidence of conversion to dementia in the groups classified as having mild or global cognitive impairments. In addition to Braak stage, atrophy of the neocortex was significantly related to the presence of dementia. Our data indicate that Alzheimer's neurofibrillary pathology is one of the neuropathologic substrates of mild cognitive impairments. Additional studies are needed to help explain the variability in neuropathologic findings seen in individuals whose cognitive performance falls between intact function and dementia.

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Cognitive function as a predictor of survival in patients with recurrent malignant glioma.

PURPOSE: To determine the contribution of cognitive function in predicting the survival of patients with recurrent malignant brain tumors. PATIENTS AND METHODS: A total of 80 patients with recurrent glioblastoma multiforme or anaplastic astrocytoma were seen for baseline evaluations before beginning a phase I or phase II clinical trial. Each patient received a battery of nine brief tests measuring cognitive function, ability to perform activities of daily living (ADLs), and quality of life (QOL). Tests were given monthly after treatment was begun. RESULTS: Performance on a test of verbal memory was independently and strongly related to survival after accounting for age, Karnofsky performance status score, histology, and time since diagnosis. Models incorporating three of nine and all nine tests in the battery accounted for significantly more variance in survival than did the clinical variables alone. Measures of QOL and ADLs (bathing, feeding, and so on) were not independently related to survival, although they provide clinical information that is important for patient care. CONCLUSION: These results indicate that a multifaceted assessment of cognition, QOL, and patient function is practical for brain tumor patients in clinical trials and can provide information regarding the relative risks versus benefits of new treatment regimens that supplements the information from the usual clinical variables.

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Relation of blood pressure to cognitive function in the elderly.

Clinical case-control studies of the relation between blood pressure and cognitive function have generally found lower function among hypertensives. Most of these studies were small and incompletely controlled for confounders. Two population-based studies have yielded conflicting results. This study examines cognitive function over the entire range of blood pressure in a defined elderly population. A questionnaire administered in the home to 3,809 persons aged greater than or equal to 65 years in East Boston, Massachusetts, in 1982 and 1983 contained four brief cognitive tests: immediate memory, delayed memory, a mental status questionnaire, and digit span. In linear regression analyses adjusting for age, sex, and education, the direction of the association was not consistent among the tests. An increase in diastolic pressure of 10 mmHg was associated with an increase of 1.0 in percentile scores on the immediate memory test (95% confidence interval (CI) -0.04 to 1.9); with an increase of 1.1 in percentile scores on the delayed memory test (95% CI -0.1 to 2.3); with a decrease of -0.8 in percentile scores on the mental status questionnaire (95% CI -1.8 to 0.2); and with a decrease of -0.9 in percentile scores on the attention test (95% CI -1.5 to -0.2). These results suggest that blood pressure is not a substantial contributor to cognitive status in the elderly.

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Impact of valproate and phenytoin on cognitive function in elderly patients: results of a single-blind randomized comparative study.

Thirty-eight patients (median age 77 years; range 62-88 years) with elderly-onset seizures were entered into a single-blind, randomized study designed to compare the impact of phenytoin (PHT) and valproate (VPA) on cognitive function. A stratified minimization program matched the two groups for age, sex, and seizure type. Attention, concentration, psychomotor speed, and memory were assessed twice before treatment (to minimize practice effects), at 6 weeks and (for patients remaining in the study) at 3 months, 6 months, and 1 year by an extensive battery of psychologic tests. Changes in cognitive function were minor, and some tended toward improvement. Contrary to expectation, there was little difference between PHT and VPA with regard to impact on cognitive function. Frequent noncognitive adverse effects were reported. Thus, we did not replicate the findings of previous literature. We conclude that antiepileptic drug (AED) monotherapy as used in our trial did not produce significant adverse cognitive effects. The choice of AED in the elderly may therefore be more influenced by consideration of other adverse effects.

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[Cognitive function in patients with systemic sclerosis].

Central nervous system involvement is seldom reported in patients with systemic sclerosis (SSc). Cognitive functions were determined in 21 patients with definite SSc and 42 healthy controls. Thyroid function was also measured in order to eliminate the effect of hypothyroidism on cognitive functioning. It was found that the SSc patients with normal thyroid function showed defective long-term and recent memory, learning ability, criticism, perception and visuo-perceptual skills, their simple reaction time was prolonged. Similar but less advanced cognitive defects were shown in the SSc patients with overt or latent hypothyroidism. The obtained results indicate that the central nervous system involvement is more common in patients with SSc than it has been reported earlier.

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Cognitive function in relation to hearing aid use.

Two experiments were conducted to investigate possible relationships between cognitive function and hearing aid use. In Experiment 1, 72 first-time hearing aid users were tested for speech recognition in noise (Hagerman sentence test) with and without hearing aids. Cognitive function was assessed by tests of working memory (reading span test) and verbal information-processing speed. The results indicate that, after controlling for age and hearing loss, significant correlations exist between the measures of cognitive performance and speech recognition in noise, both with and without hearing aids. High cognitive performance was associated with high performance in the speech recognition task. In Experiment 2, 17 first-time hearing aid users with either high or low working-memory capacity tested an experimental hearing aid which processed the sound differently depending on whether or not speech was detected. The results revealed that those with high working-memory capacity were better than those with low capacity at identifying and reporting the specific processing effects of the aid. This may have implications for how reported results should be interpreted in a research context, how a person's rehabilitation needs are formulated, and how hearing aid controls should be supervised. In conclusion, careful attention should be paid to the cognitive status of listeners, as it can have a significant influence on their ability to utilize their hearing aids.

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Drinking practices and cognitive functioning.

The relationships between drinking practices and cognitive functioning were examined in a non-patient sample. Neither the amount of alcohol consumed over a lifetime nor current frequency of drinking occasions was significantly (ps greater than .05) correlated with cognitive test scores. However, the quantity of alcohol consumed per drinking occasion was inversely related to performance on tests of abstraction, adaptive abilities and concept formation. The results suggest that social drinking may have deleterious effects on cognitive processes.

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Cerebral changes on MRI and cognitive function: the CASCADE study.

The aging, non-demented brain undergoes several physiological changes, some of which may affect cognitive function. The goal of the present study was to examine the associations between subcortical and periventricular white matter hyperintensities (WMHs), cortical and subcortical atrophy, and cognitive function (episodic memory, word fluency, attention, and perceptual, cognitive, and motor speed). This was done within a European collaborative study, Cardiovascular Determinants of Dementia (CASCADE), in which magnetic resonance imaging (MRI) was performed on community-dwelling individuals. The study includes 1254 persons from eight European study centers, ranging between 64 and 76 years of age (M 69.4+/-3.3; 55% men). When demographics (age, education, and sex), study center, and concurrent brain changes had been adjusted for, periventricular WMHS predicted lower performance in word fluency and the Stroop test (time), and subcortical atrophy predicted lower performance in motor speed and the Stroop test (errors). The findings are consistent with findings from lesion and functional neuroimaging studies.

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The role of acetylcholine in the cognitive function of frontal neurons in monkeys.

To study the role of acetylcholine (ACh) in the cognitive function of frontal lobes, ACh and atropine were applied iontophoretically to the task-related neurons recorded from an area around the superior ramus of arcuate sulcus in the frontal cortex of 4 rhesus monkeys during the performance of two tasks. The spontaneous discharges and task-related responses of most of the neurons which increased their discharge rate in the delay and differentiation periods of the discrimination response go/no-go task and in the cue and delay periods of the delayed discrimination go/no-go task, were further increased during the application of ACh and suppressed during atropine. These results suggest that ACh may be involved in the excitatory process of the activity of the neurons in the above-mentioned area of frontal cortex to play an important role in the cognitive functions of attention, discrimination and short-term memory.

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[A neuroradiological study on the influence of cerebral atrophy and white matter lesion on cognitive function in the elderly].

We investigated the influence of brain atrophy and white matter lesions on cognitive function in elderly people. We selected 33 subjects (mean age, 79.2 +/- 5.1yrs) with a MMSE score from 14 to 30 who had no previous history of stroke from the outpatients in the Memory Clinic of our hospital. These subjects were divided into four groups on the basis of their MMSE score as follows: 14-20; moderate dementia (Moderate-D, n = 9), 21-23; mild dementia (Mild-D, n = 9), 24-27; mild cognitive impairment (MCI, n = 10), 28-30; normal (Normal, n = 5). Among these four groups, we compared the frequency of the associated risk factors for cerebral infarction (hypertension, diabetes mellitus, hyperlipidemia, heart disease), and the severity of brain atrophy and cerebral white matter lesion which were visually evaluated by MRI technique. Brain atrophy and white matter lesions were assessed by reviewing the cerebral cortex and hippocampus, and deep white matter lesion (DWML) and periventricular hyperintensity (PVH), respectively. Brain atrophy was divided into three grades (mild, moderate, severe) and white matter lesions were classified into four grades (0-3) using Fazekas's criteria. We performed statistical analysis to detect t parameters which correlate with and influence MMSE scores from among the MRI findings. The cases with dementia were all diagnosed as Alzheimer's disease. There were no significant differences among the four groups in mean age, the incidence of individual associated risk factors, the severity of cortical atrophy, or the grade of DWML (< or = 2) and PVH (< or = 2). However, the frequency of hippocampal atrophic change greater than a moderate grade increased in parallel with the exacerbation of reduced cognitive function (Normal; 20%, MCI: 40%, Mild-D; 56%, Moderate-D 89%), and approximately 76% with such a change were AD cases. Statistical analysis showed a significant negative correlation between the grade of hippocampal atrophy and MMSE score (r = -0.518, p < 0.005) and a great influence of hippocampal atrophy on that score (step-wise regression analysis: r = 0.518, p < 0.005). From the above results, it was suggested that more than moderate atrophic change in the hippocampus might possibly be related with cognitive impairment and that both DWML and PVH less than the second grade had little influence on the decline of brain function.

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Contrast study on cognitive function with MRI and positron emission tomography imaging in transient global amnesia.

OBJECTIVE: To study cognitive function and cerebral metabolic changes in patients with transient global amnesia (TGA). METHODS: Three patients with TGA were given mini-mental state examination (MMSE), revised Wechsler memory scale (WMS-R) examination and magnetic resonance imaging (MRI) scans after they had been diagnosed as TGA. Using (18)F labelled deoxyglucose as tracer, patients were given a positron emission tomography (PET) examination at different periods during recovery. RESULTS: No obvious abnormality was found in MMSE and MRI scans in the three patients. However, WMS-R examination and cerebral PET imaging displayed cognitive dysfunction of varying degrees and low metabolism in local areas related to memory in 2 of 3 patients. CONCLUSIONS: In TGA patients, cognitive function and cerebral metabolic levels are closely correlated with duration of symptoms. It is necessary to stop the TGA attack as quickly as possible early time.

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Rate of fall of blood glucose and physiological responses of counterregulatory hormones, clinical symptoms and cognitive function to hypoglycaemia in Type I diabetes mellitus in the postprandial state.

AIMS/HYPOTHESIS: The aim of this study was to establish the effect of a rate of decreasing plasma glucose concentrations on responses to hypoglycaemia, i.e. release of counterregulatory hormones, perception of symptoms, deterioration of cognitive function, and rates of forearm noradrenaline spillover, in the postprandial condition and in the sitting position. METHODS: We studied 11 subjects with Type I (insulin-dependent) diabetes mellitus, twice during clamped insulin-induced hypoglycaemia (2.4 mmol/l) after eating in the sitting position. On one occasion, plasma glucose was decreased at the rate of 0.1+/-0.003 mmol x min(-1) x l(-1) (fast fall), on the other at the rate of 0.03+/-0.001 mmol x min(-1) x l(-1) (slow fall). Subjects underwent a control euglycaemic clamp study as well. RESULTS: In response to fast-fall as compared to slow-fall hypoglycaemia, which was about 30 min longer, cognitive tasks were performed as follows: Trail-Making B, PASAT 2 s, Digit Vigilance Test and Verbal Memory deteriorated more, adrenaline increased less (2.8+/-0.5 vs 3.5+/-0.7 nmol/l, p=0.03), forearm noradrenaline spillover was greater (6.5+/-1.0 vs 5.2+/-0.4 pmol x min(-1) x 100 ml(-1), p=0.04), and symptoms were no different. After recovery from hypoglycaemia, cognitive function was still deteriorated compared to the baseline with no difference between fast and slow-fall hypoglycaemia. The evident response of glucagon to postprandial hypoglycaemia contrasted with the blunted or absent response in the fasting state. CONCLUSION/INTERPRETATION: In the postprandial condition and sitting position, fast-fall hypoglycaemia is more dangerous than slow-fall, because it deteriorates cognitive function more, and activates responses of counterregulatory hormones less than slow-fall hypoglycaemia.

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[Cognitive function and basic activity of daily living of elderly disabled inpatients].

To elucidate the clinical characteristics of disability due to various basic disease groups, by using Japanese Minimum Data Set (MDS), Nishimura's mental scale (NM) and activity of daily living scale (N-ADL), cognitive function and basic activity of daily living (ADL) together with the grading scale of nursing care (freedom-grade of daily living: N1. frequency of bedside visits by a nurse: N2) and nutritional function (serum albumin: SA) were assessed in 926 elderly disabled inpatients in April 1998 in our long-stay chronic care hospital. Basic diseases were divided into five groups: cerebrovascular (C), senile dementia (D), bone and joint (B), Parkinson's disease (P) and other diseases (O). (1) In all patients, women were 2.9 years significantly older than men. Mean age in disease groups was significantly greater in the following decreasing order, B > D > C > P. (2) In all patients and patients with C, significant negative correlations were found between age and the scores of various scales (NM, N-ADL, N1, SA). In patients with D and B, significant negative correlations were found only between age and N-ADL and N1, but not NM or SA. In patients with P, no correlations were found between age and the various scales. (3) The cognitive function score decreased significantly as follows, B > C > P > D and the score of ADL decreased significantly as follows, B > D > C > P. (4) In patients with C and P, significant positive correlations were found between 3 scores (Cognition, ADL, SA). In patients with D, significant positive correlation was found between only two scores (ADL, SA) and in patients with B, no correlations were found between SA and other scores. (5) Because in all patients and in patients with all disease groups, significant positive correlations were found between the scores of cognition, ADL by MDS and the scores of NM, N-ADL respectively, the scales of cognition and ADL evaluated by MDS were validated for us to assess cognitive function and ADL and are probably suitable tools for evaluating elderly disabled patients. The other various functional states should also be assessed in elderly disabled patients where the quality of life of the patients must take priority over other considerations in decision making for medical interventions, including care. We should discuss care in detail and continue more medical studies to improve the quality of care.

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The impact of pacemaker implantation on cognitive functioning in elderly patients.

OBJECTIVE: To describe and quantify the impact of pacemaker implantation on cognitive functioning in the elderly. DESIGN: Prospective case-control, non-randomized trial. Data were collected from clinical and family interviews and from a psychological test battery. SETTING: Pacemaker clinic in a tertiary care hospital. PARTICIPANTS: Nineteen elderly (65+ years) patients undergoing new or replacement pacemaker implantation for dysrhythmias and volunteer controls matched for age, sex, and short Mental Status Questionnaire test results, without dysrhythmia or intervention. MAIN OUTCOME MEASURES: Subjective and clinical impressions based on family interviews; results of psychological test battery before and 6-12 months after pacemaker implantation. RESULTS: Prior to pacemaker implantation, three patients met DSM-III criteria for dementia and two for delirium. Paced patients demonstrated deficiency in immediate memory, language, memory for less structured information, and learning of abstract materials. These deficits were due primarily to the poor performance of patients with complete heart block. Despite clinical and subjective impressions of improvement, there was no change in psychologic test performance subsequent to pacemaker implantation. CONCLUSIONS: Impaired cognitive functioning is not always clinically apparent but appears common in patients with cardiac dysrhythmias; it is not altered 6-12 months after pacemaker implantation.

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Effects of anterior temporal lobectomy on cognitive function.

Sixty-three patients with intractable partial complex epilepsy were treated by anterior temporal lobectomy for seizure control. Psychometric studies before and after operation documented cognitive function and evaluated the effects of operation on cognition. The mean follow-up period was 7.7 months. Sixty-two of 63 patients had improved seizure control; 49 (78%) were seizure free. Operation had different effects on cognitive abilities in those with right vs. left temporal lobe excisions. Although both groups maintained summary IQ scores in the average range, after operation the left temporal group was less efficient on language-dependent cognitive tasks, particularly those that involved complex learning and memory. In contrast, persons who had right temporal ablations were either unchanged or slightly better cognitively after operation. Future research and clinical evaluations should focus on the components of the learning and memory processes when the ramifications of temporal lobe ablations on cognitive function are studied.

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Effect of breakfast timing on the cognitive functions of elementary school students.

OBJECTIVE: To study the effect of breakfast timing on selected cognitive functions of elementary school students. DESIGN: A 2-week randomized control intervention trial. SETTING: Five elementary schools. SUBJECTS: The subjects comprised 569 children, 51% of them boys, aged 11 to 13 years; the children were in grades 5 through 6 (17 classes). The subjects lived in different areas and had different socioeconomic backgrounds. INTERVENTION: Each subject was tested twice, by 2 versions of the Rey Auditory-Verbal Learning Test, 2 alternative forms of the logical memory subtest of the revised Wechsler Memory Scale, and 2 versions of the Benton Visual Retention Test. On the first test, before any nutritional intervention, the subjects were asked to complete a questionnaire about their food intake on the day of testing. Two thirds of the subjects received 200 ml of 3%-fat milk and 30 g of sugared cornflakes for the next 14 days, and all the subjects were reexamined on the 15th day. MAIN OUTCOME MEASURE: Scoring on the different tests was compared with baseline scores. RESULTS: After 15 days, children who ate breakfast at school scored notably higher on most of the test modules than did children who ate breakfast at home and children who did not at breakfast. CONCLUSIONS: Our results indicate that routinely eating breakfast 2 hours prior to being tested does not improve cognitive functions in 11- to 13-year-old elementary school students, but food supplementation 30 minutes prior to taking a test notably improves scoring. We suggest further studies on the relationship between meal content, feeding time, and scholastic performance.

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Change in cognitive function in idiopathic Parkinson disease.

OBJECTIVE: To study the effects of Parkinson disease (PD) on cognitive function by determining the frequency and amount of change in Mini-Mental State Examination (MMSE) performance. DESIGN: During a 4-year period, 77 patients with idiopathic PD and 43 normal elders were administered a neuropsychological test battery twice at 2 years apart. RESULTS: A 4-point score difference on the MMSE was the amount that was statistically calculated to be a significant difference at the .05 probability level. Using this metric, 17 (22%) patients with PD had a change in their MMSE performance during a 2-year period. Fifteen individuals performed poorer, and 2 individuals improved. Using the same metric, no normal subjects changed in their MMSE performance. The groups of patients with PD who had a change and did not have a change in their MMSE performance were not characterized by significant differences in their years of education, duration of illness, age at onset, age at test time 1, estimated premorbid intelligence, Hamilton Psychiatric Rating Scale for Depression score at test time I, or Unified Parkinson's Disease Rating Scale score. The singular difference was the higher frequency of change that was found in subjects who were taking dopamine agonists at the second test time. CONCLUSION: A change in cognitive function in patients with PD, as measured by a change of 4 points or more in their MMSE performance, was observed in only 22% of a sample of 77 patients with idiopathic PD during a 2-year period.

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