Cognitive status in persons with amalgam-related complaints.

Self-reported cognitive symptoms are frequent in persons with amalgam-related complaints, but few studies have focused on their cognitive function. The aim was to examine a symptom profile and whether participants with amalgam-related complaints have cognitive deficits in comparison with control individuals. We drew 342 participants with amalgam-related complaints and 342 one-to-one matched control individuals from a longitudinal population-based study. For 81 of the participants with amalgam-related complaints and controls, data were available approximately five years before the onset of complaints, making a longitudinal analysis possible. All participants were assessed by a self-reported health questionnaire and a comprehensive cognitive test battery. The participants with amalgam-related complaints reported more symptoms, mainly musculoskeletal and neuropsychological, compared with control individuals (p < 0.001). The results revealed no significant difference between the amalgam and control group, either cross-sectionally or longitudinally, for any of the cognitive tests. These results suggest that cognitive decline is not associated with amalgam-related complaints.

Optimized convective transport with automated pressure control in on-line postdilution hemodiafiltration.

PURPOSE: In a stable patient population we evaluated on-line postdilution hemodiafiltration (HDF) on the incremental improvement in blood purification versus high-flux HD, using the same dialyzer and blood flow rate. For HDF we used a new way of controlling HDF treatments based on the concept of constant pressure control where the trans-membrane pressure is automatically set by the machine using a feedback loop on the achieved filtration (HDF UC). METHODS: We enrolled 20 patients on on-line HDF treatment and during a 4-week study period recorded key treatment parameters in HDF UC. For one mid-week study treatment performed in HD and one midweek HDF UC treatment we sampled blood and spent dialysate to evaluate the removal of small- and middle-sized solutes. RESULTS: We achieved 18+/-3 liters of ultrafiltration in four-hour HDF UC treatments, corresponding to 27+/-3% of the treated blood volume. That percentage varied by patient hematocrit level. The ultrafiltration amounted to 49+/-4% of the estimated plasma water volume treated. We noted few machine alarms. For beta2m and factor D the effective reduction in plasma level by HDF (76+/-6% and 43+/-9%, respectively) was significantly greater than in HD, and a similar relation was seen in mass recovered in spent dialysate. Small solute removal was similar in HDF and HD. Albumin loss was low. CONCLUSION: The additional convective transport provided by on-line HDF significantly improved the removal of middle molecules when all other treatment settings were equal. Using the automated pressure control mode in HDF, the convective volume depended on the blood volume processed and the patient hematocrit level.

Altered deactivation in individuals with genetic risk for Alzheimer's disease.

Regions that show task-induced deactivations may be part of a default-mode network related to processes that are more engaged during passive than active task conditions. Alteration of task-induced deactivations with age and dementia is indicated by atypical engagement of default-mode network regions. Genetic studies show a relation between the apolipoprotein E4 (APOE4) allele and the common form of Alzheimer's disease (AD), and altered functional brain activation has been observed in non-demented APOE4 carriers compared to non-carriers. Here we investigate the hypothesis of altered default-mode network brain responses in individuals with genetic risk for AD. Functional MRI was used to assess task-induced deactivation in 60 subjects of which 30 carried at least one copy of the APOE4 allele, and 30 non-carriers. Subjects were scanned while performing a semantic categorization task shown to promote episodic memory encoding. The results show patterns of deactivation consistent with the default-mode network. We also found reduced deactivation in non-demented APOE4 carriers compared to non-carriers, suggesting alterations in the default-mode network in the absence of dementia. These results implicate possibilities for investigating altered properties of task-induced deactivations in individuals with genetic risk for AD, and may prove useful for pre-clinical identification of individuals susceptible to memory problems and AD.

Fatigue before and after mild traumatic brain injury: pre-post-injury comparisons in relation to Apolipoprotein E.

PRIMARY OBJECTIVE: To assess the incidence of fatigue for persons following a mild traumatic brain injury (MTBI) and to evaluate the relationship between fatigue and APOE genotype. As fatigue is often found to be influenced by anxiety, depression and sleep disturbance, these factors were also measured. METHODS AND PROCEDURES: Thirty-one persons who sustained a MTBI were drawn from a population-based longitudinal study. Each person who sustained a MTBI was matched by age, gender, education and APOE genotype with two non-head injury controls. Self-reported pre- and post-injury incidence of fatigue, anxiety, depression and sleep disturbance was compared within-group and between groups. RESULTS: For the MTBI group, incidence of fatigue was almost twice as common post- than pre-injury, whereas there was no corresponding change in a non-injured control group. Within the MTBI-group, post-injury fatigue was particularly common for carriers of the APOE epsilon4 allele. CONCLUSIONS: Fatigue is common sequela after a MTBI and especially pronounced for carriers of the APOE epsilon4 allele.

Evaluation of the Polyflux 6H dialyzer in pediatric patients receiving maintenance hemodialysis.

Hemodialysis remains the only life sustaining maintenance renal replacement therapy option for children who cannot undergo expeditious renal transplantation or who are not medical candidates for peritoneal dialysis. Provision of maintenance hemodialysis to small children entails many challenges, which arise from the limited choices for appropriately sized disposable dialysis treatment components. The dialysis extracorporeal circuit volume, comprised of the blood tubing and dialyzer, should be low enough to prevent hypotension and prevent the need for repeated blood transfusions. We performed a market acceptance evaluation of the Polyflux 6H dialyzer (0.6 m2 membrane surface area; Gambro Renal Products, Lakewood, Colorado) in six pediatric patients (3 male, 3 female, mean weight 24.4+6.5 kg, mean age 10.3+3.8 yrs). We found that the Polyflux 6H Dialyzer provided a trend for improved clearance compared to Fresenius F3 and F4 dialyzers. We found that the Polyflux 6H Dialyzer provided adequate clearance for children up to 24 kg in size and is a suitable dialyzer choice for patients 13 to 26 kg in size.

Increased risk of dementia following mild head injury for carriers but not for non-carriers of the APOE epsilon4 allele.

BACKGROUND: The epsilon4 allele of apolipoprotein E (APOE) and head injury are risk factors for dementia diseases, and may act synergistically to further increase the risk. The aim of this study was to examine the association between mild head injury, APOE and dementia. METHODS: Data were obtained from the Betula prospective population-based study of aging, memory, and health. The study included 543 participants in the age range 40-85 years, free of dementia at baseline, who were followed up within a 5-year interval. Dementia was classified using DSM-IV criteria. Information on previous head injury was obtained through screening of the participants' answers to health questionnaires at baseline and at follow-up. RESULTS: Subjects with head injury but without APOE epsilon4 had no increased risk of dementia. Subjects with APOE epsilon4 had an increased risk and those with both APOE epsilon4 and head injury had the highest risk of dementia (odds ratio = 5.2). CONCLUSIONS: APOE epsilon4 constitutes a risk factor for dementia, mild injury in isolation does not increase the risk, but head injury in combination with the APOE epsilon4 leads to increased risk of dementia.

Altered brain white matter integrity in healthy carriers of the APOE epsilon4 allele: a risk for AD?

BACKGROUND: Previous research has shown that polymorphisms of apolipoprotein E (APOE) represent genetic risk factors for dementia and for cognitive impairment in the elderly. The neural mechanisms by which these genetic variations influence behavioral performance or clinical severity are not well understood. METHODS: The authors used diffusion tensor imaging to investigate ultrastructural properties in brain white matter to detect pathologic processes that modify tissue integrity. Sixty participants were included in the study of which 30 were homozygous for the APOE epsilon3 allele, 10 were homozygous for the APOE epsilon4 allele, and 20 had the APOE epsilon34 allele combination. All individuals were non-demented, and the groups were matched on demographic variables and cognitive performance. RESULTS: The results showed a decline in fractional anisotropy, a marker for white matter integrity, in the posterior corpus callosum of epsilon4 carriers compared to non-carriers. Additional sites of altered white matter integrity included the medial temporal lobe. CONCLUSIONS: Although the mechanism underlying vulnerability of white matter tracts in APOE epsilon4 carriers is still unknown, these findings suggest that increased genetic risk for developing Alzheimer disease is associated with changes in microscopic white matter integrity well before the onset of dementia.

Regional variability in the prevalence of cerebral white matter lesions: an MRI study in 9 European countries (CASCADE).

White matter lesions (WML) on MRI of the brain are common in both demented and nondemented older persons. They may be due to ischemic events and are associated with cognitive and physical impairments. It is not known whether the prevalence of these WML in the general population differs across European countries in a pattern similar to that seen for coronary heart disease. Here we report the prevalence of WML in 1,805 men and women drawn from population-based samples of 65- to 75-year-olds in ten European cohorts. Data were collected using standardized methods as a part of the multicenter study CASCADE (Cardiovascular Determinants of Dementia). Centers were grouped by region: south (Italy, Spain, France), north (Netherlands, UK, Sweden), and central (Austria, Germany, Poland). In this 10-year age stratum, 92% of the sample had some lesions, and the prevalence increased with age. The prevalence of WML was highest in the southern region, even after adjusting for differences in demographic and selected cardiovascular risk factors. Brain aging leading to disabilities will increase in the future. As a means of hypothesis generation and for health planning, further research on the geographic distribution of WML may lead to the identification of new risk factors for these lesions.

Association of cyclin-dependent kinase 5 and neuronal activators p35 and p39 complex in early-onset Alzheimer's disease.

Malfunctioning of cyclin-dependent kinase 5 (CDK5) through aberrant proteolytic cleavage of its neuronal activators p35 and p39 is involved in neurodegeneration in Alzheimer's disease (AD) and other neurodegenerative brain diseases. By extensive genetic analysis of the genes encoding CDK5 (CDK5), p35 (CDK5R1) and p39 (CDK5R2), we excluded causal mutations in 70 familial early-onset AD patients. We performed an association study with five informative SNPs in CDK5 in two independent samples of early-onset AD patients and matched control individuals from The Netherlands and northern Sweden. Association was observed with g.149800G>C in intron 5 of CDK5, and a two times increased risk was observed in both patient samples for carriers of the C-allele. Our data are indicative for a role of the CDK5 molecular complex in the genetic etiology of early-onset AD, and suggest that a yet unknown functional variant in CDK5 or in a nearby gene might lead to increased susceptibility for early-onset AD.

Sex differences in spatial visualization and episodic memory as a function of alcohol consumption.

AIMS: Sex differences in visuospatial ability as well as episodic memory have been reliably demonstrated, irrespective of alcoholism. Studies in alcoholics have consistently documented cognitive deficits in visuospatial ability, problem solving and memory function. This cross-sectional, population-based study examined if sex differences in cognitive performance could be impacted by alcohol consumption. METHODS: Drinking data were collected from 2224 randomly sampled adults, aged between 35 and 85 years, who participated in the Betula study on memory, health and aging. Participants were classified into non-, light, moderate and heavy drinking subgroups based on sex-adjusted normative values. Cognitive tasks demonstrating clear sex differences, such as episodic memory tasks (favouring women) and spatial visualization tasks (favouring men), were conducted and performance was assessed by sex and the drinking group. RESULTS: After controlling for age and education, overall analyses found expected sex differences in episodic memory and spatial visualization that were apparent across the entire population. When these sex differences were examined by drinking group, visuospatial performance favouring men disappeared for the moderate to heavy drinking groups, but higher performance by women on episodic memory tasks was consistent across all levels of alcohol consumption. Traditional biomarkers of increased alcohol consumption (GGT and MCV) correlated with the reported drinks/day. CONCLUSIONS: These results lend support to the theory that moderate alcohol intake may be beneficial to cognitive function in women, but not necessarily in men.

APOE influences on neuropsychological function after mild head injury: within-person comparisons.

OBJECTIVE: To examine the relationship between neuropsychological outcome following mild head injury (MHI) and APOE genotype. METHODS: Data from a population-based longitudinal study (n = 3,500) were used to identify 34 adults who experienced MHI during the course of the study. Their pre- and postinjury performances on a battery of nine neuropsychological tests were compared within person, and the postinjury performance was compared with that of age- and gender-matched control subjects. RESULTS: The within-person comparisons showed that participants with at least one APOE epsilon4 allele (n = 11) had a significantly decreased postinjury performance on three of the tests, whereas the postinjury performance for APOE epsilon4-negative participants (n = 23) was unchanged. There was no significant difference in postinjury performance between participants with/without the epsilon4 allele, and neither group was impaired relative to controls. CONCLUSIONS: APOE genotype may influence the outcome following an MHI. Pre/postinjury within-person comparisons seem more sensitive than control group comparisons for detecting injury-related effects.

Cerebral atrophy as predictor of cognitive function in old, community-dwelling individuals.

OBJECTIVES: The impact of cortical and subcortical atrophy on cognitive function was examined in a sample of older community-dwelling men and women. MATERIAL AND METHODS: Magnetic resonance imaging was performed on a sample of 129 individuals [age: 68.4 +/- 3.6 years (mean +/- SD), range 64-74 years, 64 women and 65 men, Mini-Mental State Examination scores above 23] to assess cortical and subcortical atrophy. Participants also performed a number of cognitive tasks, and the measures of atrophy were used to predict performance in these tasks. RESULTS: In men, frontal cortical atrophy predicted worse performance in word fluency and the Stroop test, and occipital cortical atrophy was associated with poor performance in motor speed. In women, poor performance in motor speed was associated with subcortical atrophy at the level of the caudate nucleus. CONCLUSION: Atrophy in certain areas was associated with poor performance in specific cognitive tasks, although the amount of explained variance was rather limited in this quite homogeneous sample.

The serotonin transporter promoter repeat length polymorphism, seasonal affective disorder and seasonality.

BACKGROUND: Conflicting results have been reported in previous association studies of the serotonin transporter promoter repeat length polymorphism (5-HTTLPR), seasonal affective disorder (SAD) and seasonality (seasonal variations in mood and behaviour). The aim of this study was to test for association in new case-control and population-based materials, and to perform a combined analysis of all published studies of 5-HTTLPR and SAD. METHOD: One hundred and forty-seven new SAD cases and 115 controls were genotyped for 5-HTTLPR and in total 464 patients and 414 controls were included in the pooled analysis. In addition, 226 individuals selected for unusually high or low seasonality scores from a population based material and 46 patients with non-seasonal depression were analysed. Different genetic models were tested and seasonality was analysed both as a qualitative (high v. low) and as a quantitative trait in the different sample sets. RESULTS: No association between 5-HTTLPR and SAD was found in the new case-control material, in the combined analysis of all samples, or when only including 316 patients with controls (N = 298) selected for low seasonality. A difference was detected between the population based high and low seasonality groups, when assuming a recessive effect of the short allele (20% and 10% short allele homozygotes, respectively, OR (95% CI): 2.24 (1.03-4.91)). Quantitative analysis of seasonality revealed no association with 5-HTTLPR in any sample set. CONCLUSIONS: These results do not suggest a major role of the short variant of 5-HTTLPR in susceptibility to SAD, but provide modest evidence for an effect on seasonality.

Facilitation of source discrimination in the novelty effect.

It has been demonstrated experimentally that recognition of novel items is more accurate than recognition of previously familiarized items. Tulving and Kroll (1995) proposed that this effect is due to novelty detectors in the brain giving processing priority to novel information. Recently, Dobbins et al. (1998) suggested that the effect is due to source discrimination problems. In the present two experiments attempts were made to facilitate source discrimination by having different orienting tasks and materials in the familiarization and in the critical presentations. Degree of familiarization was manipulated by varying number of presentations one, two or three times. The results in Experiment 1 showed that the novelty effect increased linearly as a function of presentations in the familiarization phase. In the second experiment the difference between familiar and novel items was even more pronounced. Enactment at encoding was added as a manipulation during familiarization. The results of Experiment 2 showed that the novelty effect did increase linearly for items with nonenacted encoding (in which the familiarization and the critical phase were more similar) but not for enacted encoding. All subjects reported experiencing source discrimination difficulties in both experiments despite the measures taken to diminish them. It seems safe to conclude that source discrimination difficulties are a part of the novelty effect.

Reactivation of motor brain areas during explicit memory for actions.

Recent functional brain imaging studies have shown that sensory-specific brain regions that are activated during perception/encoding of sensory-specific information are reactivated during memory retrieval of the same information. Here we used PET to examine whether verbal retrieval of action phrases is associated with reactivation of motor brain regions if the actions were overtly or covertly performed during encoding. Compared to a verbal condition, encoding by means of overt as well as covert activity was associated with differential activity in regions in contralateral somatosensory and motor cortex. Several of these regions were reactivated during retrieval. Common to both the overt and covert conditions was reactivation of regions in left ventral motor cortex and left inferior parietal cortex. A direct comparison of the overt and covert activity conditions showed that activation and reactivation of left dorsal parietal cortex and right cerebellum was specific to the overt condition. These results support the reactivation hypothesis by showing that verbal-explicit memory of actions involves areas that are engaged during overt and covert motor activity.

Season of birth variations in the temperament and character inventory of personality in a general population.

BACKGROUND: Since several studies show season of birth variations in morbidity, suicidal behavior and CSF (cerebrospinal fluid) monoamine metabolites, we investigated season of birth variations in personality in the population. METHODS: We analyzed by multiple logistic regressions the Temperament and Character Inventory (TCI) for 2,130 individuals taking part in the Betula prospective random cohort study of Umeå, Sweden. RESULTS: The personality dimensions were correlated significantly with age and gender. We stratified the data according to age, gender and the season of TCI measurement. By the median split in each stratum, a high-value group and a low-value group were obtained for each of the personality dimensions. Those born during February to April were significantly more likely than those born during October to January to have high NS (novelty seeking) among women, particularly the subscale NS2 (impulsiveness vs. reflection), and to have high PS (persistence) among men. Temperament profiles also showed season of birth variations. CONCLUSIONS: We discuss the associations in the literature between personality and the monoamines serotonin and dopamine, and suggest that our results are compatible with a hypothesis of season of birth variation in the monoamine turnover. The personality traits are likely to be influenced by several genetic and environmental factors, one of them being the season of birth.

Human-figure drawing and memory functioning across the adult life span.

The main objective was to evaluate changes in the ability to draw the human figure (HFD) across adult life span and to relate these changes to those known to exist in memory function. Healthy adults (1000) from each of 10 five-year cohorts between 35 and 80 years were recruited randomly from a population in northern Sweden. Each participant was administered a health examination including cognitive testing and a drawing test, and an extensive examination of memory functions. For the drawing variables HFDarch and HFDtot, there is a steady decrease in episodic memory with poor drawers performing at a lower level. For semantic memory up to 65 years of age, there is no difference in performance, but thereafter a decrease. Good drawers show a better memory performance than poor drawers. For priming data for both HFDarch and HFDtot, there seems to be an interaction between age and drawing, such that poor drawers perform at a lower level for the two oldest groups but not for the youngest group. The HFDess is a valuable instrument and can support clinical evaluation as a screening for cognitive decline. The reduction of essential body details was strongly related to dementia progression, and thus as good a predictor of cognitive decline as episodic memory performance. The reduced capacity to perform a complex HFD declines with age and is most pronounced in the oldest age groups.

Quality of life rapidly improves with budesonide therapy for active Crohn's disease. Canadian Inflammatory Bowel Disease Study Group.

Our aims were to assess the impact on health-related quality of life (HRQOL) of a controlled ileal release (CIR) formulation of budesonide in active Crohn's disease (CD) and further define the role of HRQOL, using the Inflammatory Bowel Disease Questionnaire (IBDQ), in assessing outcome in CD. A randomized trial was conducted in 258 patients with active ileal or ileocecal CD. Budesonide CIR 1.5 mg, 4.5 mg, 7.5 mg, or placebo was given b.i.d. for 8 weeks. IBDQ score changes were compared among groups. Correlations for IBDQ and Crohn's Disease Activity Index (CDAI) scores were calculated. Mean IBDQ scores improved significantly over placebo by 2 weeks in budesonide 15 mg (155+/-38; p = 0.006) and 9 mg groups (157+/-33; p = 0.0002). Bowel, systemic, social, and emotional subscores were also significantly better (p < 0.002) at 2 and 8 weeks in the 9 mg group. Improved HRQOL scores correlated well with decreased CDAI (-0.8 < r < -0.4). Average per item change in IBDQ at remission was 1.17 to 1.48. Prior surgery (p < 0.005) or current smoker (p < 0.05) status predicted poorer initial HRQOL but not response. Budesonide CIR 9 or 15 mg/day rapidly and significantly improved HRQOL in active CD.

Activity in motor areas while remembering action events.

Episodic memory for simple commands is better following enacted than verbal encoding. This has been proposed to be due to the possibility to base retrieval on motor information. Here we used PET to test the hypothesis that motor brain areas show increased retrieval-related activity following enacted compared to verbal encoding. Brain activity was also monitored during retrieval after imaginary enactment during encoding. It was found that activity in the right motor cortex was maximal following encoding enactment, intermediate following imaginary encoding enactment, and lowest following verbal encoding. These findings provide support that one basis for the facilitating effect on memory performance of overt, and to a lesser degree covert, encoding enactment is the possibility to base retrieval on motor information.