Intraputamenal Cerebral Dopamine Neurotrophic Factor in Parkinson's Disease: A Randomized, Double-Blind, Multicenter Phase 1 Trial.

BACKGROUND: Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor that protects dopamine neurons and improves motor function in animal models of Parkinson's disease (PD). OBJECTIVE: The primary objectives of this study were to assess the safety and tolerability of both CDNF and the drug delivery system (DDS) in patients with PD of moderate severity. METHODS: We assessed the safety and tolerability of monthly intraputamenal CDNF infusions in patients with PD using an investigational DDS, a bone-anchored transcutaneous port connected to four catheters. This phase 1 trial was divided into a placebo-controlled, double-blind, 6-month main study followed by an active-treatment 6-month extension. Eligible patients, aged 35 to 75 years, had moderate idiopathic PD for 5 to 15 years and Hoehn and Yahr score ≤ 3 (off state). Seventeen patients were randomized to placebo (n = 6), 0.4 mg CDNF (n = 6), or 1.2 mg CDNF (n = 5). The primary endpoints were safety and tolerability of CDNF and DDS and catheter implantation accuracy. Secondary endpoints were measures of PD symptoms, including Unified Parkinson's Disease Rating Scale, and DDS patency and port stability. Exploratory endpoints included motor symptom assessment (PKG, Global Kinetics Pty Ltd, Melbourne, Australia) and positron emission tomography using dopamine transporter radioligand [18 F]FE-PE2I. RESULTS: Drug-related adverse events were mild to moderate with no difference between placebo and treatment groups. No severe adverse events were associated with the drug, and device delivery accuracy met specification. The severe adverse events recorded were associated with the infusion procedure and did not reoccur after procedural modification. There were no significant changes between placebo and CDNF treatment groups in secondary endpoints between baseline and the end of the main and extension studies. CONCLUSIONS: Intraputamenally administered CDNF was safe and well tolerated, and possible signs of biological response to the drug were observed in individual patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Anorexia Nervosa With Comorbid Severe Depression: A Systematic Scoping Review of Brain Stimulation Treatments.

ABSTRACT: Major depressive disorder (MDD) is highly prevalent in individuals with anorexia nervosa (AN) and is a predictor of greater clinical severity. However, there is a limited amount of evidence supporting the use of psychotropic medications for its management. A systematic scoping review was conducted to assess the current literature on brain stimulation treatments for AN with comorbid MDD, with a specific focus on MDD treatment response and weight restoration. This review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and the PubMed, PsycInfo, and MEDLINE databases were searched until July 2022 using specific key words related to AN and brain stimulation treatments. A total of 373 citations were identified, and 49 treatment studies that met the inclusion criteria were included in the review. The initial evidence suggests that electroconvulsive therapy, repetitive transcranial magnetic stimulation, and deep-brain stimulation may be effective in managing comorbid MDD in AN. Emerging evidence suggests that transcranial direct current stimulation may have a positive effect on body mass index in individuals with severe to extreme AN. However, there is a need for the development of better measurement techniques for assessing the severity of depression in the context of AN. Controlled trials that are adequately designed to account for these limitations are highly warranted for deep-brain stimulation, electroconvulsive therapy, and repetitive transcranial magnetic stimulation and hold promise for providing clinically meaningful results.

Cognitive performance in hospitalized patients with severe or extreme anorexia nervosa.

PURPOSE: Severe malnourishment may reduce cognitive performance in anorexia nervosa (AN). We studied cognitive functioning during intensive nutritional and medical stabilization in patients with severe or extreme AN and investigated associations between weight gain and cognitive improvement. METHODS: A few days after admission to a specialized hospital unit, 33 patients with severe or extreme AN, aged 16-42 years, completed assessments of memory, cognitive flexibility, processing speed, and attention. Mean hospitalization was 6 weeks. Patients completed the same assessments at discharge (n = 22) following somatic stabilization and follow-up up to 6 months after discharge (n = 18). RESULTS: The patients displayed normal cognitive performance at admission compared to normative data. During nutritional stabilization, body weight increased (mean: 11.3%; range 2.6-22.2%) and memory, attention, and processing speed improved (p values: ≤ 0.0002). No relationship between weight gain and cognitive improvement was observed at discharge or follow-up. CONCLUSIONS: Cognitive performance at hospital admission was normal in patients with severe or extreme AN and improved during treatment although without association to weight gain. Based on these results, which are in line with previous studies, patients with severe or extreme AN need not be excluded from cognitively demanding tasks, possibly including psychotherapy. As patients may have other symptoms that interfere with psychotherapy, future research could investigate cognitive functioning in everyday life in patients with severe AN. TRIAL REGISTRATION NUMBER: The study is registered at clinicaltrials.gov (NCT02502617). LEVEL OF EVIDENCE: Level III, cohort study.

Treatment studies with cannabinoids in anorexia nervosa: a systematic review.

INTRODUCTION: Anorexia nervosa (AN) is a psychiatric disorder with a high mortality and unknown etiology, and effective treatment is lacking. For decades, cannabis has been known to cause physical effects on the human body, including increasing appetite, which may be beneficial in the treatment of AN. OBJECTIVE: To systematically review the literature for evidence of an effect of cannabinoids on (1) weight gain, and (2) other outcomes, in AN. METHOD: A systematic review was done using three databases Embase, PubMed and Psychinfo. The review was registered in PROSPERO with ID number CRD42019141293 and was done according to PRISMA guidelines. RESULTS: There were 1288 studies identified and after thorough review and exclusion of copies, 4 studies met the inclusion criteria. Three studies used the same AN population and utilized data from one original study, leaving only two original studies. Both of these were Randomized Controlled Trials that explored the effects of delta-9-tetrahydrocannabinol (Δ9-THC) or dronabinol in AN, whereof one study was properly designed and powered and showed a weight increase of an added 1 kg over 4 weeks over placebo. DISCUSSION AND CONCLUSION: There are few studies and the level of evidence is low. The only properly designed, low bias and highly powered study found a weight increasing effect of dronabinol in AN, while the other, using Δ9-THC at a high dose, found no effect and where the dose may have counteracted the weight gaining effects due to adverse events. More research on cannabinoids in anorexia nervosa is warranted, especially its effects on psychopathology. LEVEL OF EVIDENCE: Level I, systematic review.

Study protocol of comprehensive risk evaluation for anorexia nervosa in twins (CREAT): a study of discordant monozygotic twins with anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is a severe disorder, for which genetic evidence suggests psychiatric as well as metabolic origins. AN has high somatic and psychiatric comorbidities, broad impact on quality of life, and elevated mortality. Risk factor studies of AN have focused on differences between acutely ill and recovered individuals. Such comparisons often yield ambiguous conclusions, as alterations could reflect different effects depending on the comparison. Whereas differences found in acutely ill patients could reflect state effects that are due to acute starvation or acute disease-specific factors, they could also reflect underlying traits. Observations in recovered individuals could reflect either an underlying trait or a "scar" due to lasting effects of sustained undernutrition and illness. The co-twin control design (i.e., monozygotic [MZ] twins who are discordant for AN and MZ concordant control twin pairs) affords at least partial disambiguation of these effects. METHODS: Comprehensive Risk Evaluation for Anorexia nervosa in Twins (CREAT) will be the largest and most comprehensive investigation of twins who are discordant for AN to date. CREAT utilizes a co-twin control design that includes endocrinological, neurocognitive, neuroimaging, genomic, and multi-omic approaches coupled with an experimental component that explores the impact of an overnight fast on most measured parameters. DISCUSSION: The multimodal longitudinal twin assessment of the CREAT study will help to disambiguate state, trait, and "scar" effects, and thereby enable a deeper understanding of the contribution of genetics, epigenetics, cognitive functions, brain structure and function, metabolism, endocrinology, microbiology, and immunology to the etiology and maintenance of AN.

Comorbid depression as a negative predictor of weight gain during treatment of anorexia nervosa: A systematic scoping review.

BACKGROUND: Anorexia nervosa (AN) is a serious mental illness with high rates of relapse and mortality. Psychiatric comorbidities are common but their impact on the prognosis is largely unknown. OBJECTIVE: The aim was to investigate the influence of psychiatric comorbidity on weight gain during treatment of AN. METHODS: A systematic search was performed in PubMed/MEDLINE, EMBASE and PsycINFO. Studies evaluating psychiatric comorbidity as a predictor for treatment outcome (weight gain) were included, however, comorbid alcohol/drug addiction was excluded from this review. RESULTS: Four thousand five hundred and twenty six publications were identified from which 15 were included. The majority of the included studies had a prospective open naturalistic study design, a short-term follow-up period, and were based on small populations of primarily adolescent and adult women. Four studies indicate depression, and two obsessiveness as negative prognostic factors, whilst one study indicated moderate depression and yet another, neuroticism, as positive predictors for weight gain. DISCUSSION: The systematic scoping review found a large number of publications whereof only a few directly described the influence of psychiatric comorbidity on weight gain in AN. Overall, studies were heterogeneous in design, purpose and outcome making comparisons difficult. Findings were divergent but depression had a negative influence on weight gain in four studies.

A systematic review of studies on the faecal microbiota in anorexia nervosa: future research may need to include microbiota from the small intestine.

PURPOSE: Anorexia nervosa (AN) is a poorly understood and often chronic condition. Deviations in the gut microbiota have been reported to influence the gut-brain axis in other disorders. Therefore, if present in AN, it may impact on symptoms and illness progression. A review of the gut microbiota studies in AN is presented. METHOD: A literature search on PubMed yielded 27 articles; 14 were selected and based on relevance, 9 articles were included. The findings were interpreted in the larger context of preclinical research and clinical observations. RESULTS: 8 out of 9 included studies analysed microbiota from faeces samples, while the last analysed a protein in plasma produced by the gut. Two studies were longitudinal and included an intervention (i.e., weight restoration), five were cross-sectional, one was a case report, and the last was a case series consisting of three cases. Deviations in abundance, diversity, and microbial composition of the faecal microbiota in AN were found. CONCLUSION: There are currently only a few studies on the gut microbiota in AN, all done on faeces samples, and not all describe the microbiota at the species level extensively. The Archaeon Methanobrevibacter smithii was increased in participants with a BMI < 25 in one study and specifically in AN patients in three studies. Methanobrevibacter smithii may, if detected, be a benchmark biomarker for future studies. We propose that microbiota samples could also be collected from the small intestine, where a major exchange of nutrients takes place and where the microbiota may have a biological impact on AN.

Effect of diagnostic criteria on prevalence of frontotemporal dementia in the elderly.

BACKGROUND: Frontotemporal dementia (FTD) is believed to be rare in the elderly, and the influence of different criteria on the prevalence of FTD is unclear. METHODS: Population-based samples of 70- to 95-year-olds (n = 2462) in Gothenburg, Sweden, underwent neuropsychiatric examinations. Behavioral variant FTD (bvFTD) was diagnosed according to the International Behavioural Variant FTD Criteria Consortium (FTDC), the Frontotemporal Lobe Degeneration Consensus criteria, and the Lund-Manchester Research Criteria. A subset (n = 1074) underwent computerized tomography (CT) of the brain. RESULTS: The prevalence of bvFTD varied between 0.2% and 0.5% at age 70 to 79 years, between 2.5% and 3.6% at age 80 to 89 years, and between 1.7% and 2.2% at age 90 to 95 years. The agreement between different criteria was low to moderate (κ = 0.20-0.42). Among those with bvFTD according to FTDC, 93.3% had frontal and/or temporal lobar atrophy on CT, compared with 12.6% of those without bvFTD (P < .001). CONCLUSIONS: The prevalence of bvFTD was higher than expected in this population. To a large extent, different criteria captured different individuals.

A randomised trial of the effect of the glycine reuptake inhibitor Org 25935 on cognitive performance in healthy male volunteers.

OBJECTIVE: Cognitive impairment is integral to many neurological illnesses. Specific enhancement of glutamatergic transmission may improve memory and learning. Org 25935 increases the synaptic availability of glycine, an obligate co-agonist with glutamate at N-methyl-D-aspartate receptors. We hypothesised that Org 25935 would acutely improve the learning and memory of healthy volunteers. METHODS: A randomised, double-blind, parallel-group, single-dose study of Org 25935 and placebo was carried out. Thirty-two healthy male volunteers took either 12-mg Org 25935 or matching placebo and were later assessed with the manikin task, digit span and verbal memory tests. Systematic assessments of cardiovascular and adverse events were also taken. RESULTS: There was no effect of Org 25935 on reaction time, number of correct responses or learning (greater or slower improvement over successive tasks) compared with placebo. Org 25935 caused significantly more dizziness and drowsiness compared with placebo; these side effects were mainly mild. CONCLUSIONS: A single dose of Org 25935 does not improve learning or memory in healthy male individuals. However, the drug was well tolerated, and it remains to be seen whether it would have a positive effect on cognition in patient groups with pre-existing cognitive deficits.

The future of blood-based biomarkers for Alzheimer's disease.

Treatment of Alzheimer's disease (AD) is significantly hampered by the lack of easily accessible biomarkers that can detect disease presence and predict disease risk reliably. Fluid biomarkers of AD currently provide indications of disease stage; however, they are not robust predictors of disease progression or treatment response, and most are measured in cerebrospinal fluid, which limits their applicability. With these aspects in mind, the aim of this article is to underscore the concerted efforts of the Blood-Based Biomarker Interest Group, an international working group of experts in the field. The points addressed include: (1) the major challenges in the development of blood-based biomarkers of AD, including patient heterogeneity, inclusion of the "right" control population, and the blood-brain barrier; (2) the need for a clear definition of the purpose of the individual markers (e.g., prognostic, diagnostic, or monitoring therapeutic efficacy); (3) a critical evaluation of the ongoing biomarker approaches; and (4) highlighting the need for standardization of preanalytical variables and analytical methodologies used by the field.

Developing novel blood-based biomarkers for Alzheimer's disease.

Alzheimer's disease is the public health crisis of the 21st century. There is a clear need for a widely available, inexpensive and reliable method to diagnosis Alzheimer's disease in the earliest stages, track disease progression, and accelerate clinical development of new therapeutics. One avenue of research being explored is blood based biomarkers. In April 2012, the Alzheimer's Association and the Alzheimer's Drug Discovery Foundation convened top scientists from around the world to discuss the state of blood based biomarker development. This manuscript summarizes the meeting and the resultant discussion, including potential next steps to move this area of research forward.

Trauma Experiences Are Common in Anorexia Nervosa and Related to Eating Disorder Pathology but Do Not Influence Weight-Gain during the Start of Treatment.

OBJECTIVE: The main characteristics of Anorexia Nervosa (AN) in adults are restriction of energy intake relative to requirements leading to significant weight loss, disturbed body image, and intense fear of becoming fat. Traumatic experiences (TE) have been reported as common, although less is known about the relationship with other symptoms in severe AN. We investigated the presence of TE, PTSD, and the relation between TE, eating disorder (ED) symptoms, and other symptoms in moderate to severe AN (n = 97) at admission to inpatient weight-restoration treatment. All patients were enrolled in the Prospective Longitudinal all-comer inclusion study on Eating Disorders (PROLED). METHODS: TE were assessed using the Post-traumatic stress disorder checklist, Civilian version (PCL-C), and ED symptoms using the Eating Disorder Examination Questionnaire (EDE-Q); depressive symptoms were assessed using the Major Depression Inventory (MDI), and the presence of Post-traumatic Stress Disorder (PTSD) was diagnosed according to ICD-10 criteria. RESULTS: The mean score on PCL-C was high (mean 44.6 SD 14.7), with 51% having a PCL-C score at or above 44 (n = 49, suggested cut-off for PTSD), although only one individual was clinically diagnosed with PTSD. There was a positive correlation between baseline scores of PCL-C and EDE-Q-global score (r = 0.43; p < 0.01) as well as of PCL-C and all EDE-Q subscores. None of the included patients were admitted for treatment of TE/PTSD during the first 8 weeks of treatment. CONCLUSIONS: In a group of patients with moderate to severe AN, TE were common, and scores were high, although only one had a diagnosis of PTSD. TE were related to ED symptoms at baseline, but this association diminished during the weight restoration treatment.

Mapping length of inpatient treatment duration and year-wise relapse rates in eating disordered populations in a well-defined Western-European healthcare region across 1998-2020.

OBJECTIVES: Updated international guideline recommendations for AN inpatient care rely on expert opinions/observational evidence and promote extended inpatient stays, warranting investigation using higher-level ecological evidence. METHODS: The study was conducted according to Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Data encompassing 13,885 ED inpatients (5336 adolescents and 8549 adults) was retrieved from Swedish public health registries. Variables analyzed included (1) ED inpatient care opportunities, (2) unique number of ED inpatients and (3) mean length of ED-related inpatient stays in age groups 15-19 and 20-88+, across 1998-2020. RESULTS: Mean length of inpatient stays was inversely correlated to relapse to ED-related inpatient care within the same year (p < 0.001, R-squaredadj  = 0.5216 and p < 0.00001, R-squaredadj  = 0.5090, in the 15-19 and 20-88+ age groups, respectively), independent of number of ED inpatients treated within a year in both age groups. Extending mean adolescent inpatient duration from 35 to 45 days was associated with a ∼30% reduction in the year-wise relapse rate. CONCLUSIONS: Mean length of ED-related inpatient treatment stays was associated with reduced relapses to inpatient care within the same year, which could be interpreted as support for recommendations to include a stabilization phase in inpatient ED treatment.

Cognitive Flexibility in Hospitalized Patients with Severe or Extreme Anorexia Nervosa: A Case-Control Study.

OBJECTIVE: To investigate whether cognitive inflexibility could be identified using the Wisconsin Card Sorting Test (WCST) in patients with severe and extreme anorexia nervosa (AN) compared to healthy control participants (HCs). METHOD: We used the WCST to assess 34 patients with AN (mean age: 25.9 years, mean body mass index (BMI): 13.2 kg/m2) 3-7 days after admission to a specialized nutrition unit and 34 HCs. The Beck Depression Inventory II and the Eating Disorder Inventory 3 were distributed. RESULTS: The patients displayed more perseveration than HCs controlled for age and years of education, with moderate effect sizes (perseverative responses (%): adjusted difference = -7.74, 95% CI: -14.29-(-1.20), p-value: 0.021; perseverative errors (%): adjusted difference = -6.01, 95% CI: -11.06-(-0.96), p-value: 0.020). There were no significant relationships between perseveration and depression, eating disorder symptoms, illness duration, or BMI. DISCUSSION: Patients with severe and extreme AN demonstrated lower cognitive flexibility compared to HCs. Performance was not related to psychopathology or BMI. Patients with severe and extreme anorexia nervosa may not differ from less severe patients in cognitive flexibility performance. As this study exclusively focused on patients suffering from severe and extreme AN, potential correlations might be masked by a floor effect.

Anorexia Nervosa: Reduction in Depression during Inpatient Treatment Is Closely Related to Reduction in Eating Disorder Psychopathology.

Objective: Anorexia nervosa (AN) is a severe mental disorder frequently associated with high scores of depressiveness. We examined the short-term effects of inpatient treatment on depressiveness and eating disorder (ED) psychopathology using the self-rating Major Depression Inventory (MDI) and Eating Disorder Examination questionnaire (EDEq) for patients with AN. Material: Forty-nine patients with AN, all part of the PROspective Longitudinal all-comer inclusion study on EDs (PROLED), were observed over eight weeks with baseline psychometric measures, EDE-q at baseline and endpoint, and weekly MDI self-scoring. Methods: Apart from the weekly Body Mass Index (BMI) measurements, patients were assessed at baseline using the Eating Disorder Inventory (EDI) and the Symptom Check List 92 (SCL-92). Results: Inpatient treatment reduced MDI consistently over 8 weeks (Wilks Lambda = 0.59, F = 4.1, p < 0.01) and this reduction in MDI was positively correlated with a reduction in EDEq (r = 0.44; p < 0.01) during inpatient treatment. Baseline medication did not predict changes in MDI during the inpatient treatment. BMI increased from 14.9 (week 1) to 17.2 (week 8). Conclusions: Inpatient treatment of AN is associated with a reduction in depressiveness. This improvement in depressiveness scores correlates with an improvement in ED psychopathology but not with weight gain.

Estimating the Effect of Motivational Interventions in Patients with Eating Disorders: A Systematic Review and Meta-Analysis.

Motivation to change behavior is seen as an important factor in achieving a better treatment effect in patients with eating disorders (ED). The aim of this systematic review was to assess whether motivational interviewing (MI) and motivational enhancement therapy (MET) might (1) increase motivation to change behavior and (2) improve eating disorder psychopathology (EDP) and body mass index (BMI) in patients with ED. To investigate this, a literature search was conducted on 9 March 2021 on four scientific databases: Cochrane, Embase (Ovid), MEDLINE (PubMed), and PsycInfo (EBSCO). A total of 2647 publications were identified and following a rigorous stepwise procedure to assess titles and abstracts and, thereafter, full texts of relevant publications, 13 studies were included in the data extraction and analyses. A few individual studies (n = 5) found a significant increase in motivation, two a decrease in ED symptoms (n = 2), while none found an effect on BMI. However, the meta-analysis of each outcome found effect sizes near zero, thereby confirming the results of previous narrative reviews that have described a lack of effect of MET/MI on motivation in ED. Since the individual studies differ substantially in design, and the outcomes were inconsistently assessed with regards to instruments and duration, the effect of MET/MI on motivation for behavioral change, ED psychopathology, and BMI is still unclear.

Weight Gain in Adults with Avoidant/Restrictive Food Intake Disorder Compared to Restrictive Anorexia Nervosa-Pilot Findings from a Longitudinal Study.

BACKGROUND: Avoidant/Restrictive Food Intake Disorder (ARFID) is characterized by persistent failure to meet nutritional needs, absence of body image distortion and often low body weight. Weight restorative treatment in ARFID-adults is provided for as in Anorexia Nervosa (AN), while the effect is unknown. The aim was to compare weight gain between ARFID and restrictive subtype of AN (AN-R), including exploring impact of medical factors and psychopathology. METHODS: Individuals with ARFID (n = 7; all cases enrolled over 5 years) and AN-R (n = 80) were recruited from the Prospective Longitudinal All-comers inclusion study in Eating Disorders (PROLED) during 5 years. All underwent weight restorative inpatient treatment. Clinical characteristics at baseline and weekly weight gain were recorded and compared. RESULTS: There were no significant differences at baseline weight, nor in weight gain between groups. Anxiety was statistically significantly higher in AN-R at baseline. CONCLUSIONS: Although there were differences in several clinical measures at baseline (Autism Quotient, symptom checklist, mood scores and Morgan Russel Outcome Scale), only anxiety was higher in AN-R. No differences in weight gain were observed, although mean values indicate a faster weight gain in the ARFID group. Standard weight restorative treatment in this study in adults with ARFID has similar weight gaining effect as in AN-R.

Inpatient Weight Restoration Treatment Is Associated with Decrease in Post-Meal Anxiety.

OBJECTIVE: Anorexia nervosa (AN) is characterized by weight loss, distorted body image with fear of becoming fat and associated with anxiety, especially in relation to food intake. Anxiety in relation to meals and weight restoration remains a major challenge in the treatment of AN. We examined the effects of inpatient weight restoration treatment on levels of post-meal anxiety using visual analogue scale (VAS) ratings in patients with AN. MATERIALS: Thirty-two patients with AN, all part of the PROspective Longitudinal all-comer inclusion study on Eating Disorders (PROLED) were followed over eight weeks with baseline psychometric measures and weekly VAS anxiety self-scoring. METHODS: Apart from the weekly body mass index (BMI) and VAS, patients were characterized at baseline using the Eating Disorder Examination Questionnaire (EDE-Q), Eating Disorder Inventory (EDI), Symptom Check List 92 (SCL-92), Major Depression Inventory (MDI), and Autism Quotient (AQ). RESULTS: The results showed a significant time effect, Wilks Lambda = 0.523, F = 3.12, p < 0.05 (power of 0.862), indicating a reduction in VAS scores of anxiety from baseline to week 8. There was no effect of baseline medication or scores of MDI on the results. BMI increased from a mean of 15.16 (week 1) to 17.35 (week 8). In comparison, patients dropping out after only three weeks (n = 31) also had a trend toward a reduction in VAS anxiety (ns). CONCLUSIONS: Inpatient weight restoration treatment is associated with a decrease in post-meal anxiety in AN, an effect that occurs early and becomes clinically significant in patients who stay in treatment.

Genetically Targeted Clinical Trials in Parkinson's Disease: Learning from the Successes Made in Oncology.

Clinical trials in neurodegenerative disorders have been associated with high rate of failures, while in oncology, the implementation of precision medicine and focus on genetically defined subtypes of disease and targets for drug development have seen an unprecedented success. With more than 20 genes associated with Parkinson's disease (PD), most of which are highly penetrant and often cause early onset or atypical signs and symptoms, and an increasing understanding of the associated pathophysiology culminating in dopaminergic neurodegeneration, applying the technologies and designs into the field of neurodegeneration seems a logical step. This review describes some of the methods used in oncology clinical trials and some attempts in Parkinson's disease and the potential of further implementing genetics, biomarkers and smart clinical trial designs in this disease area.

Cognitive Function in Adults with Enduring Anorexia Nervosa.

Anorexia Nervosa (AN) is a severe and often enduring disorder characterized by restriction of food intake, low body weight, fear of weight gain, and distorted body image. Investigations on cognition performance in AN patients have yielded conflicting results. Using an established and sensitive computerized cognitive test battery, we aimed to assess core aspects of cognitive function, including attention span, information processing, reasoning, working and episodic memory, in AN patients and controls. Patients were recruited from the Danish Prospective Longitudinal all-comer inclusion study in Eating Disorders (PROLED). Included were 26 individuals with AN and 36 healthy volunteers (HV). All were tested with CogTrack (an online cognitive assessment system) at baseline, and AN patients were tested again at a follow-up time point after weight increase (n = 13). At baseline, AN patients showed faster reaction times in the attention tasks, as well as increased accuracy in grammatical reasoning compared to HV. There were no differences in cognitive function between AN patients and HV in the other cognitive domains measured (sustained attention, working and episodic memory, speed of retrieval, and speed of grammatical reasoning). No differences were visible in the AN sample between baseline and follow-up. Performance did not correlate with any clinical variables in the AN sample. These findings supplement results from other studies suggesting increased concentration and reasoning accuracy in patients suffering from AN, who showed increased performance in cognitive tasks despite their illness.