The association between migraine and dementia - a national register-based matched cohort study.

OBJECTIVES: Migraine and dementia, two major public health challenges, are associated, but more knowledge is needed to understand their relationship. Objectives of this study were to investigate 1) the association between non-self-reported measures of migraine and dementia, and whether dementia was associated with 2) migraine without aura (MO) and with aura (MA) in combination with migraine medication use, and 3) migraine severity operationalized as the number of migraine prescriptions. STUDY DESIGN: Matched cohort study. METHODS: National register data were obtained from individuals born between 1934 and 1958. Migraine cases (aged 25-58 years) were identified by migraine diagnoses and redeemed migraine medication. Migraine cases were matched with non-cases (N = 340,850) and date of diagnosis or medication redemption was defined as index year. Dementia was identified by dementia diagnoses and redeemed dementia medication. RESULTS: We observed a 1.46 (95% CI: 1.26-1.69) times higher dementia rate in individuals with a migraine diagnosis and a 0.86 (95% CI: 0.76-0.97) times lower rate when using migraine medication. We found the highest dementia rate among individuals with MA, who also used migraine medication (HR = 2.23; 95% CI: 1.19-4.17), and the lowest rate among individuals with MO, who also used medication (HR = 1.25; 95% CI: 0.75-2.10). The number of migraine medication prescriptions was not associated with dementia. CONCLUSIONS: Being registered with a migraine diagnosis was associated with a higher dementia rate, while use of prescribed migraine medication was not. The differences in the dementia rate among migraine cases identified via diagnoses versus medications warrants further investigation.

Increased short- and long-term mortality following infections in dementia: a nationwide registry-based cohort study.

BACKGROUND AND PURPOSE: Mortality following infections in dementia has not yet been comprehensively explored. The aim of this cohort study was to investigate the short- and long-term mortality following infections in dementia. METHODS: Follow-up was from 1 January 2000 or the 65-year birthday until death, immigration, or 31 December 2015. Exposure was incident dementia and a first infection. The outcome was all-cause mortality. Mortality rate ratios (MRRs) were calculated using Poisson regression in 4 exposure groups (dementia yes/no, infection yes/no) by sex, infection site, and time since infection. RESULTS: 1,496,436 people were followed with 12,739,135 person-years. MRR in dementia/infection was 6.52 (95% confidence interval: 6.43-6.60) and was increased for infections of all sites. Increased mortality was short term (30 days) and long term (10 years). CONCLUSIONS: Increased mortality in people with dementia identifies them as a particularly vulnerable group that needs clinical attention.

Electroencephalographic functional connectivity is altered in persons with Down syndrome and Alzheimer's disease.

BACKGROUND: Persons with Down syndrome (DS) are at increased risk of developing Alzheimer's dementia (DS-AD). Due to heterogeneity in the functioning in persons with DS, it is difficult to use cognitive testing to assess whether a person with DS has developed dementia due to AD. Electroencephalography (EEG) functional connectivity has shown promising results as a diagnostic tool for AD in persons without DS. In the current exploratory study, we investigated whether EEG functional connectivity could be used as a diagnostic marker of AD in persons with DS and the association with symptoms. METHODS: Electroencephalography from 12 persons with DS and 16 persons with DS-AD were analysed, and both coherence and weighted phase lag index were calculated. In addition, we calculated the average coherence for fronto-parietal and temporo-parietal connections. Lastly, we investigated the correlation between the informant-based Dementia Screening Questionnaire in Intellectual Disability (DSQIID) and total alpha coherence. RESULTS: Decreased alpha and increased delta coherence and weighted phase lag index were observed in DS-AD as compared with DS. The decrease in alpha coherence was more marked in the fronto-parietal connections as compared with the temporo-parietal connections. No significant correlation was found between DSQIID and total alpha coherence (P value = 0.095, rho = -0.335). CONCLUSION: The decreased alpha coherence and weighted phase lag index have previously been found in AD. The increased delta coherence and weighted phase lag index may indicate a different initial neurophysiological presentation as compared with patients with AD or may be a sign of more advanced disease. Larger studies are needed to confirm the current findings.

A European Academy of Neurology guideline on medical management issues in dementia.

BACKGROUND AND PURPOSE: Dementia is one of the most common disorders and is associated with increased morbidity, mortality and decreased quality of life. The present guideline addresses important medical management issues including systematic medical follow-up, vascular risk factors in dementia, pain in dementia, use of antipsychotics in dementia and epilepsy in dementia. METHODS: A systematic review of the literature was carried out. Based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework, we developed a guideline. Where recommendations based on GRADE were not possible, a good practice statement was formulated. RESULTS: Systematic management of vascular risk factors should be performed in patients with mild to moderate dementia as prevention of cerebrovascular pathology may impact on the progression of dementia (Good Practice statement). Individuals with dementia (without previous stroke) and atrial fibrillation should be treated with anticoagulants (weak recommendation). Discontinuation of opioids should be considered in certain individuals with dementia (e.g. for whom there are no signs or symptoms of pain or no clear indication, or suspicion of side effects; Good Practice statement). Behavioral symptoms in persons with dementia should not be treated with mild analgesics (weak recommendation). In all patients with dementia treated with opioids, assessment of the individual risk-benefit ratio should be performed at regular intervals. Regular, preplanned medical follow-up should be offered to all patients with dementia. The setting will depend on the organization of local health services and should, as a minimum, include general practitioners with easy access to dementia specialists (Good Practice statement). Individuals with dementia and agitation and/or aggression should be treated with atypical antipsychotics only after all non-pharmacological measures have been proven to be without benefit or in the case of severe self-harm or harm to others (weak recommendation). Antipsychotics should be discontinued after cessation of behavioral disturbances and in patients in whom there are side effects (Good Practice statement). For treatment of epilepsy in individuals with dementia, newer anticonvulsants should be considered as first-line therapy (Good Practice statement). CONCLUSION: This GRADE-based guideline offers recommendations on several important medical issues in patients with dementia, and thus adds important guidance for clinicians. For some issues, very little or no evidence was identified, highlighting the importance of further studies within these areas.

Associations between electroencephalography power and Alzheimer's disease in persons with Down syndrome.

BACKGROUND: It is complicated to diagnose dementia in persons with Down syndrome (DS). Older studies have, however, demonstrated low-frequency activity in electroencephalography (EEG) in persons with concurrent DS and Alzheimer's disease (DS-AD). The aim of this study was to examine whether it was possible to identify AD-associated changes (increased high-frequency power and decreased low-frequency power) in persons with DS-AD compared with DS. METHODS: We included 21 persons with DS-AD and 16 with DS without cognitive deterioration assessed by the informant-based Dementia Screening Questionnaire in Intellectual Disability. EEG was recorded for all participants. Absolute power for each electrode and global power were calculated for all frequency bands for both eyes open and eyes closed. RESULTS: For global power in the eyes closed condition, we found an increased global slow-frequency activity and a decreased global high-frequency activity in DS-AD compared with DS. In addition, we found a significant difference in the global alpha/delta ratio with the largest difference found for global alpha power in DS-AD compared with DS. CONCLUSIONS: In the current study, we found that changes known to be associated with AD could also be identified when comparing DS-AD with DS using quantitative EEG. In general, these findings suggest that EEG might be a useful tool in diagnosing AD in persons with DS, but larger studies are needed.

Validation of the Arabic Rowland Universal Dementia Assessment Scale (A-RUDAS) in elderly with mild and moderate dementia.

OBJECTIVES: Validated screening tests for dementia in Arabic are lacking. Given the low levels of education among elderly in the Middle East and North Africa region, the commonly used screening instrument, the Mini Mental State Examination, is not best suited. Alternatively, the Rowland Universal Dementia Assessment Scale (RUDAS) was especially designed to minimize the effects of cultural learning and education. The aim of this study was to validate the RUDAS in the Arabic language (A-RUDAS), evaluate its ability to screen for mild and moderate dementia, and assess the effect of education, sex, age, depression, and recruitment site on its performance. METHODS: A-RUDAS was administered to 232 elderly aged ≥65 years recruited from the communities, community-based primary care clinics, and hospital-based specialist clinics. Of these, 136 had normal cognition, and 96 had dementia. Clinicians diagnosed dementia according to the Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV) criteria. Interviewers, blind to the cognitive status of participants, administered A-RUDAS. The psychometric properties of A-RUDAS were examined for three cutoffs. RESULTS: At the cutoff of ≤22, A-RUDAS exhibited good sensitivity (83%) and specificity (85%) with an area under the receiver operating characteristic curve of 83.95%. Adjusting for age, sex, education, depression, and recruitment site, A-RUDAS score demonstrated a high level of accuracy in screening for mild and moderate dementia against DSM-IV diagnosis. CONCLUSION: The A-RUDAS is proposed for dementia screening in clinical practice and in research in Arabic-speaking populations with an optimal cutoff of ≤22.

Subjective cognitive complaints included in diagnostic evaluation of dementia helps accurate diagnosis in a mixed memory clinic cohort.

OBJECTIVE: Our objective was to examine the quantity and profile of subjective cognitive complaints in young patients as compared with elderly patients referred to a memory clinic. METHODS: Patients were consecutively recruited from the Copenhagen University Hospital Memory Clinic at Rigshospitalet. In total, 307 patients and 149 age-matched healthy controls were included. Patients were classified in 4 diagnostic groups: dementia, mild cognitive impairment, affective disorders and no cognitive impairment. Subjective memory was assessed with subjective memory complaints (SMC) scale. Global cognitive functions were assessed with the Mini-mental state examination (MMSE) and Addenbrooke's cognitive examination (ACE), and symptoms of depression were rated with Major Depression Inventory (MDI). All interviews and the diagnostic conclusion were blinded to the SMC score. RESULTS: We found that young patients with dementia have a significantly higher level and a different profile of subjective cognitive complaints as compared with elderly patients with dementia. Furthermore, young patients, diagnosed with an affective disorder, had the highest level of subjective cognitive complaints of all patients in a memory clinic. The age of the patients and MDI score (but not MMSE or ACE) had significant impact on the level of subjective cognitive complaints. CONCLUSIONS: We have established that young patients with dementia have a different profile of subjective cognitive complaints than elderly patients, and further studies are needed to clarify possible relation to specific subtypes of dementia. Altogether, a systematic interview on subjective cognitive complaints may contribute to the diagnostic evaluation of patients referred to a memory clinic.

Harmonized diagnostic criteria for Alzheimer's disease: recommendations.

BACKGROUND: Two major sets of criteria for the clinical diagnosis of Alzheimer's disease (AD) recently have been published, one from an International Working Group (IWG) and the other from working groups convened by the National Institute on Aging (NIA) and the Alzheimer's Association (AA) in the United States. These criteria both aim to support a clinical diagnosis with in vivo evidence of AD pathology, using imaging methods and detection of biofluid biomarkers, and emphasize an aetiological diagnosis even in the prodromal stages of the disorder. Nonetheless, there are substantial differences in these two sets of criteria. METHODS: An international group of investigators with experience in the clinical diagnosis of AD met at the Key Symposium in Stockholm, Sweden on 6 & 7 December 2012, to develop recommendations to harmonize these criteria. The group was led by individuals who were integral to the development of both the IWG and the NIA-AA criteria. The similarities and differences between the two sets of criteria were identified and open discussion focused on ways to resolve the differences and thus yield a harmonized set of criteria. RESULTS: Based on both published evidence as well as the group's collective clinical experience, the group was tasked with achieving consensus, if not unanimity, as it developed recommendations for harmonized clinical diagnostic criteria for AD. CONCLUSION: The recommendations are to: (i) define AD as a brain disorder, regardless of clinical status; (ii) refer to the clinically expressed disorder, including its prodromal stages, as symptomatic AD; (iii) after the successful completion of standardization efforts, consider incorporating biomarkers into diagnostic algorithms for AD; and (iv) allow nonamnestic, atypical presentations to be included as symptomatic AD, especially when there is supportive biomarker evidence.

Application of the PredictAD decision support tool to a Danish cohort of patients with Alzheimer's disease and other dementias.

BACKGROUND: The diagnosis of Alzheimer's disease (AD) is based on an ever-increasing body of data and knowledge making it a complex task. The PredictAD tool integrates heterogeneous patient data using an interactive user interface to provide decision support. The aim of this project was to investigate the performance of the tool in distinguishing AD from non-AD dementia using a realistic clinical dataset. METHODS: We retrieved clinical data from a group of patients diagnosed with AD (n = 72), vascular dementia (VaD, n = 30), frontotemporal dementia (FTD, n = 25) or dementia with Lewy bodies (DLB, n = 14) at the Copenhagen Memory Clinic at Rigshospitalet. Three classification methods were applied to the data in order to differentiate between AD and a group of non-AD dementias. The methods were the PredictAD tool's Disease State Index (DSI), the naïve Bayesian classifier and the random forest. RESULTS: The DSI performed best for this realistic dataset with an accuracy of 76.6% compared to the accuracies for the naïve Bayesian classifier and random forest of 67.4 and 66.7%, respectively. Furthermore, the DSI differentiated between the four diagnostic groups with a p value of <0.0001. CONCLUSION: In this dataset, the DSI method used by the PredictAD tool showed a superior performance for the differentiation between patients with AD and those with other dementias. However, the methods need to be refined further in order to optimize the differential diagnosis between AD, FTD, VaD and DLB.

The spatial distribution of age-related white matter changes as a function of vascular risk factors--results from the LADIS study.

White matter hyperintensities (WMH) are a frequent finding on brain MRI of elderly subjects, and have been associated with various risk factors, as well as with development of cognitive and functional impairment. While an overall association between WMH load and risk factors is well described, possible spatially restricted vulnerability remains to be established. The aim of this study was to investigate the spatial distribution of WMH in normally functioning elderly subjects. We introduce a voxel-based approach in which lesion probability is mapped as a function of clinical risk factors using logistic regression, and validate the method using simulated datasets. The method was then applied in a total of 605 participants of the LADIS study (age 74 ± 5 years, all with WMH), and the location of manually delineated WMH was investigated after spatial normalisation. Particularly strong and widespread associations were found for age, gender and hypertension. Different distribution patterns were found for men and women. Further, increased probability was found in association with self-reported alcohol and tobacco consumption, as well as in those with a history of migraine. It is concluded that the location of WMH is dependent on the risk factors involved pointing towards a regionally different pathogenesis and/or vulnerability of the white matter.

Overdiagnosis of dementia in young patients - a nationwide register-based study.

BACKGROUND: Little is known about the quality of the diagnostic evaluation and the validity of dementia diagnoses in young patients established in routine clinical practice. The aim of this study was to investigate the validity of the diagnosis of dementia registered in the Danish nationwide hospital registers in young patients. METHODS: Two hundred patients were randomly selected from 891 patients <65 years registered with a dementia diagnosis for the first time in 2008. The patients' medical records were reviewed to evaluate if they fulfilled ICD-10 and/or DSM-IV criteria for dementia and current clinical criteria for specific dementia subtypes. RESULTS: A registered diagnosis was found to be correct in only 59%. A misdiagnosis of dementia occurred primarily in patients with depression or alcohol abuse. CONCLUSION: Our results suggest that dementia is overregistered and overdiagnosed in young patients. This may be due to a different symptom profile of dementia in young patients, lack of knowledge among clinical physicians and the wide range of conditions which may be misinterpreted as dementia.

Cognitive testing in non-demented Turkish immigrants--comparison of the RUDAS and the MMSE.

Methods for culturally and linguistically appropriate cognitive testing of elderly minority populations are lacking in Europe. The aim of this study was to compare performance on the Rowland Universal Dementia Assessment Scale (RUDAS) and the Mini Mental State Examination (MMSE) in Turkish immigrants in Denmark and determine the impact of demographic and health-related variables on test performance. A sample of non-demented community-dwelling Turkish immigrants was recruited from the greater Copenhagen area. All participants completed a structured interview regarding demographic, physical and mental health status, as well as measures of depression and acculturation, and cognitive testing with the RUDAS and the MMSE. A total of 76 non-demented participants aged 50 or more were included in the study. The mean performance on the RUDAS and the MMSE was 26.8 (SD 2.4) and 23.7 (SD 4.3), respectively. In group comparisons, correlation analyses and regression analyses, level of schooling represented a more significant variable for RUDAS and MMSE performance than any other variable. However, the impact of schooling was considerably more pronounced on the MMSE and the test was not found to be a valid measure of general cognitive function in subjects with less than five years of schooling. Although not entirely free of educational bias, the RUDAS can be a valuable supplement to the MMSE for assessment of general cognitive function in Turkish minority populations.

The Danish Alzheimer intervention study: rationale, study design and baseline characteristics of the cohort.

BACKGROUND: There is a lack of appropriately designed trials investigating the efficacy of psychosocial interventions for patients with mild dementia and their family caregivers. This paper reports the rationale and design of the Danish Alzheimer Disease Intervention Study and baseline characteristics of the cohort. METHODS: The study was a 1-year multicentre randomized controlled rater-blinded trial with randomization to follow-up and a multifaceted semitailored intervention programme or to follow-up only (with extension of follow-up to 3 years). The intervention included a counselling programme, teaching courses, written information and logbooks. The outcomes included clinical efficacy parameters, patient satisfaction and health economic consequences. RESULTS: A total of 330 patients and their 330 caregivers were included during a period of 18 months. The majority (65.2 %) of the caregivers were spouses. At inclusion the mean age of the patients and caregivers was 76.2 and 66.0 years, respectively. CONCLUSION: The study will explore the added value of a multifaceted intervention programme and contribute to the design of future interventions for patients with mild dementia and their caregivers.

Over- and under-diagnosis of dementia in ethnic minorities: a nationwide register-based study.

OBJECTIVE: Among dementia professionals in several European countries, it is believed that dementia is under-diagnosed and under-treated to a greater extent among ethnic minorities than in the native population. It is unknown whether this belief holds true. The objective of this study was to compare the prevalence of register-based dementia diagnoses in the largest ethnic minority groups in Denmark with the prevalence of register-based dementia diagnoses in the general Danish population. METHODS: By linking the Danish hospital registers with the Danish Civil Registration System, nationwide dementia cases for three main ethnic minorities were identified. Age- and gender-specific prevalence rates for dementia were calculated and compared to previously published data for the general population. RESULTS: The study population consisted of 68 219 persons aged 20 and older. A total of 174 dementia cases were identified. The mean age at diagnosis was 57.7 years (SD = 16.2). Compared to the general population, there was a higher prevalence of dementia among those younger than 60 years, and a markedly lower prevalence of dementia among those 60 years and older. CONCLUSIONS: Dementia is under-diagnosed to a greater extent among ethnic minorities in the age group 60 years and older but is over-diagnosed in the age group younger than 60 years. Several factors may contribute to this pattern, including cultural differences in help-seeking behaviour, and problems in navigating the health-care system. Furthermore, cross-cultural assessment of dementia can be difficult because of language barriers and cultural differences.

Tensile bond strength of ceramic crowns to dentin using resin cements.

PURPOSE: This study measured the bond strength of the self-adhesive resin cements and a bonded resin cement for crowns bonded to extracted teeth with preparations having a total taper greater than 30 degrees. A crown pull-off test was used with direction of pull along the path of insertion. The CAD/CAM system Cerec was used to create crowns with the pull-off loop as an integral part of the crown structure. MATERIALS AND METHODS: One hundred extracted human molars were prepared for all-ceramic crowns with a 1.5-mm shoulder, greater than 30-degree axial wall convergence, a flat occlusal surface and 3 to 5 mm occlusal/ gingival height. All-ceramic crowns were cemented with five different self-adhesive cements (Rely X Unicem, Maxcem Elite, BisCem, SmartCem 2, and G-Cem) and one bonded resin cement (Multilink). Forfour cements (excluding GCem and Multilink) there were 2 groups, one with HF etching and one without ceramic surface treatment. The crowns were then subject to tensile stress until either the crown fractured or the crown was lifted off from the tooth. RESULTS: For several cements, the bond strength exceeded the tensile strength of the all-ceramic crown; thus, the crown fractured, leaving the cemented part of the crown on the tooth. The effect of ceramic surface etching was not statistically significant at p = 0.05; however, for each cement, the treated crowns showed a lower coefficient of variance (COV). For this study, the COV ranged from 24.9 % to 97.9 %. Loads ranged from 41.3 to 190.3 N. CONCLUSION: Some of the new self-etching resin cements can create bonds to non-retentive crown preparations that are stronger than the strength of a ceramic crown; however, these high bond strengths may not be able to be achieved consistently.

Relationship between baseline white-matter changes and development of late-life depressive symptoms: 3-year results from the LADIS study.

BACKGROUND: Growing evidence suggests that cerebral white-matter changes and depressive symptoms are linked directly along the causal pathway. We investigated whether baseline severity of cerebral white-matter changes predict longer-term future depressive outcomes in a community sample of non-disabled older adults. METHOD: In the Leukoaraiosis and Disability in the Elderly (LADIS) study, a longitudinal multi-centre pan-European study, 639 older subjects underwent baseline structural magnetic resonance imaging (MRI) and clinical assessments. Baseline severity of white-matter changes was quantified volumetrically. Depressive outcomes were assessed in terms of depressive episodes and depressive symptoms, as measured by the Geriatric Depression Scale (GDS). Subjects were clinically reassessed annually for up to 3 years. Regression models were constructed to determine whether baseline severity of white-matter changes predicted future depressive outcomes, after controlling for confounding factors. RESULTS: Baseline severity of white-matter changes independently predicted depressive symptoms at both 2 (p<0.001) and 3 years (p=0.015). Similarly, white-matter changes predicted incident depression (p=0.02). Over the study period the population became significantly more disabled (p<0.001). When regression models were adjusted to account for the influence of the prospective variable transition to disability, baseline severity of white-matter changes no longer predicted depressive symptoms at 3 years (p=0.09) or incident depression (p=0.08). CONCLUSIONS: Our results support the vascular depression hypothesis and strongly implicate white-matter changes in the pathogenesis of late-life depression. Furthermore, the findings indicate that, over time, part of the relationship between white-matter changes and depression may be mediated by loss of functional activity.

Genetic testing in familial AD and FTD: mutation and phenotype spectrum in a Danish cohort.

Autosomal dominantly transmitted Alzheimer's disease (AD) and frontotemporal dementia (FTD) are genetically heterogeneous disorders. To date, three genes have been identified in which mutations cause early-onset autosomal dominant inherited AD: APP, PSEN1, and PSEN2. Mutations in two genes on chromosome 17, the MAPT and the PGRN genes, are associated with autosomal dominant inherited FTD. The aim of this study was to characterize the mutation spectrum and describe genotype-phenotype correlations in families with inherited dementia. The identification of novel mutations and/or atypical genotype-phenotype correlations contributes to further characterizing the disorders. DNA-samples from the 90 index cases from a Danish referral-based cohort representing families with presumed autosomal dominant inherited AD or FTD were screened for mutations in the known genes with sequencing, denaturing high-performance liquid chromatography (DHPLC) and multiplex ligation-dependent probe amplification (MLPA) techniques. Seven presumed pathogenic mutations (two PSEN1, one PSEN2, one APP, one MAPT, and two PGRN) were identified, including a novel PSEN2 mutation (V393M). No dosage aberrations were identified.

Deep frontal and periventricular age related white matter changes but not basal ganglia and infratentorial hyperintensities are associated with falls: cross sectional results from the LADIS study.

BACKGROUND: Global age related white matter changes (ARWMC) are associated with progressive gait disturbances and falls, hypothesised to result from interruptions of cortico-subcortical circuits controlling balance, posture and locomotion. METHODS: The location of ARWMC in a large cohort of elderly non-disabled individuals with reported falls was analysed, using the cross sectional data of the Leukoaraiosis and Disability (LADIS) study. Detailed anatomical distributions of ARWMC assessed by MRI studies were analysed with respect to falls and balance performance. RESULTS: The severity of global ARWMC was significantly associated with a history of falls in the year prior to study inclusion (22.2% in the mild, 31.6% in the moderate and 37.3% in the severe ARWMC group according to the Fazekas scale; p = 0.002). Analysing the anatomical distribution of ARWMC, using the semiquantitative Scheltens scale, in multivariate analysis, periventricular (p = 0.006) and frontal deep (p = 0.033) ARWMC were independently associated with falls. Furthermore, logistic regression identified frontal deep (p = 0.003) ARWMC, but not basal ganglia and infratentorial hyperintensities, as significantly associated with balance disturbances. CONCLUSION: The association of frontal and periventricular ARWMC with falls supports the hypothesis that interruption of frontal subcortical motor circuits lead to balance disturbances and hence to an increased risk for falls in ARWMC.

Antibiotic-coated ePTFE decreases graft colonization and neointimal hyperplasia.

BACKGROUND: Synthetic vascular conduits used in traumatic or infected fields have a high failure rate leading to catastrophic consequences including amputation and death. Although efforts to coat vascular grafts with antibiotics have had varying results, we developed a novel coating technique for expanded-polytetrafluoroethylene (ePTFE), which has proven to be effective in vitro. Thus, we hypothesized that the coated grafts would resist infection and have decreased neointimal hyperplasia when used in vivo in a large animal model. METHODS: Minocycline and rifampin suspended in a mixture of methacrylates were coated onto a 3cm segment of 6mm ePTFE (Bard, Tempe, AZ). An antibiotic-coated (ABX), adhesive-coated (AC), or control (C) ePTFE graft was then placed as an end-to-side graft into the left iliac artery of a male mongrel pig. Sterile saline or innoculum containing 3x10(8)Staphylococcus aureus (SA) or Staphylococcus epidermidis (SE) was then placed directly on the graft and the reflected peritoneum re-approximated to confine the bacteria. After 6 wk, the graft was harvested, cultured, and morphometric analyses of neointimal hyperplasia were performed. RESULTS: Twenty-seven pigs had grafts placed (9 ABX, 9 AC, 9 C) and harvested. Of the nine grafts exposed to SA, the uncoated and adhesive-coated grafts averaged greater than 50,000 colonies of SA while the antibiotic-coated grafts averaged less than 50 colonies. Although not statistically significant, neointimal hyperplasia was decreased by 15% to 20% when using an ABX graft in an infected field. CONCLUSIONS: The coated grafts appeared to decrease NIH formation although not significantly in this small pilot study. The methacrylate antibiotic-coated ePTFE graft did provide resistance to infection when used in infected fields.

Reduced parietooccipital white matter glutamine measured by proton magnetic resonance spectroscopy in treated graves' disease patients.

CONTEXT: Graves' disease is an autoimmune disease of the thyroid gland. Patients often have affective and cognitive complaints, whether these disappear after treatment remains disputed. OBJECTIVE: Our objective was to evaluate cerebral biochemistry in acute and treated Graves' disease. DESIGN: We conducted a prospective study, investigating volunteers once and patients before and 1 yr after treatment. SETTING: The study was performed at a radiology department, a memory disorder clinic, and two endocrinology clinics. PATIENTS AND OTHER PARTICIPANTS: Of 53 consecutively referred, newly diagnosed, and untreated patients with Graves' thyrotoxicosis, 27 patients (34 +/- 8 yr) and 33 matched volunteers were included. INTERVENTIONS: Patients were treated with thionamide. MAIN OUTCOME MEASURES: We assessed brain metabolite concentrations. METHODS: Proton magnetic resonance spectroscopy of the brain and a battery of biochemical, affective, and cognitive tests were used. RESULTS: Previously reported findings of reduced choline and myo-inositol in acute Graves' disease were confirmed and reversibility was demonstrated. Parieto-occipital white matter glutamine was and remained significantly reduced (P < 0.01). Acute phase parieto-occipital white matter total choline correlated significantly (r = -0.57; P < 0.01) with impaired thyroid function. Pretreatment total T(3) predicted posttreatment occipital gray matter glutamine (r = -0.52; P < 0.01). Occipital gray matter total choline (r = -0.53; P < 0.01) and parietooccipital white matter glutamate (r = -0.54; P < 0.01) correlated with initial values of selected attention and concentration cognitive scores and predicted them at follow-up. CONCLUSIONS: The persistent reduction of glutamine in white matter, the decreasing glutamate in occipital gray matter, and the correlation with severity of the initial disease as well as with attention and concentration cognitive scores indicated that there was a persistent and possibly progressive disturbance of the glutamate glutamine cycling in Graves' disease.