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BACKGROUND: Microvascular dysfunction is involved in the development of various cerebral disorders. It may contribute to these disorders by disrupting white matter tracts and altering brain connectivity, but evidence is scarce. We investigated the association between multiple biomarkers of microvascular function and whole-brain white matter connectivity. METHODS AND RESULTS: Cross-sectional data from The Maastricht Study, a Dutch population-based cohort (n=4326; age, 59.4±8.6 years; 49.7% women). Measures of microvascular function included urinary albumin excretion, central retinal arteriolar and venular calibers, composite scores of flicker light-induced retinal arteriolar and venular dilation, and plasma biomarkers of endothelial dysfunction (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and von Willebrand factor). White matter connectivity was calculated from 3T diffusion magnetic resonance imaging to quantify the number (average node degree) and organization (characteristic path length, global efficiency, clustering coefficient, and local efficiency) of white matter connections. A higher plasma biomarkers of endothelial dysfunction composite score was associated with a longer characteristic path length (β per SD, 0.066 [95% CI, 0.017-0.114]) after adjustment for sociodemographic, lifestyle, and cardiovascular factors but not with any of the other white matter connectivity measures. After multiple comparison correction, this association was nonsignificant. None of the other microvascular function measures were associated with any of the connectivity measures. CONCLUSIONS: These findings suggest that microvascular dysfunction as measured by indirect markers is not associated with whole-brain white matter connectivity.

Abstract Background Germany is the second most common country of immigration after the US. However, people with own or familial history of migration are not represented proportionately to the population within public health monitoring and reporting. To bridge this data gap and enable differentiated analyses on migration and health, we conducted the health interview survey GEDA Fokus among adults with Croatian, Italian, Polish, Syrian, or Turkish citizenship living throughout Germany. The aim of this paper is to evaluate the effects of recruitment efforts regarding participation and sample composition. Methods Data collection for this cross-sectional and multilingual survey took place between 11/2021 and 5/2022 utilizing a sequential mixed-mode design, including self-administered web- and paper-based questionnaires as well as face-to-face and telephone interviews. The gross sample (n = 33436; age range 18–79 years) was randomly drawn from the residents’ registers in 120 primary sampling units based on citizenship. Outcome rates according to the American Association for Public Opinion Research, the sample composition throughout the multistage recruitment process, utilization of survey modes, and questionnaire languages are presented. Results Overall, 6038 persons participated, which corresponded to a response rate of 18.4% (range: 13.8% for Turkish citizenship to 23.9% for Syrian citizenship). Home visits accounted for the largest single increase in response. During recruitment, more female, older, as well as participants with lower levels of education and income took part in the survey. People with physical health problems and less favourable health behaviour more often took part in the survey at a later stage, while participants with symptoms of depression or anxiety more often participated early. Utilization of survey modes and questionnaire languages differed by sociodemographic and migration-related characteristics, e.g. participants aged 50 years and above more often used paper- than web-based questionnaires and those with a shorter duration of residence more often used a translated questionnaire. Conclusion Multiple contact attempts, including home visits and different survey languages, as well as offering different modes of survey administration, increased response rates and most likely reduced non-response bias. In order to adequately represent and include the diversifying population in public health monitoring, national public health institutes should tailor survey designs to meet the needs of different population groups considered hard to survey to enable their survey participation.

Abstract Background Asymptomatic bacteriuria (ASB) – the presence of bacteria in urine without urinary tract infection (UTI) related signs & symptoms (S&S) – is common in the elderly bladder and is not considered pathogenic for UTI. We hypothesise that colonisation with non-uropathogenic bacteria could protect the bladder from invasion of more harmful bacteria. The exact role and dynamics of bacteriuria in the relation to the development of a UTI is still unknown. We aim to provide insight into the course of bacteriuria in the elderly bladder and its relation to UTI in frail older adults. Methods and analysis A prospective observational cohort study is being conducted in Dutch nursing homes (NHs) between February 2024 and December 2025. Urine samples and case report forms (CRF) on UTI-related S&S will be collected from each consenting NH resident every 3 months for a follow-up period of 18 months. Whenever a UTI-suspicion occurs in between the 3 monthly time points, additional data and a urine sample will be collected. Urine samples undergo several urinalyses (e.g. dipstick and bacterial culture). Additional molecular analysis will be conducted on a selection of cultured Escherichia coli (E. coli) for virulence genes. Primary analyses will be conducted between residents with and without ASB at each time point. The primary outcome is UTI incidence during follow-up. In secondary analyses we will also take into account the low versus high presence of virulence genes of the E. coli. Discussion The combination of high ASB prevalence and a reduced ability of frail older adults to express UTI-related S&S may lead to UTI misdiagnosis and inappropriate antibiotic use. To our knowledge, this is the first study to investigate the dynamics and role of bacteriuria in the elderly bladder and their potential protective effect on the development of UTI. The study findings with comprehensive analysis of epidemiological, clinical and molecular data could set the fundamental base for future guidelines and studies, and contribute to improving prevention, diagnosis and treatment of UTI in frail older adults, in addition to contributing to antibiotic stewardship in NHs.

In normal aging, the cognitive domain of semantic memory remains preserved, while the domain of episodic memory declines to some extent. In Alzheimers disease dementia, both semantic and episodic memory become impaired early in the disease process. Given the need to develop sensitive and accessible cognitive markers for early detection of dementia, we investigated among older adults without dementia whether item-level metrics of semantic fluency related to episodic memory decline above and beyond existing neuropsychological measures and total fluency score. Participants were drawn from the community-based Washington Heights-Inwood Columbia Aging Project cohort (N = 583 English speakers, Mage = 76.3 ± 6.8) followed up to five visits across up to 11 years. We examined the association of semantic fluency metrics with subsequent declines in memory performance using latent growth curve models covaried for age and recruitment wave. Results showed that item-level metrics (e.g., lexical frequency, age of acquisition, and semantic neighborhood density) were associated with a decline in episodic memory-even when covarying for other cognitive tests-while the standard total score was not. Moderation analyses showed that the relationship of semantic fluency metrics with memory decline did not differ across race, sex/gender, or education. In conclusion, item-level data hold a wealth of information with potential to reveal subtle semantic memory impairment, which tracks with episodic memory impairment, among older adults without dementia beyond existing neuropsychological measures. Implementation of psycholinguistic metrics may point to cognitive tools that have better prognostic value or are more sensitive to cognitive change in the context of clinical trials or observational studies. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: Cystitis is commonly treated with antibiotics, although non-antibiotic options could be considered for healthy non-pregnant women. Shared decision making (SDM) can be used in cystitis management to discuss the various treatment options but is not frequently applied in general practice. Aim: To identify barriers and facilitators for applying SDM in cystitis management in general practice. Design & setting: Qualitative explorative research in general practice with healthcare professionals (HCPs; GPs and GP assistants) and healthy non-pregnant women with a recent history of cystitis (patients). Method: Individual semi-structured interviews were conducted between May and October 2022. We applied a combination of thematic and framework analysis. Results: Ten GPs, seven GP assistants, and 15 patients were interviewed. We identified the following three main barriers and one key facilitator: (1) applying SDM is deemed inefficient; (2) HCPs assume that patients expect antibiotic treatment and some HCPs consider non-antibiotic treatment inferior; (3) patients are largely unaware of the various non-antibiotic treatment options for cystitis; and (4) HCPs recognise some benefits of applying SDM in cystitis management, including reduced antibiotic use and improved patient empowerment, and patients appreciate involvement in treatment decisions, but preferences for SDM vary. Conclusion: SDM is infrequently applied in cystitis treatment in general practice owing to the current focus on efficient cystitis management that omits patient contact, HCPs’ perceptions, and patient unawareness. Nevertheless, both HCPs and patients recognise the long-term benefits of applying SDM in cystitis management. Our findings facilitate the development of tailored interventions to increase the application of SDM, which should be co-created with HCPs and patients, and fit into the current efficient cystitis management.

Summary: Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.

Abstract Several lines of evidence have indicated that depression might be a prodromal symptom of Alzheimer’s disease (AD). This systematic review and meta-analysis investigated the cross-sectional association between amyloid-beta, one of the key pathologies defining AD, and depression or depressive symptoms in older adults without dementia. A systematic search in PubMed yielded 689 peer-reviewed articles. After full-text screening, nine CSF studies, 11 PET studies, and five plasma studies were included. No association between amyloid-beta and depression or depressive symptoms were found using cerebrospinal fluid (CSF) (0.15; 95% CI: −0.08; 0.37), positron emission topography (PET) (Cohen’s d: 0.09; 95% CI: −0.05; 0.24), or plasma (−0.01; 95% CI: −0.23; 0.22). However, subgroup analyses revealed an association in plasma studies of individuals with cognitive impairment. A trend of an association was found in the studies using CSF and PET. This systematic review and meta-analysis suggested that depressive symptoms may be part of the prodromal stage of dementia.

Purpose: In this study, we aim to understand whether and how performance in animal fluency (i.e., total correct word count) relates to linguistic levels and/or executive functions by looking at sequence information and item-level metrics (i.e., clusters, switches, and word properties). Method: Seven hundred thirty-one Dutch-speaking individuals without dementia from the Second Manifestations of ARTerial disease-Magnetic Resonance study responded to an animal fluency task (120 s). We obtained cluster size and number of switches for the task, and eight different word properties for each correct word produced. We detected variables that determine total word count with random forests, and used conditional inference trees to assess points along the scales of such variables, at which total word count changes significantly. Results: Number of switches, average cluster size, lexical decision response times, word frequency, and concreteness determined total correct word count in animal fluency. People who produced more correct words produced more switches and bigger clusters. People who produced fewer words produced fewer switches and more frequent words. Conclusions: Concurrent with existing literature, individuals without dementia rely on language and executive functioning to produce words in animal fluency. The novelty of our work is that such results were shown based on a data-driven approach using sequence information and item-level metrics.

Abstract Background In the Netherlands, general practitioners (GPs) play a key role in provider-initiated HIV testing, but opportunities for timely diagnosis are regularly missed. We implemented an educational intervention to improve HIV testing by GPs from 2015 to 2020, and observed a 7% increase in testing in an evaluation using laboratory data. The objective for the current study was to gain a deeper understanding of whether and how practices and perceptions of GPs’ HIV/sexually transmitted infection (STI) testing behaviour changed following the intervention. Methods We performed a mixed-methods study using questionnaires and semi-structured interviews to assess self-reported changes in HIV/STI testing by participating GPs. Questionnaires were completed by participants at the end of the final educational sessions from 2017 through 2020, and participating GPs were interviewed from January through March 2020. Questionnaire data were analysed descriptively, and open question responses were categorised thematically. Interview data were analysed following thematic analysis methods. Results In total, 101/103 participants completed questionnaires. Of 65 participants that were included in analyses on the self-reported effect of the programme, forty-seven (72%) reported it had changed their HIV/STI testing, including improved STI consultations, adherence to the STI consultation guideline, more proactive HIV testing, and more extragenital STI testing. Patients’ risk factors, patients’ requests and costs were most important in selecting STI tests ordered. Eight participants were interviewed and 15 themes on improved testing were identified, including improved HIV risk-assessment, more proactive testing for HIV/STI, more focus on HIV indicator conditions and extragenital STI testing, and tools to address HIV during consultations. However, several persistent barriers for optimal HIV/STI testing by GPs were identified, including HIV-related stigma and low perceived risk. Conclusions Most GPs reported improved HIV/STI knowledge, attitude and testing, but there was a discrepancy between reported changes in HIV testing and observed increases using laboratory data. Our findings highlight challenges in implementation of effective interventions, and in their evaluation. Lessons learned from this intervention may inform follow-up initiatives to keep GPs actively engaged in HIV testing and care, on our way to zero new HIV infections.

Background and objectivesTo investigate sociodemographic and medical predictors of incident mild cognitive impairment (MCI) and subsequent course of MCI at follow-up, including sustained MCI diagnosis, classification as cognitively normal, and progression to dementia.MethodsWithin a community-based cohort, diagnoses of MCI were made with a published algorithm. Diagnosis of dementia was based on clinical consensus. Cox regressions estimated hazard ratios of incident MCI associated with several predictors. Modified Poisson regressions estimated relative risks associated with predictors of diagnostic status at follow-up after incidence.ResultsAmong 2,903 cognitively normal participants at baseline, 752 developed MCI over an average of 6.3 (SD 4.5) years (incidence rate 56 per 1,000 person-years). Presence of APOE ε4 and higher medical burden increased risk of incident MCI, while more years of education, more leisure activities, and higher income decreased this risk. Of the incident MCI cases, after an average of 2.4 years of follow-up, 12.9% progressed to dementia, 9.6% declined in functioning and did not meet the algorithmic criteria for MCI but did not meet the clinical criteria for dementia, 29.6% continued to meet MCI criteria, and 47.9% no longer met MCI criteria. Multidomain MCI, presence of APOE ε4, depressive symptoms, and antidepressant use increased the risk of progression to dementia.DiscussionThis community-based study showed that almost half of the individuals with incident MCI diagnoses were classified as cognitively normal at follow-up. Predictors of incident MCI demonstrably differed from those of subsequent MCI course; these findings can refine expectations for cognitive and functional course of those presenting with MCI.

IntroductionCoronavirus disease 2019 (COVID-19) has caused >3.5 million deaths worldwide and affected >160 million people. At least twice as many have been infected but remained asymptomatic or minimally symptomatic. COVID-19 includes central nervous system manifestations mediated by inflammation and cerebrovascular, anoxic, and/or viral neurotoxicity mechanisms. More than one third of patients with COVID-19 develop neurologic problems during the acute phase of the illness, including loss of sense of smell or taste, seizures, and stroke. Damage or functional changes to the brain may result in chronic sequelae. The risk of incident cognitive and neuropsychiatric complications appears independent from the severity of the original pulmonary illness. It behooves the scientific and medical community to attempt to understand the molecular and/or systemic factors linking COVID-19 to neurologic illness, both short and long term.MethodsThis article describes what is known so far in terms of links among COVID-19, the brain, neurological symptoms, and Alzheimer's disease (AD) and related dementias. We focus on risk factors and possible molecular, inflammatory, and viral mechanisms underlying neurological injury. We also provide a comprehensive description of the Alzheimer's Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2) harmonized methodology to address these questions using a worldwide network of researchers and institutions.ResultsSuccessful harmonization of designs and methods was achieved through a consensus process initially fragmented by specific interest groups (epidemiology, clinical assessments, cognitive evaluation, biomarkers, and neuroimaging). Conclusions from subcommittees were presented to the whole group and discussed extensively. Presently data collection is ongoing at 19 sites in 12 countries representing Asia, Africa, the Americas, and Europe.DiscussionThe Alzheimer's Association Global Consortium harmonized methodology is proposed as a model to study long-term neurocognitive sequelae of SARS-CoV-2 infection.Key pointsThe following review describes what is known so far in terms of molecular and epidemiological links among COVID-19, the brain, neurological symptoms, and AD and related dementias (ADRD)The primary objective of this large-scale collaboration is to clarify the pathogenesis of ADRD and to advance our understanding of the impact of a neurotropic virus on the long-term risk of cognitive decline and other CNS sequelae. No available evidence supports the notion that cognitive impairment after SARS-CoV-2 infection is a form of dementia (ADRD or otherwise). The longitudinal methodologies espoused by the consortium are intended to provide data to answer this question as clearly as possible controlling for possible confounders. Our specific hypothesis is that SARS-CoV-2 triggers ADRD-like pathology following the extended olfactory cortical network (EOCN) in older individuals with specific genetic susceptibility.The proposed harmonization strategies and flexible study designs offer the possibility to include large samples of under-represented racial and ethnic groups, creating a rich set of harmonized cohorts for future studies of the pathophysiology, determinants, long-term consequences, and trends in cognitive aging, ADRD, and vascular disease.We provide a framework for current and future studies to be carried out within the Consortium. and offers a "green paper" to the research community with a very broad, global base of support, on tools suitable for low- and middle-income countries aimed to compare and combine future longitudinal data on the topic.The Consortium proposes a combination of design and statistical methods as a means of approaching causal inference of the COVID-19 neuropsychiatric sequelae. We expect that deep phenotyping of neuropsychiatric sequelae may provide a series of candidate syndromes with phenomenological and biological characterization that can be further explored. By generating high-quality harmonized data across sites we aim to capture both descriptive and, where possible, causal associations.

Objective: Urinary tract infections (UTIs) represent the most prevalent infections among pregnant women. Many pregnant women experience frequent voiding or lower abdominal pain during pregnancy due to physiologic changes. Due to the possible consequences of a UTI in pregnancy, pregnant women are more often tested for UTIs. This study aimed to assess the diagnostic accuracy of dipsticks in diagnosing UTIs in pregnant women while using the urine culture as the reference standard. Study design: This was a retrospective cohort study, conducted at two academic hospitals in the Netherlands among pregnant women. Pseudonymized data were collected from patient files. The results of the urine dipstick and the urine culture in pregnant women were linked. Additionally, nitrofurantoin prescriptions were linked to culture results. A positive urine culture was considered the reference test for a UTI. Results: Between 1 January 2017 and 28 February 2021, a total of 718 urine samples with leukocyte esterase dipstick results within 24 h of the urine culture were analyzed. Of these samples, a nitrite dipstick result was also available in 337 cases. Only 6.8% of the 718 urine samples yielded positive cultures. The sensitivity and specificity of leukocyte esterase were 75.5% and 40.4%, respectively; for nitrite, 72.0% sensitivity and 73.4% specificity were found. When at least one of the two tests was positive, the sensitivity and specificity were 92.0% and 27.9%, respectively. When both tests were positive, the sensitivity and specificity were 52.0% and 82.7%, respectively. In only 16.8% of the women to whom nitrofurantoin was prescribed, the urine cultures returned positive using a cut-off of 105 colony forming units/mL. Conclusion: The diagnostic performance of leukocyte esterase, nitrite, or their combination in clinical practice is lower than previously reported in study settings among pregnant women. A significant proportion of women treated with nitrofurantoin were found to have no UTI, suggesting potential over-prescription based on dipstick test results. Healthcare providers should be aware of this reduced performance in clinical practice and carefully weigh the risks of antibiotic treatment by suspicion of a UTI against the possibility of delayed treatment awaiting culture results in individual patients.

We aimed to evaluate the external performance of prediction models for all-cause dementia or AD in the general population, which can aid selection of high-risk individuals for clinical trials and prevention. We identified 17 out of 36 eligible published prognostic models for external validation in the population-based AGES-Reykjavik Study. Predictive performance was assessed with c statistics and calibration plots. All five models with a c statistic > .75 (.76-.81) contained cognitive testing as a predictor, while all models with lower c statistics (.67-.75) did not. Calibration ranged from good to poor across all models, including systematic risk overestimation or overestimation for particularly the highest risk group. Models that overestimate risk may be acceptable for exclusion purposes, but lack the ability to accurately identify individuals at higher dementia risk. Both updating existing models or developing new models aimed at identifying high-risk individuals, as well as more external validation studies of dementia prediction models are warranted.

Abstract Background Early identification of dementia is crucial for prompt intervention for high-risk individuals in the general population. External validation studies on prognostic models for dementia have highlighted the need for updated models. The use of machine learning in dementia prediction is in its infancy and may improve predictive performance. The current study aimed to explore the difference in performance of machine learning algorithms compared to traditional statistical techniques, such as logistic and Cox regression, for prediction of all-cause dementia. Our secondary aim was to assess the feasibility of only using clinically accessible predictors rather than MRI predictors. Methods Data are from 4,793 participants in the population-based AGES-Reykjavik Study without dementia or mild cognitive impairment at baseline (mean age: 76 years, % female: 59%). Cognitive, biometric, and MRI assessments (total: 59 variables) were collected at baseline, with follow-up of incident dementia diagnoses for a maximum of 12 years. Machine learning algorithms included elastic net regression, random forest, support vector machine, and elastic net Cox regression. Traditional statistical methods for comparison were logistic and Cox regression. Model 1 was fit using all variables and model 2 was after feature selection using the Boruta package. A third model explored performance when leaving out neuroimaging markers (clinically accessible model). Ten-fold cross-validation, repeated ten times, was implemented during training. Upsampling was used to account for imbalanced data. Tuning parameters were optimized for recalibration automatically using the caret package in R. Results 19% of participants developed all-cause dementia. Machine learning algorithms were comparable in performance to logistic regression in all three models. However, a slight added performance was observed in the elastic net Cox regression in the third model (c = 0.78, 95% CI: 0.78–0.78) compared to the traditional Cox regression (c = 0.75, 95% CI: 0.74–0.77). Conclusions Supervised machine learning only showed added benefit when using survival techniques. Removing MRI markers did not significantly worsen our model’s performance. Further, we presented the use of a nomogram using machine learning methods, showing transportability for the use of machine learning models in clinical practice. External validation is needed to assess the use of this model in other populations. Identifying high-risk individuals will amplify prevention efforts and selection for clinical trials.

Abstract Background Providing informal care for a person with Parkinson’s disease (PD) can be a demanding process affecting several dimensions of a caregiver’s life and potentially causing caregiver burden. Despite the emerging literature on caregiver burden in people with PD, little is known about the inter-relationship between quantitative and qualitative findings. Filling this knowledge gap will provide a more holistic approach to develop and design innovations aiming at reducing or even preventing caregiver burden. This study aimed to characterize the determinants of caregiver burden among informal caregivers of persons with PD, in order to facilitate the development of tailored interventions that reduce caregiver burden. Methods We conducted a cross-sectional study in The Netherlands using a sequential mixed methods approach, entailing a quantitative study of 504 persons with PD and their informal caregivers as well as a qualitative study in a representative subsample of 17 informal caregivers. The quantitative study included a standardized questionnaire of caregiver burden (Zarit Burden Inventory) and patient-related (Beck Depression Inventory, State-Trait Anxiety Inventory, Acceptance of Illness Scale, MDS-Unified Parkinson’s Disease Rating Scale part II on motor functions in daily life, Self-assessment Parkinson’s Disease Disability Score), caregiver-related (Brief Coping Orientation to Problems Experience Inventory, Caregiver Activation Measurement, Multidimensional Scale of Perceived Social Support) and interpersonal determinants (sociodemographic variables including among others gender, age, education, marital status and working status). The qualitative study consisted of semi-structured interviews. Multivariable regression and thematic analysis were used to analyse quantitative and qualitative data, respectively. Results A total of 337 caregivers were women (66.9%), and the majority of people with PD were men (N = 321, 63.7%). The mean age of persons with PD was 69.9 (standard deviation [SD] 8.1) years, and the mean disease duration was 7.2 (SD 5.2) years. A total of 366 (72.6%) persons with PD had no active employment. The mean age of informal caregivers was 67.5 (SD 9.2) years. Most informal caregivers were female (66.9%), had no active employment (65.9%) and were the spouse of the person with PD (90.7%). The mean Zarit Burden Inventory score was 15.9 (SD 11.7). The quantitative study showed that a lack of active employment of the person affected by PD was associated with a higher caregiver burden. The qualitative study revealed cognitive decline and psychological or emotional deficits of the person with PD as additional patient-related determinants of higher caregiver burden. The following caregiver-related and interpersonal determinants were associated with higher caregiver burden: low social support (quantitative study), concerns about the future (qualitative study), the caregiving-induced requirement of restrictions in everyday life (qualitative study), changes in the relationship with the person with PD (qualitative study) and a problem-focused or avoidant coping style (both studies). Integration of both data strands revealed that qualitative findings expanded quantitative findings by (1) distinguishing between the impact of the relationship with the person with PD and the relationship with others on perceived social support, (2) revealing the impact of non-motor symptoms next to motor symptoms and (3) revealing the following additional factors impacting caregiver burden: concern about the future, perceived restrictions and limitations in performing daily activities due to the disease, and negative feelings and emotional well-being. Qualitative findings were discordant with the quantitative finding demonstrating that problem-focused was associated with a higher caregiver burden. Factor analyses showed three sub-dimensions of the Zarit Burden Inventory: (i) role intensity and resource strain, (2) social restriction and anger and (3) self-criticism. Quantitative analysis showed that avoidant coping was a determinant for all three subscales, whereas problem-solved coping and perceived social support were significant predictors on two subscales, role intensity and resource strain and self-criticism. Conclusions The burden experienced by informal caregivers of persons with PD is determined by a complex interplay of patient-related, caregiver-related and interpersonal characteristics. Our study highlights the utility of a mixed-methods approach to unravel the multidimensional burden experienced by informal caregivers of persons with chronic disease. We also offer starting points for the development of a tailored supportive approach for caregivers.

Abstract Little is known about how people with Parkinson’s disease (PD) cope with stressful life events. We examined the determinants of specific coping strategies and whether specific choices have any impact on quality of life (QoL). We recruited patients with PD who had been seen at a neurology outpatient clinic at least once during the past year as part of the PRIME-NL cohort study. Coping was measured using the Ways of Coping Questionnaire (WCQ) and QoL was measured using the Parkinson’s Disease Questionnaire (PDQ-39). 977 out of 988 participants completed the questionnaires and 935 participants were diagnosed with PD. Factor analysis was undertaken to test if ways of coping were similar or different to previous findings in a PD population. We used linear regression analyses to examine predictors of coping styles. We then used multivariable linear regression to test how coping style was associated with the domains of QoL conditional on potential confounders. The five coping styles identified by the factor analysis were: “taking action and emphasizing the positive”, “distancing and fantasizing”, “goal oriented and planful problem solving”, “seeking social support” and “avoidance and acceptance”. Age, gender, education and anxiety were associated with the type of coping strategy. For example, higher education was associated with more active coping strategies (e.g. β = 4.39, p

Background Two of the main causes for dementia are Alzheimer's disease (AD) and vascular pathology, with most patients showing mixed pathology. Plasma biomarkers for Alzheimer's disease‐related pathology have recently emerged, including Aβ (amyloid‐beta), p‐tau (phosphorylated tau), NfL (neurofilament light), and GFAP (glial fibrillary acidic protein). There is a current gap in the literature regarding whether there is an association between these plasma biomarkers with vascular pathology and neurodegeneration. Methods and Results Cross‐sectional data from 594 individuals (mean [SD] age: 64 [8] years; 17% female) were included from the SMART‐MR (Second Manifestations of Arterial Disease‐Magnetic Resonance) study, a prospective cohort study of individuals with a history of arterial disease. Plasma markers were assessed using single molecular array assays (Quanterix). Magnetic resonance imaging markers included white matter hyperintensity volume, presence of infarcts (yes/no), total brain volume, and hippocampal volume assessed on 1.5T magnetic resonance imaging. Linear regressions were performed for each standardized plasma marker with white matter hyperintensity volume, total brain volume, and hippocampal volume as separate outcomes, correcting for age, sex, education, and intracranial volume. Logistic regressions were performed for the presence of lacunar and cortical infarcts. Higher p‐tau181 was associated with larger white matter hyperintensity volume (b per SD increase=0.16 [95% CI, 0.06–0.26], P=0.015). Higher NfL (b=−5.63, [95% CI, −8.95 to −2.31], P=0.015) was associated with lower total brain volume and the presence of infarcts (odds ratio [OR], 1.42 [95% CI, 1.13–1.78], P=0.039). Higher GFAP levels were associated with cortical infarcts (OR, 1.45 [95% CI, 1.09–1.92], P=0.010). Conclusions Plasma biomarkers that have been associated with tau pathology, axonal injury, and astrocytic activation are related to magnetic resonance imagingmarkers of vascular pathology and neurodegeneration in patients with manifest arterial disease.

Background and purposeArterial calcifications on unenhanced CT scans and vessel wall lesions on MRI are often used interchangeably to portray intracranial arterial disease. However, the extent of pathology depicted with each technique is unclear. We investigated the presence and distribution of these two imaging findings in patients with a history of cerebrovascular disease.Materials and methodsWe analyzed CT and MRI data from 78 patients admitted for stroke or TIA at our institution. Vessel wall lesions were assessed on 7 T MRI sequences, while arterial calcifications were assessed on CT scans. The number of vessel wall lesions, severity of intracranial internal carotid artery (iICA) calcifications, and overall presence and distribution of the two imaging findings were visually assessed in the intracranial arteries.ResultsAt least one vessel wall lesion or arterial calcification was assessed in 69 (88%) patients. Only the iICA and vertebral arteries (VA) showed a substantial number of both calcifications and vessel wall lesions. The other vessels showed almost exclusively vessel wall lesions. The number of vessel wall lesions was associated with the severity of iICA calcification (p = 0.013).ConclusionsThe number of vessel wall lesions increases with the severity of iICA calcifications. Nonetheless, the distribution of vessel wall lesions on MRI and arterial calcifications on CT shows remarkable differences. These findings support the need for a combined approach to examine intracranial arterial disease.

Background Microvascular dysfunction is involved in the development of various cerebral disorders. It may contribute to these disorders by disrupting white matter tracts and altering brain connectivity, but evidence is scarce. We investigated the association between multiple biomarkers of microvascular function and whole‐brain white matter connectivity. Methods and Results Cross‐sectional data from The Maastricht Study, a Dutch population‐based cohort (n=4326; age, 59.4±8.6 years; 49.7% women). Measures of microvascular function included urinary albumin excretion, central retinal arteriolar and venular calibers, composite scores of flicker light–induced retinal arteriolar and venular dilation, and plasma biomarkers of endothelial dysfunction (intercellular adhesion molecule‐1, vascular cell adhesion molecule‐1, E‐selectin, and von Willebrand factor). White matter connectivity was calculated from 3T diffusion magnetic resonance imaging to quantify the number (average node degree) and organization (characteristic path length, global efficiency, clustering coefficient, and local efficiency) of white matter connections. A higher plasma biomarkers of endothelial dysfunction composite score was associated with a longer characteristic path length (β per SD, 0.066 [95% CI, 0.017–0.114]) after adjustment for sociodemographic, lifestyle, and cardiovascular factors but not with any of the other white matter connectivity measures. After multiple comparison correction, this association was nonsignificant. None of the other microvascular function measures were associated with any of the connectivity measures. Conclusions These findings suggest that microvascular dysfunction as measured by indirect markers is not associated with whole‐brain white matter connectivity.

Introduction: Two of the main causes for dementia are Alzheimer's disease (AD) pathology and vascular pathology. Plasma biomarkers for AD pathology have recently emerged, including amyloid-beta, p-tau, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP). Vascular pathology can be assessed on MRI via white matter hyperintensities (WMH) and infarcts. Our aim was to estimate the relationship between plasma AD biomarkers and MRI markers of vascular pathology and neurodegeneration in non-demented individuals with manifest arterial disease. Methods: Data from 594 individuals (mean (SD) age: 64 (8) years; 17% female) were included from the SMART-MR Study, a prospective cohort study from the UMC Utrecht in the Netherlands. Vascular and neurodegenerative MRI markers included WMH volume, presence of infarcts (yes/no), total brain volume (TBV), and hippocampal volume (HV) assessed on 1.5T MRI. AD plasma markers (amyloid-beta 42/40 ratio, ptau-181, NfL, and GFAP) were assessed using Single Molecular Array (Simoa; Quanterix) assays. Linear regressions were performed for each plasma marker with WMH volume, TBV, and HV, correcting for age, sex, education, and ICV. Additionally, logistic regressions were performed for the presence of lacunar and cortical infarcts. Plasma AD levels were converted to z-scores. Results: Higher ptau-181 was associated with larger WMH volume (β=0.16, 95% CI=0.06; 0.26, p=0.001). Higher NfL (β=-5.63, 95% CI=-8.95; -2.31, p=0.001) was associated with lower TBV. Higher NfL levels (.R=1.58, 95% CI=1.20; 2.08, p=0.001) and higher GFAP levels (OR=1.45, 95% CI=1.09; 1.92, p=0.010) were associated with cortical infarcts. Discussion: In our sample of patients with manifest arterial disease, NfL was related to both brain volume and infarcts. Further, an association between ptau-181 and WMH was found, as well as between GFAP and cortical infarcts. Plasma biomarkers offer the potential to easily measure a wider range of pathophysiological processes related to cognitive decline.

Introduction: Endothelial dysfunction has various detrimental effects on the brain that may lead to cognitive decline. However, data on the direct association between endothelial dysfunction and cognitive performance in humans are scarce. The aim of the present study was to assess the cross-sectional association between plasma biomarkers of endothelial dysfunction and cognitive performance. Methods: Data from 9,344 individuals without dementia from seven Dutch cohorts participating in the Netherlands Consortium of Dementia Cohorts (NCDC) were included: Doetinchem Cohort Study, Rotterdam Study, The Maastricht Study, Leiden Longevity Study, the EMIF-AD 90+ cohort, Longitudinal Aging Study Amsterdam, and SMART-MR Study (mean age range: 57-93 years, 18-58% women). Plasma biomarkers of endothelial dysfunction included intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble E-selectin (sE-selectin), which were measured in EDTA plasma samples with commercially available ELISA kits (MSD and R&D Systems Europe), or the Olink Cardiometabolic 96-plex panels. Subsequently, a standardized endothelial dysfunction composite score was calculated. Cognitive performance was measured on six domains: executive function, processing speed, immediate and delayed memory, attention, and language. A two-step individual participant data (IPD) meta-analysis was performed: linear regressions were run in the individual cohorts. Resulting standardized regression coefficients were subsequently pooled using random-effects models. Results: Pooled analyses showed an association between a higher endothelial dysfunction composite score and worse executive function (β = -0.04; 95% CI -0.06, -0.02), slower processing speed (β = -0.03; 95% CI -0.05, -0.01), worse immediate memory (β = -0.03; 95% CI -0.04, -0.01), worse delayed memory (β = -0.03; 95% CI -0.05, -0.00), and lower attention scores (β = -0.02; 95% CI -0.04, -0.00) (Figure 1). These associations were consistent across cohorts and independent of demographics, lifestyle and cardiovascular risk factors. No association was found between endothelial dysfunction and language (β = -0.02; 95% CI -0.05, 0.01). Discussion: Endothelial dysfunction was consistently associated with worse cognitive functioning across all domains, except for language. These findings support the hypothesis that endothelial dysfunction may contribute to cognitive impairment and may identify a new prevention target.Future research is needed to assess any longitudinal association between endothelial dysfunction and cognitive decline.

Aneurysmal subarachnoid hemorrhage (aSAH) can be prevented by early detection and treatment of intracranial aneurysms in high-risk individuals. We investigated whether individuals at high risk of aSAH in the general population can be identified by developing an aSAH prediction model with electronic health records (EHR) data. To assess the aSAH model's relative performance, we additionally developed prediction models for acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH) and compared the discriminative performance of the models. We included individuals aged ≥35 years without history of stroke from a Dutch routine care database (years 2007-2020) and defined outcomes aSAH, AIS and ICH using International Classification of Diseases (ICD) codes. Potential predictors included sociodemographic data, diagnoses, medications, and blood measurements. We cross-validated a Cox proportional hazards model with an elastic net penalty on derivation cohorts and reported the c-statistic and 10-year calibration on validation cohorts. We examined 1,040,855 individuals (mean age 54.6 years, 50.9% women) for a total of 10,173,170 person-years (median 11 years). 17,465 stroke events occurred during follow-up: 723 aSAH, 14,659 AIS, and 2,083 ICH. The aSAH model's c-statistic was 0.61 (95%CI 0.57-0.65), which was lower than the c-statistic of the AIS (0.77, 95%CI 0.77-0.78) and ICH models (0.77, 95%CI 0.75-0.78). All models were well-calibrated. The aSAH model identified 19 predictors, of which the 10 strongest included age, female sex, population density, socioeconomic status, oral contraceptive use, gastroenterological complaints, obstructive airway medication, epilepsy, childbirth complications, and smoking. Discriminative performance of the aSAH prediction model was moderate, while it was good for the AIS and ICH models. We conclude that it is currently not feasible to accurately identify individuals at increased risk for aSAH using EHR data.

Background: The health situation of people with a history of migration is influenced by a variety of factors. This article provides an overview of the health of people with selected citizenships using various indicators. Methods: The analyses are based on the survey ‘German Health Update: Fokus (GEDA Fokus)’, which was conducted from November 2021 to May 2022 among people with Croatian, Italian, Polish, Syrian and Turkish citizenship. The prevalence for each health outcome is presented and differentiated by sociodemographic and migration-related characteristics. Poisson regressions were performed to identify relevant factors influencing health situation. Results: Self-assessed general health, the presence of depressive symptoms, prevalence of current smoking and the utilisation of general and specialist healthcare differed according to various factors considered here. In addition to sociodemographic determinants, the sense of belonging to society in Germany and self-reported experiences of discrimination were particularly associated with health outcomes. Conclusions: This article highlights the heterogeneity of the health situation of people with a history of migration and points to the need for further analyses to identify the reasons for health inequalities.

Background: the COVID-19 vaccination offers protection against severe disease progression. Data show that people with a history of migration are less likely to be vaccinated against COVID-19 than people without a history of migration, but are at increased risk of infection. Methods: Data were used from the GEDA Fokus interview survey (November 2021 – May 2022), which included people living in Germany with Croatian, Italian, Polish, Syrian or Turkish citizenship (n=5,495). In addition to bivariate analyses, Poisson regressions were used to examine the association between uptake of at least one COVID-19 vaccination and sociodemographic, health- and migration-related factors. Results: 90.0% of participants reported having received at least one COVID-19 vaccination. Having visited a general practitioner or specialist in the past 12 months, living in Germany for 31 years or more, and having a greater sense of belonging to society in Germany were associated with vaccination uptake in bivariate analyses. Regression analysis showed that older people and those with higher education were more likely to be vaccinated. Conclusions: Sociodemographic factors are associated with uptake of the COVID-19 vaccine among individuals with selected citizenships. Low-threshold information and vaccination offers are important to ensure equal access to vaccination.

Pre-university enabling programs provide an important pathway to university for underprepared and disadvantaged students. In order to adequately prepare students for their university journey, enabling educators need to understand and respond to the evolving needs of their learners; not only their academic disparity, but also their past learning experiences and perceptions towards particular subjects. In the current study, students entering an Australian enabling program, 'OnTrack', were surveyed on their attitudes, emotions and aspirations towards the study of science and mathematics. Responses were associated with student perceptions of their past science and maths learning experiences. There was incongruity between student expectations of what future study would entail and the realities of their degree choices and career aspirations. This study suggests the need for social and emotional learning and teacher training. Greater attention should be given to both student's affective needs and their understanding of future course content during their enabling education experience to redress negative emotional learning experiences and safeguard student expectations, satisfaction, and retention in the future.

Introduction This study aimed to evaluate the use and dose of loop diuretics (LDs) across the entire ejection fraction (EF) spectrum in a large, ‘real-world’ cohort of chronic heart failure (HF) patients.Methods A total of 10 366 patients with chronic HF from 34 Dutch outpatient HF clinics were analysed regarding diuretic use and diuretic dose. Data regarding daily diuretic dose were stratified by furosemide dose equivalent (FDE)>80 mg or ≤80 mg. Multivariable logistic regression models were used to assess the association between diuretic dose and clinical features.Results In this cohort, 8512 (82.1%) patients used diuretics, of which 8179 (96.1%) used LDs. LD use was highest among HF with reduced EF (HFrEF) patients (81.1%) followed by HF with mild-reduced EF (76.1%) and HF with preserved ejection fraction EF (73.8%, p80 mg, across all HF categories. Renal impairment was associated with a higher FDE across the entire EF spectrum.Conclusion In this large registry of real-world HF patients, LD use was highest among HFrEF patients. Advanced symptoms, diabetes mellitus and worse renal function were significantly associated with a higher diuretic dose regardless of left ventricular ejection fraction.

Introduction Successful antiviral therapy has transformed HIV infection into a chronic condition, where optimising quality of life (QoL) has become essential for successful lifelong treatment. Patient-reported outcome measures (PROMs) can signal potential physical and mental health problems related to QoL. This study aims to determine whether PROMs in routine clinical care improve quality of care as experienced by people with HIV (PWH).Methods and analysis We report the protocol of a multicentre longitudinal cohort studying PWH at Amsterdam University Medical Centres in the Netherlands. PROMs are offered annually to patients via the patient portal of the electronic health record. Domains include anxiety, depression, fatigue, sleep disturbances, social isolation, physical functioning, stigma, post-traumatic stress disorder, adherence, drug and alcohol use and screening questions for sexual health and issues related to finances, housing and migration status. Our intervention comprises (1) patients’ completion of PROMs, (2) discussion of PROMs scores during annual consultations and (3) documentation of follow-up actions in an individualised care plan, if indicated. The primary endpoint will be patient-experienced quality of care, measured by the Patient Assessment of Chronic Illness Care, Short Form (PACIC-S). Patients will provide measurements at baseline, year 1 and year 2. We will explore change over time in PACIC-S and PROMs scores and examine the sociodemographical and HIV-specific characteristics of subgroups of patients who participated in all or only part of the intervention to ascertain whether benefit has been achieved from our intervention in all subgroups.Ethics and dissemination Patients provide consent for the analysis of data collected as part of routine clinical care to the AIDS Therapy Evaluation in the Netherlands study (ATHENA) cohort through mechanisms described in Boender et al. Additional ethical approval for the analysis of these data is not required under the ATHENA cohort protocol. The results will be presented at national and international academic meetings and submitted to peer-reviewed journals for publication.

ObjectivesSemantic fluency is a prominent neuropsychological task, typically administered within the category ‘animals’. With the increasing development of novel item-level metrics of semantic fluency, a concern around the validity of item-level analyses could be that personal background factors (e.g., hobbies like birdwatching or fishing) may disproportionally influence performance. We analyzed animal fluency performance at the item level and investigated the prevalence of individuals with abundant knowledge in specific classes of animals (e.g., birds, fish, insects) and the relationship of such knowledge with personal background factors and other cognitive tasks (episodic memory and executive functioning).MethodParticipants included 736 Dutch middle-aged to older adults from the SMART-MR cohort (mean age 58 ± 9.4 years, 18% women). Individuals were asked to name as many animals as possible for 2 min. Number of people with abundant animal class knowledge was calculated for the ability to recall a series of minimum ≥5 and up to ≥15 animals within a specific class with at most one interruption by an animal from another class. Subsequent analyses to investigate relationships of abundant class knowledge with sociodemographic characteristics (t-tests and chi-square tests) and cognitive performance (linear regressions) were performed for a cut-off of ≥10 animals within a specific class (90th percentile), with a sensitivity analysis for ≥7 animals (67th percentile).ResultsA total of 416 (56.2%) participants recalled a series of ≥5 animals from a specific class, 245 (33.3%) participants recalled ≥7, 78 (10.6%) participants recalled ≥10, and 8 (1.1%) participants recalled ≥15. Those who recalled a series of at least 10 animals within a class were older, more often men, and more often retired than those who did not. Moreover, they had a higher total score on animal fluency, letter fluency (i.e., executive functioning), and episodic memory tasks compared to those who did not.DiscussionOur results suggest that the benefit of abundant animal class knowledge gained by personal background does not disproportionally influence animal fluency performance as individuals with such knowledge also performed better on other cognitive tasks unrelated to abundant knowledge of animal classes.

Abstract Background During the COVID-19 pandemic hospitals reorganized their resources and delivery of care, which may have affected the number of healthcare-associated infections (HAIs). We aimed to quantify changes in trends in the number of HAIs in Dutch hospitals during the COVID-19 pandemic. Methods National surveillance data from 2016 to 2020 on the prevalence of HAIs measured by point prevalence surveys, and the incidence of surgical site infections (SSIs) and catheter-related bloodstream infections (CRBSIs) were used to compare rates between the pre-pandemic (2016–February 2020) and pandemic (March 2020–December 2020) period. Results The total HAI prevalence among hospitalised patients was higher during the pandemic period (7.4%) compared to pre-pandemic period (6.4%), mainly because of an increase in ventilator-associated pneumonia (VAP), gastro-intestinal infections (GIs) and central nervous system (CNS) infections. No differences in SSI rates were observed during the pandemic, except for a decrease after colorectal surgeries (6.3% (95%-CI 6.0–6.6%) pre-pandemic versus 4.4% (95%-CI 3.9–5.0%) pandemic). The observed CRBSI incidence in the pandemic period (4.0/1,000 CVC days (95%-CI 3.2–4.9)) was significantly higher than predicted based on pre-pandemic trends (1.4/1000 (95%-CI 1.0–2.1)), and was increased in both COVID-19 patients and non-COVID-19 patients at the intensive care unit (ICU). Conclusions Rates of CRBSIs, VAPs, GIs and CNS infections among hospitalised patients increased during the first year of the pandemic. Higher CRBSI rates were observed in both COVID-19 and non-COVID-19 ICU population. The full scope and influencing factors of the pandemic on HAIs needs to be studied in further detail.

IntroductionHeterogeneity of segmentation protocols for medial temporal lobe regions and hippocampal subfields on in vivo magnetic resonance imaging hinders the ability to integrate findings across studies. We aim to develop a harmonized protocol based on expert consensus and histological evidence.MethodsOur international working group, funded by the EU Joint Programme-Neurodegenerative Disease Research (JPND), is working toward the production of a reliable, validated, harmonized protocol for segmentation of medial temporal lobe regions. The working group uses a novel postmortem data set and online consensus procedures to ensure validity and facilitate adoption.ResultsThis progress report describes the initial results and milestones that we have achieved to date, including the development of a draft protocol and results from the initial reliability tests and consensus procedures.DiscussionA harmonized protocol will enable the standardization of segmentation methods across laboratories interested in medial temporal lobe research worldwide.

Abstract Background Urinary tract infections (UTIs) are common, especially among women. Antibiotics are commonly used to treat UTIs, but might not always be necessary, for example in the case of uncomplicated UTIs such as cystitis. Shared decision making (SDM) could reduce the risk of unnecessary antibiotic prescriptions for uncomplicated cystitis. We investigated the current management and the use of SDM for uncomplicated cystitis in primary care. Methods We performed a qualitative semi-structured interview study among 23 women with a history of cystitis, 12 general practitioner (GP) assistants, and 12 GPs in the Netherlands from July to October 2020. All interviews were individually performed by telephone. The data were analyzed through the use of using open and axial coding. Results The GP assistants managed the initial diagnostics and treatment of uncomplicated cystitis in all general practices. Usually, antibiotics were considered the standard treatment of cystitis. In most general practices, SDM was not used in the treatment of uncomplicated cystitis, mainly because of a lack of time. Women reported that they valued being involved in the treatment decision-making process, but they were not always involved. Further, both GP assistants and GPs indicated that SDM would improve the care pathway of uncomplicated UTIs. Conclusion In our study, SDM was infrequently used to help women with uncomplicated cystitis. To reduce the use of antibiotics for uncomplicated UTIs, a tailored intervention is needed to implement SDM for the treatment of uncomplicated cystitis in primary care.

Abstract Informal carers gain unique experience and knowledge when caring for a loved person. However, this knowledge often remains unused after their loved one with Parkinson’s disease (PD) has passed away. Hence, two opportunities are currently being missed: sharing this unique experience could support current informal carers and offer the bereaved former carers the option to continue to fulfil a meaningful role. This study aimed to identify the unmet needs of current carers, and to examine the interest, willingness and requirements of both current and former carers for peer-to-peer support. Data were collected from August 2020 to February 2021 through questionnaires examining (1) resources and needs for support; (2) topics for support and advice; and (3) preferences for peer-to-peer initiatives. Open questions were analyzed thematically, after open coding. In total, 141 current and 15 former informal carers participated. Current carers were mainly women (68%) and partner of a person with PD (86%). Former carers were mainly women (80%) who had cared for a partner or parent (53%; 47%) with PD. Almost half of the current carers expressed need for additional support in finding balance, changing relationships, and learning how to cope with lack of emotions and motivation. Half of the carers were positive about the opportunity to exchange experiences and knowledge with former carers. Willingness among former carers for providing peer-to-peer support was high (87%). In both groups, having a degree of commonality with peers was considered an essential requirement. These findings provide guidance for developing peer-to-peer support programs, incorporating former carers.

Summary: Background: Post-acute sequela of SARS-CoV-2 infection (PASC) encompass fatigue, post-exertional malaise and cognitive problems. The abundant expression of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase-2 (IDO2) in fatal/severe COVID-19, led us to determine, in an exploratory observational study, whether IDO2 is expressed and active in PASC, and may correlate with pathophysiology. Methods: Plasma or serum, and peripheral blood mononuclear cells (PBMC) were obtained from well-characterized PASC patients and SARS-CoV-2-infected individuals without PASC. We assessed tryptophan and its degradation products by UPLC-MS/MS. IDO2 activity, its potential consequences, and the involvement of the aryl hydrocarbon receptor (AHR) in IDO2 expression were determined in PBMC from another PASC cohort by immunohistochemistry (IHC) for IDO2, IDO1, AHR, kynurenine metabolites, autophagy, and apoptosis. These PBMC were also analyzed by metabolomics and for mitochondrial functioning by respirometry. IHC was also performed on autopsy brain material from two PASC patients. Findings: IDO2 is expressed and active in PBMC from PASC patients, as well as in brain tissue, long after SARS-CoV-2 infection. This is paralleled by autophagy, and in blood cells by reduced mitochondrial functioning, reduced intracellular levels of amino acids and Krebs cycle-related compounds. IDO2 expression and activity is triggered by SARS-CoV-2-infection, but the severity of SARS-CoV-2-induced pathology appears related to the generated specific kynurenine metabolites. Ex vivo, IDO2 expression and autophagy can be halted by an AHR antagonist. Interpretation: SARS-CoV-2 infection triggers long-lasting IDO2 expression, which can be halted by an AHR antagonist. The specific kynurenine catabolites may relate to SARS-CoV-2-induced symptoms and pathology. Funding: None.