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Nutritional factors in physical and cognitive functions of elderly people.

The quality of life of aging individuals depends profoundly on their capacity for physical mobility, mental alertness, and cognitive function. Independence and self-esteem are strongly determined by physical and mental capacities. Stimulated by reports of declining function with age, investigators have examined the relationships between lifestyle factors and maintenance of functional status. Growing evidence supports the view that continued physical activity and good nutritional status are important determinants of physical and cognitive function. It is possible that some of the decline in cognitive function associated with aging is preventable or reversible with improved vitamin nutriture, especially vitamin B-12, vitamin B-6, and folate. It might well be argued that the most practical outcome of research on the relationship of diet and nutrition to the aging process would be a better understanding of the ways in which our behavior can maintain a vigorous quality of life.

Aged↗

Adverse drug reactions and cognitive function among hospitalized older adults.

OBJECTIVE: To explore the relationship between cognitive function and the detection of adverse drug reactions (ADRs) and to evaluate whether cognitive function could influence the association between age and ADRs. METHODS: A total of 16,926 patients admitted to 81 hospitals throughout Italy between 1991 and 1997 were included in the study. ADRs detected the during hospital stay were recorded by a study physician. Patients with a Hodkinson Abbreviated Mental Test (AMT) score <7 at hospital admission were considered cognitively impaired. RESULTS: A total of 1,444 ADRs were diagnosed in 976 patients (5.8% of the total sample). Overall, gastrointestinal complications (18.0% of all ADRs) were the most frequent ADRs, followed by cardiovascular (12.3%) and dermatological/allergic complications (12.3%). An ADR was recorded in 232/4,883 (4.8%) patients with cognitive impairment and in 744/12,043 (6.2%) patients cognitively intact. After adjusting for potential confounders, cognitive impairment was associated with a reduced risk of ADRs (OR 0.70; 95% CI: 0.60-0.83). This result was not consistent for all types of ADRs, since the risk of neuropsychiatric complications was significantly increased among patients with cognitive impairment (OR 2.23; 95% CI 1.40-3.54). The overall rate of ADRs was 5.2% in patients younger than 65, 6.1% in patients between 65 and 79, and 5.8% in those 80 or older. When adjusting for potential confounders, not including the AMT score, age was not found to be significantly associated with ADRs. However, when the variable for the AMT score was introduced into the model, the risk for ADRs significantly increased with increasing age. CONCLUSION: Cognitive impairment is associated with a lower detection rate of ADRs, and it represents a confounder of the association between age and ADRs.

Aged↗

Search for correlations between serotonin 5-HT1A receptor expression and cognitive functions--a strategy in translational psychopharmacology.

RATIONALE: Animal studies and studies of human aging have suggested that the serotonin 5-HT1A receptor may serve as a biomarker for cognitive functioning and a target for pharmacological treatment of cognitive deficits. OBJECTIVES: The purpose of this positron emission tomography (PET) study was to search for relationships between interindividual variability in serotonin 5-HT1A receptor binding potential (BP) and cognitive functioning. MATERIALS AND METHODS: Twenty-four male control subjects, age 20-55 years, were examined with [11C]WAY100635 PET and a battery of cognitive tests. 5-HT1A receptor binding potential were calculated for the raphe nuclei, the hippocampus and the neocortex. Correlation coefficients between BP and cognitive performance were obtained for each region. RESULTS: There was a severalfold of variability in 5-HT1A BP between individuals. We found no significant correlation between regional [11C]WAY100635 binding and cognitive performance. CONCLUSIONS: The results do not provide support for involvement of the 5-HT1A receptor in cognitive functioning in man and question the predictive validity of some currently used animal models in translational neuroscience.

Adult↗

The acute effects of amisulpride (50 mg and 200 mg) and haloperidol (2 mg) on cognitive function in healthy elderly volunteers.

In this double-blind, placebo controlled, four-way cross-over trial in 16 healthy elderly volunteers, the acute effects of haloperidol 2 mg, amisulpride 50 mg and 200 mg, were assessed on a range of tests of cognitive function. On each study day, cognitive performance was assessed prior to dosing and at 2, 4, 6, 9, 12 and 24 h after dosing with the following tests from the Cognitive Drug Research computerized assessment system: simple reaction time, digit vigilance task, choice reaction time, visual tracking, Critical Flicker Fusion, body sway, numeric working memory, immediate and delayed word recall, word recognition and self-ratings of mood and alertness. Haloperidol showed a general tendency to impair performance, and although this did not reach significance compared to placebo, for two tasks there were significant impairments with haloperidol compared to amisulpride. Amisulpride 50 mg and 200 mg, was not associated with impairment. In fact, there was some suggestion of improvement over placebo on three measures. The timings of assessment were appropriate for the study compounds. Furthermore, in a recent study in which a smaller number of elderly volunteers was tested on the same cognitive assessment system, a clear profile of acute impairments of haloperidol 3 mg, was identified. This indicates that haloperidol 2 mg, is not a sufficient dose to affect cognitive function in the elderly, supporting the general absence of effects with this dose in the young. Thus, the general absence of cognitive impairments with amisulpride at the doses used in this study suggests that this compound does not impair cognitive function in the elderly.

Aged↗

Relation of cerebral infarctions to dementia and cognitive function in older persons.

BACKGROUND: Cerebral infarctions are common in older persons but their relationship with dementia and cognitive function remains controversial. METHODS: Participants were 164 older Catholic nuns, priests, and brothers who underwent annual clinical evaluation and brain autopsy at death. The authors quantified number and volume of old cerebral infarctions on postmortem examination and determined the association with dementia and cognitive function proximate to death. Analyses controlled for age, sex, and education. RESULTS: A total of 58 (35.4%) subjects had cerebral infarctions: 29 had one infarction and 29 had multiple infarctions. In logistic regression analyses, infarctions increased the odds of dementia twofold (OR 2.12; 95% CI 1.06 to 4.25). The odds of dementia increased by 2.67-fold for multiple infarctions (95% CI 1.08 to 6.61), whereas the odds of dementia with single infarctions increased by 69% (95% CI 0.70 to 4.09). In linear regression analyses, there was a trend for multiple infarctions to be associated with lower global cognitive scores (-0.44 standard units, p = 0.057). Multiple infarctions were related to perceptual speed, visuospatial skills, and working memory, but not to episodic or semantic memory. The authors found similar results with infarction volume. In secondary analyses, only infarctions that were clinically evident during life were associated with dementia and cognitive function. CONCLUSION: Cerebral infarctions are associated with a twofold increase in odds of dementia. Odds are higher in persons with multiple, large, or clinically evident infarctions. In addition, cerebral infarctions do not affect all cognitive systems equally, showing the strongest association with perceptual speed and the weakest with episodic memory.

Aged↗

Changes in cognitive functioning with risperidone and olanzapine treatment: a large-scale, double-blind, randomized study.

OBJECTIVE: The effects of risperidone and olanzapine on cognitive functioning in patients with schizophrenia were compared in a randomized, double-blind trial. METHOD: Three hundred and seventy-seven patients were randomly assigned to receive 2-6 mg/day of risperidone or 5-20 mg/day of olanzapine for 8 weeks. Cognitive function was assessed with a focused cognitive assessment battery; in addition, extrapyramidal symptoms were assessed using the extrapyramidal symptom rating scale (ESRS), and the positive and negative syndrome scale (PANSS) was rated for all patients. RESULTS: Treatment with these two atypical antipsychotic medications was associated with improved performance on the Wisconsin card sorting test, the trail-making test, the California verbal learning test, the continuous performance test, and some aspects of verbal fluency and spatial working memory. No differences in the effects of the drugs on any of the cognitive tests were noted. Correcting for the effects of anticholinergic treatment did not alter the magnitude of cognitive effects. CONCLUSIONS: Atypical antipsychotic treatment is associated with wide-ranging benefits on cognitive functioning. Previous reports of greater benefits of olanzapine over risperidone in a small-sample pilot study were not substantiated. These results are not due in general to changes in clinical symptoms or movement disorders, suggesting a direct effect of atypical antipsychotic medications on cognitive deficits in schizophrenia.

Adolescent↗

Endogenous sex hormones and cognitive function in older men.

The objective of this study was to determine whether endogenous sex hormone levels predict cognitive function in older men. Our study design was an exploratory analysis in a population-based cohort in Rancho Bernardo, California. The study participants were 547 community-dwelling men 59-89 yr of age at baseline who were not using testosterone or estrogen therapy. Between 1984 and 1987, sera were collected for measurement of endogenous total and bioavailable testosterone and estradiol levels. Between 1988 and 1991, 12 standard neuropsychological instruments were administered, including two items from the Blessed Information-Memory-Concentration (BIMC) Test, three measures of retrieval from the Buschke-Fuld Selective Reminding Test, a category fluency test, immediate and delayed recall from the Visual Reproduction Test, the Mini-Mental State Examination with individual analysis of the Serial Sevens and the "World" Backwards components, and the Trail-Making Test Part B. In age- and education-adjusted analyses, men with higher levels of total and bioavailable estradiol had poorer scores on the BIMC Test and Mini-Mental State Examination. Men with higher levels of bioavailable testosterone had better scores on the BIMC Test and the Selective Reminding Test (long-term storage). Five associations were U-shaped: total testosterone and total and bioavailable estradiol with the BIMC Test; bioavailable testosterone with the "World" test; and total estradiol with the Trail-Making Test. All associations were relatively weak but independent of age, education, body mass index, alcohol use, cigarette smoking and depression. In these older men, low estradiol and high testosterone levels predicted better performance on several tests of cognitive function. Linear and nonlinear associations were also found, suggesting that an optimal level of sex hormones may exist for some cognitive functions.

Aged↗

[Cognitive function as the factor determining higher-level competence in community-dwelling elderly: comprehensive health examination for the community elderly for the prevention of the geriatric syndrome and a bed-ridden state ("otasha-kenshin")].

PURPOSE: This study was conducted to examine age-related differences in cognitive function, and their relation to higher-level competence of elderly living in an urban community. METHOD: Participants were 438 individuals (males 168, females 270) aged 70 to 84 years living in an urban community in Tokyo. Three cognitive performance tests, the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol, Word Fluency Test, and the WAIS-R Digit Span, were employed for estimating cognitive function, and the TMIG Index of Competence for measuring higher-level competence. In the Index, three constructions: "Instrumental Self-Maintenance", "Intellectual Activity", and "Social Role" were involved. RESULTS AND CONCLUSIONS: Age-related differences in the cognitive tests were analyzed using ANCOVA controlling for educational year. Age-related differences between younger elderly (70-79 years old) and older elderly (80-84 years old) were observed with the WAIS-R Digit Symbol, Word Fluency Test and the WAIS-R Digit Span. The results indicate that information processing speed, executive function and primary memory in community-dwelling elderly continue to decline in old age, and this trend is salient in the old-old. We carried out partial correlation analysis and multiple regression analysis for exploring the relationships between cognitive function and the sub-scales in the TMIG Index of Competence, controlling for age and educational year. Cognitive function was significantly and positively related with the sub-scales in the Index, this being especially robust for "Intellectual Activity". The results suggest that higher-level competence can be modestly determined with reference to cognitive function, and "Intellectual Activity" may have a stronger relation with cognitive function than the other two sub-scales in the Index.

Activities of Daily Living↗

Systematic review of the effect of therapeutic dietary supplements and drugs on cognitive function in subjects with Down syndrome.

The objective was to evaluate the effects of therapeutic dietary supplements and drugs on cognitive function in subjects with Down syndrome. The study design was a systematic review of randomized controlled trials of dietary supplements and/or drugs reporting any assessment of cognitive function in subjects with Down syndrome. Eleven trials were identified with 373 randomized participants. None of the trials reported cognitive enhancing effect in subjects with Down syndrome. Meta-analysis was not conducted due to the heterogeneous nature of the population, interventions and outcome measures used. Overall, the quality of the trials was poor with few subjects and generally inadequate allocation concealment of the treatments given. This comprehensive systematic review provides no positive evidence that any combination of drugs, vitamins and minerals enhance either cognitive function or psychomotor development in people with Down syndrome. However, because of the small number of subjects involved and the overall unsatisfactory quality of the trials, an effect cannot be excluded at this point. At present there is no justification for the use of such regimes outside the context of large well designed trials. Parents of children with Down syndrome should be actively discouraged from giving these 'miracle drugs' to their children.

Adolescent↗

Cognitive functioning after stroke: a one-year follow-up study.

Cognitive disorders after stroke are one of the main causes of disability in daily activities. The main aim of this study was to investigate the frequency of post-stroke dementia, post-stroke mild cognitive impairment (MCI) and post-stroke amnestic MCI at different times after first-ever stroke; 196 patients were included in the study. In addition, cognitive disorders and their clinical course were studied. Frequency of post-stroke dementia was about 10% at all evaluation times; most patients had post-stroke MCI. Of the cognitive functions investigated, mental speed and calculation were most frequently affected. Performance on almost all cognitive tests was improved 6 and 12 months after stroke. Thus, while the frequency of post-stroke dementia is low, the frequency of post-stroke MCI is high, but improvement of cognitive function is possible.

Activities of Daily Living↗

Effects of altitude on mood, behaviour and cognitive functioning. A review.

Alterations in psychological mood, personality, behaviour and cognitive functioning associated with altitude have been recognised for many years. Psychological and behavioural changes resulting from the effects of hypoxia often include increases in euphoria, irritability, hostility and impairment of neuropsychological functions such as vision and memory. There is limited research to indicate that some decrements may persist for up to a year, or longer, after return to lower elevation. However, generalisations of the effects of altitude on mood, behaviour and cognitive function are complicated by differences between studies including the specific tasks or dimensions measured, methods of measurement, degree of altitude, duration of exposure and types of participants. There also appear to be wide individual differences in the response to altitude sojourns. Investigations designed to measure symptoms and mood changes during actual mountain climbs are needed, since most of the systematic research has been conducted in altitude chambers. The extent to which these simulations can be generalised to actual altitude settings remains to be documented.

Affect↗

Effects of low-dose risperidone and low-dose zuclopenthixol on cognitive functions in first-episode drug-naive schizophrenic patients.

BACKGROUND: Studies on the effects of antipsychotics on cognitive deficits in schizophrenia mostly suggest a superior effect of atypical over typical compounds, although findings are inconsistent and effect sizes small. Several methodological issues, such as heterogeneous patient samples, incomparable drug doses, effects of prior medication, construct validity, and retest effects on neuropsychological tasks, confound most results and the comparability between studies. Consequently, the conclusion concerning effects of antipsychotics on cognition is still equivocal. OBJECTIVE: The present randomized clinical trial examined the effects on cognition of comparatively low doses of a typical antipsychotic (zuclopenthixol) and an atypical antipsychotic (risperidone) in a homogeneous group of drug-naive first-episode schizophrenic patients in a longitudinal setting. METHODS: First-episode schizophrenic patients who had never previously been exposed to antipsychotic treatment (N=25) were randomly allocated to treatment with flexible doses of zuclopenthixol or risperidone in an open-label design. Cognitive functions were examined both when patients were drug-naive, and after 13 weeks of treatment. A comprehensive neuropsychological battery was used in order to optimize construct validity, and principal components of cognitive functions were extrapolated in order to reduce type I errors. A healthy control group was tested at baseline and after 13 weeks, in order to examine retest effects. The cognitive domains studied were executive functions, selective attention, and reaction time. RESULTS: The patients showed considerable cognitive deficits when drug-naive. There were few differential effects of risperidone and zuclopenthixol on cognitive deficits, except for a differential significance, respectively, tendency towards improved reaction and movement times in the risperidone group, and a lack of such in the zuclopenthixol group. These differences were no longer significant after covarying for extrapyramidal side effects and anticholinergic medication that were more prevalent in the zuclopenthixol group and the increases after medication were comparable with retest effects in controls. CONCLUSION: The study underscores the importance of examining impact of factors, such as clinical improvement, extrapyramidal side effects, anticholinergic medication and retest effects in longitudinal efficacy studies. This study does not support efficacy of either risperidone or zuclopenthixol on cognitive functions in drug-naive schizophrenia patients after 3 months of medication, because neither could be distinguished from retest effects of the healthy control group.

Adult↗

A double-blind, cross-over comparison of the effects of amantadine or placebo on visuomotor and cognitive function in medicated schizophrenia patients.

The present study aimed to test the hypothesis that dopamine agonists may enhance cognitive function. The effect of amantadine on neuropsychological function in medicated schizophrenia patients was investigated. The study comprised an add-on, double-blind, placebo-controlled, cross-over 6-week trial. Participants comprised 29 inpatients at Sha'ar Menashe Mental Health Center who were diagnosed with chronic schizophrenia or schizoaffective disorder. Amantadine 200 mg/day or identical placebo was added to ongoing antipsychotic treatment for 3 weeks. Study medications were then switched for an additional 3 weeks. Assessments were performed at baseline, and weeks 3 and 6, including cognitive and visuomotor assessments. Clinical ratings included positive, negative and depressive symptoms and extrapyramidal side-effects. Blood prolactin levels were assayed. A mixed model was used to examine differences in the data at the three assessment points. Amantadine was associated with improved visuomotor coordination compared to placebo. No significant changes in cognitive functions were noted. Clinical symptoms, extrapyramidal side-effects and blood prolactin levels were not altered. Amantadine improved visuomotor coordination independently of extrapyramidal side-effects but not cognitive function. Because prolactin concentrations were unchanged, the mechanism is more likely to involve glutaminergic NMDA than dopaminergic mechanisms. Further studies of amantadine with different doses and treatment duration, as well as more glutamate selective agents such as memantine, are indicated.

Adult↗

Change in cognitive function in older persons from a community population: relation to age and Alzheimer disease.

OBJECTIVE: To examine change in cognitive function in older persons sampled from a community population, and its relation to age and Alzheimer disease. DESIGN: Prospective cohort study with an average of 3.5 years of follow-up. SETTING: East Boston, Mass--a geographically defined, urban, working-class community. PARTICIPANTS: A stratified, random sample of persons 65 years and older underwent uniform, structured clinical evaluation for Alzheimer disease. The 388 persons (89.2% of those eligible) who completed at least 1 annual follow-up evaluation were studied: 97 had Alzheimer disease at baseline; 95 developed Alzheimer disease during the study; and 196 were unaffected. OUTCOME MEASURES: Eight cognitive performance tests were administered, then converted to population-weighted z scores and averaged to create a composite summary measure of cognitive function. Initial level of and change in this score were the outcome measures. RESULTS: In the population as a whole, many persons experienced a decline in cognitive performance, and age was related to both initial level and rate of decline. Analyses were conducted in 3 subgroups: persons with Alzheimer disease at baseline, those who developed Alzheimer disease during the study, and those who remained unaffected. In both Alzheimer disease subgroups, substantial cognitive decline was observed, but neither initial level nor rate of decline was related to age. In unaffected persons, little cognitive decline was evident, and there was a small, inverse association of age with initial level of cognitive function. CONCLUSION: In a general population sample, there was little evidence of cognitive decline during a 3.5-year period among persons who remained free of Alzheimer disease.

Aged↗

Recovery and cognitive function after fentanyl or remifentanil administration for carotid endarterectomy.

STUDY OBJECTIVE: To compare recovery and restoration of cognitive function after fentanyl-propofol or remifentanil-propofol anesthesia administration in patients undergoing carotid endarterectomy. DESIGN: Randomized, double-blind, prospective study. SETTING: Department of Anesthesiology, University hospital. PATIENTS: Seventy patients with ASA physical statuses II and III (53 men and 17 women) undergoing elective carotid endarterectomy. INTERVENTIONS: Anesthetic technique and drugs were identical in the 2 groups, with the exception of remifentanil and fentanyl administration. Induction of anesthesia was obtained with a bolus dose of propofol (1-2 mg/kg), maintenance was achieved with a propofol infusion according to hemodynamics and nitrous oxide/oxygen (FIO(2), 0.50). Muscle relaxation was achieved with rocuronium. The remifentanil group received 1 microg/kg of remifentanil as a single dose during the induction of anesthesia and 0.5 microg/kg per minute as an infusion throughout the procedure. The fentanyl group received 2 microg/kg of fentanyl as a single dose during the induction of anesthesia. MEASUREMENTS: Intraoperative hemodynamic adverse events were recorded. All patients were also evaluated with regard to their recovery and the restoration of their cognitive function, recording the immediate recovery times and using the Aldrete score 15 and 60 minutes after surgery and the Hasegawa scale 6 hours after surgery. For evaluation of postoperative pain, the Numeric Pain Scale (0-10) was used. MAIN RESULTS: Patients receiving remifentanil had significantly (P < .05) fewer episodes of intraoperative hypertension and needed nitroglycerine administration less frequently (P < .05) than those receiving fentanyl. Immediate recovery was significantly earlier (P < .05) with remifentanil (eye opening, 5.1 +/- 1.3 [remifentanil] and 7.2 +/- 3.7 [fentanyl] minutes; extubation time, 5.4 +/- 1.9 [remifentanil] and 7.8 +/- 4.1 [fentanyl] minutes). The Hasegawa Dementia Scale scores 6 hours after surgery and Aldrete scores 15 and 60 minutes after surgery did not differ significantly between the 2 groups. Pain levels were also similar for patients taking remifentanil and fentanyl. CONCLUSIONS: Although intraoperative hemodynamics were better preserved and immediate recovery was more rapid with remifentanil, overall postoperative recovery and restoration of cognitive functions as well as postoperative pain intensity seem to be similar for patients receiving remifentanil and for those receiving fentanyl combined with propofol for carotid endarterectomy operations.

Aged↗

Improvement in cognitive functions and psychiatric symptoms in treatment-refractory schizophrenic patients receiving clozapine.

Cognitive functions and psychopathology were assessed in 36 treatment-refractory schizophrenic patients before initiation of clozapine, and at 6 weeks and 6 months, thereafter. Before treatment, cognitive impairment was found in each measure of memory, attention, and executive function as compared with 26 normal controls. After both 6 weeks and 6 months of treatment, significant improvement occurred in the Controlled Oral Word Association Test, a measure of retrieval from reference memory. Improvement was also noted at 6 months in the Category Instance Generation Test, another measure of retrieval from reference memory, and in some, but not all, tests of executive function, attention, and recall memory. Clozapine treatment also resulted in significant improvement in Brief Psychiatric Rating Scale (BPRS) Total and Positive symptom scores at both 6-week and 6-month assessment points. There was some evidence for a relationship between improvement in psychopathology and cognitive function. The improvement in cognitive function during clozapine treatment could have consequences for capacity to work and social function.

Adult↗

The lymphotoxin Cys13Arg polymorphism and cognitive functioning in individuals with schizophrenia.

Genetic factors that modulate the immune response have been implicated as risk factors for schizophrenia and cognitive impairment. We assessed the correlation between cognitive functioning and the LTA Cys13Arg polymorphism in 351 individuals with schizophrenia, 122 with bipolar disorder, and 160 controls. There was a significant association between cognitive functioning and the LTA Cys13Arg polymorphism within the schizophrenia (p<0.008) but not the other diagnostic groups. There was no association between cognitive functioning and the two other polymorphisms in the same gene complex. The LTA Cys13Arg polymorphism may represent a risk factor for cognitive impairment in individuals with schizophrenia.

Adult↗

Histamine-selective H3 receptor ligands and cognitive functions: an overview.

This review presents a link between histamine and cognition and provides an overview on the effect of histamine and selective ligands of histamine receptors on experimental models for learning, memory and cognitive functions, with a special focus on recently developed H(3) receptor ligands. Studies suggest a tremendous potential for H(3) antagonists in cognitive function disorders.

Animals↗