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Exposure to anaesthetic agents, cognitive functioning and depressive symptomatology in the elderly.

BACKGROUND: Anaesthesia could provoke persistent alterations in specific cognitive domains in the elderly where ageing-related neuronal changes may exacerbate pharmacotoxic effects. AIMS: To evaluate anaesthesia effects on the incidence of cognitive dysfunction after orthopaedic surgery in elderly patients. METHOD: A total of 140 patients over the age of 64 years completed a full range of computerised cognitive tests. The study takes into account effects of pre-operative cognitive dysfunction, depressive symptomatology and ability to perform activities of daily living. RESULTS: Postoperative cognitive decline persisted for up to 3 months in 56% of subjects. Dysfunction was limited to verbal, visuo-spatial and semantic abilities and secondary and implicit memory. Age, low educational level, pre-operative cognitive impairment or depression are risk factors. CONCLUSIONS: Cognitive functions are not equally affected, type of impairment being determined by the risk factors described above and anaesthesia type.

Activities of Daily Living↗

Glucocorticoids and cognitive function: from physiology to pathophysiology.

This paper reviews the literature on the relationship between glucocorticoids and cognitive functioning, including memory and selective attention. The main body of evidence suggests that hypothalamic-pituitary-adrenal (HPA) axis dysfunction or a state of hypercortisolaemia can be correlated with cognitive deficits specific to the medial temporal lobe declarative memory system. These impairments are discussed in relation to patients with HPA abnormalities, as seen in a significant number of patients with major depression or Cushing's syndrome, and also in relation to healthy volunteers after administration of glucocorticoids. It remains to be seen whether there are differential effects on acquisition, consolidation or retrieval processes. However, it would seem that glucocorticoids have a preferential effect on recall of information as opposed to recognition, possibly because recognition is more automatic.Type 2 glucocorticoid receptors (GRs), which are occupied by cortisol in humans in times of stress, are thought to be responsible for the glucocorticoid-induced memory impairment. GRs alter the feedback of the HPA axis, which in turn disrupts hippocampal functioning. While this can be reversible, animal studies suggest that chronic elevation of glucocorticoid levels can lead to the loss of hippocampal neurons and irreversible decline in declarative memory. Copyright 2001 John Wiley & Sons, Ltd.

Journal Article↗

Long-term effects of cerebellar pathology on cognitive functions.

Twelve patients with circumscribed chronic neocerebellar lesions but without CT-evidence of forebrain damage (other than the effects of shunting) were investigated for deficits of cognitive functions. Two different mechanisms were considered as possible causes of cognitive impairment: (1) Damage to the dentato-thalamo-cortical projection leading to impairments of cortical functions, and (2) prolonged intracranial pressure resulting in diffuse forebrain damage and subcortical dementia. Patients with lesions in the left neocerebellum showed deficits in cognitive operations in three dimensional space, consistent with the right forebrain dominance for spatial functions. Prolonged intracranial pressure, on the other hand, resulted in a mild overall cognitive impairment.

Brain Damage, Chronic↗

Poor sleep is associated with impaired cognitive function in older women: the study of osteoporotic fractures.

BACKGROUND: The association between objectively measured sleep and cognition among community-dwelling elderly persons remains understudied. This observational, cross-sectional analysis examined this association. METHODS: Results are from 2932 women (mean age 83.5 years) in the Study of Osteoporotic Fractures between 2002 and 2004. Cognitive function was measured by Mini-Mental State Examination (MMSE) and Trail Making B Test (Trails B). Cognitive impairment was defined as MMSE < 26 or Trails B > 278 seconds. Sleep parameters measured objectively using actigraphy included total sleep time, sleep efficiency, sleep latency, wake after sleep onset (WASO), and total nap time. RESULTS: There were 305 women (10.6%) with MMSE < 26 and 257 women (9.3%) with Trails B > 278 seconds. Compared with women with sleep efficiency > or = 70%, those with <70% had a higher risk of cognitive impairment (MMSE < 26 multivariate odds ratio [MOR] = 1.61; 95% confidence interval [CI], 1.20-2.16; Trails B > 278 MOR = 1.96; 95% CI, 1.43-2.67). Higher sleep latency was associated with higher risk of cognitive impairment (per half hour: MMSE < 26 MOR = 1.23; 95% CI, 1.13-1.33; Trails B > 278 MOR = 1.13; 95% CI, 1.04-1.24), as was higher WASO (per half hour: MMSE < 26 MOR = 1.15; 95% CI, 1.06-1.23; Trails B > 278 MOR = 1.24; 95% CI, 1.15-1.34). Women who napped > or = 2 hours per day had a higher risk (MMSE < 26 MOR = 1.42; 95% CI, 1.05-1.93; Trails B > 278 MOR = 1.74; 95% CI, 1.26-2.40). There was no significant relationship for total sleep time. CONCLUSION: Objectively measured disturbed sleep was consistently related to poorer cognition, whereas total sleep time was not. This finding may suggest that it is disturbance of sleep rather than quantity that affects cognition.

Aged↗

Effect of interferon-beta-1b on cognitive functions in multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is recognised as a central nervous system disease also affecting cognition. The rate of cognitive dysfunction in MS is in the range of 45-65% and adversely affect the quality of life. OBJECTIVE: To evaluate the effect of 1 year of treatment with interferon-beta-1b (IFNbeta-1b) on cognitive functions in patients suffering from relapsing-remitting MS. METHODS: A battery of cognitive tests was used to assess verbal learning, delayed recall, visual learning and recall, complex attention, concentration and verbal fluency at baseline and after 1 year of treatment with IFNbeta-1b. A group of 23 relapsing-remitting MS patients matched for neurological disability served as controls. RESULTS: Eighteen of 23 patients treated with IFNbeta-1b (74%) completed the study. In the IFNbeta-1b-treated group, complex attention, concentration as well as visual learning and recall improved significantly (p = 0.024, p = 0.006 and p = 0.005, respectively), while no deterioration was observed in the other dimensions. In the control group, complex attention, verbal fluency, as well as visual learning and recall deteriorated significantly (p = 0.02, p = 0.004 and p = 0.01, respectively), while no deterioration was observed in the other dimensions. CONCLUSION: Immunomodulating drugs that reduce the relapse rate and slow the disease progression also inhibit cognitive deterioration in patients with MS.

Adjuvants, Immunologic↗

Nutrition and the development of cognitive functions: interpretation of behavioral studies in animals and human infants.

A rapidly accumulating body of evidence on the neural basis of cognition suggests that cognition is not a unitary function but rather depends on the functions of multiple and dissociable neural systems. The nonlinear interactions in the differing trajectories of these systems during development result in changing patterns of cognitive functions over time; they may also lead to paradoxical outcomes, for which enhancement of one function through dietary intervention may be at the expense of another. This emerging understanding has important implications for the design and interpretation of studies on the cognitive effects of specific nutrients during development. It is important that researchers move away from global tests of development and strive rather to ensure that their choice of behavioral task is based on specific hypotheses of the systems expected to be altered by a dietary manipulation and on an understanding of which behavioral tests are valid, sensitive, and reliable indicators of this disruption. Furthermore, to understand whether accelerated or delayed development related to a particular cognitive function is beneficial or problematic, it is important to study the entire behavioral profile over different time points, rather than relying on one outcome measured at one time point. It is also necessary to control for sensory or motivational differences that will affect performance on the behavioral tasks. Implementation of these methodologic recommendations may contribute to a deeper understanding of the mechanisms involved in the nutrition-associated changes in cognitive functions and thereby aid in the development of an appropriate population-based dietary policy.

Animals↗

Anticholinergic challenge and cognitive functions: a comparison between young and elderly normal subjects.

Challenges of the central cholinergic function with anticholinergic agents have been shown to produce disruption of cognitive performance in young normal people. The purpose of the study was to compare the effects of a low dose of scopolamine in young and elderly subjects and to determine which cognitive functions are most sensitive to disruption by anticholinergics in an elderly population. Scopolamine (0.2 mg) and placebo were given to 12 normal elderly subjects (mean age 64.1 years) and 14 young subjects (mean age 26.7 years) and neuropsychological tests were designed to measure the functions of verbal memory, praxis and language. Scopolamine significantly impaired new learning in the elderly as measured by Selective Reminding Test (SRT) (p less than 0.04) and SRT delayed recall (p less than 0.05), but had no effect in the young subjects. Following the anticholinergic challenge, the elderly people also showed significantly poorer performance in all tests used for the praxis function. Results suggest a role of the cholinergic neurotransmission in verbal memory and constructional praxis. The language function was not impaired in the elderly and is not affected by anticholinergic agents.

Adult↗

Clinicometabolic dissociation of cognitive functions and social behavior in frontal lobe lesions.

OBJECTIVE/BACKGROUND: Case studies suggest a dissociation between cognitive functions that have been impaired after damage to the dorsolateral prefrontal cortex and social skills disturbed when the ventromedial prefrontal areas are affected. Because this dissociation had not been confirmed in a clinical setting, clinicometabolic correlations were sought in 13 patients with various lesions of the prefrontal cortex. DESIGN/METHODS: The clinical assessment included extensive testing of executive functions and evaluation of behavioral abnormalities based on an informant questionnaire. Regional cerebral glucose metabolism (rCMRGlu) was measured with [l8F] fluorodeoxyglucose ([18F] FDG) and 31-slide high-resolution PET. RESULTS: Executive-function test performance was significantly correlated with rCMRGlu in the dorsolateral prefrontal cortex (Brodmann's areas 8, 9, 45, 46, and 47) and anterior cingulate cortex (Brodmann's areas 24 and 32). Behavioral scores were significantly correlated with rCMRGlu in the frontopolar (Brodmann's area 10) and orbitofrontal cortex (Brodmann's areas 11, 12, 13, and 14). CONCLUSION: These results show that impaired executive functions and serial skill deficits are associated with distinct metabolic patterns in patients with frontal lobe pathology. In agreement with activation studies in normal subjects, our data suggest the existence of a modular organization of the frontal cortex in humans, as previously reported in nonhuman primates.

Adult↗

The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects.

RATIONALE: Extracts of Bacopa monniera have been reported to exert cognitive enhancing effects in animals. However, the effects on human cognition are inconclusive. OBJECTIVE: The current study examined the chronic effects of an extract of B. monniera (Keenmind) on cognitive function in healthy human subjects. METHODS: The study was a double-blind placebo-controlled independent-group design in which subjects were randomly allocated to one of two treatment conditions, B. monniera (300 mg) or placebo. Neuropsychological testing was conducted pre-(baseline) and at 5 and 12 weeks post drug administration. RESULTS: B. monniera significantly improved speed of visual information processing measured by the IT task, learning rate and memory consolidation measured by the AVLT (P<0.05), and state anxiety (P<0.001) compared to placebo, with maximal effects evident after 12 weeks. CONCLUSIONS: These findings suggest that B. monniera may improve higher order cognitive processes that are critically dependent on the input of information from our environment such as learning and memory.

Adolescent↗

Pyritinol hydrochloride and cognitive functions: influence on children in slow learner classes.

Pyritinol-HCl was tested for its impact on the cognitive functions of children with learning disabilities. This study is a contribution to scientific discussion on the complicated methodologic problems in evaluating the clinical efficacy of psychopharmacologic agents. Sixty-seven pupils of slow learner classes between the ages of 11 and 16 years were treated for 6 months with 300 mg pyritinol-HCl/24 hr or placebo under strict double-blind conditions. Drug intake was stimulated and controlled by means of intense psychosocial interaction with the mothers of the subjects. The dependence variables used to test medication effects were 22 parameters of cognitive performance measured in psychologic tests for perceptual and intellectual functions which were administered immediately before and after the medication phase. First the gainscores before and after treatment with pyritinol or placebo within the 22 cognitive parameters were statistically compared. In addition, an analysis of covariance on the corrected results of the second test (treating the results of first testing as covariates) and a two group discriminant analysis for overall differences were performed. None of the 22 parameters showed statistically significant treatment effects with respect to average performance (t (pyritinol - placebo) = 1.96 to 1.31), neither could the two groups be separated by discriminant analysis (Hotelling's T2 = 35.4, df - 22 and 43, P = 0.465). With respect to a variability of gainscores, however, in four parameters there was a significantly higher variance in the pyritinol group (F = 1.85-2.33, P less than 0.05, less than 0.02, respectively). This fact may signify that pyritinol-HCl had different effects on different subjects. By means of prognostic stratification we therefore attempted to define objective criteria for a selection of subjects with probable positive treatment effects. None of the 15 tested criteria, such as body weight, age, perceptual handicaps, or reduced short term memory, IQ range, proved, however, to be critical for a prognosis of pyritinol effects within the present test population.

Adolescent↗

Cognitive functioning after subarachnoid haemorrhage of unknown origin.

Twenty patients, who had sustained a proven subarachnoid haemorrhage (SAH) and in whom cerebral panangiography had failed to reveal any source of the bleeding (SAH-NUD), were subjected to a neuropsychological examination involving memory functions, spatial perceptual organization, visuoconstructive abilities, reasoning, perceptual speed and accuracy, and concept formation. Cognitive functioning in SAH-NUD patients was compared with normal reference values and also related to the cognitive performance of neurologically intact patients having sustained an aneurysmal bleeding (SAH-AN). SAH-NUD patients showed significant reduction of verbal learning and retention, and of abilities involving abstract attitude and concept formation, i.e., functions related to frontotemporal structures. In all other respects the performance of these patients approached normality. Unexpectedly, there were no significant differences in mean test scores separating SAH-NUD from aneurysmal SAH patients. Collapsing the patient groups produced an increased number of significant deviations from normality, which was interpreted as the effect of the contribution of a greater number of relatively more impaired SAH-AN patients. This was supported by the finding that the ratio of impaired individuals to total number of subjects differed in the groups; the proportion of individuals showing cognitive sequelae was larger among SAH-AN patients throughout all comparisons but one. Although SAH of unknown aetiology represents much less of a catastrophe as compared with haemorrhage of aneurysmal origin, it does not preclude cognitive disturbances. Thus, the presence of blood per se anywhere in the subarachnoid spaces appears to affect higher brain function(s).

Adolescent↗

Impairments of some cognitive functions are common in crash-involved older drivers.

The relationship between limitations in different cognitive functions, measured with a neuropsychological test battery, and moving traffic violations among older drivers was investigated. Thirty-seven drivers aged 65 years or more, with temporarily suspended driving licenses (suspended drivers) were identified 23 were crash-involved and 14 were not. When compared to 31 controls with clean driving records, crash-involved suspended drivers performed less well on tests of visuoconstructive ability (p = 0.008), psychomotor speed (p = 0.019) and visuospatial memory (p = 0.036). Non-crash-involved suspended drivers did not differ from controls. A combination of three tests (of visuoconstructive ability, visuospatial memory and verbal episodic memory) succeeded in correctly classifying 65.2% of the crash-involved suspended drivers. The results support the idea of cognitive decrements as an important causal factor in crashes of older drivers.

Accidents, Traffic↗

Untreated blood pressure level is inversely related to cognitive functioning: the Framingham Study.

It was hypothesized that blood pressure would be inversely related to cognitive functioning, if unconfounded with antihypertensive medication and measured over many occasions prior to neuropsychological testing. For stroke-free Framingham Study participants aged 55-88 years (n = 1,702), blood pressure levels were averaged over five biennial examinations (1956-1964) when few hypertensives were being treated, and examined in relation to neuropsychological tests administered between 1976 and 1978. With age, education, occupation, cigarette smoking, alcohol consumption, and gender controlled, blood pressure levels and chronicity of hypertension were inversely related to the composite score and measures of attention and memory. This was true for the full sample, for a subsample untreated during blood pressure measurement (n = 1,485), and for a subsample untreated throughout the entire study period (n = 1,038). For example, decline per 10 mmHg increment in blood pressure ranged from -0.04 to -0.07 standard score units (z) for the composite score. A negative finding previously was most likely due to blood pressure measurement concurrently with neuropsychological testing, or too few measurements. Hypertension-associated pathogenic processes may cause mild cognitive impairment, but other mechanisms need to be considered.

Aged↗

Cognitive functioning in sporadic amyotrophic lateral sclerosis: a six month longitudinal study.

OBJECTIVE: To observe changes in cognition over six months in subjects with recently diagnosed sporadic amyotrophic lateral sclerosis (ALS). METHODS: The study used a between-group and within-group longitudinal design. Nineteen ALS subjects and eight matched caregivers were recruited to participate in baseline neuropsychological assessments that were repeated six months later. Between group comparisons for these variables were undertaken at baseline and six months later. Within group/across time comparisons for these variables were carried out for both groups. Individual analyses for the neuropsychological variables using z scores were done for the ALS subjects using their baseline performance as the basis for comparison with their six month performance. RESULTS: The between-group and within-group comparisons did not show significant differences in cognitive function over time. In individual analyses, however, seven of 19 ALS subjects (36.84%) developed abnormal neuropsychological performance over six months. CONCLUSIONS: Early in the disease course, over one third of the ALS subjects developed cognitive deficits over six months. These findings support the hypothesis that cognitive deficits in ALS become more prominent over time.

Aged↗

Effects of oxcarbazepine on cognitive function in children and adolescents with partial seizures.

The authors investigated the effect of oxcarbazepine on cognitive function in children and adolescents (6 to younger than 17 years of age) with newly diagnosed partial seizures in an open-label comparison with standard antiepileptic drug therapy (carbamazepine and valproate). No differences in cognitive tests were observed between oxcarbazepine and carbamazepine/valproate over a 6-month treatment period.

Adolescent↗

Cognitive conjunction and cognitive functions.

We argue that conjunction analysis does not solve the problems with subtraction analyses that it sets out to solve and that it has additional problems of its own. We argue that detailed analyses of the tasks set to identify cognitive functions are required for both conjunction and subtraction analyses to achieve their goals of localizing cognitive operations using functional neuroimaging techniques.

Attention↗

Cognitive function and neurophysiological evaluation in early-treated hypothyroid children.

In this study, we assessed cognitive function and neurophysiological development in congenitally hypothyroid (CH) children. We performed a cross-sectional study at the outpatient Pediatric Clinic and Department of Neurophysiology at San Raffaele Hospital, Milan. The study enrolled 25 CH patients (6.00-10.83 years of age) detected by neonatal screening, and 34 healthy control children (4-11 years of age). Patients and controls had comparable scores at neuropsychological tests (WISC-R), and at auditory P300 tests. In contrast, we found significantly longer LLSEP latencies in CH patients (p < 0.03). CH patients treated 30 days after birth showed lower scores at neuropsychological tests, but not at neurophysiological tests, compared to patients who started the replacement therapy earlier. Patients with more severe fetal hypothyroidism (T4 levels at diagnosis < or = 2 micrograms/dl) had lower neuropsychological scores, and similar neurophysiological results, compared with patients with moderate fetal hypothyroidism. The severity of fetal hypothyroidism and early treatment influence the mental outcome of CH patients. Neurophysiological results show that central nervous system damage occurs in some patients despite early treatment.

Child↗

Detrimental effects of tumor progression on cognitive function of patients with high-grade glioma.

PURPOSE: There is growing recognition that the primary cause of cognitive deficits in adult patients with primary brain tumors is the tumor itself and more significantly, tumor progression. To assess the cognitive performance of high-grade glioma patients, prospectively collected cognitive performance data were analyzed. PATIENTS AND METHODS: We studied 1,244 high-grade brain tumor patients entered onto eight consecutive North Central Cancer Treatment Group treatment trials that used radiation and nitrosourea-based chemotherapy. Imaging studies and Folstein Mini-Mental State Examination (MMSE) scores recorded at baseline, 6, 12, 18, and 24 months were analyzed to assess tumor status and cognitive function over time. RESULTS: The proportion of patients without tumor progression who experienced clinically significant cognitive deterioration compared with baseline was stable at 6, 12, 18, and 24 months (18%, 16%, 14%, and 13%, respectively). In patients without radiographic evidence of progression, clinically significant deterioration in MMSE scores was a strong predictor of a more rapid time to tumor progression and death. At evaluations preceding interval radiographic evidence of progression, there was significant deterioration in MMSE scores for patients who were to experience progression, whereas the scores remained stable for the patients who did not have tumor progression. CONCLUSION: The proportion of high-grade glioma patients with cognitive deterioration over time is stable, most consistent with the constant pressure of tumor progression over time. Although other factors may contribute to cognitive decline, the predominant cause of cognitive decline seems to be subclinical tumor progression that precedes radiographic changes.

Adult↗