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Abstract Background Polypharmacy and inappropriate drug use are associated with adverse health outcomes in older people. Collaborative interventions between geriatricians and general practitioners have demonstrated effectiveness in improving clinical outcomes for complex medication regimens in home-dwelling patients. Since 2012, Norwegian municipalities have established municipal in-patient acute care (MipAC) units, designed to contribute towards reducing the number of hospital admissions. These units predominantly serve older people who typically benefit from multidisciplinary approaches. The primary objective of this study is to evaluate the effect of cooperative medication reviews conducted by MipAC physicians, supervised by geriatricians, and in collaboration with general practitioners, on health-related quality of life and clinical outcomes in MipAC patients ≥ 70 years with polypharmacy. Additionally, the study aims to assess the carbon footprint of the intervention. Methods This is a randomized, single-blind, controlled superiority trial with 16 weeks follow-up. Participants will be randomly assigned to either the control group, receiving usual care at the MipAC unit, or to the intervention group which in addition receive clinical medication reviews that go beyond what is considered usual care. The medication reviews will evaluate medication appropriateness using a structured but individualized framework, and the physicians will receive supervision from geriatricians. Following the clinical medication reviews, the MipAC physicians will arrange telephone meetings with the participants’ general practitioners to combine their assessments in a joint medication review. The primary outcome is health-related quality of life as measured by the 15D instrument. Secondary outcomes include physical and cognitive functioning, oral health, falls, admissions to healthcare facilities, and mortality. Discussion This study aims to identify potential clinical benefits of collaborative, clinical medication reviews within community-level MipAC units for older patients with polypharmacy. The results may offer valuable insights into optimizing patient care in comparable municipal healthcare settings. Trial registration The study was registered prospectively on ClinicalTrials.gov 30.08.2023 with identifier NCT06020391.

Abstract Background The aetiology of delirium is not known, but pre-existing cognitive impairment is a predisposing factor. Here we explore the associations between delirium and cerebrospinal fluid (CSF) levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), proteins with important roles in both acute injury and chronic neurodegeneration. Methods Using a 13-plex Discovery Assay®, we quantified CSF levels of 9 MMPs and 4 TIMPs in 280 hip fracture patients (140 with delirium), 107 cognitively unimpaired individuals, and 111 patients with Alzheimer’s disease dementia. The two delirium-free control groups without acute trauma were included to unravel the effects of acute trauma (hip fracture), dementia, and delirium. Results Here we show that delirium is associated with higher levels of MMP-2, MMP-3, MMP-10, TIMP-1, and TIMP-2; a trend suggests lower levels of TIMP-4 are also associated with delirium. Most delirium patients had pre-existing dementia and low TIMP-4 is the only marker associated with delirium in adjusted analyses. MMP-2, MMP-12, and TIMP-1 levels are clearly higher in the hip fracture patients than in both control groups and several other MMP/TIMPs are impacted by acute trauma or dementia status. Conclusions Several CSF MMP/TIMPs are significantly associated with delirium in hip fracture patients, but alterations in most of these MMP/TIMPs could likely be explained by acute trauma and/or pre-fracture dementia. Low levels of TIMP-4 appear to be directly associated with delirium, and the role of this marker in delirium pathophysiology should be further explored.

Abstract Background In older patients with polypharmacy and multiple comorbidities, even low grades of statin-associated muscle symptoms may have clinical implications. The aim of this study was therefore to investigate the potential associations between statin use and measures of physical performance and muscle function. Methods Participants were aged 70+, treated with at least seven regular systemic medications, and not expected to die or become institutionalized within 6 months. Physical performance measured as gait speed and Short Physical Performance Battery (SPPB) score, and muscle function measured as grip strength, were compared between users and non-users of statins. In the subgroup of statin users, the dose-response relationship was assessed using harmonized simvastatin equivalents adjusted for statin potency, pharmacokinetic interactions and SLCO1B1 c.521 T > C genotype. Multiple linear regression analyses were applied to investigate potential associations between stain use and exposure as independent variables, and physical performance and muscle function as outcomes, adjusted for age, gender, body mass, comorbidity, disability and dementia. Results 174 patients (87 users and 87 non-users of statins) with a mean (SD) age of 83.3 (7.3) years were included. In analyses adjusted only for gender, grip strength was significantly higher in users than in non-users of statins [regression coefficient (B) 2.7, 95% confidence interval (CI) 1.0 to 4.4]. When adjusted for confounders, the association was no longer statistically significant (B 1.1, 95% CI − 0.5 to 2.7). SPPB and gait speed was also better in statin users than in non-users, but the differences were not statistically significant. In dose-response analyses adjusted for confounders, we found a statistically significant increase in SPPB score (B 0.01, 95% CI 0.00 to 0.02) and gait speed (B 0.001, 95% CI 0.000 to 0.002) per mg increase in simvastatin equivalents. Conclusions In contrast to our hypothesis, statin use and exposure was associated with better measures of physical performance and muscle function in older patients with complex drug treatment. The unexpected findings of this cross-sectional, observational study should be further investigated by comparing physical performance before and after statin initiation or statin withdrawal in prospective studies. Trial registration ClinicalTrials.gov identifier: NCT02379455 , registered March 5, 2015.

Abstract Background The prognostic value of frailty measures for post-stroke neurocognitive disorder (NCD) remains to be evaluated. Aims The aim of this study was to compare the predictive value of pre-stroke FI with pre-stroke modified Rankin Scale (mRS) for post-stroke cognitive impairment. Further, we explored the added value of including FI in prediction models for cognitive prognosis post-stroke. Methods We generated a 36-item Frailty Index (FI), based on the Rockwood FI, to measure frailty based on pre-stroke medical conditions recorded in the Nor-COAST multicentre prospective study baseline assessments. Consecutive participants with a FI score and completed cognitive test battery at three months were included. We generated Odds Ratio (OR) with NCD as the dependent variable. The predictors of primary interest were pre-stroke frailty and mRS. We also measured the predictive values of mRS and FI by the area (AUC) under the receiver operating characteristic curve. Results 598 participants (43.0% women, mean/SD age = 71.6/11.9, mean/SD education = 12.5/3.8, mean/SD pre-stroke mRS = 0.8/1.0, mean/SD GDS pre-stroke = 1.4/0.8, mean/SD NIHSS day 1 3/4), had a FI mean/SD score = 0.14/0.10. The logistic regression analyses showed that FI (OR 3.09), as well as the mRS (OR 2.21), were strong predictors of major NCD. When FI and mRS were entered as predictors simultaneously, the OR for mRS decreased relatively more than that for FI. AUC for NCD post-stroke was higher for FI than for mRS, both for major NCD (0.762 vs 0.677) and for any NCD (0.681 vs 0.638). Conclusions FI is a stronger predictor of post-stroke NCD than pre-stroke mRS and could be a part of the prediction models for cognitive prognosis post-stroke. Trial Registration ClinicalTrials.gov Identifier: NCT02650531 .

Objective: To evaluate prevalence and factors determining not returning to full-time work 1 year after first-ever mild ischemic stroke. Design: Prospective, observational cohort study with 12-month follow-up. Setting: Stroke units and outpatient clinics at 2 Norwegian hospitals. Participants: We included 84 (N=84) full-time working, cognitively healthy patients aged 70 years or younger who suffered an acute first-ever mild ischemic stroke, defined as National Institutes of Health Stroke Scale (NIHSS) score ≤3 points. Interventions: Not applicable. Main Outcome Measures: Vascular risk factors, sociodemographic factors, stroke localization, and etiology were recorded at inclusion. Cognitive impairment, anxiety, depression, fatigue, and apathy 12 months after stroke were assessed with validated instruments. Logistic regression analyses were performed to find correlates of not returning to full-time employment. Results: Of 78 patients assessed 1 year after stroke, 63 (81%) had returned to work, 47 (60%) to full-time employment status. Modified Rankin scale score >1 (adjusted odds ratio, 12.44 [95% confidence interval, 2.37-65.43], P=.003) at follow-up was significantly associated, and diabetes (adjusted odds ratio, 10.56 [95% confidence interval, 0.98-113.47], P=.052) was borderline significantly associated with not returning to full-time work. Female sex, NIHSS at discharge, anxiety per point on the anxiety scale, depression per point on the depression scale, and fatigue per point on the fatigue scale were significantly associated with not returning to full-time work after 1 year, but these associations were only seen in the unadjusted models. Conclusions: Low functional level that persists 12 months after stroke is related to not returning to full-time work. Patients with diabetes mellitus, female patients, and patients with a higher score on fatigue, anxiety, and depression scales may also be at risk of not returning to full-time work post stroke. Working patients should be followed up with a particular focus on factors determining participation in work and social life.

BackgroundThere is limited evidence regarding predictors of functional trajectories after hip fracture. We aimed to identify groups with different trajectories of functional recovery the first year after hip fracture, and to determine predictors for belonging to such groups.MethodsThis longitudinal study combined data from two large randomized controlled trials including patients with hip fracture. Participants were assessed at baseline, four and 12 months. We used the Nottingham Extended Activities of Daily Living (NEADL) as a measure of instrumental ADL (iADL) and Barthel Index for personal ADL (pADL). A growth mixture model was estimated to identify groups of patients following distinct trajectories of functioning. Baseline characteristics potentially predicting group-belonging were assessed by multiple nominal regression.ResultsAmong 726 participants (mean age 83.0; 74.7% women), we identified four groups of patients following distinct ADL trajectories. None of the groups regained their pre-fracture ADL. For one of the groups identified in both ADL outcomes, a steep decline in function was shown the first four months after surgery, and none of the groups showed functional recovery between four and 12 months after surgery.ConclusionsNo groups regained their pre-fracture ADL. Some of the patients with relatively high pre-fracture function, had a steep ADL decline. For this group there is a potential for recovery, but more knowledge and research is needed in this group. These findings could be useful in uncovering groups of patients with different functioning after a hip fracture, and aid in discharge planning.

Abstract Background and Aims It is unclear whether patients with previous intracerebral hemorrhage (ICH) should receive antithrombotic treatment to prevent ischemic events. We assessed stroke physicians' opinions about this, and their views on randomizing patients in trials assessing this question. Methods We conducted three web‐based surveys among stroke physicians in Scandinavia and the United Kingdom. Results Eighty‐nine of 205 stroke physicians (43%) responded to the Scandinavian survey, 161 of 180 (89%) to the UK antiplatelet survey, and 153 of 289 (53%) to the UK anticoagulant survey. In Scandinavia, 19 (21%) stroke physicians were uncertain about antiplatelet treatment after ICH for ischemic stroke or transient ischemic attack (TIA) and 21 (24%) for prior myocardial infarction. In the United Kingdom, 116 (77%) were uncertain for ischemic stroke or TIA and 115 (717%) for ischemic heart disease. In Scandinavia, 32 (36%) were uncertain about anticoagulant treatment after ICH for atrial fibrillation, and 26 (29%) for recurrent deep vein thrombosis or pulmonary embolism. In the United Kingdom, 145 (95%) were uncertain about anticoagulants after ICH in at least some cases. In both regions combined, 191 of 250 (76%) would consider randomizing ICH survivors in a trial of starting versus avoiding antiplatelets, and 176 of 242 (73%) in a trial of starting versus avoiding anticoagulants. Conclusion Considerable proportions of stroke physicians in Scandinavia and the United Kingdom were uncertain about antithrombotic treatment after ICH. A clear majority would consider randomizing patients in trials assessing this question. These findings support the need for such trials.

Abstract Background Chronic brain pathology and pre-stroke cognitive impairment (PCI) is predictive of post-stroke dementia. The aim of the current study was to measure pre-stroke neurodegenerative and vascular disease burden found on brain MRI and to assess the association between pre-stroke imaging pathology and PCI, whilst also looking for potential sex differences. Methods This prospective brain MRI cohort is part of the multicentre Norwegian cognitive impairment after stroke (Nor-COAST) study. Patients hospitalized with acute ischemic or hemorrhagic stroke were included from five participating stroke units. Visual rating scales were used to categorize baseline MRIs (N = 410) as vascular, neurodegenerative, mixed, or normal, based on the presence of pathological imaging findings. Pre-stroke cognition was assessed by interviews of patients or caregivers using the Global Deterioration Scale (GDS). Stroke severity was assessed with the National Institute of Health Stroke Scale (NIHSS). Univariate and multiple logistic regression analyses were performed to investigate the association between imaging markers, PCI, and sex. Results Patients’ (N = 410) mean (SD) age was 73.6 (±11) years; 182 (44%) participants were female, the mean (SD) NIHSS at admittance was 4.1 (±5). In 68% of the participants, at least one pathological imaging marker was found. Medial temporal lobe atrophy (MTA) was present in 30% of patients, white matter hyperintensities (WMH) in 38% of patients and lacunes in 35% of patients. PCI was found in 30% of the patients. PCI was associated with cerebrovascular pathology (OR 2.5; CI = 1.4 to 4.5, p = 0.001) and mixed pathology (OR 3.4; CI = 1.9 to 6.1, p = 0.001) but was not associated with neurodegeneration (OR 1.0; CI = 0.5 to 2.2; p = 0.973). Pathological MRI markers, including MTA and lacunes, were more prevalent among men, as was a history of clinical stroke prior to the index stroke. The OR of PCI for women was not significantly increased (OR 1.2; CI = 0.8 to 1.9; p = 0.3). Conclusions Pre-stroke chronic brain pathology is common in stroke patients, with a higher prevalence in men. Vascular pathology and mixed pathology are associated with PCI. There were no significant sex differences for the risk of PCI. Trial registration NCT02650531 , date of registration: 08.01.2016.

Abstract Background The incidence of hip fractures are expected to increase in the following years. Hip fracture patients have in addition to their fracture often complex medical problems, which constitute a substantial burden on society and health care systems. It is thus important to optimize the treatment of these patients to reduce negative outcomes. The aim of this study was to assess the effect of comprehensive orthogeriatric care (CGC) on basic and instrumental activities of daily living (B-ADL and I-ADL). Methods This study is based on two randomized controlled trials; the Oslo Orthogeriatric Trial and the Trondheim Hip Fracture Trial. The two studies were planned in concert, and data were pooled and analyzed using linear mixed models. I-ADL function was assessed by the Nottingham Extended ADL Scale (NEADL) and B-ADL by the Barthel ADL (BADL) at four and twelve months after surgery. Results Seven hundred twenty-six patients were included in the combined database, of which 365 patients received OC and 361 patients received CGC. For the primary endpoint, I-ADL at four months was better in the CGC group, with a between-group difference of 3.56 points (95 % CI 0.93 to 6.20, p = 0.008). The between-group difference at 12 months was 4.28 points (95 % CI 1.57 to 7.00, p = 0.002). For B-ADL, between-group difference scores were only statistically significant at 12 months. When excluding the patients living at a nursing home at admission, both I-ADL and B-ADL function was significantly better in the CGC group compared to the OC group at all time points. Conclusions Merged data of two randomized controlled trials showed that admitting hip fracture patients to an orthogeriatric care unit directly from the emergency department had a positive effect on ADL up to twelve months after surgery.

Abstract Background Neurocognitive disorder (NCD) is common in stroke survivors. We aimed to identify clinically accessible imaging markers of stroke and chronic pathology that are associated with early post-stroke NCD. Methods We included 231 stroke survivors from the “Norwegian Cognitive Impairment after Stroke (Nor-COAST)” study who underwent a standardized cognitive assessment 3 months after the stroke. Any NCD (mild cognitive impairment and dementia) and major NCD (dementia) were diagnosed according to “Diagnostic and Statistical Manual of Mental Disorders (DSM-5)” criteria. Clinically accessible imaging findings were analyzed on study-specific brain MRIs in the early phase after stroke. Stroke lesion volumes were semi automatically quantified and strategic stroke locations were determined by an atlas based coregistration. White matter hyperintensities (WMH) and medial temporal lobe atrophy (MTA) were visually scored. Logistic regression was used to identify neuroimaging findings associated with major NCD and any NCD. Results Mean age was 71.8 years (SD 11.1), 101 (43.7%) were females, mean time from stroke to imaging was 8 (SD 16) days. At 3 months 63 (27.3%) had mild NCD and 65 (28.1%) had major NCD. Any NCD was significantly associated with WMH pathology (odds ratio (OR) = 2.73 [1.56 to 4.77], p = 0.001), MTA pathology (OR = 1.95 [1.12 to 3.41], p = 0.019), and left hemispheric stroke (OR = 1.8 [1.05 to 3.09], p = 0.032). Major NCD was significantly associated with WMH pathology (OR = 2.54 [1.33 to 4.84], p = 0.005) and stroke lesion volume (OR (per ml) =1.04 [1.01 to 1.06], p = 0.001). Conclusion WMH pathology, MTA pathology and left hemispheric stroke were associated with the development of any NCD. Stroke lesion volume and WMH pathology were associated with the development of major NCD 3 months after stroke. These imaging findings may be used in the routine clinical setting to identify patients at risk for early post-stroke NCD. Trial registration ClinicalTrials.gov, NCT02650531 , Registered 8 January 2016 – Retrospectively registered.

BackgroundReadmission to hospital is frequent among older patients and reported as a post-discharge adverse outcome. The effect of treatment in a geriatric ward for acutely admitted older patients on mortality and function is well established, but less is known about the possible influence of such treatment on the risk of readmission, particularly in the oldest and most vulnerable patients. Our aim was to assess the risk for early readmission for multimorbid patients > 75 years treated in a geriatric ward compared to medical wards and to identify risk factors for 30-day readmissions.MethodsProspective cohort study of patients acutely admitted to a medical department at a Norwegian regional hospital. Eligible patients were community-dwelling, multimorbid, receiving home care services, and aged 75+. Patients were consecutively included in the period from 1 April to 31 October 2012. Clinical data were retrieved from the referral letter and medical records.ResultsWe included 227 patients with a mean (SD) age of 86.0 (5.7) years, 134 (59%) were female and 59 (26%) were readmitted within 30 days after discharge. We found no statistically significant difference in readmission rate between patients treated in a geriatric ward versus other medical wards. In adjusted Cox proportional hazards regression analyses, lower age (hazard ratio (95% confidence interval) 0.95 (0.91-0.99) per year), female gender (2.17 (1.15-4.00)) and higher MMSE score (1.03 (1.00-1.06) per point) were significant risk factors for readmission.ConclusionsLower age, female gender and higher cognitive function were the main risk factors for 30-day readmission to hospital among old patients with multimorbidity. We found no impact of geriatric care on the readmission rate.

Objective: To evaluate the prevalence of cognitive and emotional impairments one year after first-ever mild stroke in younger patients Design: Prospective, observational, cohort study. Subjects: A consecutive sample of 117 previously cognitively healthy patients aged 18–70 years with mild stroke (National Institutes of Health Stroke Scale score ≤ 3) were included in 2 hospitals in Norway during a 2-year period. Methods: At 12-month follow-up, patients were assessed using validated instruments for essential cognitive domains, fatigue, depression, anxiety, apathy and pathological laughter and crying. Results: In total, 78 patients (67%) had difficulty with one or a combination of the cognitive domains psychomotor speed, attention, executive and visuospatial function, and memory. Furthermore, 50 patients (43%) had impairment in either one or a combination of the emotional measures for anxiety, depressive symptoms, fatigue, apathy or emotional lability. A total of 32 patients (28%) had both cognitive and emotional impairments. Only 21 patients (18%) scored within the reference range in all the cognitive and emotional tools. Conclusion: Hidden impairments are common after first-ever mild stroke in younger patients. Stroke physicians should screen for hidden impairments using appropriate tools.

Abstract Background Alterations in autonomic nervous system (ANS) activity might be involved in the pathophysiology of delirium. The aim was to explore autonomic cardiovascular control in older patients with and without delirium. Methods Fourteen patients (five with delirium) acutely admitted to the geriatric ward with an infection were enrolled in the study. Patients with atrial fibrillation, a pacemaker, or on treatment with beta-blockers, calcium channel blockers or acetylcholinesterase inhibitors were not eligible. Continuous, non-invasive hemodynamic variables were measured during supine rest (5 min) and head-up tilt (HUT) to 15 degrees (10 min). Heart rate (HR), blood pressure (BP) and stroke volume (SV) were recorded beat-to-beat. Cardiac output (CO), total peripheral resistance (TPR), end-diastolic volume (EDV) and heart rate variability (HRV) values were calculated. Results Median age was 86 years. HR, BP, SV, CO, TPR and EDV were similar across the two groups at rest, but there was a trend towards a greater increase in systolic BP and HR during HUT in the delirium group. At rest, all HRV indices were higher in the delirium group, but the differences were not statistically significant. During HUT, the delirium group had higher power spectral density (PSD) (representing total variability) (p = 0.06) and a lower low frequency (LF)/high frequency (HF)-ratio (an index of sympathovagal balance) than the control group (p = 0.06). Also, delirious patients had a significantly greater reduction in standard deviation of RR-intervals (SDNN) (representing total variability) from baseline than controls (p = 0.01) during HUT. Conclusions This explorative pilot study on autonomic cardiovascular control in delirium suggests that there may be differences in HRV that should be further investigated in larger samples.

Abstract Background Patients with delirium have increased risk of death, dementia and institutionalization, and prognosis differs between delirium motor subtypes. A few studies have identified associations between environmental factors like room-transfers and time spent in the emergency department (ED) and delirium, but no studies have investigated if environmental factors may influence delirium motor subtypes. We wanted to explore if potentially stressful events like ward-transfers, arriving ED at nighttime, time spent in ED and nigthttime investigations were associated with development of delirium (incident delirium) and delirium motor subtypes. Methods We used the DSM-5 criteria to diagnose delirium and the Delirium Motor Subtype Scale for motor subtyping. We defined hyperactive and mixed delirium as delirium with hyperactive symptoms, and hypoactive and no-subtype delirium as delirium without hyperactive symptoms. We registered ward-transfers, time of arrival in ED, time spent in ED and nighttime investigations (8 p.m. to 8 a.m.), and calculated Global Deterioration Scale (GDS) and Cumulative Illness Rating Scale (CIRS) to adjust for cognitive impairment and comorbidity. We used logistic regression analyses with incident delirium and delirium with hyperactive symptoms as outcome variables, and ward-transfers, arriving ED at nighttime, time spent in ED and nighttime investigations as exposure variables, adjusting for age, GDS and CIRS in the analyses for incident delirium. Results We included 254 patients, mean age 86.1 years (SD 5.2), 49 (19.3%) had incident delirium, 22 with and 27 without hyperactive symptoms. There was a significant association between nighttime investigations and incident delirium in both the unadjusted (odds ratio (OR) 2.22, 95% confidence interval (CI) 1.17 to 4.22, p = 0.015) and the multiadjusted model (OR 2.61, CI 1.26 to 5.40, p = 0.010). There were no associations between any other exposure variables and incident delirium. No exposure variables were associated with delirium motor subtypes. Conclusions Nighttime investigations were associated with incident delirium, even after adjusting for age, cognitive impairment and comorbidity. We cannot out rule that the medical condition leading to nighttime investigations is the true delirium-trigger, so geriatric patients must still receive emergency investigations at nighttime. Hospital environment in broad sense may be a target for delirium prevention.

Abstract Background The Oslo Study of Clonidine in Elderly Patients with Delirium (LUCID) is an RCT investigating the effect of clonidine in medical patients > 65 years with delirium. To assess the dosage regimen and safety measures of this study protocol, we measured the plasma concentrations and hemodynamic effects of clonidine in the first 20 patients. Methods Patients were randomised to clonidine (n = 10) or placebo (n = 10). The treatment group was given a loading dose (75μg every 3rd hour up to a maximum of 4 doses) to reach steady state, and further 75μg twice daily until delirium free for 2 days, discharge or a maximum of 7 days. Blood pressure (BP) and heart rate (HR) were measured just before every dose. If the systolic BP was

Objectives: This study aimed to investigate the relationship between cerebrospinal fluid (CSF) S100B astrocyte-derived protein and delirium and to perform stratified analyses according to clinical and CSF markers of dementia. Methods: We performed a prospective cohort study in a university hospital setting. The participants were patients admitted for hip fracture (n = 98) or for elective surgery (n = 50). Delirium was assessed daily perioperatively in hip fracture patients using the Confusion Assessment Method. A consensus-based diagnosis of prefracture dementia was made using all available information. CSF was drawn at the onset of spinal anesthesia. S100B and phosphorylated tau (P-tau) concentrations were measured using electrochemiluminescence immunoassay and enzyme-linked immunosorbent assays, respectively. Results: In the hip fracture population (n = 98) there was no significant difference in CSF S100B concentrations between patients with ongoing preoperative (i.e., prevalent) delirium (n = 36, median [interquartile range] 1.11 μg/L [0.91–1.29]) and patients who never developed delirium (n = 46, 1.08 μg/L [0.92–1.28], p = 0.92). In patients without preoperative delirium, those who developed delirium postoperatively (i.e., incident delirium) (n = 16, 1.38 μg/L [1.08–1.62]) had higher concentrations of S100B than the 46 who never did (p = 0.013). This difference was confined to patients with pathological concentrations of P-tau (≥60 ng/L, n = 38). We also found that P-tau and S100B were correlated in CSF in the elective surgery patients. Conclusions: CSF S100B was elevated in patients with incident delirium who also had pathological levels of the Alzheimer disease biomarker P-tau, suggesting vulnerability caused by a preexisting process of astrocytic activation and tau pathology.

Abstract Background In Norway, as in many Western countries, a shift from institutional care to home care is taking place. Our knowledge is limited regarding which needs for nursing interventions patients being cared for in their home have, and how they are met. We aimed at assessing aspects of health and function in a representative sample of the most vulnerable home-dwelling elderly, to identify their needs for nursing interventions and how these needs were met. Methods In this observational study we included patients aged 75+ living in their own homes in Oslo, who received daily home care, had three or more chronic diagnoses, received daily medication, and had been hospitalized during the last year. Focused attention and cognitive processing speed were assessed with the Trail Making Test A (TMT-A), handgrip strength was used as a measure of sarcopenia, mobility was assessed with the “Timed Up-and-Go” test, and independence in primary activities of daily living by the Barthel Index. Diagnoses and medication were collected from electronic medical records. For each diagnosis, medication and functional impairment, a consensus group defined which nursing service that the particular condition necessitated. We then assessed whether these needs were fulfilled for each participant. Results Of 150 eligible patients, 83 were included (mean age 87 years, 25% men). They had on average 6 diagnoses and used 9 daily medications. Of the 83 patients, 61 (75%) had grip strength indicating sarcopenia, 27 (33%) impaired mobility, and 69 (83%) an impaired TMT-A score. Median amount of home nursing per week was 3.6 h (interquartile range 2.6 to 23.4). Fulfilment of pre-specified needs was >60% for skin and wound care in patients with skin diseases, observation of blood glucose in patients taking antidiabetic drugs, and in supporting food intake in patients with eating difficulties. Most other needs as defined by the consensus group were fulfilled in

Aims: Phosphate is essential for neuronal activity. We aimed to investigate whether delirium is associated with altered phosphate concentrations in cerebrospinal fluid (CSF) and serum. Methods: Seventy-seven patients with hip fracture were assessed for delirium before and after acute surgery. Prefracture dementia was diagnosed by an expert panel. Phosphate was measured in CSF obtained immediately before spinal anesthesia (n = 77) and in serum (n = 47). CSF from 23 cognitively healthy elderly patients undergoing spinal anesthesia was also analyzed. Results: Hip fracture patients with prevalent delirium had higher CSF phosphate concentrations than those without delirium (median 0.63 vs. 0.55 mmol/L, p = 0.001). In analyses stratified on dementia status, this difference was only significant in patients with dementia. Serum phosphate was ∼1 mmol/L; there was no association between serum phosphate concentration and delirium status. CSF phosphate did not correlate with serum levels. Conclusion: Patients with delirium superimposed on dementia have elevated phosphate levels.

Abstract Background Polypharmacy and inappropriate drug use is associated with negative health outcomes among older people. Various interventions for improving drug treatment have been evaluated, but the majority of studies are limited by the use of surrogate outcomes or suboptimal design. Thus, the potential for clinically significant improvements from different interventions is still unclear. The main objective of this study is therefore to evaluate the effect upon patient-relevant endpoints of a cooperation between geriatricians and general practitioners on complex drug regimens in home-dwelling elderly people. Methods This is a cluster randomised, single-blind, controlled trial where general practitioners are invited to participate with patients from their lists. The patients must be 70 years or older, use at least seven different medications and have their medications administered by the home nursing service. We plan to recruit 200 patients, with randomisation at physician level. The intervention consists of three main parts: (1) clinical geriatric assessment of the patient, combined with a thorough review of their medications; (2) a meeting between the geriatrician and general practitioner, where the two physicians combine their competence and knowledge and discuss the drug list systematically; (3) clinical follow-up, depending on the medication changes that have been done. The study period is 24 weeks, and the patients are assessed at baseline, 16 and 24 weeks. The primary outcome measure is health-related quality of life according to the 15D instrument. Secondary outcome measures include physical and cognitive functioning, medication appropriateness, falls, carer burden, use of health services (hospital or nursing home admissions, use of home nursing services) and mortality. Discussion Our choice of patient-relevant outcome measures will hopefully provide new knowledge on the potential for clinical improvements after performing comprehensive medication reviews in home-dwelling elderly people receiving polypharmacy. Trial registration ClinicalTrials.gov, NCT02379455 . Registered on 27 February 2015.

Abstract Introduction Post‐stroke neurocognitive disorder (NCD) is common; prevalence varies between studies, partially related to lack of consensus on how to identify cases. The aim was to compare the prevalence of post‐stroke NCD using only cognitive assessment (model A), DSM‐5 criteria (model B), and the Global Deterioration Scale (model C) and to determine agreement among the three models. Methods In the Norwegian Cognitive Impairment After Stroke study, 599 patients were assessed 3 months after suffering a stroke. Results The prevalence of mild NCD varied from 174 (29%) in model B to 83 (14%) in model C; prevalence of major NCD varied from 249 (42%) in model A to 68 (11%) in model C. Cohen's kappa and Cohen's quadratic weighted kappa showed fair to very good agreement among models; the poorest agreement was found for identification of mild NCD. Discussion The findings indicate a need for international harmonization to classify post‐stroke NCD.

ObjectivesTo identify factors associated with QOL in carers of persons with young-onset Alzheimer's (AD) and frontotemporal dementia (FTD) and explore development in QOL over a two-year period.MethodsEighty-eight family carers of community-dwelling people with young-onset AD (n = 50) and FTD (n = 38) recruited from Nordic memory clinics. Carer QOL was assessed using the Quality of Life-Alzheimer's Disease questionnaire. Carer burden was assessed by the Relatives' Stress scale and depressive symptoms by the Montgomery-Åsberg Depression Rating Scale. Factors associated with QOL in YOD and development in QOL over time were explored with growth mixture model trajectories and mixed model analyses.ResultsWe identified two carer groups of persons with YOD following trajectories with better (n = 53) versus poorer (n = 30) QOL. Carers who reported more burden at baseline had greater odds of belonging to the poorer QOL group (OR 1.1 (1.0-1.2), p = 0.004). Analyses of the development in QOL showed a significant decline in QOL-AD scores among the AD-carers from baseline to two-year follow-up (p = 0.044), while the score remained stable among the FTD-carers. The FTD-carer group had significantly higher mean QOL-AD scores at one- and two-year follow-up (p = 0.022 and 0.045, respectively). However, the difference between the two groups regarding time trend was non-significant. Poorer QOL was associated with increased carer burden (p = 0.01), more depressive symptoms (p = 0.024), and being male carer (p = 0.038).ConclusionHigher care burden, more depressive symptoms, and being a male carer was associated with poorer QOL in family carers for persons with YOD. Carers of persons with AD may experience greater challenges in preserving QOL compared to carers of persons with FTD.

Background: Hemodynamic control was compared in patients with mild cognitive impairment (MCI) or mild Alzheimer's dementia (AD) as well as in healthy elderly subjects. Methods: Noninvasive, continuous hemodynamic recordings were obtained from 14 patients and 48 controls during supine rest (tilt of 30 and 70°). Cardiac output, end-diastolic volume, total peripheral resistance, heart rate variability (HRV), systolic blood pressure variability (SBPV), and baroreceptor sensitivity were calculated. Results: At 70° tilt, the HRV indices differed significantly, with higher high-frequency (HF) variability as well as lower low-frequency (LF) variability and LF/HF ratios in the patients. The patients had significantly lower SBPV in the LF range at 30° tilt. Conclusions: The results indicate a poorer sympathetic response to orthostatic stress in MCI and mild AD.

To explore relevant associations between deviations in linear and nonlinear heart rate variability (HRV) scores, and short-term morbidity and mortality in patients undergoing hip-surgery after a fracture.165 patients with hip fractures being admitted for surgery at two hospitals were included in a prospective cohort study. A short-term ECG was recorded within 24 hours of arrival. 15 patients had to be excluded due to insufficient quality of the ECG recordings. 150 patients were included in the final analysis. Linear parameters were calculated in time domain: standard deviation of NN intervals (SDNN), root mean square of successive differences (rMSSD); and frequency domain: Total Power (TP), High Frequency Power (HF), Low Frequency Power (LF), Very Low Frequency Power (VLF), and the ratio of LF/HF. Postoperative outcome was evaluated at the time of discharge. This included occurrence of pneumonia, overall infection rate, stroke, myocardial infarction, and all-cause mortality.Patients experiencing complications had significantly lower rMSSD (p = 0.04), and TP (p = 0.03) preoperatively. Postoperative infections were predicted by decreased VLF preoperatively (p = 0.04). There was a significant association between pneumonia and LF/HF

Delirium is common in hip fracture patients and many risk factors have been identified. Controversy exists regarding the possible impact of intraoperative control of blood pressure upon acute (delirium) and long term (dementia) cognitive decline. We explored possible associations between perioperative hemodynamic changes, use of vasopressor drugs, risk of delirium and risk of new-onset dementia.Prospective follow-up study of 696 hip fracture patients, assessed for delirium pre- and postoperatively, using the Confusion Assessment Method. Pre-fracture cognitive function was assessed using the Informant Questionnaire of Cognitive Decline in the Elderly and by consensus diagnosis. The presence of new-onset dementia was determined at follow-up evaluation at six or twelve months after surgery. Blood pressure was recorded at admission, perioperatively and postoperatively.Preoperative delirium was present in 149 of 536 (28%) assessable patients, and 124 of 387 (32%) developed delirium postoperatively (incident delirium). The following risk factors for incident delirium in patients without pre-fracture cognitive impairment were identified: low body mass index, low level of functioning, severity of physical illness, and receipt of ≥ 2 blood transfusions. New-onset dementia was diagnosed at follow-up in 26 of 213 (12%) patients, associated with severity of physical illness, delirium, receipt of vasopressor drugs perioperatively and high mean arterial pressure postoperatively.Risk factors for incident delirium seem to differ according to pre-fracture cognitive status. The use of vasopressors during surgery and/or postoperative hypertension is associated with new-onset dementia after hip fracture.

Background/Aim: Post-stroke cognitive impairment and dementia may be caused by pure vascular, pure degenerative or mixed disease. The relation between post-stroke cognitive impairment and the combination of vascular pathology and degenerative changes is less evaluated. We aimed to evaluate the associations between white matter lesions (WMLs) and patient performance 1 year after stroke on tests of executive functioning, memory and visuospatial function, adjusted for the effects of lifestyle and disease-related factors, including medial temporal lobe atrophy (MTLA). Methods: Patients with a first-ever stroke or transient ischemic attack were invited to participate in the study. The associations between the cognitive test performances and WMLs were studied using linear regression [Trail Making Test B (TMT B) and 10-word test] and logistic regression (Clock Drawing Test). Results: In total, 199 patients completed the follow-up. The TMT B (p = 0.029) and the 10-word test (p = 0.014) were significantly associated with WMLs; however, the Clock Drawing Test (p = 0.19) was not. The TMT B (p = 0.018) and the 10-word test (p ≤ 0.001) were both significantly associated with MTLA. Conclusion: Impaired executive functioning and memory are significantly associated with WMLs and MTLA. The mechanisms explaining post-stroke cognitive impairment are multifactorial, including different types of vascular pathology and coexisting vascular and degenerative changes.

The psychosocial adjustment process after stroke is complicated and protracted. The language is the most important tool for making sense of experiences and for human interplay, making persons with aphasia especially prone to psychosocial problems. Persons with aphasia are systematically excluded from research projects due to methodological challenges. This study explored how seven persons with aphasia experienced participating in a complex nursing intervention aimed at supporting the psychosocial adjustment process and promoting psychosocial well-being. The intervention was organized as an individual, dialogue-based collaboration process based upon ideas from “Guided self-determination.” The content addressed psychosocial issues as mood, social relationships, meaningful activities, identity, and body changes. Principles from “Supported conversation for adults with aphasia” were used to facilitate the conversations. The data were obtained by participant observation during the intervention, qualitative interviews 2 weeks, 6 months, and 12 months after the intervention and by standardized clinical instruments prior to the intervention and at 2 weeks and 12 months after the intervention. Assistance in narrating about themselves and their experiences with illness, psychological support and motivation to move on during the difficult adjustment process, and exchange of knowledge and information were experienced as beneficial and important by the participants in this study.

Background We investigated outcomes in patients with intracerebral haemorrhage (ICH) according to prior anticoagulation treatment with Vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs) or no anticoagulation.Methods This is an individual patient data study combining two prospective national stroke registries from Switzerland and Norway (2013–2019). We included all consecutive patients with ICH from both registries. The main outcomes were favourable functional outcome (modified Rankin Scale 0–2) and mortality at 3 months.Results Among 11 349 patients with ICH (mean age 73.6 years; 47.6% women), 1491 (13.1%) were taking VKAs and 1205 (10.6%) DOACs (95.2% factor Xa inhibitors). The median percentage of patients on prior anticoagulation was 23.7 (IQR 22.6–25.1) with VKAs decreasing (from 18.3% to 7.6%) and DOACs increasing (from 3.0% to 18.0%) over time. Prior VKA therapy (n=209 (22.3%); adjusted ORs (aOR), 0.64; 95% CI, 0.49 to 0.84) and prior DOAC therapy (n=184 (25.7%); aOR, 0.64; 95% CI, 0.47 to 0.87) were independently associated with lower odds of favourable outcome compared with patients without anticoagulation (n=2037 (38.8%)). Prior VKA therapy (n=720 (49.4%); aOR, 1.71; 95% CI, 1.41 to 2.08) and prior DOAC therapy (n=460 (39.7%); aOR, 1.28; 95% CI, 1.02 to 1.60) were independently associated with higher odds of mortality compared with patients without anticoagulation (n=2512 (30.2%)).Conclusions The spectrum of anticoagulation-associated ICH changed over time. Compared with patients without prior anticoagulation, prior VKA treatment and prior DOAC treatment were independently associated with lower odds of favourable outcome and higher odds of mortality at 3 months. Specific reversal agents unavailable during the study period might improve outcomes of DOAC-associated ICH in the future.