Upper Limb Robots for Recovery of Motor Arm Function in Patients With Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Robot technology to support upper limb (UL) rehabilitation poststroke has rapidly developed over the past 3 decades. We aimed to assess the effects of UL-robots (UL-RTs) on recovery of UL motor functioning and capacity poststroke when compared with any non-UL-RT and to identify variables that are associated with the found effect sizes (ESs). METHODS: Randomized controlled trials (RCTs) comparing UL-RTs with any other intervention on patients with UL limitations poststroke were identified in electronic searches from PubMed, Wiley/Cochrane Libraries, Embase, Cumulative Index of Nursing and Allied Health Literature, Web of Science, SportDISCUS, Physiotherapy Evidence Database (PEDro), and Google Scholar from inception until August 1, 2022. Two reviewers independently extracted relevant data using a Microsoft Excel spreadsheet. Meta-analyses were performed for measures of UL-muscle synergism, muscle power, muscle tone, capacity, self-reported motor performance, and basic activities of daily living (ADLs). Subgroup, sensitivity, and meta-regression analyses were applied to identify factors potentially associated with found ESs. Analyses were performed using Review Manager version 5.4 or IBM SPSS statistics version 27. RESULTS: Ninety RCTs (N = 4,311) were included (median PEDro score 6 [6-7]). Meta-analyses of 86 trials (N = 4,240) showed small significant improvements in UL-muscle synergism (Fugl-Meyer Assessment of the UL [FM-UL]) (mean difference 2.23 [1.11-3.35]), muscle power (standardized mean difference [SMD] 0.39 [0.16-0.61]), motor performance (SMD 0.11 [0.00-0.21]), and basic ADLs (SMD 0.28 [0.10-0.45]). No overall effects were found for muscle tone (SMD -0.1 [-0.26 to 0.07]) or UL-capacity (SMD 0.04 [-0.10 to 0.18]), except with exoskeletons (SMD 0.27 [0.10-0.43]). Meta-regressions showed a significant positive association between baseline mean FM-UL and ESs for UL-capacity (r = 0.339; p = 0.03), in particular in the acute and early-subacute phases poststroke (r = 0.65; p = 0.01). No further significant subgroup differences or associations were found in our analyses. DISCUSSION: The small significant effects found at the level of motor impairment do not show generalization to clinically meaningful effects at the level of UL-capacity. Meta-regressions suggest that selected participants with some potential of UL-recovery may benefit most from UL-RT, especially earlier poststroke. The robustness and consistency of our findings suggest that the development of the next generation of UL-RT needs to be guided by a better mechanistic understanding about assumed underlying interaction effects between motor learning and motor recovery poststroke. TRIAL REGISTRATION INFORMATION: A prospectively registered study protocol is available in the PROSPERO database under ID CRD42020197450.

Relative risk of second malignant neoplasms highest among young adult cancer patients - a population-based registry study in Finland.

BACKGROUND AND PURPOSE: The objective of this study was to explore the incidence of second malignant neoplasms (SMNs) among adult cancer patients in Finland diagnosed with their first primary cancer (FPC) in 1992-2021. MATERIAL AND METHODS: The study used data from the population-based Finnish Cancer Registry (FCR). Risk estimates were calculated using the standardised incidence ratio (SIR), the ratio of observed second cancers compared to the expected numbers assuming the same cancer incidence as the corresponding sex-age-calendar year -split of the general population. RESULTS: A total of 573,379 FPCs were diagnosed during 1992-2021. During the follow-up, 60,464 SMNs were diagnosed. Male cancer patients had neither a decreased nor an increased risk (SIR 1.00 [95% CI, 0.99-1.01]) and female patients had an 8% increased risk (SIR 1.08 [95% CI, 1.06-1.09]) of developing any SMN compared to a FPC in the general population. The highest SIR of any SMN was observed in patients aged 20-39 -years at FPC diagnosis, and the SIR decreased by increasing age at diagnosis. Patients with lymphoid and haematopoietic tissue neoplasms, cancers of the mouth and pharynx, endocrine glands, respiratory and intrathoracic organs, skin, and urinary organs had the highest SIRs, while patients with cancers of the male genital organs and the female breast had the lowest SIRs. INTERPRETATION: Elevated SIRs were observed in cancer patients diagnosed at an early age and for FPCs known to be in large part attributable to lifestyle factors, which highlights the importance of monitoring and encouraging lifestyle changes.

Enhancing Cognitive Performance Prediction through White Matter Hyperintensity Connectivity Assessment: A Multicenter Lesion Network Mapping Analysis of 3,485 Memory Clinic Patients.

Introduction: White matter hyperintensities of presumed vascular origin (WMH) are associated with cognitive impairment and are a key imaging marker in evaluating cognitive health. However, WMH volume alone does not fully account for the extent of cognitive deficits and the mechanisms linking WMH to these deficits remain unclear. We propose that lesion network mapping (LNM), enables to infer if brain networks are connected to lesions, and could be a promising technique for enhancing our understanding of the role of WMH in cognitive disorders. Our study employed this approach to test the following hypotheses: (1) LNM-informed markers surpass WMH volumes in predicting cognitive performance, and (2) WMH contributing to cognitive impairment map to specific brain networks. Methods & results: We analyzed cross-sectional data of 3,485 patients from 10 memory clinic cohorts within the Meta VCI Map Consortium, using harmonized test results in 4 cognitive domains and WMH segmentations. WMH segmentations were registered to a standard space and mapped onto existing normative structural and functional brain connectome data. We employed LNM to quantify WMH connectivity across 480 atlas-based gray and white matter regions of interest (ROI), resulting in ROI-level structural and functional LNM scores. The capacity of total and regional WMH volumes and LNM scores in predicting cognitive function was compared using ridge regression models in a nested cross-validation. LNM scores predicted performance in three cognitive domains (attention and executive function, information processing speed, and verbal memory) significantly better than WMH volumes. LNM scores did not improve prediction for language functions. ROI-level analysis revealed that higher LNM scores, representing greater disruptive effects of WMH on regional connectivity, in gray and white matter regions of the dorsal and ventral attention networks were associated with lower cognitive performance. Conclusion: Measures of WMH-related brain network connectivity significantly improve the prediction of current cognitive performance in memory clinic patients compared to WMH volume as a traditional imaging marker of cerebrovascular disease. This highlights the crucial role of network effects, particularly in attentionrelated brain regions, improving our understanding of vascular contributions to cognitive impairment. Moving forward, refining WMH information with connectivity data could contribute to patient-tailored therapeutic interventions and facilitate the identification of subgroups at risk of cognitive disorders.

Subsequent malignant neoplasms after primary hematological malignancy in adult patients.

Patients with primary hematological malignancy (HM) are at an elevated risk of subsequent malignant neoplasms (SMNs), which is a common concern after treatment of primary cancer. We identified 45,533 patients aged ≥20 years and diagnosed with primary HM in Finland from 1992 to 2019 from the Finnish Cancer Registry and estimated standardized incidence ratios (SIR) and excess absolute risks per 1000 person-years (EAR) for SMNs. A total of 6076 SMNs were found (4604 solid and 1472 hematological SMNs). The SIRs were higher for hematological SMNs (SIR 4.9, 95% confidence interval [CI] 4.7-5.2) compared to solid SMNs (SIR 1.5, 95% CI 1.4-1.5). The SIRs for hematological SMNs were highest in the young HM patients aged 20-39 years (SIR 9.2, 95% CI 6.8-12.2 in males and SIR 10.5, 95% CI 7.2-14.7 in females) and decreased by age of first primary HM. However, EARs for hematological SMNs were highest in the older patients, aged 60-79 years at their first primary HM (EAR 5.7/1000 and 4.7/1000 in male and female patients, respectively). In conclusion, the incidence of both hematological and solid SMNs were increased in hematological cancer patients. The relative risk (SIR) was highest among younger HM patients with hematological SMNs. The absolute second cancer burden reflected by high EAR arises from solid malignancies in older patients. Our results accentuate the need for vigilance in the surveillance of HM patients.

Amyloid pathology and vascular risk are associated with distinct patterns of cerebral white matter hyperintensities: A multicenter study in 3132 memory clinic patients.

INTRODUCTION: White matter hyperintensities (WMH) are associated with key dementia etiologies, in particular arteriolosclerosis and amyloid pathology. We aimed to identify WMH locations associated with vascular risk or cerebral amyloid-ß1-42 (Aß42)-positive status. METHODS: Individual patient data (n = 3,132; mean age 71.5 ± 9 years; 49.3% female) from 11 memory clinic cohorts were harmonized. WMH volumes in 28 regions were related to a vascular risk compound score (VRCS) and Aß42 status (based on cerebrospinal fluid or amyloid positron emission tomography), correcting for age, sex, study site, and total WMH volume. RESULTS: VRCS was associated with WMH in anterior/superior corona radiata (B = 0.034/0.038, p < 0.001), external capsule (B = 0.052, p < 0.001), and middle cerebellar peduncle (B = 0.067, p < 0.001), and Aß42-positive status with WMH in posterior thalamic radiation (B = 0.097, p < 0.001) and splenium (B = 0.103, p < 0.001). DISCUSSION: Vascular risk factors and Aß42 pathology have distinct signature WMH patterns. This regional vulnerability may incite future studies into how arteriolosclerosis and Aß42 pathology affect the brain's white matter. HIGHLIGHTS: Key dementia etiologies may be associated with specific patterns of white matter hyperintensities (WMH). We related WMH locations to vascular risk and cerebral Aß42 status in 11 memory clinic cohorts. Aß42 positive status was associated with posterior WMH in splenium and posterior thalamic radiation. Vascular risk was associated with anterior and infratentorial WMH. Amyloid pathology and vascular risk have distinct signature WMH patterns.

The feasibility of the adapted H-GRASP program for perceived and actual daily-life upper limb activity in the chronic phase post-stroke.

(Purpose: Assessing feasibility and initial impact of the Home-Graded Repetitive Arm Supplementary Program combined with in-home accelerometer-based feedback (AH-GRASP) on perceived and actual daily-life upper limb (UL) activity in stroke survivors during the chronic phase with good UL motor function but low perceived daily-life activity. Material and methods: A 4-week intervention program (4 contact hours, 48 h self-practice) encompassing task-oriented training, behavioral techniques, phone-based support, monitoring, and weekly feedback sessions using wrist-worn accelerometery was implemented using a pre-post double baseline repeated measures design. Feasibility, clinical assessments, patient-reported outcomes, and accelerometer data were investigated. Results: Of the 34 individuals approached, nineteen were included (recruitment rate 56%). Two dropped out, one due to increased UL pain (retention rate 89%). Seven (41%) achieved the prescribed exercise target (120 min/day, six days/week). Positive patient experiences and improvements in UL capacity, self-efficacy, and contribution of the affected UL to overall activity (p < 0.05, small to large effect sizes) were observed. Additionally, seven participants (41%) surpassed the minimal clinically important difference in perceived UL activity.Conclusions: A home-based UL exercise program with accelerometer-based feedback holds promise for enhancing perceived and actual daily-life UL activity for our subgroup of chronic stroke survivors.

Implementing a home-based exercise program with accelerometer-based feedback and telephone supervision may effectively improve upper limb activity after stroke.This program is most suitable for individuals with mild upper limb impairment and should be tailored to their abilities, preferences, and limitations to enhance engagement.The AH-GRASP program shows promising recruitment and retention rates, safety, and positive patient experiences.To improve adherence, consider dividing exercises into shorter sessions that accommodate patient's schedules, attention and endurance levels.

Small vessel disease burden and functional brain connectivity in mild cognitive impairment.

Background: The role of small vessel disease in the development of dementia is not yet completely understood. Functional brain connectivity has been shown to differ between individuals with and without cerebral small vessel disease. However, a comprehensive measure of small vessel disease quantifying the overall damage on the brain is not consistently used and studies using such measure in mild cognitive impairment individuals are missing. Method: Functional brain connectivity differences were analyzed between mild cognitive impairment individuals with absent or low (n = 34) and high (n = 34) small vessel disease burden using data from the Parelsnoer Institute, a Dutch multicenter study. Small vessel disease was characterized using an ordinal scale considering: lacunes, microbleeds, perivascular spaces in the basal ganglia, and white matter hyperintensities. Resting state functional MRI data using 3 Tesla scanners was analyzed with group-independent component analysis using the CONN toolbox. Results: Functional connectivity between areas of the cerebellum and between the cerebellum and the thalamus and caudate nucleus was higher in the absent or low small vessel disease group compared to the high small vessel disease group. Conclusion: These findings might suggest that functional connectivity of mild cognitive impairment individuals with low or absent small vessel disease burden is more intact than in mild cognitive impairment individuals with high small vessel disease. These brain areas are mainly responsible for motor, attentional and executive functions, domains which in previous studies were found to be mostly associated with small vessel disease markers. Our results support findings on the involvement of the cerebellum in cognitive functioning.

Standardized measurement of balance and mobility post-stroke: Consensus-based core recommendations from the third Stroke Recovery and Rehabilitation Roundtable.

BACKGROUND: Mobility is a key priority for stroke survivors. Worldwide consensus of standardized outcome instruments for measuring mobility recovery after stroke is an essential milestone to optimize the quality of stroke rehabilitation and recovery studies and to enable data synthesis across trials. METHODS: Using a standardized methodology, which involved convening of 13 worldwide experts in the field of mobility rehabilitation, consensus was established through an a priori defined survey-based approach followed by group discussions. The group agreed on balance- and mobility-related definitions and recommended a core set of outcome measure instruments for lower extremity motor function, balance and mobility, biomechanical metrics, and technologies for measuring quality of movement. RESULTS: Selected measures included the Fugl-Meyer Motor Assessment lower extremity subscale for motor function, the Trunk Impairment Scale for sitting balance, and the Mini Balance Evaluation System Test (Mini-BESTest) and Berg Balance Scale (BBS) for standing balance. The group recommended the Functional Ambulation Category (FAC, 0-5) for walking independence, the 10-meter Walk Test (10 mWT) for walking speed, the 6-Minute Walk Test (6 MWT) for walking endurance, and the Dynamic Gait Index (DGI) for complex walking. An FAC score of less than three should be used to determine the need for an additional standing test (FAC < 3, add BBS to Mini-BESTest) or the feasibility to assess walking (FAC < 3, 10 mWT, 6 MWT, and DGI are "not testable"). In addition, recommendations are given for prioritized kinetic and kinematic metrics to be investigated that measure recovery of movement quality of standing balance and walking, as well as for assessment protocols and preferred equipment to be used. CONCLUSIONS: The present recommendations of measures, metrics, technology, and protocols build on previous consensus meetings of the International Stroke Recovery and Rehabilitation Alliance to guide the research community to improve the validity and comparability between stroke recovery and rehabilitation studies as a prerequisite for building high-quality, standardized "big data" sets. Ultimately, these recommendations could lead to high-quality, participant-specific data sets to aid the progress toward precision medicine in stroke rehabilitation.

Standardized measurement of balance and mobility post-stroke: Consensus-based core recommendations from the third Stroke Recovery and Rehabilitation Roundtable.

BACKGROUND: Mobility is a key priority for stroke survivors. Worldwide consensus of standardized outcome instruments for measuring mobility recovery after stroke is an essential milestone to optimize the quality of stroke rehabilitation and recovery studies and to enable data synthesis across trials. METHODS: Using a standardized methodology, which involved convening of 13 worldwide experts in the field of mobility rehabilitation, consensus was established through an a priori defined survey-based approach followed by group discussions. The group agreed on balance- and mobility-related definitions and recommended a core set of outcome measure instruments for lower extremity motor function, balance and mobility, biomechanical metrics, and technologies for measuring quality of movement. RESULTS: Selected measures included the Fugl-Meyer Motor Assessment lower extremity subscale for motor function, the Trunk Impairment Scale for sitting balance, and the Mini Balance Evaluation System Test (Mini-BESTest) and Berg Balance Scale (BBS) for standing balance. The group recommended the Functional Ambulation Category (FAC, 0-5) for walking independence, the 10-meter Walk Test (10 mWT) for walking speed, the 6-Minute Walk Test (6 MWT) for walking endurance, and the Dynamic Gait Index (DGI) for complex walking. An FAC score of less than three should be used to determine the need for an additional standing test (FAC < 3, add BBS to Mini-BESTest) or the feasibility to assess walking (FAC < 3, 10 mWT, 6 MWT, and DGI are "not testable"). In addition, recommendations are given for prioritized kinetic and kinematic metrics to be investigated that measure recovery of movement quality of standing balance and walking, as well as for assessment protocols and preferred equipment to be used. CONCLUSIONS: The present recommendations of measures, metrics, technology, and protocols build on previous consensus meetings of the International Stroke Recovery and Rehabilitation Alliance to guide the research community to improve the validity and comparability between stroke recovery and rehabilitation studies as a prerequisite for building high-quality, standardized "big data" sets. Ultimately, these recommendations could lead to high-quality, participant-specific data sets to aid the progress toward precision medicine in stroke rehabilitation.

Combining Surgical Innovations in Amputation Surgery-Robotic Harvest of the Rectus Abdominis Muscle, Transplantation and Targeted Muscle Reinnervation Improves Myocontrol Capability and Pain in a Transradial Amputee.

Adding robotic surgery to bionic reconstruction might open a new dimension. The objective was to evaluate if a robotically harvested rectus abdominis (RA) transplant is a feasible procedure to improve soft-tissue coverage at the residual limb (RL) and serve as a recipient for up to three nerves due to its unique architecture and to allow the generation of additional signals for advanced myoelectric prosthesis control. A transradial amputee with insufficient soft-tissue coverage and painful neuromas underwent the interventions and was observed for 18 months. RA muscle was harvested using robotic-assisted surgery and transplanted to the RL, followed by end-to-end neurroraphy to the recipient nerves of the three muscle segments to reanimate radial, median, and ulnar nerve function. The transplanted muscle healed with partial necrosis of the skin mesh graft. Twelve months later, reliable, and spatially well-defined Hoffmann-Tinel signs were detectable at three segments of the RA muscle flap. No donor-site morbidities were present, and EMG activity could be detected in all three muscle segments. The linear discriminant analysis (LDA) classifier could reliably distinguish three classes within 1% error tolerance using only the three electrodes on the muscle transplant and up to five classes outside the muscle transplant. The combination of these surgical procedure advances with emerging (myo-)control technologies can easily be extended to different amputation levels to reduce RL complications and augment control sites with a limited surface area, thus facilitating the usability of advanced myoelectric prostheses.

Spatial distributions of white matter hyperintensities on brain MRI: A pooled analysis of individual participant data from 11 memory clinic cohorts.

INTRODUCTION: The spatial distribution of white matter hyperintensities (WMH) on MRI is often considered in the diagnostic evaluation of patients with cognitive problems. In some patients, clinicians may classify WMH patterns as "unusual", but this is largely based on expert opinion, because detailed quantitative information about WMH distribution frequencies in a memory clinic setting is lacking. Here we report voxel wise 3D WMH distribution frequencies in a large multicenter dataset and also aimed to identify individuals with unusual WMH patterns. METHODS: Individual participant data (N = 3525, including 777 participants with subjective cognitive decline, 1389 participants with mild cognitive impairment and 1359 patients with dementia) from eleven memory clinic cohorts, recruited through the Meta VCI Map Consortium, were used. WMH segmentations were provided by participating centers or performed in Utrecht and registered to the Montreal Neurological Institute (MNI)-152 brain template for spatial normalization. To determine WMH distribution frequencies, we calculated WMH probability maps at voxel level. To identify individuals with unusual WMH patterns, region-of-interest (ROI) based WMH probability maps, rule-based scores, and a machine learning method (Local Outlier Factor (LOF)), were implemented. RESULTS: WMH occurred in 82% of voxels from the white matter template with large variation between subjects. Only a small proportion of the white matter (1.7%), mainly in the periventricular areas, was affected by WMH in at least 20% of participants. A large portion of the total white matter was affected infrequently. Nevertheless, 93.8% of individual participants had lesions in voxels that were affected in less than 2% of the population, mainly located in subcortical areas. Only the machine learning method effectively identified individuals with unusual patterns, in particular subjects with asymmetric WMH distribution or with WMH at relatively rarely affected locations despite common locations not being affected. DISCUSSION: Aggregating data from several memory clinic cohorts, we provide a detailed 3D map of WMH lesion distribution frequencies, that informs on common as well as rare localizations. The use of data-driven analysis with LOF can be used to identify unusual patterns, which might serve as an alert that rare causes of WMH should be considered.

Three alginate lyases provide a new gut Bacteroides ovatus isolate with the ability to grow on alginate.

Humans consume alginate in the form of seaweed, food hydrocolloids, and encapsulations, making the digestion of this mannuronic acid (M) and guluronic acid (G) polymer of key interest for human health. To increase knowledge on alginate degradation in the gut, a gene catalog from human feces was mined for potential alginate lyases (ALs). The predicted ALs were present in nine species of the Bacteroidetes phylum, of which two required supplementation of an endo-acting AL, expected to mimic cross-feeding in the gut. However, only a new isolate grew on alginate. Whole-genome sequencing of this alginate-utilizing isolate suggested that it is a new Bacteroides ovatus strain harboring a polysaccharide utilization locus (PUL) containing three ALs of families: PL6, PL17, and PL38. The BoPL6 degraded polyG to oligosaccharides of DP 1-3, and BoPL17 released 4,5-unsaturated monouronate from polyM. BoPL38 degraded both alginates, polyM, polyG, and polyMG, in endo-mode; hence, it was assumed to deliver oligosaccharide substrates for BoPL6 and BoPL17, corresponding well with synergistic action on alginate. BoPL17 and BoPL38 crystal structures, determined at 1.61 and 2.11 Å, respectively, showed (α/α)6-barrel + anti-parallel ß-sheet and (α/α)7-barrel folds, distinctive for these PL families. BoPL17 had a more open active site than the two homologous structures. BoPL38 was very similar to the structure of an uncharacterized PL38, albeit with a different triad of residues possibly interacting with substrate in the presumed active site tunnel. Altogether, the study provides unique functional and structural insights into alginate-degrading lyases of a PUL in a human gut bacterium.IMPORTANCEHuman ingestion of sustainable biopolymers calls for insight into their utilization in our gut. Seaweed is one such resource with alginate, a major cell wall component, used as a food hydrocolloid and for encapsulation of pharmaceuticals and probiotics. Knowledge is sparse on the molecular basis for alginate utilization in the gut. We identified a new Bacteroides ovatus strain from human feces that grew on alginate and encoded three alginate lyases in a gene cluster. BoPL6 and BoPL17 show complementary specificity toward guluronate (G) and mannuronate (M) residues, releasing unsaturated oligosaccharides and monouronic acids. BoPL38 produces oligosaccharides degraded by BoPL6 and BoPL17 from both alginates, G-, M-, and MG-substrates. Enzymatic and structural characterization discloses the mode of action and synergistic degradation of alginate by these alginate lyases. Other bacteria were cross-feeding on alginate oligosaccharides produced by an endo-acting alginate lyase. Hence, there is an interdependent community in our guts that can utilize alginate.

Sublithospheric diamond ages and the supercontinent cycle.

Subduction related to the ancient supercontinent cycle is poorly constrained by mantle samples. Sublithospheric diamond crystallization records the release of melts from subducting oceanic lithosphere at 300-700 km depths1,2 and is especially suited to tracking the timing and effects of deep mantle processes on supercontinents. Here we show that four isotope systems (Rb-Sr, Sm-Nd, U-Pb and Re-Os) applied to Fe-sulfide and CaSiO3 inclusions within 13 sublithospheric diamonds from Juína (Brazil) and Kankan (Guinea) give broadly overlapping crystallization ages from around 450 to 650 million years ago. The intracratonic location of the diamond deposits on Gondwana and the ages, initial isotopic ratios, and trace element content of the inclusions indicate formation from a peri-Gondwanan subduction system. Preservation of these Neoproterozoic-Palaeozoic sublithospheric diamonds beneath Gondwana until its Cretaceous breakup, coupled with majorite geobarometry3,4, suggests that they accreted to and were retained in the lithospheric keel for more than 300 Myr during supercontinent migration. We propose that this process of lithosphere growth-with diamonds attached to the supercontinent keel by the diapiric uprise of depleted buoyant material and pieces of slab crust-could have enhanced supercontinent stability.

Young-onset dementia in memory clinics in the Netherlands: Study design and description of PRECODE-GP.

The disease trajectory and healthcare requirements of patients with young-onset dementia (YOD) differ from those of older patients. Accurate data about YOD is crucial to improve diagnosis and optimize care. PRECODE-GP aims to set up a prospective national database of patients with YOD to gain insight into the occurrence and characteristics of patients with YOD in memory clinics in the Netherlands. The national database includes data from dementia patients aged <70 years at diagnosis, collected by local memory clinics (MCs). Data included demographic information, clinical variables, and (etiological) diagnoses. Between July 2019 and December 2022, 781 patients with a mean age of 62±6y at diagnosis (range 37 to 69y) were included from 39 MCs. Most (n = 547,70%) were diagnosed with dementia due to Alzheimer's disease (AD). Patients with Frontotemporal lobe dementia (FTD, n = 87, 11%) were youngest (61±6.0y). Over half (55%) of patients were experiencing symptoms for ≥2 years. We initiated a Dutch national YOD database to improve diagnosis and care for this underrepresented and vulnerable patient group. The database provides a basis for future in-depth studies on YOD.

Profiling Daily Life Performance Recovery in the Early Subacute Phase After Stroke Using a Graphical Modeling Approach.

Background Laboratory-based assessments have shown that stroke recovery is heterogeneous between patients and affected domains such as motor and language function. However, laboratory-based assessments are not ecologically valid and do not necessarily reflect patients' daily life performance. Therefore, we aimed to give an innovative view on stroke recovery by profiling daily life performance recovery across domains in patients with early subacute stroke and determine their interrelatedness, taking stroke localization into account. Methods and Results Daily life performance was observed at neurorehabilitation admission and weekly thereafter until discharge, using a scale containing 7 daily life domains. Graphical modeling was applied to investigate the conditional independence between recovery of these domains depending on stroke localization. There were 592 patients analyzed. Four clusters of interrelated domains were identified within the first 6 weeks poststroke. The first cluster included recovery in learning and applying knowledge, general tasks and demands, and domestic life. The second cluster comprised recovery in self-care and general tasks and demands. The third cluster included recovery in mobility and self-care; it incorporated interpersonal interactions and relationships in left supratentorial stroke, and learning and applying knowledge in right supratentorial stroke. The final cluster included only communication recovery. Conclusions Daily life recovery dynamics early poststroke show that although impairments in body functions are anatomically determined, their impact on performance is comparable. Second, some, but by no means all, domains show an interrelated recovery. Domains requiring cognitive abilities are especially interrelated and seem to be essential for concomitant recovery in mobility and domestic life.

Rationale and design of the ABOARD project (A Personalized Medicine Approach for Alzheimer's Disease).

The key to stopping Alzheimer's disease (AD) lies in the pre-dementia stages, with the goal to stop AD before dementia has started. We present the rationale and design of the ABOARD (A Personalized Medicine Approach for Alzheimer's Disease) project, which aims to invest in personalized medicine for AD. ABOARD is a Dutch public-private partnership of 32 partners, connecting stakeholders from a scientific, clinical, and societal perspective. The 5-year project is structured into five work packages on (1) diagnosis, (2) prediction, (3) prevention, (4) patient-orchestrated care, and (5) communication and dissemination. ABOARD functions as a network organization in which professionals interact cross-sectorally. ABOARD has a strong junior training program "Juniors On Board." Project results are shared with society through multiple communication resources. By including relevant partners and involving citizens at risk, patients, and their care partners, ABOARD builds toward a future with personalized medicine for AD. Highlights: ABOARD (A Personalized Medicine Approach for Alzheimer's Disease) is a public-private research project executed by 32 partners that functions as a network organization.Together, the project partners build toward a future with personalized medicine for Alzheimer's disease.Although ABOARD is a Dutch consortium, it has international relevance.ABOARD improves diagnosis, prediction, prevention, and patient-orchestrated care.

Effects of the DICE Method to Improve Timely Recognition and Treatment of Neuropsychiatric Symptoms in Early Alzheimer's Disease at the Memory Clinic: The BEAT-IT Study.

BACKGROUND: Neuropsychiatric symptoms (NPS) are highly prevalent in Alzheimer's disease (AD) and are associated with negative outcomes. However, NPS are currently underrecognized at the memory clinic and non-pharmacological interventions are scarcely implemented. OBJECTIVE: To evaluate the effectiveness of the Describe, Investigate, Create, Evaluate (DICE) method™ to improve the care for NPS in AD at the memory clinic. METHODS: We enrolled sixty community-dwelling people with mild cognitive impairment or AD dementia and NPS across six Dutch memory clinics with their caregivers. The first wave underwent care as usual (n = 36) and the second wave underwent the DICE method (n = 24). Outcomes were quality of life (QoL), caregiver burden, NPS severity, NPS-related distress, competence managing NPS, and psychotropic drug use. Reliable change index was calculated to identify responders to the intervention. A cost-effectiveness analysis was performed and semi-structured interviews with a subsample of the intervention group (n = 12). RESULTS: The DICE method did not improve any outcomes over time compared to care as usual. Half of the participants of the intervention group (52%) were identified as responders and showed more NPS and NPS-related distress at baseline compared to non-responders. Interviews revealed substantial heterogeneity among participants regarding NPS-related distress, caregiver burden, and availability of social support. The intervention did not lead to significant gains in quality-adjusted life years and well-being years nor clear savings in health care and societal costs. CONCLUSION: The DICE method showed no benefits at group-level, but individuals with high levels of NPS and NPS-related distress may benefit from this intervention.

Bioimpedance and Duration of Organ Dysfunction in Septic Shock-A Prospective Observational Study.

Rationale: Bioimpedance may be a useful tool to guide fluid treatment and avoid organ dysfunction related to fluid overload. Objective: We examined the correlation between bioimpedance and organ dysfunction in patients with septic shock. Methods: Prospective observational study of adult intensive care unit patients fulfilling the sepsis-3 criteria. Bioimpedance was measured using a body composition monitor (BCM) and BioScan Touch i8 (MBS). We measured impedance at inclusion and after 24 h and reported the impedance, change in impedance, bioimpedance-derived fluid balance, and changes in bioimpedance-derived fluid balance. Organ markers on respiratory, circulatory, and kidney function and overall disease severity were ascertained on days 1-7. The effect of bioimpedance on the change in organ function was assessed by mixed effects linear models. We considered P < .01 as significant. Measurements and Main Results: Forty-nine patients were included. None of the single baseline measurements or derived fluid balances were associated with the course of organ dysfunction. Changes in impedance were associated with the course of overall disease severity (P < .001; with MBS), and with changes in noradrenaline dose (P < .001; with MBS) and fluid balance (P < .001; with BCM). The changes in bioimpedance-derived fluid balance were associated with changes in noradrenaline dose (P < .001; with BCM), cumulative fluid balances (P < .001; with MBS), and lactate concentrations (P < .001; with BCM). Conclusions: Changes in bioimpedance were correlated with the duration of overall organ failure, circulatory failure, and fluid status. Single measurements of bioimpedance were not associated with any changes in organ dysfunction.

Cerebral blood flow velocity progressively decreases with increasing levels of verticalization in healthy adults. A cross-sectional study with an observational design.

Background: Autoregulation of the cerebral vasculature keeps brain perfusion stable over a range of systemic mean arterial pressures to ensure brain functioning, e.g., in different body positions. Verticalization, i.e., transfer from lying (0°) to upright (70°), which causes systemic blood pressure drop, would otherwise dramatically lower cerebral perfusion pressure inducing fainting. Understanding cerebral autoregulation is therefore a prerequisite to safe mobilization of patients in therapy. Aim: We measured the impact of verticalization on cerebral blood flow velocity (CBFV) and systemic blood pressure (BP), heart rate (HR) and oxygen saturation in healthy individuals. Methods: We measured CBFV in the middle cerebral artery (MCA) of the dominant hemisphere in 20 subjects using continuous transcranial doppler ultrasound (TCD). Subjects were verticalized at 0°, -5°, 15°, 30°, 45° and 70° for 3-5 min each, using a standardized Sara Combilizer chair. In addition, blood pressure, heart rate and oxygen saturation were continuously monitored. Results: We show that CBFV progressively decreases in the MCA with increasing degrees of verticalization. Systolic and diastolic BP, as well as HR, show a compensatory increase during verticalization. Conclusion: In healthy adults CBFV changes rapidly with changing levels of verticalization. The changes in the circulatory parameters are similar to results regarding classic orthostasis. Registration: ClinicalTrials.gov, identifier: NCT04573114.