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Randomized trial of the effect of supplementation on the cognitive function of older people with subnormal cobalamin levels.

BACKGROUND: Low serum cobalamin levels are often found in apparently normal older subjects. A major worry of leaving cobalamin deficiency untreated is that it may lead to subtle deterioration in cognitive function. OBJECTIVES: To investigate the effect of supplementation on the cognitive function of older people with cobalamin deficiency by a randomized trial. METHODS: Fifty Chinese subjects more than 60 years old with serum cobalamin level < 120 pmol/l were randomized into supplement and control groups. Fasting serum methylmalonic acid levels (MMA) were measured. A battery of neuropsychological tests was administered. The supplement group received intramuscular cyanocobalamin injections, while the control group received no intervention. They were followed up at around 4 months. RESULTS: 78% of the subjects had raised MMA, indicating metabolic cobalamin deficiency. Supplemented subjects improved in performance IQ, but the amount of improvement was not significantly more than that of control subjects. Moreover, the supplement group fared worse than the control group at follow-up in some motor function scores. Three out of seven demented subjects had improvement in Mini-Mental State Examination scores, but there was no consistent improvement in other neuropsychological scores. CONCLUSIONS: This study suggested that cobalamin deficiency did not invariably cause cognitive impairment in older people. There remain the possibilities that cobalamin deficiency causes cognitive impairment or exacerbates coexisting dementia in some older people.

Aged↗

Regular exercise improves cognitive function and decreases oxidative damage in rat brain.

The biochemical mechanisms by which regular exercise significantly benefits health and well being, including improved cognitive function, are not well understood. Four-week-old (young) and 14-month-old (middle aged) Wistar rats were randomly assigned to young control and young exercised, middle-aged control and middle-aged exercised groups. Exercise groups were exposed to a swimming regime of 1 h a day, 5 days a week for 9 weeks. The passive avoidance test showed that middle-aged exercised rats had significantly (P<0.05) better short- (24 h) and long-term (72 h) memory than aged-matched control rats. Conditioned pole-jumping avoidance learning was improved markedly in both age groups by exercise. Brain thiobarbituric acid-reactive substances and 8-hydroxy-2'deoxyguanosine content in the DNA did not change significantly, while the protein carbonyl levels decreased significantly (P<0.05) in both exercised groups. This decrease was accompanied by an increase in the chymotrypsin-like activity of proteasome complex in the exercised groups, whereas trypsin-like activity did not differ significantly between all groups. The DT-diaphorase activity increased significantly (P<0.05) in the brain of young exercised animals. These data show that swimming training improves some cognitive functions in rats, with parallel attenuation of the accumulation of oxidatively damaged proteins.

Age Factors↗

Cognitive function impairment in patients with neuropathic pain under standard conditions of care.

The objective of this study is to analyze the prevalence to cognitive function impairment (CI) in a pragmatic cohort of subjects with different types of neuropathic pain under standard conditions of care by means of a cross-sectional baseline analysis of a sample of patients with NeP enrolled in a pragmatic, prospective, multicenter study evaluating the effectiveness of gabapentin. A total of 1519 patients (58.8% women), aged > or =18 years (mean [SD]=56.0 [13.7]), with neuropathic or mixed neuropathic and nociceptive pain for a mean (SD) of 1.1 (2.8) years were enrolled in the study. Pain was assessed with the short form of the McGill Pain Questionnaire, and cognitive function was measured with the Mini-Mental State Examination (MMSE). A score < or =24 on the MMSE was considered as CI. Multivariate logistic regression models were used to estimate CI prevalence. CI prevalence was substantially higher in patients with NeP than that reported in the general Spanish population, and significantly higher than in patients with mixed neuropathic and nociceptive pain: 11.4% (8.5%-14.3%) vs. 6.4% (4.6%-8.7%), P=0.006 (adjusted odds ratio=1.88 [1.21-2.91]). Prevalence significantly increased with age, up to 32.2% (20.6%-45.6%) in those with NeP, and to 28.2% (15.0%-44.9%) in those with mixed syndromes, for the age group > or =75 years, P<0.001 within age groups. Symptoms of anxiety and obesity, and to a lesser extent, symptoms of depression, were also factors associated with a higher prevalence rate of CI. This analysis showed that, after adjusting for confounding factors, the prevalence of CI was substantially higher in patients with NeP than those with mixed pain and the reference general population. Age, anxiety, depression, and obesity were factors found to be significantly associated with CI.

Adult↗

Cardiovascular risk factors and cognitive function in adults 30-59 years of age (NHANES III).

In the Third National Health and Nutrition Examination Survey (NHANES III), three measures of cognitive function [Simple Reaction Time Test (SRTT), Symbol Digit Substitution Test (SDST), and Serial Digit Learning Test (SDLT)] were administered to a half-sample of 3,385 adult men and nonpregnant women 30-59 years of age with no history of stroke. We used multiple linear regression analysis to determine whether there was an independent association between performance on each cognitive function measure and defined hypertension (HTN) alone, type 2 diabetes mellitus (DM) alone, and coexistent HTN and DM after adjustment for demographic and socioeconomic variables and selected health behaviors. After adjustment for the sociodemographic variables, the combination of HTN + DM, but not HTN alone or DM alone, was significantly associated with worse performance on the SRTT (p = 0.031) and the SDST (p = 0.011). A similar pattern was observed for SDLT performance, but the relationship did not reach statistical significance (p = 0.101). We conclude that HTN in combination with DM is associated with detectable cognitive decrements in persons under age 60.

Adult↗

Psychoneurophysiological assessment of recovery of cognitive function in patients with asthenia during rehabilitation.

Forty patients with severe asthenia were subjected to clinical, neurological, psychometric, and neurophysiologic examination before and after Enerion therapy. Psychoneurophysiological assessment with cognitive evoked potentials P300 and psychometric tests revealed serious impairment of cognitive functions in patients before therapy (compared to healthy individuals). Enerion therapy decreased the degree of psychoautonomic syndrome and asthenia and improved cognitive functions.

Adolescent↗

Relation between health status and cognitive functioning: a 6-year follow-up of the Maastricht Aging Study.

The aim of this study was to determine whether physical and psychological functioning can predict 6-year cognitive decline in older adults. A group of 669 participants aged 60 to 81 years was recruited from a longitudinal study (the Maastricht Aging Study). Physical functioning was measured in terms of perceived health and instrumental activities of daily living. Psychological functioning or mood was evaluated by the Depression and Anxiety subscales of the Symptom Check List-90. Although physical functioning and psychological functioning were related to several measures of cognitive functioning at baseline, psychological functioning was specifically related to memory functioning 6 years later. Poor psychological functioning (i.e., depressive and anxiety symptomatology), rather than poor physical health, may have the strongest implications for long-term cognitive functioning in older men and women.

Activities of Daily Living↗

Postprandial plasma glucose excursions and cognitive functioning in aged type 2 diabetics.

BACKGROUND: Postprandial plasma glucose (PPG) excursion is a significant determinant of overall metabolic control as well as an increased risk for diabetic complications. Older persons with type 2 diabetes mellitus (DM2) are more likely to have moderate cognitive deficits and neurophysiologic and structural changes in brain tissue. Considering that poor metabolic control is considered a deranging factor for tissue/organ damage in diabetics, the authors hypothesized that PPG excursion is associated with a decline in cognitive functioning and that a tighter control of PPG may prevent cognitive decline. METHODS: Two groups of aged diabetic patients were randomly selected to be treated with repaglinide (n = 77) or glibenclamide (n = 79). RESULTS: Coefficient of variation of PPG (CV-PPG) was associated with Mini-Mental State Examination (MMSE) scores (r = -0.3410; p < 0.001) and a composite score of executive and attention functioning (r = -0.3744; p < 0.001) after adjusting for multiple confounders. Both groups showed a significant decline in hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG), but only the repaglinide group demonstrated a significant decline of CV-PPG over time. In models investigating the change in cognitive functioning over time, adjusted for HbA1c and CV-FPG, a decline in cognitive functioning was observed only in the glibenclamide group (p < 0.001). After adjusting for CV-PPG, the authors no longer found a decline in executive and attention functioning composite score (p = 0.085) or the MMSE (p = 0.080) with glibenclamide. CONCLUSIONS: Exaggerated postprandial glucose (PPG) excursions are associated with a derangement of both global, executive, and attention functioning. A tighter control of PPG may prevent cognitive decline in older diabetic individuals.

Aged↗

[Does supplementation of essential fatty acids influence the visual acuity and cognitive function of term infants?].

BACKGROUND: Norwegian health authorities recommend supplementation of essential fatty acids such as cod liver oil to term infants from four weeks of age. The essential fatty acids are seen as contributing to optimal development of the visual acuity and cognitive functions. This study reviews recent research on this issue. MATERIAL AND METHODS: We assessed six randomized controlled trials, published in 1998 and 1999, of which two evaluated visual function and four cognitive development. Outcome were measured by a number of standardized tests. We compared the results from our review with results from a Cochrane review which evaluated six studies published from 1995 to 1997. RESULTS: Only one of the tests used in the visual acuity studies showed significant effect at three out of the four age-related points in time at which the test was administered. Only one of the tests used in the cognitive development studies showed significant effect. INTERPRETATION: The studies reviewed here are in accordance with previous research and do not provide evidence for the claim that supplementation with essential fatty acids as such is significant in order to achieve optimal visual function and cognitive development in healthy term infants.

Child Development↗

Cognitive function in healthy older European adults: the ZENITH study.

OBJECTIVE: Baseline data are reported from a study of the effects of zinc supplementation on cognitive function in older adults as assessed by the CANTAB computerised test battery. DESIGN: This is a multicentre prospective intervention study employing a randomised double-blind design. SETTING: European community-based study. PARTICIPANTS: There are 387 healthy adults aged 55-87 y from centres in France, Italy and Northern Ireland. INTERVENTIONS: Measures of visual memory, working memory and attention were obtained at baseline (prior to supplementation). RESULTS: Younger adults (<70 y) performed significantly better than older adults (>70 y) on all tests, with minimal differences between centres. In addition, men outperformed women on tests of spatial span, pattern recognition memory and reaction times, although these gender differences varied somewhat between centres. CONCLUSIONS: The results are generally consistent with previous age- and gender-related effects on cognitive functioning.

Age Factors↗

Relationships between extrapyramidal signs and cognitive function in a community-dwelling cohort of patients with Parkinson's disease and normal elderly individuals.

The relationship between extrapyramidal sign (EPS) severity and cognitive function was investigated in 184 patients with idiopathic Parkinson's disease (PD) and 301 normal elderly individuals from a community-dwelling cohort in northern Manhattan, New York City. Fifty-six of the patients with PD met criteria for dementia of the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised, and of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association. EPS were rated according to the Unified Parkinson's Disease Rating Scale. Cognitive function was assessed by neuropsychological tests of memory, orientation, abstract reasoning, language, construction, and psychomotor speed. Significant associations were found between EPS and neuropsychological performance in PD patients without dementia. Yet EPS severity was unable to account for the pronounced cognitive impairment in PD dementia. Individuals in the normal group with subtle EPS, but without overt idiopathic PD, showed widespread cognitive changes, including impairment in most of the tests that differentiated PD patients from normal subjects. Prospective follow-up of these individuals will determine whether this represents a preclinical stage of PD or constitutes an early manifestation of dementia.

Aged↗

Association of vitamin E and C supplement use with cognitive function and dementia in elderly men.

OBJECTIVE: To determine whether use of vitamin E and C supplements protects against subsequent development of dementia and poor cognitive functioning. METHODS: The Honolulu-Asia Aging Study is a longitudinal study of Japanese-American men living in Hawaii. Data for this study were obtained from a subsample of the cohort interviewed in 1982, and from the entire cohort from a mailed questionnaire in 1988 and the dementia prevalence survey in 1991 to 1993. The subjects included 3,385 men, age 71 to 93 years, whose use of vitamin E and C supplements had been ascertained previously. Cognitive performance was assessed with the Cognitive Abilities Screening Instrument, and subjects were stratified into four groups: low, low normal, mid normal, and high normal. For the dementia analyses, subjects were divided into five mutually exclusive groups: AD (n = 47), vascular dementia (n = 35), mixed/other types of dementia (n = 50), low cognitive test scorers without diagnosed dementia (n = 254), and cognitively intact (n = 2,999; reference). RESULTS: In a multivariate model controlling for other factors, a significant protective effect was found for vascular dementia in men who had reported taking both vitamin E and C supplements in 1988 (odds ratio [OR], 0.12; 95% CI, 0.02 to 0.88). They were also protected against mixed/other dementia (OR, 0.31; 95% CI, 0.11 to 0.89). No protective effect was found for Alzheimer's dementia (OR, 1.81; 95% CI, 0.91 to 3.62). Among those without dementia, use of either vitamin E or C supplements alone in 1988 was associated significantly with better cognitive test performance at the 1991 to 1993 examination (OR, 1.25; 95% CI, 1.04 to 1.50), and use of both vitamin E and C together had borderline significance (OR, 1.18; 95% CI, 0.995 to 1.39). CONCLUSIONS: These results suggest that vitamin E and C supplements may protect against vascular dementia and may improve cognitive function in late life.

Aged↗

Central hemodynamic and cognitive function in the short- and long-term periods after coronary bypass grafting.

The aim of the present work was to study cerebral hemodynamics and cognitive function in patients suffering from coronary artery disease (CAD) in the short- and long-term periods after coronary bypass grafting (CBG). The study accrued 65 patients who underwent myocardial revascularization using cardiopulmonary bypass (43 persons) and without heart interruption (22 persons). In 21 cases, CBG using cardiopulmonary bypass with a purpose of preventing cerebral events was supplemented by administration of instenon manufactured by the Nycomed Company, Perfusion tomoscintigraphy of the brain and neuropsychological testing were provided to all the patients prior to CBG, 14 days and 6 months following surgery. CBG coupled with preventive administration of instenon or beating heart operation allow to appreciably minimize the risk of disorders of cerebral hemodynamics and cognitive function in the long-term postoperative period.

Brain↗

Effects of valium and librium on human psychomotor and cognitive functions.

Research on the effect of the benzodiazepines, Valium, and Librium on human psychomotor and cognitive functions is reviewed. Benzodiazepines which are the most important antianxiety medications also have anticonvulsant, hypnotic-sedative, and muscle-relaxant properties. Research on the benzodiazepine hypnotic "hangover" effects on cognitive and motor behavior is cited. The benzodiazepines Valium and Librium probably interact with neurotransmitters, especially GABA and very likely have specific receptors in the brain and central nervous system. Absorption and elimination rate vary with dosage, method of administration, and age. Valium and Librium have no gravely harmful side effects, little addictive potential; danger from overdosage is minimal. Although controlled studies of the impact of psychoactive drugs on psychomotor and cognitive performance are relatively recent, Valium and Librium apparently have little, if any, adverse effect on well established higher mental functions and may affect the speed with which simple repetitive motor actions are performed. None of their effects are irreversible. Benzodiazepines (BZ) have been remarkable drugs. They have virtually replaced all other forms of antianxiety medications (48, 95, 109, 225). All the BZ drugs additionally have anticonvulsant, sedative-hypnotic, and muscle-relaxant properties (4, 77, 88, 112, 252). Two of the BZ drugs, Valium (diazepam) and Librium (chlordiazepoxide) have been the best sellers of the BZ drug family and the most frequently prescribed drugs in the world (7, 15, 17, 77, 110, 137, 215, 257). The impact of Valium and Librium on human psychomotor and cognitive functions is the focus of this review of research. Since millions of people are using these drugs, how do Valium and Librium affect alertness and responsiveness, for example, in driving a car to work, or operating a machine in a factory (240)? Tranquilizing drugs like Valium and Librium were hailed when they replaced sedatives like barbiturates because they did not cloud the mind. Is decision-making or mental alertness affected in those who use Valium or Librium (69)? In studying the impact of drugs on the central nervous system (CNS) and brain, animal subjects frequently are employed. However, the human condition of anxiety for which Valium and Librium are usually prescribed is hard to evaluate and human subjects vary greatly, so that this review of research has been limited for the most part to studies with human subjects (8, 26, 50, 107, 108, 262, 263, 264).

Aged↗

Hemispheric lateralization of cognitive functions in children with centrotemporal spikes.

We assessed the impact of unilateral epileptic foci in benign idiopathic partial epilepsy of childhood with rolandic discharges (BECT) on performance and hemispheric specialization in lateralized cognitive functions. Six children with BECT with a left-sided focus (BECT-L), 6 children with BECT with a right-sided focus (BECT-R), and 12 control children were tested in verbal, visual-spatial, and visual-attention tasks, with visual hemifield presentation. Children with BECT-R were impaired in the visual-spatial task relative to those with BECT-L, and the typical left-hemisphere (LH) advantage was not reported in the verbal task in children with BECT-L. Additionally, the classic global superiority effect was lacking in children with BECT-R, which may be due to impaired performance of the right hemisphere specialized in global (vs local)-level processing. These data argue for the deleterious effect of epileptic discharges per se on cognitive functions in the developing brain, and the decisive role of epileptic focus lateralization in specific cognitive impairments and hemispheric specialization.

Child↗

Cognitive function after radiotherapy for supratentorial low-grade glioma: a North Central Cancer Treatment Group prospective study.

PURPOSE: To evaluate the effects of cranial radiotherapy (RT) on cognitive function in patients with supratentorial low-grade glioma. METHODS AND MATERIALS: Twenty adult patients with supratentorial low-grade glioma were treated with 50.4 Gy (10 patients) or 64.8 Gy (10 patients) localized RT. The patients then were evaluated with an extensive battery of psychometric tests at baseline (before RT) and at approximately 18-month intervals for as long as 5 years after completing RT. To allow patients to serve as their own controls, cognitive performance was evaluated as change in scores over time. All patients underwent at least two evaluations. RESULTS: Baseline test scores were below average compared with age-specific norms. At the second evaluation, the groups' mean test scores were higher than their initial performances on all psychometric measures, although the improvement was not statistically significant. No changes in cognitive performance were seen during the evaluation period when test scores were analyzed by age, treatment, tumor location, tumor type, or extent of resection. CONCLUSIONS: Cognitive function was stable after RT in these patients evaluated prospectively during 3 years of follow-up. Slight improvements in some cognitive areas are consistent with practice effects attributable to increased familiarity with test procedures and content.

Adolescent↗

Homocysteine and cognitive function.

The prevention and treatment of age-related cognitive impairment and dementia is one of the greatest and most elusive challenges of our time. The prevalence of dementia increases exponentially with age, as does the prevalence of those with micronutrient deficiency. Several studies have shown that elevated homocysteine is correlated with cognitive decline and with cerebral atrophy and that it predicts the subsequent development of dementia in cognitively intact middle-aged and elderly individuals. If elevated homocysteine promotes cognitive dysfunction, then lowering homocysteine by means of B-vitamin supplementation may protect cognitive function by arresting or slowing the disease process.

Cognition↗

Cognitive functioning in Parkinson's disease: in relation to prevalence of dementia and psychiatric diagnosis.

Forty-three neurologically and psychiatrically assessed patients with idiopathic Parkinson's disease (PD) underwent detailed cognitive assessment. Cognitive deficits typical of senile dementia of Alzheimer's type (SDAT) were found in 7% but the majority showed definite impairments not typical of SDAT. Cognitive impairment was significantly more likely in those with more severe PD symptoms. There was substantial agreement between psychiatric diagnosis and psychological picture of SDAT and some links were found between other diagnostic categories and nature of cognitive functioning. However, cognitive deficits were also found in two-thirds of patients with no psychiatric diagnosis.

Aged↗