Effects of the Multicomponent Cognitive Training Program BrainProtect in Cognitively Healthy Adults: A Randomized Controlled Trial.

BACKGROUND: Cognitive integrity is a fundamental driver of health. The exact structure of strategies against cognitive impairment is still under debate. OBJECTIVE: To compare the short-term effects of a multicomponent cognitive training (BrainProtect) with those of general health counseling (GHC) on cognitive abilities and health-related quality of life (HRQoL) in healthy adults in Germany. METHODS: In this parallel randomized controlled trial (RCT), 132 eligible cognitively healthy adults (age ≥50 years, Beck Depression Inventory ≤9/63; Montreal Cognitive Assessment ≥26/30) were randomized to either GHC (N = 72) or to intervention with BrainProtect (intervention group, IG; N = 60). IG participants received 8 weekly sessions of 90 min of the group-based BrainProtect program focusing on executive functions, concentration, learning, perception, and imagination, plus nutritional and physical exercise units. Before and after intervention, all participants underwent neuropsychological testing and HRQoL evaluation, blinded for pretest. RESULTS: No significant training effect was observed for the primary endpoint of global cognition as assessed by CERAD-Plus-z Total Score (p = 0.113; ηp2 = 0.023). Improvements in several cognitive subtests were shown in the IG (N = 53) compared to the GHC (N = 62) without adverse events. Differences reached significance for verbal fluency (p = 0.021), visual memory (p = 0.013), visuo-constructive functions (p = 0.034), and HRQoL (p = 0.009). Significance was lost after adjustment, though several changes were clinically relevant. CONCLUSION: BrainProtect did not significantly impact global cognition in this RCT. Nevertheless, the results of some outcomes indicate clinically meaningful changes, so that a strengthening of the cognitive performance by BrainProtect cannot be excluded. Further studies with larger sample size are needed to confirm these findings.

A Stepped Health Services Intervention to Improve Care for Mental and Neurological Diseases: Protocol for a Prospective Cohort Trial.

BACKGROUND: Mental and neurological disorders cause a large proportion of morbidity burden and require adequate health care structures. However, deficits in the German health care system like long waiting times for access to specialized care and a lack of coordination between health care providers lead to suboptimal quality of care and elevated health care costs. OBJECTIVE: To overcome these deficits, we implement and evaluate a unique stepped and coordinated model of care (the Neurologisch-psychiatrische und psychotherapeutische Versorgung [NPPV] program) for patients with mental and neurological diseases. METHODS: Patients included in the program receive an appropriate treatment according to medical needs in a multiprofessional network of ambulatory health care providers. The therapy is coordinated by a managing physician and complemented by additional therapy modules, such as group therapy, internet-based cognitive behavioral therapy, and a case management. Statutory health insurance (SHI) routine data and data from a longitudinal patient survey will be used to compare the program with regular care and evaluate SHI expenditures and patient-related outcomes. A health care provider survey will evaluate the quality of structure and processes and provider satisfaction. Finally, an analysis of ambulatory claims data and drug prescription data will be used to evaluate if health care providers follow a needs-led approach in therapy. Ethics approval for this trial was obtained from the ethics committee of the chamber of physicians in North Rhine (September 13, 2017, reference No. 2017287). RESULTS: Patient enrollment of NPPV ended in September 2021. Data analysis has been completed in 2022. The results of this study will be disseminated through scientific publications, academic conferences, and a publicly available report to the German Federal Joint Committee, which is expected to be available in the first half of 2023. CONCLUSIONS: The NPPV program is the first intervention to implement a stepped model of care for both mental and neurological diseases in Germany. The analysis of several data sources and a large sample size (more than 14,000 patients) enable a comprehensive evaluation of the NPPV program. TRIAL REGISTRATION: German Clinical Trials Register DRKS00022754; https://tinyurl.com/3mx9pz5z. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37569.

Real-world evidence on siponimod treatment in patients with secondary progressive multiple sclerosis.

BACKGROUND: Therapeutic options targeting inflammation in multiple sclerosis (MS) have evolved rapidly for relapsing-remitting MS, whereas few therapies are available for progressive forms of MS, in particular secondary progressive MS (SPMS). The approval of siponimod for SPMS has allowed for optimism in the otherwise discouraging therapeutic landscape. METHODS: We conducted a retrospective, multicenter, non-interventional study analyzing the efficacy and safety of siponimod under real-world conditions in 227 SPMS patients. According to the retrospective study framework, data was acquired at prespecified time points. Clinical readouts were assessed every three months. Disease progression was determined as increase in expanded disability status scale (EDSS), radiological progression, or the occurrence of new relapses under treatment. For safety analyses, adverse events (AE) and reasons for discontinuation were documented. The collected data points were analyzed at baseline and after 6, 12 and 18 months. However, data were predominately collected at the 6- and 12-month time points as many patients were lost to follow-up. In a group consisting of 41 patients, a more detailed investigation regarding disease progression was conducted, including data from measurement of cognitive and motoric functions. RESULTS: Under siponimod therapy, 64.8% of patients experienced sustained clinical disease stability at 12 months. Out of the stable patients 21.4% of patients improved. Of the remaining patients, 31.5% experienced EDSS progression, 3.7% worsened without meeting the threshold for progression. Relapses occurred in 7.4%. Radiological disease activity was detected in 24.1% of patients after six months of treatment and in 29.6% of patients at 12 months follow-up. The in-depth cohort consisting of 41 patients demonstrated no substantial changes in cognitive abilities measured by Paced Auditory Serial Addition Test and Symbol Digit Modalities Test or motoric functions measured with Timed 25-Foot Walk, 100-m timed test, and 9-Hole Peg Test throughout the 12-month study period. Radiological assessment showed a stable volume of white and grey matter, as well as a stable lesion count at 12 months follow-up. AE were observed in nearly half of the included patients, with lymphopenia being the most common. Due to disease progression or AE, 31.2% of patients discontinued therapy. CONCLUSION: Treatment with siponimod had an overall stabilizing effect regarding clinical and radiological outcome measures. However, there is a need for more intensive treatment management and monitoring to identify disease progression and AE.

Safety and clinical effectiveness of peginterferon beta-1a for relapsing multiple sclerosis in the real-world setting: Interim results from the Plegridy Observational Program.

BACKGROUND: The Plegridy Observational Program (POP) is an ongoing, 5-year, phase 4 real-world study of the safety and effectiveness of subcutaneous peginterferon beta-1a in patients with relapsing multiple sclerosis (RMS). METHODS: This interim analysis from POP assessed the safety and effectiveness of peginterferon beta-1a, including subgroup analyses of patients aged < 50 and ≥ 50 years, newly diagnosed and non-newly diagnosed patients, and new and experienced peginterferon beta-1a users. RESULTS: A total of 1208 patients enrolled in POP. Mean (standard deviation) peginterferon treatment duration in the overall population was 757.0 (529.5) days. The overall incidence of treatment-emergent adverse events (AEs) was 65.5%, and the incidence was higher in new than experienced peginterferon beta-1a users (78.1 vs 52.4%). The overall incidence of treatment-emergent serious AEs was 7.6%, and the incidence was lower in younger than older patients (5.8 vs 11.1%). No new or unexpected safety signals were reported. Overall treatment discontinuation due to AEs occurred in 20.7% of patients, with a higher proportion of new than experienced peginterferon beta-1a users (27.0 vs 14.2%) discontinuing treatment due to AEs. Flu-like symptoms and injection site reactions were significant predictors of time to treatment discontinuation. The adjusted annualized relapse rate (ARR) was 0.12 (95% confidence interval 0.11-0.13) in the overall population and was similar across all subgroups. In the overall population at 4 years, 79.1% of patients were relapse free, the estimated cumulative proportion of patients with confirmed disability worsening was 1.8%, and > 67% of patients achieved clinical no evidence of disease activity (NEDA). CONCLUSIONS: Safety data of patients enrolled in POP are consistent with the established clinical safety profile of peginterferon beta-1a. In addition, the low ARR and high proportion of patients achieving clinical NEDA at 4 years across all subgroups indicates the effectiveness of peginterferon beta-1a in treating RMS in real-world clinical settings.

Communication, Coordination, and Security for People with Multiple Sclerosis (COCOS-MS): a randomised phase II clinical trial protocol.

INTRODUCTION: Patients with multiple sclerosis (MS) have complex needs that range from organising one's everyday life to measures of disease-specific therapy monitoring to palliative care. Patients with MS are likely to depend on multiple healthcare providers and various authorities, which are often difficult to coordinate. Thus, they will probably benefit from comprehensive cross-sectoral coordination of services provided by care and case management (CCM). Though studies have shown that case management improves quality of life (QoL), functional status and reduces service use, such benefits have not yet been investigated in severely affected patients with MS. In this explorative phase ll clinical trial, we evaluated a CCM with long-term, cross-sectoral and outreaching services and, in addition, considered the unit of care (patients and caregivers). METHODS AND ANALYSIS: Eighty patients with MS and their caregivers will be randomly assigned to either the control (standard care) or the intervention group (standard care plus CCM (for 12 months)). Regular data assessments will be done at baseline and then at 3-month intervals. As primary outcome, we will evaluate patients' QoL. Secondary outcomes are patients' treatment-related risk perception, palliative care needs, anxiety/depression, use of healthcare services, caregivers' burden and QoL, meeting patients' and caregivers' needs, and evaluating the CCM intervention. We will also evaluate CCM through individual interviews and focus groups. The sample size calculation is based on a standardised effect of 0.5, and one baseline and four follow-up assessments (with correlation 0.5). Linear mixed models for repeated measures will be applied to analyse changes in quantitative outcomes over time. Multiple imputation approaches are taken to assess the robustness of the results. The explorative approach (phase ll clinical trial) with embedded qualitative research will allow for the development of a final design for a confirmative phase lll trial. ETHICS AND DISSEMINATION: The trial will be conducted under the Declaration of Helsinki and has been approved by the Ethics Commission of Cologne University's Faculty of Medicine. Trial results will be published in an open-access scientific journal and presented at conferences. TRIAL REGISTRATION NUMBER: German Register for Clinical Studies (DRKS) (DRKS00022771).

Influence of a 12-Month Structured Exercise Program on the Micronutrient-Cognitive Fitness-Physical Association Profiles in Mild Cognitive Impairment.

Background: Preventive lifestyle strategies have shown promise to slow down or prevent age-related cognitive decline. However, evidence on the reciprocal longitudinal relationships between nutrition biomarkers and cognitive and physical performance is lacking. Studying nutritional, cognitive, and physical profiles over time may help to overcome this knowledge gap. Objective: To investigate the relationship of plasma levels of the robust nutritional- and antioxidant defense-related biomarkers carotenoids and tocopherols with both indicators of cognitive and physical performance in persons with mild cognitive impairment (MCI) participating in a structured exercise program. Methods: Data from 40 participants with MCI of the NeuroExercise study were analyzed. Participants had undergone a blood withdrawal for the analysis of plasma concentrations of six carotenoids, two tocopherols and retinol prior to and after one-year of structured exercise. All participants had undergone a broad spectrum of cognitive and physical performance tests. Results: Significant associations between lipophilic micronutrients and cognitive/physical measures were observed that were previously found to play a role in cognitive and physical frailty. In particular, lutein, zeaxanthin, and lycopene are confirmed as robust, reliable, and stable indicators of nutritional defense. Importantly, these micronutrients were associated with cognitive measures prior to the physical training program and to a more prominent extent with indicators of motoric function after the physical exercise program. Conclusion: Specific profiles of lipophilic micronutrients are associated to cognitive performance measures and, especially after a structured exercise program, to indicators of physical performance.

Associations of Lipophilic Micronutrients with Physical and Cognitive Fitness in Persons with Mild Cognitive Impairment.

Age-associated cognitive impairment in general and dementia in particular are a global concern. Preventive lifestyle strategies are highly used but there is a lack of information on the reciprocal relationships between nutrition biomarkers and measures of both cognitive and physical performance. To fill this gap of knowledge, the relationship between plasma levels of the robust nutrition- and antioxidant defense-related biomarkers carotenoid and tocopherols and both indicators of cognitive and physical performance was investigated in a group of persons with mild cognitive impairment participating in the NeuroExercise Study at the German Sport University in Cologne, Germany. In 56 participants with full dataset, significant correlations independently of fruit and vegetable intake were found between plasma levels of ß-cryptoxanthin and Timed Up&Go test (p < 0.05), γ-tocopherol and number of daily steps (p < 0.01), as well as between four out of six measured carotenoids-lutein; zeaxanthin; ß-cryptoxanthin and ß-carotene-and the computerized CogState International Shopping List subtest (p < 0.01). In light of the increasing attention towards the nutritional cognitive neuroscience of carotenoids, computerized measures of cognitive performance might be further implemented in future studies investigating the effects of lifestyle interventions against cognitive and physical impairment.

Long-term outcomes of peginterferon beta-1a in multiple sclerosis: results from the ADVANCE extension study, ATTAIN.

BACKGROUND: ADVANCE was a phase III trial of the efficacy and safety of subcutaneous peginterferon beta-1a 125 µg every 2 or 4 weeks in patients with relapsing-remitting multiple sclerosis (RRMS). ATTAIN was a 2-year extension study of ADVANCE. The aim was to evaluate the long-term safety, tolerability, and efficacy of peginterferon beta-1a 125 µg every 2 or 4 weeks in ATTAIN. METHODS: ADVANCE dosing schedules were maintained in ATTAIN, except that every-4-weeks dosing patients were switched to every-2-weeks dosing after conversion of the study to an open-label protocol. ATTAIN was considered complete when the last patient completed the 96-week extension study. Primary endpoints included adverse event (AE) and serious AE (SAE) incidence. Secondary endpoints included relapse, magnetic resonance imaging, and disability outcomes. RESULTS: Of the 1512 patients randomized in ADVANCE, 1076 (71%) continued treatment in ATTAIN; of these, 842 (78%) completed the open-label extension study. During ATTAIN, 478 patients (87%) in the every-2-weeks group and 471 patients (89%) in the every-4-weeks group experienced an AE; SAEs were reported in 90 patients (16%) in the every-2-weeks group and 113 patients (21%) in the every-4-weeks group. The most frequent AEs reported were injection site reactions and flu-like symptoms, both of which numerically decreased over time. Peginterferon beta-1a every 2 weeks versus every 4 weeks significantly reduced the adjusted annualized relapse rate over 6 years (0.188 versus 0.263, p = 0.0052) and the risk of relapse over 5 years (36% versus 49%, p = 0.0018). Fewer new T1, new/newly enlarging T2, and gadolinium-enhancing magnetic resonance imaging lesions were observed with every-2-weeks dosing than every-4-weeks dosing over 4 years. CONCLUSIONS: Results from the ADVANCE extension study, ATTAIN, confirm the favorable long-term safety and tolerability profile of peginterferon beta-1a in patients with RRMS and provide additional evidence for the clinical and radiological benefits associated with this therapy.

Plasma levels of HDL and carotenoids are lower in dementia patients with vascular comorbidities.

Elevated serum cholesterol concentrations in mid-life increase risk for Alzheimer's disease (AD) in later life. However, lower concentrations of cholesterol-carrying high density lipoprotein (HDL) and its principal apolipoprotein A1 (ApoA1) correlate with increased risk for AD. As HDL transports oxocarotenoids, which are scavengers of peroxynitrite, we have investigated the hypothesis that lower HDL and oxocarotenoid concentrations during AD may render HDL susceptible to nitration and oxidation and in turn reduce the efficiency of reverse cholesterol transport (RCT) from lipid-laden cells. Fasting blood samples were obtained from subjects with (1) AD without cardiovascular comorbidities and risk factors (AD); (2) AD with cardiovascular comorbidities and risk factors (AD Plus); (3) normal cognitive function; for carotenoid determination by HPLC, analysis of HDL nitration and oxidation by ELISA, and 3H-cholesterol export to isolated HDL. HDL concentration in the plasma from AD Plus patients was significantly lower compared to AD or control subject HDL levels. Similarly, lutein, lycopene, and zeaxanthin concentrations were significantly lower in AD Plus patients compared to those in control subjects or AD patients, and oxocarotenoid concentrations correlated with Mini-Mental State Examination scores. At equivalent concentrations of ApoA1, HDL isolated from all subjects irrespective of diagnosis was equally effective at mediating RCT. HDL concentration is lower in AD Plus patients' plasma and thus capacity for RCT is compromised. In contrast, HDL from patients with AD-only was not different in concentration, modifications, or function from HDL of healthy age-matched donors. The relative importance of elevating HDL alone compared with elevating carotenoids alone or elevating both to reduce risk for dementia should be investigated in patients with early signs of dementia.

Antioxidant clinical trials in mild cognitive impairment and Alzheimer's disease - challenges and perspectives.

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder representing the most common form of dementia and the most feared highly disabling age-related condition of our time. Hallmarks of AD include a dramatically increasing number of cases due to prospected demographics and the absence of a cure. AD is incurable as it escapes the formula "one disease, one mechanism, one drug". AD has a multifaceted pathophysiology only in part uncovered. Even the proven chronological primacy of free radical-related damage in AD-related neurodegeneration has not yield successful oxidative stress - lowering trial designs. As a consequence, clinical trials of antioxidants in AD have brought largely negative conclusions. The aims of this review are to discuss 1. rationale for antioxidant trials, 2. reasons for failure of antioxidants in AD therapy, 3. potential preventive benefits of natural nutrition against AD onset and 4. the enormous relevance of detecting and treating AD risk factors as long as possible prior to AD manifestation.

Prevention of dementia: focus on lifestyle.

The objective of this paper is to summarize current knowledge on the possible advantages of lifestyle interventions, with particular attention to physical fitness, cognitive activity, leisure and social activity as well as nutrition. There is a large amount of published papers providing partial evidence and asserting the need for immediate, appropriate preventive lifestyle measures against dementia and AD development. Nevertheless, there are currently great difficulties in drafting effective guidelines in this field. This depends mainly upon lack of randomized controlled trials assessing benefits versus risks of particular lifestyle interventions strategies. However, due to the rapid increase of dementia burden, lifestyle factors and their amelioration should be already made part of decision making in light of their health-maintaining effects while awaiting for results of well-designed large prospective cohort studies in dementia.

Modulation of cholesterol in midlife affords cognitive advantage during ageing - a role for altered redox balance.

General practitioners, geriatricians, neurologists and health care professionals all over the world will be facing by 2040 the diagnostic, therapeutic and socioeconomic challenges of over 80 million people with dementia. Dementia is one of the most common diseases in the elderly which drastically affects daily life and everyday personal activities, is often associated with behavioural symptoms, personality change and numerous clinical complications and increases the risk for urinary incontinence, hip fracture, and - most markedly - the dependence on nursing care. The costs of care for patients with dementia are therefore immense. Serum cholesterol levels above 6.5 mmol/L are known to be associated with an increased RR of 1.5 and 2.1 to develop Alzheimer's disease, the most common form of dementia, and a reduction of serum cholesterol in midlife is associated with a lowered dementia risk. The aim of this work is to critically discuss some of the main results reported recently in the literature in this respect and to provide the pathophysiological rationale for the control of dyslipidemia in the prevention of dementia onset and progression.

Eye-movement training-induced changes of visual field representation in patients with post-stroke hemianopia.

Changes in neuronal activity have been described in patients with hemianopia following ischemic lesions of the visual cortex. This reorganization may facilitate compensation of lost visual function that is rarely fully restituted. Improving exploratory eye movements with appropriate training has been shown to partially compensate for the visuoperceptive impairment during daily life activities. The changes in cortical processing of visual stimuli that may be induced by these training strategies, however, are less well described. We used fMRI to study the training effects of eye-movement training on cortical representation of visual hemifields. Brain activation during hemifield stimulation was measured in eight patients with an occipital cortical lesion of the striate cortex causing homonymous hemianopia. Starting 8 weeks after the stroke, patients received 4 weeks of eye movement training. fMRI measurements were performed at baseline and after training. In five patients, follow-up fMRI was performed 4 weeks after the end of training. Differences in activation between rest and hemifield stimulation as well as before and after training were assessed with statistical parametric mapping. Twelve healthy subjects were scanned twice at a 4-week interval. During stimulation of the affected hemifield, significant activation at baseline was found bilaterally in extrastriate cortical areas, with the strongest increases in the contralesional hemisphere. This activation pattern was maintained after training. Four weeks after the end of training, there was an additional activation of the extrastriate cortex in the contralesional hemisphere compared to baseline. No changes in the size of visual field defects were found. In this group of patients, eye-movement training induced altered brain activation in the unaffected extrastriate cortex.

Prevention of episodic migraines with topiramate: results from a non-interventional study in a general practice setting.

The majority of patients with migraine headaches are treated in non-specialized institutions though data on treatment outcomes are largely derived from tertiary care centers. The current non-interventional study explores efficacy and tolerability outcomes of patients with episodic migraines receiving topiramate as preventive agent in a general practice setting. A total of 366 patients (87% female, mean age 41.8 +/- 11.6 years) were eligible for migraine prevention and treated with flexible dose topiramate for 6 months (core phase), and optionally for a total of 12 months (follow-up phase). Overall, 261 patients (77.7% of safety analysis set, SAF) completed the core phase. Reasons for discontinuation included adverse events (2.1%), lost to follow-up (1.8%), other reasons (1.5%), and end of therapy (0.3%) though in the majority of patients who discontinued no reasons were listed. The median daily dose at endpoint was 50 mg/day (range, 25-187.5 mg/day). The median days with migraine headaches decreased from 6.0 to 1.2 days (p < 0.001), median pain intensity score decreased from 17.0 to 3.2 points (p < 0.001). In women with reported menstruation-associated migraine, the median number of migraine attacks decreased from 4.0 to 0.9 (p < 0.001). Absenteeism as well as triptan use decreased significantly, and significant improvements in activities of daily living and quality of life were reported. The most frequently reported AEs were paraesthesia (4.2%) and nausea (3%). Results suggest that migraine prevention with topiramate in a general practice is generally well tolerated and associated with a significant improvement in migraine headaches and related functional impairment.

Brain activation of eye movements in subjects with refractive error.

PURPOSE: Recent functional magnetic resonance imaging (fMRI) studies have described reorganized activation of the oculomotor and visual cortex after focal brain lesions. These studies are based on comparison with healthy individuals who may have a very heterogenous refractive error. The influence of refractive error on the cortical control of an oculomotor task such as a prosaccade trial, however, is unknown. METHODS: To investigate the influence of visual acuity on changes of cortical oculomotor control, we studied the representation of visually guided prosaccades in nine subjects with refractive error and 11 normally sighted subjects using fMRI. Correction of refractive error was not allowed during fMRI. Differences in activation between rest and saccades as well as between subjects with refractive error vs subjects with normal vision were assessed with statistical parametric mapping. RESULTS: In both groups, activation of a frontoparietal network was observed. Subjects with refractive errors showed increased activation compared to normally sighted subjects, with overactivation in bilateral frontal and parietal eye fields, supplementary eye fields, as well as in the bilateral extrastriate cortex. CONCLUSIONS: This group of subjects with refractive error showed increased activation in an extended oculomotor and visual network to maintain performance during simple prosaccades. This observation underlines the importance of using appropriate control groups in fMRI-studies after brain lesions.

Topiramate for migraine prevention in a naturalistic setting: results from an open label, flexible dose study.

BACKGROUND: Headaches are one of the most common neurological symptoms and migraines are the most common primary headache disorder. The global prevalence of migraines is around 10% and the condition is associated with a high burden of disease. Despite an abundance of good quality evidence, only 1 in 5 of patients who fulfill the criteria for preventive migraine therapy are appropriately treated. Data on patient outcomes with preventive medication derive mostly from specialized academic centers, which contrasts with normal clinical practice where the majority of patients are treated outside tertiary care centers. OBJECTIVE: To explore tolerability, safety and efficacy outcomes of patients receiving topiramate for migraine prevention in a naturalistic setting. METHODS: After a 4-week prospective baseline, patients with a diagnosis of migraine according to International Headache Society criteria and eligible for migraine prevention were treated with flexible dosing of topiramate for 24 weeks (core phase), and optionally for a total of 48 weeks. The primary safety analysis included adverse events (AEs) during the core phase. For the main efficacy measures, the absolute changes from baseline to end of core phase as well as last follow-up visit were calculated for migraine days per 4 weeks, migraine attacks per 4 weeks, mean maximum visual analogue scale of migraine headache per 4 weeks and mean maximum pain intensity of migraine headache (4-point scale) per 4 weeks. In addition, changes in individual quality of life aspects were captured. RESULTS: The intention-to-treat population (ITT) consisted of 161 patients (90.7% female, mean age 45.7 +/- 11.1 years). Topiramate median dose was 45.7 mg/day at endpoint. Some 74.1% of patients reported treatment emergent AEs, most frequently paresthesias (18.4%) and nausea (12.4%). Some 20.0% of patients withdrew from the study due to AEs. The mean number of migraine days per 4 week decreased from 6.2 +/- 3.9 days at baseline to 3.9 +/- 3.5 days at last core visit (P < .001). Mean maximum pain intensity per 4 week changed from 7.0 +/- 2.3 at baseline to 4.7 +/- 3.2 at last visit core phase (P < .001). Consumption of triptans and analgesics reduced during the course of the core phase (P < .005). Fifty-one percent of all patients experienced at least a 50% reduction in migraine days during the core phase. CONCLUSION: Topiramate used for migraine prevention in non-academic institutions is generally safe, well tolerated and results in good control of migraine headaches and improvement in several aspects of quality of life.

High fruit and vegetable intake is positively correlated with antioxidant status and cognitive performance in healthy subjects.

A higher daily intake of fruits and vegetables in healthy elderly is associated with an improved antioxidant status in comparison to subjects consuming diets poor in fruits and vegetables, but the impact on cognitive performance is unclear. Healthy community dwellers (45 to 102 years old, n=193) underwent cognitive testing and blood withdrawal for the measurement of antioxidant micronutrients and biomarkers of oxidative stress as well as administration of a food frequency questionnaire to assess the daily intake of fruits and vegetables (high intake HI, low intake LI). Ninety-four subjects of the HI group had significantly higher cognitive test scores, higher levels of carotenoids, alpha- and gamma-tocopherol as well as lower levels of F2 alpha isoprostanes than the 99 subjects of the LI group. Cognitive scores were directly correlated with blood levels of alpha-tocopherol and lycopene and negatively correlated with F2 alpha isoprostanes and protein carbonyls. The results were independent of age, gender, body mass index, education, total cholesterol, LDL- and HDL-cholesterol, triglycerides, and albumin. Healthy subjects of any age with a high daily intake of fruits and vegetables have higher antioxidant levels, lower levels of biomarkers of oxidative stress, and better cognitive performance than healthy subjects of any age consuming low amounts of fruits and vegetables. Modification of nutritional habits aimed at increasing intake of fruits and vegetables should be encouraged to lower prevalence of cognitive impairment in later life.

Age-related differences of saccade induced cortical activation.

Recent functional MRI (fMRI) studies have described the increased task-related brain activation in older subjects during motor, cognitive and perceptual tasks. Age affects the ability to control saccadic eye movements. To investigate the age-related changes of oculomotor control, we studied the representation of saccades in 11 young (median age 29 years) and 11 older (median age 62 years) healthy individuals using fMRI. Brain activation was measured during a visually guided prosaccade trial. Differences in activation between rest and saccades as well as between younger and older subjects were assessed with statistical parametric mapping (SPM). In both age groups, activation of a frontoparietal network was observed. Older subjects showed increased activation compared to younger subjects with overactivation in bilateral parietal eye fields, the right frontal eye field, as well as in the right extrastriate cortex. We conclude that older adults increase activation in an extended oculomotor and visual network to maintain performance during simple prosaccades. This observation also underlines the importance of using appropriate age-matched control groups in fMRI studies after brain lesions.

Eye-movement training-induced plasticity in patients with post-stroke hemianopia.

Substantial disability in patients with hemianopia results from reduced visual perception. Previous studies have shown that these patients have impaired saccades. Improving exploratory eye movements with appropriate training of saccades may help to partially compensate for the visuoperceptive impairment during daily life activities. The changes in cortical control of eye movements that may be induced by these training strategies, however, are not known. We used functional magnetic resonance imaging (fMRI) to study the training effects of eye-movement training on cortical control of saccades. Brain activation during visually guided saccades was measured in eight patients with an occipital cortical lesion causing homonymous hemianopia. Starting 8 weeks after the stroke, patients received 4 weeks of visual field training. The fMRI measurements were performed at baseline and after training. In five patients, follow-up fMRI was performed 4 weeks after the end of training. Differences in activation between rest and saccades as well as before and after training were assessed with statistical parametric mapping software (SPM'99). Twelve healthy subjects were scanned twice at a 4-week interval. In patients, significant activation at baseline was found in the frontal and parietal eye fields (FEF and PEF, respectively) bilaterally and in the supplementary eye field (SEF). Immediately after training, an area of increased activation was found in the left extrastriate cortex of the affected hemisphere. At follow-up, relatively more activation was found in the right peristriate cortex and in the SEF of the unaffected side. A relative decrease of activation was found in the left FEF. In this group of patients, eye-movement training induced altered brain activation in the striate and extrastriate cortex as well as in oculomotor areas.

Cortical activation in hemianopia after stroke.

Changes in neuronal activity of the visual cortex have been described in patients with hemianopia. The anatomical areas that are involved in neuroplastic changes have not been studied in a larger group of stroke patients with a homogenous structural pathology of the visual cortex. Brain activation was measured in 13 patients with a single ischemic lesion of the striate cortex and partially recovered hemianopia and in 13 age-matched control subjects using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). Differences in activation between rest and visual hemifield stimulation were assessed with statistical parametric mapping using group and multi-group studies. In normal subjects, the most significant activation was found in the contralateral primary visual cortex (area 17) and bilaterally in the extrastriate cortex (areas 18 and 19). In patients, these areas were also activated when the intact hemifield was stimulated. During stimulation of the hemianopic side, bilateral activation was seen within the extrastriate cortex, stronger in the ipsilateral (contralesional) hemisphere. Stimulation of the hemianopic visual field is associated with ipsilateral activation of the extrastriate visual cortex. This pattern of activation suggests extensive neuronal plasticity within the visual cortex after postgeniculate ischemic lesions and may have implications for therapeutic interventions.