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Neuropsychiatric symptoms (NPS) are common in older people and may represent early symptoms of dementia, in particular in Alzheimer's disease (AD). Little is known about the underlying pathological mechanisms. We used untargeted proteomics to investigate CNS molecular pathway alterations related to the presence and severity of NPS in older people. Individuals with normal cognition (NC), mild cognitive impairment (MCI) or mild AD dementia from the Amsterdam Dementia Cohort with available untargeted mass spectrometry-based cerebrospinal fluid (CSF) proteomics data were included. A total of 1962 proteins was considered for analysis. NPS were measured using the Neuropsychiatric Inventory-Questionnaire (NPI-Q), an informant-based questionnaire assessing twelve behavioral symptoms. Linear and logistic regression models were applied to study relationships of protein CSF levels (predictor) with the total NPI-Q severity score (range 0-36, outcome) and presence of individual NPS (outcome). Interaction terms of amyloid status and CSF protein levels on NPS were tested to study if results were specific to AD. Pathway enrichment analysis using the Reactome and Gene Ontology databases were used to characterize the identified proteins. A total of 362 individuals (120 with NC, 78 with MCI, 164 with AD dementia) with mean age of 64.0±7.7 years and 41.7% women were included. Men presented with more severe NPS (NPI-Q score 5.0 vs. 4.0 in women, p = 0.011) and more frequently experienced symptoms of apathy (57.3% vs. 43.0%), irritability (56.9% vs. 40.4%), agitation (20.4% vs. 9.9%), and disinhibition (20.4% vs. 8.6%) than women (p <0.01). Preliminary findings revealed twelve CSF proteins associated with NPI-Q severity scores (p <0.01), independent of amyloid status. We identified distinct protein alterations related to the presence of single symptoms. Notably, we found no overlap of proteins associated (p <0.01) with the three most frequent symptoms, i.e., apathy (51.4%, 13 proteins), irritability (50.0%, 19 proteins), and depression (35.6%, 25 proteins), respectively. Next, we will perform pathway enrichment analysis to identify the specific biological pathways involved in NPS. Using untargeted CSF proteomics, we identified different protein profiles related to overall NPS severity and presence of individual symptoms. First results suggest distinct pathological mechanisms involved in NPS, which may represent specific intervention targets.

Background Neuropsychiatric symptoms (NPS) are common in older people and may represent early symptoms of dementia, in particular in Alzheimer's disease (AD). Little is known about the underlying pathological mechanisms. We used untargeted proteomics to investigate CNS molecular pathway alterations related to the presence and severity of NPS in older people. Method Individuals with normal cognition (NC), mild cognitive impairment (MCI) or mild AD dementia from the Amsterdam Dementia Cohort with available untargeted mass spectrometry‐based cerebrospinal fluid (CSF) proteomics data were included. A total of 1962 proteins was considered for analysis. NPS were measured using the Neuropsychiatric Inventory‐Questionnaire (NPI‐Q), an informant‐based questionnaire assessing twelve behavioral symptoms. Linear and logistic regression models were applied to study relationships of protein CSF levels (predictor) with the total NPI‐Q severity score (range 0‐36, outcome) and presence of individual NPS (outcome). Interaction terms of amyloid status and CSF protein levels on NPS were tested to study if results were specific to AD. Pathway enrichment analysis using the Reactome and Gene Ontology databases were used to characterize the identified proteins. Result A total of 362 individuals (120 with NC, 78 with MCI, 164 with AD dementia) with mean age of 64.0±7.7 years and 41.7% women were included. Men presented with more severe NPS (NPI‐Q score 5.0 vs. 4.0 in women, p = 0.011) and more frequently experienced symptoms of apathy (57.3% vs. 43.0%), irritability (56.9% vs. 40.4%), agitation (20.4% vs. 9.9%), and disinhibition (20.4% vs. 8.6%) than women (p <0.01). Preliminary findings revealed twelve CSF proteins associated with NPI‐Q severity scores (p <0.01), independent of amyloid status. We identified distinct protein alterations related to the presence of single symptoms. Notably, we found no overlap of proteins associated (p <0.01) with the three most frequent symptoms, i.e., apathy (51.4%, 13 proteins), irritability (50.0%, 19 proteins), and depression (35.6%, 25 proteins), respectively. Next, we will perform pathway enrichment analysis to identify the specific biological pathways involved in NPS. Conclusion Using untargeted CSF proteomics, we identified different protein profiles related to overall NPS severity and presence of individual symptoms. First results suggest distinct pathological mechanisms involved in NPS, which may represent specific intervention targets.

The phenocopy syndrome of behavioral variant FTD (phFTD) refers to patients exhibiting clinical characteristics of bvFTD but without objective progression during follow-up. As no diagnostic criteria currently exist, we aimed to assess clinicians' perspectives on the diagnostic process for phFTD. By integrating these perspectives, we aim to develop research criteria for phFTD. We established the Phenocopy Working Group within the Neuropsychiatric International Consortium on Frontotemporal Dementia (NIC-FTD), a consortium of researchers with expertise in FTD and psychiatric disorders. We employed an international Delphi methodology comprising three rounds, each involving an online survey followed by a group meeting to discuss controversies. Here we present the results of the first round. We recently sent out the second-round survey, in which we aim to reach consensus on the remaining categories, incorporating clinical presentation, diagnostic tools and follow-up. In a third and final round we will establish consensus on the final criteria. The expert panel of the first Delphi round consisted of 50 clinicians with a median of 10 (IQR: 5-20) years of experience in phFTD. According to panelists' estimations, Raskovsky (2011) criteria most frequently met in phFTD were apathy (90%), loss of empathy (64%) and disinhibition (60%). Additionally, memory complaints and depressive symptoms were considered often present. Genetic screening for C9orf72 was almost unanimously endorsed, as were structural MRI and [18F]-FDG-PET as minimally required neuroimaging (Figure 1). Most frequent differential diagnoses were bvFTD (76%), mood disorders (48%), personality disorders (32%) and bvAD (24%) (Figure 2). Two thirds of panelists presumed the likelihood of a neurodegenerative etiology for phFTD to be ≤50% (Figure 3). 85% considered clinical follow-up of at least two years appropriate before appointing a label of phFTD. The first Delphi round showed expert consensus on several components of the diagnostic process for phFTD, including genetic testing for C9orf72, baseline and repeated structural MRI and FDG-PET and follow-up duration. Completing the full Delphi procedure will result in a set of research criteria. Establishment of these criteria will enhance accurate identification of phFTD, facilitate research and advance clinical care for this rare and poorly understood patient group.

Background The phenocopy syndrome of behavioral variant FTD (phFTD) refers to patients exhibiting clinical characteristics of bvFTD but without objective progression during follow‐up. As no diagnostic criteria currently exist, we aimed to assess clinicians’ perspectives on the diagnostic process for phFTD. By integrating these perspectives, we aim to develop research criteria for phFTD. Method We established the Phenocopy Working Group within the Neuropsychiatric International Consortium on Frontotemporal Dementia (NIC‐FTD), a consortium of researchers with expertise in FTD and psychiatric disorders. We employed an international Delphi methodology comprising three rounds, each involving an online survey followed by a group meeting to discuss controversies. Here we present the results of the first round. We recently sent out the second‐round survey, in which we aim to reach consensus on the remaining categories, incorporating clinical presentation, diagnostic tools and follow‐up. In a third and final round we will establish consensus on the final criteria. Result The expert panel of the first Delphi round consisted of 50 clinicians with a median of 10 (IQR: 5‐20) years of experience in phFTD. According to panelists’ estimations, Raskovsky (2011) criteria most frequently met in phFTD were apathy (90%), loss of empathy (64%) and disinhibition (60%). Additionally, memory complaints and depressive symptoms were considered often present. Genetic screening for C9orf72 was almost unanimously endorsed, as were structural MRI and [18F]‐FDG‐PET as minimally required neuroimaging (Figure 1). Most frequent differential diagnoses were bvFTD (76%), mood disorders (48%), personality disorders (32%) and bvAD (24%) (Figure 2). Two thirds of panelists presumed the likelihood of a neurodegenerative etiology for phFTD to be ≤50% (Figure 3). 85% considered clinical follow‐up of at least two years appropriate before appointing a label of phFTD. Conclusion The first Delphi round showed expert consensus on several components of the diagnostic process for phFTD, including genetic testing for C9orf72, baseline and repeated structural MRI and FDG‐PET and follow‐up duration. Completing the full Delphi procedure will result in a set of research criteria. Establishment of these criteria will enhance accurate identification of phFTD, facilitate research and advance clinical care for this rare and poorly understood patient group.

Background Patients with sarcopenia have a higher risk of poor recovery after coronary artery bypass grafting (CABG). Little is known about the impact of changes in muscle strength (the primary indicator for sarcopenia) on health-related quality of life (HR-QoL). This study aimed to (1) identify subgroups with different muscle strength trajectories, (2) identify differences in preoperative risk factors among trajectory group membership, and (3) explore their prognostic value on postoperative HR-QoL in patients undergoing CABG. Methods In this prospective observational study 131 patients undergoing elective CABG completed grip strength tests and HR-QoL questionnaires. Latent Class Growth Mixture Modelling (LCGMM) was used to identify clinically relevant trajectories (> 5% of study population) for weight-normalised grip strength, measured at admission, 3 days, and 6 months after surgery. Differences between trajectory group membership at baseline were evaluated. The impact of trajectory group membership on postoperative HR-QoL was evaluated with multiple linear regression models. Results Due to low numbers (n = 15), female patients were excluded from LCGMM and subsequent statistical analyses. In males (n = 116), we identified two main weight-normalised grip strength trajectories: a “stable average” trajectory with a slight decline immediately post-surgery and recovery to preoperative levels (n = 85) and a “high” trajectory with a considerable immediate decline after surgery but followed towards a higher level of recovery compared to preoperative level (n = 27). The “stable average” patients were older (68 vs. 57 years; P  = 0.003), had more diabetes (27% vs. 4%; P  = 0.01) and had a higher BMI (27.8 vs. 24.8; P  = 0.005) compared to the “high” group. After correction for age, diabetes, and baseline HR-QoL, group trajectory membership was not associated with postoperative HR-QoL, yet an increase in individual change scores of weight-normalised grip strength was associated with a better postoperative HR-QoL. We also identified one small trajectory group (n = 4, ≤ 5%). Conclusions This study showed two relevant weight-normalised grip strength trajectories in male patients undergoing CABG, varying in important preoperative risk factors. While change scores of grip strength per weight did predict postoperative HR-QoL, the trajectory subgroups could not predict postoperative HR-QoL. Future research should focus on female patients, reacting potentially different on CABG and/or rehabilitation treatment. Trial registration NCT03774342, 12-12-2018.

IntroductionThe rising prevalence of modifiable risk factors (eg, obesity, hypertension and physical inactivity) is causing an increase in possible avoidable complications in patients undergoing cardiac surgery. This study aims to assess whether a combined preoperative and postoperative multidisciplinary cardiac rehabilitation (CR) programme (Heart-ROCQ programme) can improve functional status and reduce surgical complications, readmissions and major adverse cardiac events (MACE) as compared with standard care.Methods and analysisPatients (n=350) are randomised to the Heart-ROCQ programme or standard care. The Heart-ROCQ programme consists of a preoperative optimisation phase while waiting for surgery (three times per week, minimum of 3 weeks), a postoperative inpatient phase (3 weeks) and an outpatient CR phase (two times per week, 4 weeks). Patients receive multidisciplinary treatment (eg, physical therapy, dietary advice, psychological sessions and smoking cessation). Standard care consists of 6 weeks of postsurgery outpatient CR with education and physical therapy (two times per week). The primary outcome is a composite weighted score of functional status, surgical complications, readmissions and MACE, and is evaluated by a blinded endpoint committee. The secondary outcomes are length of stay, physical and psychological functioning, lifestyle risk factors, and work participation. Finally, an economic evaluation is performed. Data are collected at six time points: at baseline (start of the waiting period), the day before surgery, at discharge from the hospital, and at 3, 7 and 12 months postsurgery.Ethics and disseminationThis study will be conducted according to the principles of the Declaration of Helsinki (V.8, October 2013). The protocol has been approved by the Medical Ethical Review Board of the UMCG (no 2016/464). Results of this study will be submitted to a peer-reviewed scientific journal and can be presented at national and international conferences.Trial registration number NCT02984449.