The aim of this thesis was to assess the efficacy (part 1) and tolerability (part 2) of antiseizure medications (ASMs) in glioma patients with epilepsy. In addition, we aimed to get insight into... Show moreThe aim of this thesis was to assess the efficacy (part 1) and tolerability (part 2) of antiseizure medications (ASMs) in glioma patients with epilepsy. In addition, we aimed to get insight into the ASM prescription behavior and treatment policy in brain tumor-related epilepsy (part 3).First-line levetiracetam seems to be the most efficacious ASM in glioma patients, with favourable tolerability. This is demonstrated in multicenter retrospective observational cohort studies, a systematic review, and is the opinion among the vast majority of European neuro-oncology professionals. Enzyme-inducing AMSs should be avoided in glioma patients due to the high risk of adverse effects. ASM use was not independently associated with neuropsychiatric symptoms in glioma patients, but alternative factors seem to pose a greater risk for developing neuropsychiatric symptoms. If patients experience uncontrolled seizures on ASM monotherapy, levetiracetam combined with valproic acid has better efficacy than other ASM combinations in glioma patients, while toxicity is similar. Subsequently, potential add-on ASMs in glioma patients experiencing uncontrolled seizures on ASM dual therapy include clobazam, lamotrigine, and lacosamide. Show less
Ekels, A.; Oerlemans, S.; Schagen, S.B.; Issa, D.E.; Thielen, N.; Nijziel, M.R.; ... ; Poll-franse, L.V. van de 2023
Purpose To investigate the proportion of patients with lymphoma with persistent clinically relevant cognitive impairment, and its relation to treatment, fatigue, and psychological distress.Methods... Show morePurpose To investigate the proportion of patients with lymphoma with persistent clinically relevant cognitive impairment, and its relation to treatment, fatigue, and psychological distress.Methods Patients with diffuse-large-B-cell-lymphoma (DLBCL), follicular-lymphoma (FL), and chronic-lymphocytic-leukemia (CLL)/small-lymphocytic-lymphoma (SLL), diagnosed between 2004-2010 or 2015-2019, were followed up to 8 years post-diagnosis. Sociodemographic and clinical data were obtained from the Netherlands Cancer Registry and the Population-based HAematological Registry for Observational Studies. The EORTC QLQ-C30 was used to assess cognitive functioning and fatigue, and the HADS to assess psychological distress. Individual growth curve models were performed. Results were compared with an age- and sex-matched normative population.Results A total of 924 patients were included (70% response rate). Persistent cognitive impairment was twice as high in patients (30%) compared to the normative population (15%). Additionally, 74% of patients reported co-occurring symptoms of persistent fatigue and/or psychological distress. Patients with FL (- 23 points, p < 0.001) and CLL/SLL (- 10 points, p < 0.05) reported clinically relevant deterioration of cognitive functioning, as did the normative population (FLnorm - 5 points, DLBCLnorm - 4 points, both p < 0.05). Younger age, higher fatigue, and/or psychological distress at inclusion were associated with worse cognitive functioning (all p's < 0.01). Treatment appeared less relevant.Conclusion Almost one-third of patients with lymphoma report persistent cognitive impairment, remaining present up to 8 years post-diagnosis. Early onset and co-occurrence of symptoms highlight the need for clinicians to discuss symptoms with patients early.Implications for Cancer Survivors Early recognition of cognitive impairment could increase timely referral to suitable supportive care (i.e., lifestyle interventions) and reduce (long-term) symptom burden. Show less
In this chapter, I have attempted to reconstruct part of the debate on hylomorph- ism in which Alexander of Aphrodisias participated, insofar as it emerges from Alexander’s Quaestiones and Mantissa... Show moreIn this chapter, I have attempted to reconstruct part of the debate on hylomorph- ism in which Alexander of Aphrodisias participated, insofar as it emerges from Alexander’s Quaestiones and Mantissa 5. The debate addresses Physics I-IL1 and the distinctions in the Categories that Aristotle used in that context. Alexander takes away from the debate that he needs to situate his discussion of the relation between soul and body into a general theory of hylomorphism in which form and matter need each other, both for their existence and their definition. It also needs argument that soul is the form and actuality of the body so as to apply the general theory to this paradigm case, and to further apply hylomorphism to the levels and powers of soul. The story culminates in the application of hylomorphism to the development of dispositional intellect, in which Alexander combines Phys. VII.3, De An. II.5, and APo 11.19 with the view of form as completion (teleiotes). The intellect of accomplished knowers comes out as the sum total of knowable things, This is the pinnacle of hylomorphism as a physical, metaphysical, and epistemo- logical theory. As such it is also a perfect example of how Alexander innovatives by connecting Aristotelian dots in unprecedented ways. Show less
AimRhythmic and periodic patterns (RPPs) on the electroencephalogram (EEG) in comatose patients after cardiac arrest have been associated with high case fatality rates. A good neurological outcome... Show moreAimRhythmic and periodic patterns (RPPs) on the electroencephalogram (EEG) in comatose patients after cardiac arrest have been associated with high case fatality rates. A good neurological outcome according to the Cerebral Performance Categories (CPC) has been reported in up to 10% of cases. Data on cognitive, emotional, and quality of life outcomes are lacking. We aimed to provide insight into these outcomes at one-year follow-up.MethodsWe assessed outcome of surviving comatose patients after cardiac arrest with RPPs included in the ‘treatment of electroencephalographic status epilepticus after cardiopulmonary resuscitation’ (TELSTAR) trial at one-year follow-up, including the CPC for functional neurological outcome, a cognitive assessment, the hospital anxiety and depression scale (HADS) for emotional outcomes, and the 36-item short-form health survey (SF-36) for quality of life. Cognitive impairment was defined as a score of more than 1.5 SD below the mean on ≥ 2 (sub)tests within a cognitive domain.ResultsFourteen patients were included (median age 58 years, 21% female), of whom 13 had a cognitive impairment. Eleven of 14 were impaired in memory, 9/14 in executive functioning, and 7/14 in attention. The median scores on the HADS and SF-36 were all worse than expected. Based on the CPC alone, 8/14 had a good outcome (CPC 1–2).ConclusionNearly all cardiac arrest survivors with RPPs during the comatose state have cognitive impairments at one-year follow-up. The incidence of anxiety and depression symptoms seem relatively high and quality of life relatively poor, despite ‘good’ outcomes according to the CPC. Show less
Dijk, B.M.A. van; Spruit, M.R.; Duijn, M.J. van 2023
Children are the focal point for studying the link between language and Theory of Mind (ToM) competence. Language and ToM are often studied with younger children and standardized tests, but as both... Show moreChildren are the focal point for studying the link between language and Theory of Mind (ToM) competence. Language and ToM are often studied with younger children and standardized tests, but as both are social competences, data and methods with higher ecological validity are critical.We leverage a corpus of 442 freely-told stories by Dutch children aged 4-12, recorded in their everyday classroom environments, to study language and ToM with NLP-tools. We labelled stories according to the mental depth of story characters children create, as a proxy for their ToM competence ‘in action’, and built a classifier with features encoding linguistic competences identified in existing work as predictive of ToM.We obtain good and fairly robust results (F1-macro = .71), relative to the complexity of the task for humans. Our results are explainable in that we link specific linguistic features such as lexical complexity and sentential complementation, that are relatively independent of children’s ages, to higher levels of character depth. This confirms and extends earlier work, as our study includes older children and socially embedded data from a different domain. Overall, our results support the idea that language and ToM are strongly interlinked, and that in narratives the former can scaffold the latter. Show less
BackgroundPatients with carotid artery occlusion (CAO) are vulnerable to cognitive impairment (CI). Anaemia is associated with CI in the general population. We hypothesized that lower haemoglobin... Show moreBackgroundPatients with carotid artery occlusion (CAO) are vulnerable to cognitive impairment (CI). Anaemia is associated with CI in the general population. We hypothesized that lower haemoglobin is associated with cognitive impairment (CI) in patients with CAO and that this association is accentuated by cerebral blood flow (CBF).Methods104 patients (mean age 66±8 years, 77% men) with complete CAO from the Heart-Brain Connection study were included. Anaemia was defined as haemoglobin < 12 g/dL for women and < 13 g/dL for men. Cognitive test results were standardized into z-scores (using a reference group) in four cognitive domains. Patients were classified as cognitively impaired when ≥ one domain was impaired. The association between lower haemoglobin and both cognitive domain z-scores and the presence of CI was assessed with adjusted (age, sex, education and ischaemic stroke) regression models. Total CBF (measured with phase contrast MRI) and the interaction term haemoglobin*CBF were additionally added to the analyses.ResultsAnaemia was present in 6 (6%) patients and was associated with CI (RR 2.54, 95% CI 1.36; 4.76). Lower haemoglobin was associated with the presence of CI (RR per minus 1 g/dL haemoglobin 1.15, 95% CI 1.02; 1.30). This association was strongest for the attention-psychomotor speed domain (RR for impaired attention-psychomotor speed functioning per minus 1 g/dL haemoglobin 1.27, 95% CI 1.09;1.47) and ß for attention-psychomotor speed z-scores per minus 1 g/dL haemoglobin -0.19, 95% CI -0.33; -0.05). Adjustment for CBF did not affect these results and we found no interaction between haemoglobin and CBF in relation to cognition.ConclusionLower haemoglobin concentrations are associated with CI in patients with complete CAO, particularly in the domain attention-psychomotor speed. CBF did not accentuate this association. If validated in longitudinal studies, haemoglobin might be a viable target to prevent cognitive deterioration in patients with CAO. Show less
Ploeg, M.A. van der; Poortvliet, R.K.E.; Bogaerts, J.M.K.; Klei, V.M.G.T.H. van der; Kerse, N.; Rolleston, A.; ... ; TULIPS Consortium 2023
BackgroundIn the general population, an increase in low-density lipoprotein cholesterol (LDL-C) predicts higher cardiovascular disease risk, and lowering LDL-C can prevent cardiovascular disease... Show moreBackgroundIn the general population, an increase in low-density lipoprotein cholesterol (LDL-C) predicts higher cardiovascular disease risk, and lowering LDL-C can prevent cardiovascular disease and reduces mortality risk. Interestingly, in cohort studies that include very old populations, no or inverse associations between LDL-C and mortality have been observed. This study aims to investigate whether the association between LDL-C and mortality in the very old is modified by a composite fitness score.MethodsA 2-stage meta-analysis of individual participant data from the 5 observational cohort studies. The composite fitness score was operationalized by performance on a combination of 4 markers: functional ability, cognitive function, grip strength, and morbidity. We pooled hazard ratios (HR) from Cox proportional-hazards models for 5-year mortality risk for a 1 mmol/L increase in LDL-C. Models were stratified by high/low composite fitness score.ResultsComposite fitness scores were calculated for 2 317 participants (median 85 years, 60% females participants), of which 994 (42.9%) had a high composite fitness score, and 694 (30.0%) had a low-composite fitness score. There was an inverse association between LDL-C and 5-year mortality risk (HR 0.87 [95% CI: 0.80–0.94]; p < .01), most pronounced in participants with a low-composite fitness score (HR 0.85 [95% CI: 0.75–0.96]; p = .01), compared to those with a high composite fitness score (HR = 0.98 [95% CI: 0.83–1.15]; p = .78), the test for subgroups differences was not significant.ConclusionsIn this very old population, there was an inverse association between LDL-C and all-cause mortality, which was most pronounced in participants with a low-composite fitness scores. Show less
BackgroundAs there is a need to prepare doctors to minimize errors, we wanted to determine how doctors go about reflecting upon their medical errors.MethodsWe conducted a thematic analysis of the... Show moreBackgroundAs there is a need to prepare doctors to minimize errors, we wanted to determine how doctors go about reflecting upon their medical errors.MethodsWe conducted a thematic analysis of the published reflection reports of 12 Dutch doctors about the errors they had made. Three questions guided our analysis: What triggers doctors to become aware of their errors? What topics do they reflect upon to explain what happened? What lessons do doctors learn after reflecting on their error?ResultsWe found that the triggers which made doctors aware of their errors were mostly death and/or a complication. This suggests that the trigger to recognize that something might be wrong came too late. The 12 doctors cited 20 topics’ themes that explained the error and 16 lessons-learnt themes. The majority of the topics and lessons learnt were related more to the doctors’ inner worlds (personal features) than to the outer world (environment).ConclusionTo minimize errors, doctors should be trained to become earlier and in time aware of distracting and misleading features that might interfere with their clinical reasoning. This training should focus on reflection in action and on discovering more about doctors’ personal inner world to identify vulnerabilities. Show less
Prins, S.; Borghans, L.; Kam, M.L. de; Groeneveld, G.J.; Gerven, J. van 2023
Background The prevalence of neurodegenerative diseases increases significantly with increasing age. Neurodegeneration is the progressive loss of function of neurons that eventually leads to cell... Show moreBackground The prevalence of neurodegenerative diseases increases significantly with increasing age. Neurodegeneration is the progressive loss of function of neurons that eventually leads to cell death, which in turn leads to cognitive disfunction. Cognitive performance can therefore also be considered age dependent. The current study investigated if the NeuroCart can detect age related decline on drug-sensitive CNS-tests in healthy volunteers (HV), and whether there are interactions between the rates of decline and sex. This study also investigated if the NeuroCart was able to differentiate disease profiles of neurodegenerative diseases, compared to age-matched HV and if there is age related decline in patient groups. Methods This retrospective study encompassed 93 studies, performed at CHDR between 2005 and 2020 that included NeuroCart measurements, which resulted in data from 2729 subjects. Five NeuroCart tests were included in this analysis: smooth and saccadic eye movements, body sway, adaptive tracking, VVLT and N-back. Data from 84 healthy male and female volunteer studies, aged 16-90, were included. Nine studies were performed in patients with Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) or vascular dementia (VaD). The data were analyzed with regression analyses on age by group, sex, sex by age, group by sex and group by sex by age. Least square means (LSMs) and 95% confidence intervals (CIs) were calculated for each group at the average age of the group, and at the average age of each of the other groups, and per sex. Results Mean age and standard deviation (SD) for all groups was: HV 36.2 years (19.3), AD 68.3 years (8), PD 62.7 years (8.5), HD 51.4 years (9.8) and VaD 66.9 years (8.1). Performance on all NeuroCart tests decreased significantly each year in HV. Saccadic peak velocity (SPV) was increased in AD compared to age-matched HV (+26.28 degrees/s, p =0.007), while SPV was decreased for PD and HD compared to age-matched HV (PD: -15.87 degrees/s, p=0.038, HD: -22.52 degrees/s, p=0.018). In HD patients SPV decreased faster with age compared to HV. On saccadic peak velocity the slopes between HD vs HV were significantly different, indicating a faster decline in performance on this task for HD patients compared to HV per age year. Smooth pursuit showed an overall significant difference between subject groups (p=0.037. Significantly worse performance was found for AD (-12.87%, p=<0.001), PD (-4.45%, p=<0.001) and VaD (-5.69%, p=0.005) compared to age-matched HV. Body sway significantly increased with age (p=0.021). Postural stability was decreased for both PD and HD compared to age-matched HV (PD: +38.8%, p=<0.001, HD: 154.9%, p=<0.001). The adaptive tracking was significantly decreased with age (p=<0.001). Adaptive tracking performance by AD (-7.54%, p=<0.001), PD (-8.09%, p=<0.001), HD (-5.19%, p=<0.001) and VaD (-5.80%, p=<0.001) was decreased compared to age-matched HV. Adaptive tracking in PD patients vs HV and in PD vs HD patients was significantly different, indicating a faster decline on this task per age year for PD patients compared to HV and HD. The VVLT delayed word recall showed an overall significant effect of subject group (p=0.006. Correct delayed word recall was decreased for AD (-5.83 words, p=<0.001), HD (-3.40 words, p=<0.001) and VaD (-5.51 words, p=<0.001) compared to age-matched HV. Conclusion This study showed that the NeuroCart can detect age-related decreases in performance in HV, which were not affected by sex. The NeuroCart was able to detect significant differences in performance between AD, PD, HD, VaD and age-matched HV. Disease durations were unknown, therefore this cross-sectional study was not able to show age-related decline after disease onset. This article shows the importance of investigating age-related decline on digitalized neurocognitive test batteries. Performance declines with age, which emphasizes the need to correct for age when including HV in clinical trials. Patients with different neurogenerative diseases have distinct performance patterns on the NeuroCart , which this should be considered when performing NeuroCart tasks in patients with AD, PD, HD and VaD. Show less
This thesis reinforce that children born preterm are at risk for long-term impairments. Being able to predict who is at risk, by neonatal neuroimaging or early assessment, remains difficult,... Show moreThis thesis reinforce that children born preterm are at risk for long-term impairments. Being able to predict who is at risk, by neonatal neuroimaging or early assessment, remains difficult, especially in children who have milder forms of brain injury and/or experience milder difficulties at two years of age. Currently, most follow-up assessments use standardized outcome measures that might not show the full extent of a child’s daily functioning. Additional measurements and/or the implementation of qualitative research can be of great additional value. Show less
The aim of this thesis is to explore fear of choking and fear of falling in people with Huntington's disease (HD) and their caregivers. Dysphagia and falls are common in HD and may lead to fear of... Show moreThe aim of this thesis is to explore fear of choking and fear of falling in people with Huntington's disease (HD) and their caregivers. Dysphagia and falls are common in HD and may lead to fear of choking and fear of falling. However, knowledge about this is mostly lacking, as well as knowledge about the relationship between cognitive and emotional factors and these types of fear. The study confirms that fall prevalence (29% over a 30-day period) and prevalence of dysphagia symptoms (90%) are high. However, a prevalence of about 50% is also reported for fear of choking and fear of falling in people with HD. However, their informal caregivers report the most fear. Severity of dysphagia symptoms was a predictor of fear of choking, and anticipatory awareness of fall risks and gender were found to be predictors of fear of falling. In most individuals with HD, a combination of preventive measures was used.Future research can improve both management of dysphagia and fear of choking and management of falls and fear of falling. Because questioning people with HD is sometimes difficult, due to speech and cognitive difficulties, diagnostic tools may be sought to facilitate this, such as wearable electronic devices. Show less
This thesis describes studies of individuals with systemic lupus erythematosus (SLE) presenting with neuropsychiatric (NP) symptoms at the Leiden NPSLE clinic. A diverse range of studies, including... Show moreThis thesis describes studies of individuals with systemic lupus erythematosus (SLE) presenting with neuropsychiatric (NP) symptoms at the Leiden NPSLE clinic. A diverse range of studies, including laboratory, radiological, clinical and patient´s reported outcomes are presented.The Leiden NPSLE clinic is a tertiary referral center for patients with SLE and neuropsychiatric (NP) symptoms. In the NPSLE clinic, patients are assessed by a multidisciplinary team. Thereafter, clinical, radiological and laboratory measures are weighed in a consensus meeting to correctly attribute the NP symptoms: related to lupus activity (NPSLE) or not. This extensive and standardized assessment of NPSLE, a rare and heterogenous disease lacking a gold standard, is unique and creates the opportunity to explore many aspects of NPSLE in well-defined phenotypes.In the first part of this thesis, we evaluate both classification and treatment of patients withSLE and NP symptoms. The second part of this thesis focuses on a diverse range of clinicaloutcomes of NPSLE, including both morbidity and mortality. The last part of this thesisassesses potential biomarkers for (specific manifestations of) NPSLE. Show less
Introduction: Studies investigating the long-term effects of breast cancer treatment on cognition in older women with breast cancer are lacking, even though preserving cognition is highly valued by... Show moreIntroduction: Studies investigating the long-term effects of breast cancer treatment on cognition in older women with breast cancer are lacking, even though preserving cognition is highly valued by the older population. Specifically, concerns have been raised regarding the detrimental effects of endocrine therapy (ET) on cognition. Therefore, we investigated cogni-tive functioning over time and predictors for cognitive decline in older women treated for early breast cancer.Methods: We prospectively enrolled Dutch women aged >70 years with stage I-III breast can-cer in the observational CLIMB study. The Mini-Mental State Examination (MMSE) was performed before ET initiation and after 9, 15 and 27 months. Longitudinal MMSE scores were analysed and stratified for ET. Linear mixed models were used to identify possible pre-dictors of cognitive decline.Results: Among the 273 participants, the mean age was 76 years (standard deviation 5), and 48% received ET. The mean baseline MMSE score was 28.2 (standard deviation 1.9). Cogni-tion did not decline to clinically meaningful differences, irrespective of ET. MMSE scores of women with pre-treatment cognitive impairments slightly improved over time (significant interaction terms) in the entire cohort and in women receiving ET. High age, low educational level and impaired mobility were independently associated with declining MMSE scores over time, although the declines were not clinically meaningful.Conclusion: Cognition of older women with early breast cancer did not decline in the first two years after treatment initiation, irrespective of ET. Our findings suggest that the fear of declining cognition does not justify the de-escalation of breast cancer treatment in older women. 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Blaauw, J.; Hertog, H.M.D.; Holl, D.C.; Thuss, N.S.; Gaag, N.A. van der; Jellema, K.; ... ; Naalt, J. van der 2023
ObjectiveChronic subdural hematoma (CSDH) is a common neurological condition, often affecting the elderly. Cognitive impairment is frequently observed at presentation. However, the course and... Show moreObjectiveChronic subdural hematoma (CSDH) is a common neurological condition, often affecting the elderly. Cognitive impairment is frequently observed at presentation. However, the course and longer term aspects of the cognitive status of CSDH patients are unknown. In this study, we aim to explore the cognitive status of CSDH patients after treatment.MethodsAn exploratory study in which CSDH patients were assessed 3 months after treatment and compared to healthy controls. A total of 56 CSDH patients (age 72.1 SD +/- 10.8 years with 43 [77%] males) and 60 healthy controls were included (age 67.5 +/- SD 4.8 with 34 [57%] males). Cognitive testing was performed using the Telephonic Interview of Cognitive Status-modified (TICS-m), a 12-item questionnaire in which a total of 50 points can be obtained on several cognitive domains.ResultsMedian time between treatment and cognitive testing was 93 days (range 76-139). TICS-m scores of CSDH patients were significantly lower than healthy controls, after adjusting for age and sex: mean score 34.6 (95% CI: 33.6-35.9) vs. 39.6 (95% CI: 38.5-40.7), p value < 0.001. More than half (54%) of CSDH patients have cognitive scores at follow-up that correspond with cognitive impairment.ConclusionA large number of CSDH patients show significantly worse cognitive status 3 months after treatment compared to healthy controls. This finding underlines the importance of increased awareness for impaired cognition after CSDH. Further research on this topic is warranted. Show less
Because aggressive behavior during early childhood has been related to negative developmental outcomes, a further understanding of the underlying mechanisms of aggression during the first years of... Show moreBecause aggressive behavior during early childhood has been related to negative developmental outcomes, a further understanding of the underlying mechanisms of aggression during the first years of life is essential. Although the factors prenatal risk, parenting behavior, temperament and cognitive functions have consistently been related to externalizing behavior during preschool and school age, research focusing on their interplay in relation to aggressive behavior earlier in life is scarce. The aim of the current dissertation was to gain more insight into these associations during infancy and toddlerhood. Our studies indicated that impairments in children’s early cognitive regulation abilities play a role in the development of aggressive behavior. It can also be concluded that both adverse pre- and postnatal environmental influences have an impact on child aggression: higher prenatal risk and adverse parenting behavior were directly or indirectly (via poor cognitive functioning) related to higher levels of aggression. In addition, it was found that poor cognitive skills increased the risk of aggression in case of high prenatal risk or a highly reactive temperament during early development. These results suggest that early intervention programs to prevent aggression should focus on prenatal risk, parenting behavior and cognitive development during the first years of life. Show less
Anxiety disorders are globally one of the most prevalent and disabling forms of psychopathology in adults and children. Having a parent with an anxiety disorder multiplies the risk of anxiety... Show moreAnxiety disorders are globally one of the most prevalent and disabling forms of psychopathology in adults and children. Having a parent with an anxiety disorder multiplies the risk of anxiety disorders in the ofspring, although the specifc mechanisms and processes that play a role in this intergenerational transmission remain largely unknown. According to information processing theories, threat-related biases in cognitive processing are a causal mechanism in the development and maintenance of anxiety. These theories propose that individuals with anxiety are more likely to cognitively process novel stimuli in their environment as threatening. Creswell and colleagues proposed a theoretical model that highlighted the role of these cognitive biases as a mechanism in the intergenerational transmission of anxiety (Creswell et al., in Hadwin, Field (eds) Information processing biases and anxiety: a developmental perspective, Wiley, pp 279–295, 2010). This model postulated signifcant associations between (1) parents’ and children’s threat-related cognitive biases (2) parents’ threatrelated cognitive biases in their own and their child’s environment, (3) parents’ threat-related cognitive biases and parenting behaviors that convey anxiety risk to the ofspring (e.g., modeling of fear, and verbal threat information transmission), and (4) parenting behaviors and child threat-related biases. This theoretical review collated the recent empirical work testing these four core hypotheses of the model. Building on the reviewed empirical work, an updated conceptual model focusing on threat-related attention and interpretation is proposed. This updated model incorporates the links between cognition and anxiety in parents and children and addresses the potential bidirectional nature of parent–child infuences. Show less
Background: Though mediotemporal lobe volume changes are well-known features of Alzheimer's disease (AD), grey matter volume changes may be distributed throughout the brain. These distributed... Show moreBackground: Though mediotemporal lobe volume changes are well-known features of Alzheimer's disease (AD), grey matter volume changes may be distributed throughout the brain. These distributed changes are not independent due to the underlying network structure and can be described in terms of a structural covariance network (SCN).Objective: To investigate how the cortical brain organization is altered in AD we studied the mutual connectivity of hubs in the SCN, i.e., the rich-club.Methods: To construct the SCNs, cortical thickness was obtained from structural MRI for 97 participants (normal cognition, n = 37; mild cognitive impairment, n = 41; Alzheimer-type dementia, n = 19). Subsequently, rich-club coefficients were calculated from the SCN, and related to memory performance and hippocampal volume using linear regression.Results: Lower rich-club connectivity was related to lower memory performance as well as lower hippocampal volume.Conclusion: Therefore, this study provides novel evidence of reduced connectivity in hub areas in relation to AD-related cognitive impairments and atrophy. Show less
Bruijnen, C.P.; Groot, L.G.R. de; Vondeling, A.M.; Bree, R. de; Bos, F. van den; Witteveen, P.O.; Emmelot-Vonk, M.H. 2021
Introduction: In addition to classical endpoints such as survival and complication rates, other outcomes such as quality of life and functional status are increasingly recognized as important... Show moreIntroduction: In addition to classical endpoints such as survival and complication rates, other outcomes such as quality of life and functional status are increasingly recognized as important endpoints, especially for elderly patients. However, little is known about the long-term effect of surgery with regard to these other outcomes. Our aim is to investigate the functional status and self-reported health status of patients > 70 years one year after surgery for head and neck cancer. Methods: We present one-year follow-up data of patients > 70 year who underwent surgery for HNC. During an interview by telephone, functional status was evaluated by using the Katz-15 Index of Independence questionnaire including six items covering basic Activities of Daily Living (ADL) and nine items covering Instrumental Activities of Daily Living (IADL). Measurements were compared with those obtained preoperatively. Results: In total, 126 patients were included and eventually we collected follow-up data of 68 patients. There was a statistically significant decrease in functional status on the total Katz-15 and on the IADL questionnaire scores one year after surgery (mean 1.34 versus 2.42, p -value 0.00 and mean 1.21 versus 1.94, p- value 0.00). There was no significant change concerning ADL dependence ( p -value 0.18) and cognitive status ( p -value 0.11). The self-reported health status improved postoperatively, although not statistically significantly so (mean 67.36 versus 71.25, p -value 0.12). Conclusion: Approximately-one year after surgery for HNC, there is a significant decline in functional status indicating a higher level of dependency. Show less
Background and Purpose Cerebral amyloid angiopathy (CAA) is a common pathology of the leptomeningeal and cortical small vessels associated with hemorrhagic and non-hemorrhagic brain injury. Given... Show moreBackground and Purpose Cerebral amyloid angiopathy (CAA) is a common pathology of the leptomeningeal and cortical small vessels associated with hemorrhagic and non-hemorrhagic brain injury. Given previous evidence for CAA-related loss of cortical thickness and white matter volume, we hypothesized that CAA might also cause tissue loss in the basal ganglia. Methods We compared basal ganglia volumes expressed as a percentage of total intracranial volume (pBGV) of non-demented patients with sporadic and hereditary CAA to age-matched healthy control (HC) and Alzheimer's disease (AD) cohorts.Results Patients with sporadic CAA had lower pBGV (n=80, 1.16%+/- 0.14%) compared to HC (n=80, 1.30%+/- 0.13%, P<0.0001) and AD patients (n=80, 1.23%+/- 0.11%, P=0.001). Similarly, patients with hereditary CAA demonstrated lower pBGV (n=25, 1.26%+/- 0.17%) compared to their matched HC (n=25, 1.36%+/- 0.15%, P=0.036). Using a measurement of normalized basal ganglia width developed for analysis of clinical-grade magnetic resonance images, we found smaller basal ganglia width in patients with CAA-related lobar intracerebral hemorrhage (ICH; n=93, 12.35 +/- 1.47) compared to age-matched patients with hypertension-related deep ICH (n=93, 13.46 +/- 1.51, P<0.0001) or HC (n=93, 15.45 +/- 1.22, P<0.0001). Within the sporadic CAA research cohort, decreased basal ganglia volume was independently correlated with greater cortical gray matter atrophy (r=0.45, P<0.0001), increased basal ganglia fractional anisotropy (r=-0.36, P=0.001), and worse performance on language processing (r=0.35, P=0.003), but not with cognitive tests of executive function or processing speed.Conclusions These findings suggest an independent effect of CAA on basal ganglia tissue loss, indicating a novel mechanism for CAA-related brain injury and neurologic dysfunction. Show less
Objective: A downside of Deep Brain Stimulation (DBS) for Parkinson's Disease (PD) is that cognitive function may deteriorate postoperatively. Electroencephalography (EEG) was explored as biomarker... Show moreObjective: A downside of Deep Brain Stimulation (DBS) for Parkinson's Disease (PD) is that cognitive function may deteriorate postoperatively. Electroencephalography (EEG) was explored as biomarker of cognition using a Machine Learning (ML) pipeline.Methods: A fully automated ML pipeline was applied to 112 PD patients, taking EEG time-series as input and predicted class-labels as output. The most extreme cognitive scores were selected for class differentiation, i.e. best vs. worst cognitive performance (n = 20 per group). 16,674 features were extracted per patient; feature-selection was performed using a Boruta algorithm. A random forest classifier was modelled; 10-fold cross-validation with Bayesian optimization was performed to ensure generalizability. The predicted class-probabilities of the entire cohort were compared to actual cognitive performance.Results: Both groups were differentiated with a mean accuracy of 0.92; using only occipital peak frequency yielded an accuracy of 0.67. Class-probabilities and actual cognitive performance were negatively linearly correlated (b =-0.23 (95% confidence interval (-0.29,-0.18))).Conclusions: Particularly high accuracies were achieved using a compound of automatically extracted EEG biomarkers to classify PD patients according to cognition, rather than a single spectral EEG feature.Significance: Automated EEG assessment may have utility for cognitive profiling of PD patients during the DBS screening. (c) 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
