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Significance Mutations in ATP13A2 cause a spectrum of related neurodegenerative disorders. ATP13A2 is a lysosomal exporter of polyamines that contributes to lysosomal health and controls cellular polyamine content. Conversely, loss of ATP13A2 leads to lysosomal dysfunction, a hallmark of neurodegeneration. Here, we show that polyamines transported by ATP13A2 provide cellular protection by lowering reactive oxygen species (ROS), which may relate to the antioxidant properties of polyamines. Consequently, dysfunctional ATP13A2 sensitizes cells to oxidative stress, which impairs mitochondria, and induces toxicity and cell death. ATP13A2-mediated polyamine transport represents a conserved pathway that protects against mitochondrial oxidative stress. The combined protective impact of ATP13A2 on lysosomal health and mitochondrial oxidative stress may explain why ATP13A2 exerts potent neuroprotective effects., Recessive loss-of-function mutations in ATP13A2 (PARK9) are associated with a spectrum of neurodegenerative disorders, including Parkinson’s disease (PD). We recently revealed that the late endo-lysosomal transporter ATP13A2 pumps polyamines like spermine into the cytosol, whereas ATP13A2 dysfunction causes lysosomal polyamine accumulation and rupture. Here, we investigate how ATP13A2 provides protection against mitochondrial toxins such as rotenone, an environmental PD risk factor. Rotenone promoted mitochondrial-generated superoxide (MitoROS), which was exacerbated by ATP13A2 deficiency in SH-SY5Y cells and patient-derived fibroblasts, disturbing mitochondrial functionality and inducing toxicity and cell death. Moreover, ATP13A2 knockdown induced an ATF4-CHOP-dependent stress response following rotenone exposure. MitoROS and ATF4-CHOP were blocked by MitoTEMPO, a mitochondrial antioxidant, suggesting that the impact of ATP13A2 on MitoROS may relate to the antioxidant properties of spermine. Pharmacological inhibition of intracellular polyamine synthesis with α-difluoromethylornithine (DFMO) also increased MitoROS and ATF4 when ATP13A2 was deficient. The polyamine transport activity of ATP13A2 was required for lowering rotenone/DFMO-induced MitoROS, whereas exogenous spermine quenched rotenone-induced MitoROS via ATP13A2. Interestingly, fluorescently labeled spermine uptake in the mitochondria dropped as a consequence of ATP13A2 transport deficiency. Our cellular observations were recapitulated in vivo, in a Caenorhabditis elegans strain deficient in the ATP13A2 ortholog catp-6. These animals exhibited a basal elevated MitoROS level, mitochondrial dysfunction, and enhanced stress response regulated by atfs-1, the C. elegans ortholog of ATF4, causing hypersensitivity to rotenone, which was reversible with MitoTEMPO. Together, our study reveals a conserved cell protective pathway that counters mitochondrial oxidative stress via ATP13A2-mediated lysosomal spermine export.

A method for encryption and safe transmission of data in the shape of molecular weight distributions (MWD) is presented. Relatively simple individual distributions serve as the key to encode information by mixing those in known amounts to an overlapped MWD. Increasing molecular weights are used to denote the position of these individual sub-distributions, and the relative quantity per sub-distribution is used to store data. The concept is demonstrated by a series of messages, whereby two-letter codes can be transmitted per overall MWD. In the final step, the encryption safety is confirmed. Due to the inherent differences in SEC calibrations, samples sent from Australia to Belgium could only be deconvoluted when the recipient of the message owned the physical sub-distributions, which then act as the encryption key.

Contains fulltext : 216652.pdf (Publisher’s version ) (Open Access) Memory bias modification (MBM) is a relatively new approach at targeting biased processing - a central cognitive factor causing and maintaining depression. In this pilot study we aimed to develop a smartphone-based autobiographical memory training, a novel form of MBM. A total of 153 unselected participants were randomly allocated to one of three experimental training conditions (positive, negative or sham memory training) conducted over a period of three days. Autobiographical memory bias and depressive scores were assessed pre- and post-training, whilst recent event recall and explicit self-referent memory bias were assessed post-training. Positive memory bias significantly increased in the positive training condition, however memory bias did not significantly differ post-training between the three conditions. Participants who received positive training recalled a positive autobiographical event more frequently compared to the other conditions. No significant difference between conditions was found in the other outcomes, including symptoms. The novel smartphone-based MBM intervention seems apt to affect autobiographical memory of emotional material. Future research should explore its possible (therapeutic) application. 12 p.

Contains fulltext : 217003.pdf (Publisher’s version ) (Closed access) Achtergrond: De meeste ggz-instellingen in Nederland werken met stoornisspecifieke zorgprogramma’s. Indien er sprake is van comorbiditeit, wat eerder regel is dan uitzondering in de specialistische ggz (sggz), blijkt er onvoldoende evidentie te bestaan als het gaat om het kiezen van de focus van behandeling. Doel: Inzicht krijgen in de prevalentie van comorbiditeit met depressie bij patiënten met angststoornissen volgens de dsm-iv-classificatie (angststoornissen inclusief de dwangstoornissen en de posttraumatische stressstoornis). Tevens nagaan of er een verschil is in behandeleffect bij een protocollaire angstbehandeling tussen patiënten met één (of meerdere) angststoornissen zonder of met een comorbide depressie. Methode: Retrospectieve studie met gegevens uit routine outcome monitoring over de periode 2012-2017. In deze periode identificeerden we 127 patiënten van wie rom-data en diagnostische criteria beschikbaar waren. Diagnostiek en dsm-classificatie vonden plaats met een klinisch interview. De behandeling werd uitgevoerd conform de Multidisciplinaire richtlijn Angststoornissen en elke 12 weken systematisch gemonitord met zelfrapportagelijsten, waaronder de Inventory of Depressive Symptomatology (ids) en de Beck Anxiety Inventory (BAI). Resultaten: Bij 46,5% van de onderzochte patiënten was er een comorbide depressieve stoornis aanwezig. De behandeleffecten bij patiënten met of zonder comorbide depressie verschilden niet van elkaar. Als opvallende bevinding werd gevonden dat de mate van vermindering van de depressieve klachten (gemeten met de ids) voorspellend bleek te zijn voor de mate van vermindering van de angstklachten (gemeten met de BAI): een sterkere vermindering van de stemmingsklachten bleek een gunstiger beloop van het effect van de protocollaire angstbehandeling te voorspellen. Conclusie: Bij iets minder dan de helft van de patiënten in het zorgprogramma angststoornissen was sprake van een comorbide depressieve stoornis. Traag of niet afnemen van de depressieve symptomen lijkt geassocieerd met een slechter behandelresultaat op de angstklachten. 7 p.

UNSTRUCTURED These are author responses to peer review of ms#31269

BackgroundClassic theories posit that depression is driven by a negative learning bias. Most studies supporting this proposition used small and selected samples, excluding patients with comorbidities. However, comorbidity between psychiatric disorders occurs in up to 70% of the population. Therefore, the generalizability of the negative bias hypothesis to a naturalistic psychiatric sample as well as the specificity of the bias to depression, remain unclear. In the present study, we tested the negative learning bias hypothesis in a large naturalistic sample of psychiatric patients, including depression, anxiety, addiction, attention-deficit/hyperactivity disorder, and/or autism. First, we assessed whether the negative bias hypothesis of depression generalized to a heterogeneous (and hence more naturalistic) depression sample compared with controls. Second, we assessed whether negative bias extends to other psychiatric disorders. Third, we adopted a dimensional approach, by using symptom severity as a way to assess associations across the sample.MethodsWe administered a probabilistic reversal learning task to 217 patients and 81 healthy controls. According to the negative bias hypothesis, participants with depression should exhibit enhanced learning and flexibility based on punishment v. reward. We combined analyses of traditional measures with more sensitive computational modeling.ResultsIn contrast to previous findings, this sample of depressed patients with psychiatric comorbidities did not show a negative learning bias.ConclusionsThese results speak against the generalizability of the negative learning bias hypothesis to depressed patients with comorbidities. This study highlights the importance of investigating unselected samples of psychiatric patients, which represent the vast majority of the psychiatric population.

Background Anhedonia is apparent in different mental disorders and is suggested to be related to dysfunctions in the reward system and/or affect regulation. It may hence be a common underlying feature associated with symptom severity of mental disorders. Methods We constructed a cross-sectional graphical Least Absolute Shrinkage and Selection Operator (LASSO) network and a relative importance network to estimate the relationships between anhedonia severity and the severity of symptom clusters of major depressive disorder (MDD), anxiety sensitivity (AS), attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD) in a sample of Dutch adult psychiatric patients (N = 557). Results Both these networks revealed anhedonia severity and depression symptom severity as central to the network. Results suggest that anhedonia severity may be predictive of the severity of symptom clusters of MDD, AS, ADHD, and ASD. MDD symptom severity may be predictive of AS and ADHD symptom severity. Conclusions The results suggest that anhedonia may serve as a common underlying transdiagnostic psychopathology feature, predictive of the severity of symptom clusters of depression, AS, ADHD, and ASD. Thus, anhedonia may be associated with the high comorbidity between these symptom clusters and disorders. If our results will be replicated in future studies, it is recommended for clinicians to be more vigilant about screening for anhedonia and/or depression severity in individuals diagnosed with an anxiety disorder, ADHD and/or ASD.

ObjectiveIndividuals with a parental family history (PFH) of dementia have an increased risk to develop dementia, regardless of genetic risks. The aim of this study is to investigate the association between a PFH of dementia and currently known modifiable risk factors for dementia among middle-aged individuals using propensity score matching (PSM).DesignA cross-sectional study.Setting and participantsA subsample of Lifelines (35–65 years), a prospective population-based cohort study in the Netherlands was used.Outcome measuresFourteen modifiable risk factors for dementia and the overall Lifestyle for Brain Health (LIBRA) score, indicating someone’s potential for dementia risk reduction (DRR).ResultsThe study population included 89 869 participants of which 10 940 (12.2%) had a PFH of dementia (mean (SD) age=52.95 (7.2)) and 36 389 (40.5%) without a PFH of dementia (mean (SD) age=43.19 (5.5)). Of 42 540 participants (47.3%), PFH of dementia was imputed. After PSM, potential confounding variables were balanced between individuals with and without PFH of dementia. Individuals with a PFH of dementia had more often hypertension (OR=1.19; 95% CI 1.14 to 1.24), high cholesterol (OR=1.24; 95% CI 1.18 to 1.30), diabetes (OR=1.26; 95% CI 1.11 to 1.42), cardiovascular diseases (OR=1.49; 95% CI 1.18 to 1.88), depression (OR=1.23; 95% CI 1.08 to 1.41), obesity (OR=1.14; 95% CI 1.08 to 1.20) and overweight (OR=1.10; 95% CI 1.05 to 1.17), and were more often current smokers (OR=1.20; 95% CI 1.14 to 1.27) and ex-smokers (OR=1.21; 95% CI 1.16 to 1.27). However, they were less often low/moderate alcohol consumers (OR=0.87; 95% CI 0.83 to 0.91), excessive alcohol consumers (OR=0.93; 95% CI 0.89 to 0.98), socially inactive (OR=0.84; 95% CI 0.78 to 0.90) and physically inactive (OR=0.93; 95% CI 0.91 to 0.97). Having a PFH of dementia resulted in a higher LIBRA score (RC=0.15; 95% CI 0.11 to 0.19).ConclusionWe found that having a PFH of dementia was associated with several modifiable risk factors. This suggests that middle-aged individuals with a PFH of dementia are a group at risk and could benefit from DRR. Further research should explore their knowledge, beliefs and attitudes towards DRR, and whether they are willing to assess their risk and change their lifestyle to reduce dementia risk.

Background Already a major health concern, late-life depression (LLD) is expected to form an increasing problem in the aging population. Moreover, despite current treatments, LLD is associated with a poor long-term prognosis and high rate of chronicity. Treatment provision and treatment accordingly warrant improvement, where add-on treatments might contribute to the efficacy of conventional therapies. Although it is known that impaired cognitive control contributes to LDD, it is not targeted sufficiently by current interventions. Research on cognitive control training (CCT) shows promising results on depressive symptoms, cognitive performance, and overall functioning. However, further research is needed to determine the long-term effects of CCT on LLD, its cost-effectiveness, and mechanisms of change. Methods In the current multicenter randomized controlled trial (RCT) with a between-subjects design participants aged 60 years and over with a current LLD receiving treatment as usual (TAU) are randomized to add-on CCT or placebo training. Randomization is stratified by depression severity. Participants will receive eight online CCT or placebo sessions spread across four consecutive weeks. They will complete a post-training assessment after 1 month and three follow-up assessments scheduled three, six and 12 months after completing the training. We expect CCT and TAU to be more (cost-)effective in reducing depressive symptoms than placebo training and TAU. Additionally, we will be looking at secondary clinical, cognitive and global functioning outcomes and likely mechanisms of change (e.g., improved cognitive functioning, reduced rumination, and improved inhibition of negative stimuli). Discussion The proposed RCT aims to contribute to the clinical and scientific knowledge on the long-term effects of CCT as an add-on treatment for LLD. Cost-effectiveness is particularly relevant considering the expected volume of the target demographic. The study will be a pragmatic trial with few inclusion restrictions, providing information on feasibility of web-based trainings in clinical settings. The outcomes are potentially generalizable to guidelines for treatment of LLD. Trial registration This trial is registered in the Netherlands Trial Register (code: NL7639). Registered 3 april 2019.

Objective: Perseverative cognition (PC) is the repeated or long-term activation of the cognitive representation of psychological stressors and is associated with prolonged stress including somatic and mental consequences. Hence, PC might represent a cognitive process linking mental and somatic pathology, but current research on this link is limited by investigating healthy samples, markers of somatic disease, and single disorders. The present study explored the importance of PC for different mental and somatic disorders in psychiatric patients. Methods: Data from 260 naturalistic psychiatric outpatients were used. Psychiatric diagnoses were based on structured clinical interviews. Somatic diseases were assessed using a well-validated questionnaire and were clustered into (cardio)vascular and immune/endocrine diseases. PC was operationalized using the Perseverative Thinking Questionnaire (PTQ). Results: Multiple regression complemented with relative importance analyses showed that the PTQ total and subscale scores were associated with the presence of mood disorders, addiction, and anxiety. Unexpectedly, no relatively important associations were found between the PTQ and autism spectrum disorder, attention-deficit/hyperactivity disorder, or somatic disease. Conclusions: Our data complement previous work linking PC to stress-related mental disorders but question its immediate role in neurodevelopmental and somatic disorders. Targeting PC in the treatment of mood disorders and perhaps also in addiction seems promising.Key words: psychiatric disorder, somatic disorder, perseverative cognition, repetitive negative thinking, stress response.

High-resolution FlowNMR was coupled to a continuous flow reactor to monitor polymer molecular weight evolution online by diffusion ordered NMR spectroscopy. Polymers were synthesized by reversible addition fragmentation chain transfer polymerization in continuous flow. The setup allows to target various polymer chain lengths in a dynamic manner without requiring additional purification or sample preparation. Obtaining molecular weight information in this manner is shown to be more accurate than classical SEC analysis at comparable measurement times, with relative errors around 5%. The authors are grateful to the Fonds Wetenschappelijk Onderzoek (FWO) for providing a SB scholarship for JHV, the Royal Society for a University Research Fellowship to UH (UF160458), and EPSRC for funding the Dynamic Reaction Monitoring Facility at the University of Bath (EP/P001475/1) and for the EPSRC Centre for Doctoral Training in Sustainable Chemical Technologies (EP/L016354/1, PhD studentship for IAT). We thank Joris Haven (Monash University), Maciek Kopec and John Lowe (University of Bath) for stimulating discussions. Junkers, T (corresponding author), Hasselt Univ, Martelarenlaan 42, B-3500 Hasselt, Belgium; Monash Univ, Sch Chem, Polymer React Design Grp, 19 Rainforest Walk,Bldg 23, Clayton, Vic 3800, Australia. u.hintermair@bath.ac.uk; tanja.junkers@monash.edu

Background In several settings, a shorter time to diagnosis has been shown to lead to improved clinical outcomes. The implementation of a rapid laboratory testing allows for a pre-visit testing in the outpatient clinic, meaning that test results are available during the first outpatient visit. Objective To determine whether the pre-visit laboratory testing leads to a shorter time to diagnosis in the general internal medicine outpatient clinic. Design An “on-off” trial, allocating subjects to one of two treatment arms in consecutive alternating blocks. Participants All new referrals to the internal medicine outpatient clinic of a university hospital were included, excluding second opinions. A total of 595 patients were eligible; one person declined to participate, leaving data from 594 patients for analysis. Intervention In the intervention group, patients had a standardized pre-visit laboratory testing before the first visit. Main Measures The primary outcome was the time to diagnosis. Secondary outcomes were the correctness of the preliminary diagnosis on the first day, health care utilization, and patient and physician satisfaction. Key Results There was no difference in time to diagnosis between the two groups (median 35 days vs 35 days; hazard ratio 1.03 [0.87–1.22]; p = .71). The pre-visit testing group had higher proportions of both correct preliminary diagnoses on day 1 (24% vs 14%; p = .003) and diagnostic workups being completed on day 1 (10% vs 3%; p < .001). The intervention group had more laboratory tests done (50.0 [interquartile range (IQR) 39.0–69.0] vs 43.0 [IQR 31.0–68.5]; p < .001). Otherwise, there were no differences between the groups. Conclusions Pre-visit testing did not lead to a shorter overall time to diagnosis. However, a greater proportion of patients had a correct diagnosis on the first day. Further studies should focus on customizing pre-visit laboratory panels, to improve their efficacy. Trial Registration NL5009

BACKGROUND It is widely acknowledged that comorbidity between psychiatric disorders is common. Shared and diverse underpinnings of psychiatric disorders cannot be systematically understood based on symptom-based categories of mental disorders, which map poorly onto pathophysiological mechanisms. In the Measuring Integrated Novel Dimensions in Neurodevelopmental and Stress-Related Mental Disorders (MIND-SET) study, we make use of current concepts of comorbidity that transcend the current diagnostic categories. We test this approach to psychiatric problems in patients with frequently occurring psychiatric disorders and their comorbidities (excluding psychosis). OBJECTIVE The main aim of the MIND-SET project is to determine the shared and specific mechanisms of neurodevelopmental and stress-related psychiatric disorders at different observational levels. METHODS This is an observational cross-sectional study. Data from different observational levels as defined in the Research Domain Criteria (genetics, physiology, neuropsychology, system-level neuroimaging, behavior, self-report, and experimental neurocognitive paradigms) are collected over four time points. Included are adult (aged ≥18 years), nonpsychotic, psychiatric patients with a clinical diagnosis of a stress-related disorder (mood disorder, anxiety disorder, or substance use disorder) or a neurodevelopmental disorder (autism spectrum disorder or attention-deficit/hyperactivity disorder). Individuals with no current or past psychiatric diagnosis are included as neurotypical controls. Data collection started in June 2016 with the aim to include a total of 650 patients and 150 neurotypical controls by 2021. The data collection procedure includes online questionnaires and three subsequent sessions with (1) standardized clinical examination, physical examination, and blood sampling; (2) psychological constructs, neuropsychological tests, and biological marker sampling; and (3) neuroimaging measures. RESULTS We aim to include a total of 650 patients and 150 neurotypical control participants in the time period between 2016 and 2022. In October 2021, we are at 95% of our target. CONCLUSIONS The MIND-SET study enables us to investigate the mechanistic underpinnings of nonpsychotic psychiatric disorders transdiagnostically. We will identify both shared and disorder-specific markers at different observational levels that can be used as targets for future diagnostic and treatment approaches.

BackgroundIt is widely acknowledged that comorbidity between psychiatric disorders is common. Shared and diverse underpinnings of psychiatric disorders cannot be systematically understood on the basis of symptom-based categories of mental disorders, which map poorly onto pathophysiological mechanisms. In the MIND-Set study, we make use of current concepts of comorbidity that transcend the current diagnostic categories. We test this approach to psychiatric problems in patients with frequently occurring psychiatric disorders and their comorbidities (excluding psychosis). The main objective of the MIND-Set project is to determine the shared and specific mechanisms of neurodevelopmental and stress-related psychiatric disorders at different observational levels.MethodsThis is an observational, cross-sectional study. Data from different observational levels as defined in the research domain criteria (RDoC; genetics, physiology, neuropsychology, system level neuroimaging, behavior, self-report and experimental neurocognitive paradigms) are collected over four time points. Included are adult (≥ 18 years), non-psychotic, psychiatric patients with a clinical diagnosis of a stress-related disorder (mood disorder, anxiety disorder and/or addiction disorder) and/or a neurodevelopmental disorder (ASD and/or ADHD). Individuals with no current or past psychiatric diagnosis are included as controls. Data collection started in June 2016 with the aim to include a total of 650 patients and 150 healthy controls by 2021. The data collection procedure includes online questionnaires and three subsequent sessions with 1) Standardized clinical examination, physical examination, and blood sampling; 2) Psychological constructs, neuropsychological tests, and biological marker sampling; 3) Neuroimaging measures.DiscussionThe MIND-Set study enables us to investigate the mechanistic underpinnings of non-psychotic psychiatric disorders transdiagnostically. We will identify both shared and disorder-specific markers at different observational levels that can be used as targets for future diagnostic and treatment approaches.

Depression ist eine der haufigsten psychischen Erkrankungen, mit oft chronischem Verlauf und schwierig zu behandeln. Zusatzliche Interventionen, die auf spezielle Risikofaktoren abzielen, konnten neue Behandlungsmoglichkeiten bieten. Vielversprechend sind Trainingsprogramme, die automatische kognitive Prozesse und Verzerrungen beeinflussen. In den letzten Jahren wurden computergestutzte Trainings entwickelt ("Cognitive-bias-modification"[CBM]-Programme), die genau auf diese Prozesse abzielen und zukunftig einfach als "Add-on" in die psychotherapeutische Praxis implementiert werden konnten. Im Folgenden wird der Stand der Forschung dargestellt und anhand eines eigenen klinischen Versuchs der detaillierte Aufbau aktueller Studien verdeutlicht.

A novel continuous flow system for automated high-throughput screening, autonomous optimization, and enhanced process control of polymerizations was developed. The computer-controlled platform comprises a flow reactor coupled to size exclusion chromatography (SEC). Molecular weight distributions are measured online and used by a machine-learning algorithm to self-optimize reactions towards a programmed molecular weight by dynamically varying reaction parameters (i.e. residence time, monomer concentration, and control agent/initiator concentration). The autonomous platform allows targeting of molecular weights in a reproducible manner with unprecedented accuracy (

Over the course of the last century, a large number of synthetic polymers has been developed and introduced. Yet, most polymer materials are based on fossil fuels as raw materials and are associated with a considerable environmental impact. trans,trans-Muconic acid esters are interesting plant-based monomers that have not received much attention yet. The synthesis of a series of dialkyl muconates from muconic acid is described, followed by an optimization of the solution free-radical polymerization of these monomers. Unlike the claim in previous studies, dialkyl muconates can be polymerized efficiently in solution to polymers with significant molecular weights above 105 g mol−1. Polymerizations are, however, relatively slow, as can be expected for diene monomers (48 h at 120 °C). Mark–Houwink coefficients have been determined for diethyl muconate, dibutyl muconate and di(2-ethylhexyl) muconate. Furthermore, glass transition temperatures and thermal stability are assessed for the polymers, showcasing that polymuconates can serve as alternatives to polyacrylate materials. In a last step, also the reversible addition–fragmentation chain transfer (RAFT) polymerization of the muconates is investigated, showing excellent control over the molecular weight when a conventional trithiocarbonate is used to control polymerizations.

Contains fulltext : 234352pub.pdf (Publisher’s version ) (Closed access) Contains fulltext : 234352.pdf (Author’s version preprint ) (Open Access) Contains fulltext : 234352appendix.pdf (Author’s version preprint ) (Open Access) Cognitive theories of depression hold that negative contextual triggers (e.g., stressful events) induce more negative and less positive mood, in turn instigating negatively biased memories. However, context-related variability in mood and emotional memory has received insufficient attention, while the dynamic interaction between these factors plays a crucial role in the kindling of new depressive episodes. Experience Sampling Method (ESM) for repeated, daily life measures of context, mood, and autobiographic emotional memory was used in 46 currently depressed, 90 remitted-depressed, and 55 never-depressed individuals. Currently depressed individuals showed strongest negative processing style and never-depressed most positive, with remitted-depressed patients scoring intermediate. The moderated mediation model indicated that context appraisal had a direct effect on the appraisal of the recalled event (i.e., our operationalization of emotional memory), which was mediated by positive (but hardly by negative) mood and was independent of depression status. This mediation strength was relatively similar to the strength of the direct effect of context on memory. Results are in line with cognitive theories of depression. Especially context seems important for emotional memory. The association between context, mood, and memory, however, may be independent of depression status. Yet, the "level" of mood, context, and event appraisal does depend on depression status. 11 p.

Background Positive health beliefs and attitudes towards dementia and dementia risk reduction may encourage adopting a healthy behaviour. Therefore, we aimed to investigate the knowledge, health beliefs and attitudes towards dementia and dementia risk reduction among the Dutch general population and its association with the intention to change health behaviours. Methods A random sample of Dutch residents (30 to 80 years) was invited to complete an online survey. We collected data on knowledge, health beliefs and attitudes towards dementia (risk reduction) and the intention to change health behaviours. Multivariable logistic regression analyses were used to obtain effect estimates. Results Six hundred fifty-five participants completed the survey. In general, participants had insufficient knowledge about dementia and dementia risk reduction. Participants had relatively high scores on general health motivation and perceived benefits, but low scores on perceived susceptibility, perceived severity, perceived barriers, cues to action and self-efficacy. Individuals with higher scores on perceived benefits and cues to action had more often the intention to change their behaviour with regard to physical activity (OR = 1.33, 95%-CI:1.11–1.58; OR = 1.13, 95%-CI:1.03–1.24, respectively) and alcohol consumption (OR = 1.30, 95%-CI:1.00–1.69; OR = 1.17, 95%-CI:1.02–1.35, respectively). Younger excessive alcohol consumers with higher perceived severity scores had more often the intention to change their alcohol consumption behaviour (OR = 2.70, 95%-CI:1.04–6.97) compared to older excessive alcohol consumers. Opposite results were found for middle-aged excessive alcohol consumers (OR = 0.81, 95%-CI:0.67–0.99). Individuals who perceived more barriers had more often the intention to change their diet (OR = 1.10, 95%-CI:1.01–1.21), but less often the intention to change their smoking behaviour (OR = 0.78, 95%-CI:0.63–0.98). Moreover, less educated individuals with higher perceived benefits scores had less often the intention to change their diet (OR = 0.78, 95%-CI:0.60–0.99), while highly educated individuals with higher perceived benefits scores had more often the intention to change their diet (OR = 1.41, 95%-CI:1.12–1.78). Conclusions The knowledge, beliefs and attitudes towards dementia and dementia risk reduction among the Dutch general population is insufficient to support dementia risk reduction. More education about dementia and dementia risk reduction is needed to improve health beliefs and attitudes towards dementia and dementia risk reduction in order to change health behaviour.

Background The Ruff Figural Fluency Test (RFFT) is a valid but time-consuming and labour-intensive cognitive paper-and-pencil test. A digital RFFT was developed that can be conducted independently using an iPad and Apple Pencil and RFFT scores are computed automatically. We investigated the validity and reliability of this digital RFFT. Methods We randomly allocated participants to the digital or paper-and-pencil RFFT. After the first test, the other test was performed immediately (cross-over). Participants were invited for a second digital RFFT 1 week later. For the digital RFFT, an (automatic) algorithm and two independent raters (criterion standard) assessed the number of unique designs (UD) and perseverative errors (PE). These raters also assessed the paper-and-pencil RFFT. We used Intraclass correlation coefficients (ICC), sensitivity, specificity, %-agreement, Kappa, and Bland–Altman plots. Results We included 94 participants (mean (SD) age 39.9 (14.8), 73.4% follow-up). Mean (SD) UD and median (IQR) PE of the digital RFFT were 84.2 (26.0) and 4 (2–7.3), respectively. Agreement between manual and automatic scoring of the digital RFFT was high for UD (ICC = 0.99, 95% CI 0.98, 0.99, sensitivity = 0.98; specificity = 0.96) and PE (ICC = 0.99, 95% CI 0.98, 0.99; sensitivity = 0.90, specificity = 1.00), indicating excellent criterion validity. Small but significant differences in UD were found between the automatic and manual scoring (mean difference: − 1.12, 95% CI − 1.92, − 0.33). Digital and paper-and-pencil RFFT had moderate agreement for UD (ICC = 0.73, 95% CI 0.34, 0.87) and poor agreement for PE (ICC = 0.47, 95% CI 0.30, 0.62). Participants had fewer UD on the digital than paper-and-pencil RFFT (mean difference: − 7.09, 95% CI − 11.80, − 2.38). The number of UD on the digital RFFT was associated with higher education (Spearman’s r = 0.43, p r = − 0.36, p Conclusions The automatic scoring of the digital RFFT has good criterion and convergent validity. There was low agreement between the digital RFFT and paper-and-pencil RFFT and moderate test–retest reliability, which can be explained by learning effects. The digital RFFT is a valid and reliable instrument to measure executive cognitive function among the general population and is a feasible alternative to the paper-and-pencil RFFT in large-scale studies. However, its scores cannot be used interchangeably with the paper-and-pencil RFFT scores.

Background Individuals with a parental family history of dementia have an increased risk of developing dementia because they share their genes as well as their psychosocial behaviour. Due to this increased risk and their experience with dementia, they may be particularly eager to receive information regarding dementia risk reduction (DRR). This study evaluated the knowledge, beliefs and attitudes towards dementia and DRR among descendants of people with dementia.Method Using a semi-structured topic guide, three focus group discussions were conducted consisting of 12 female (80%) and 3 male (20%) descendants of people with dementia with a mean age of 48.8 ± 12.0 years. Focus group discussions were audio recorded and transcribed. Each transcript was analysed thoroughly, and where appropriate, a code was generated and assigned by two researchers independently. Then, similar codes were grouped together and categorized into themes.Results The items in the topic guide could only be addressed after participants had been given the opportunity to share their experiences of having a parent with dementia. Participants were unaware or uncertain about the possibility of reducing the risk of developing dementia and therefore hesitant to assess their dementia risk without treatment options in sight. Moreover, participants indicated that their general practitioner only gave some information on heritability, not on DRR. Although participants identified a large number of modifiable risk factors as a group during the group discussions, they were eager to receive more information on dementia and DRR. In the end, participants adopted a more positive attitude towards a DRR program and provided suggestions for the development of future DRR programs.Conclusions Although the research aim was to evaluate the knowledge, beliefs and attitudes towards dementia and DRR, sharing experiences of having a parent with dementia seemed a prerequisite for considering participants’ own risk of developing dementia and participating in a DRR program. Knowledge of dementia and DRR was limited. Due to unawareness of the possibility of reducing dementia risk, participants were hesitant about assessing their dementia risk. Group discussions positively changed the perception of dementia risk assessment and participants’ willingness to participate in a DRR program.