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BACKGROUND: Sarcopenia and cognitive impairment are two leading causes of disabilities. OBJECTIVE: The objective was to examine the prevalence of sarcopenia and investigate the association between sarcopenia diagnostic components (muscle strength, muscle mass, and physical performance) and cognitive impairment in memory clinic patients. METHODS: 368 patients were included (age 59.0±7.25 years, women: 58.7%), displaying three clinical phenotypes of cognitive impairments, i.e., subjective cognitive impairment (SCI, 57%), mild cognitive impairment (MCI, 26%), and Alzheimer's disease (AD, 17%). Sarcopenia was defined according to diagnostic algorithm recommended by the European Working Group on Sarcopenia in Older People. Components of sarcopenia were grip strength, bioelectrical impedance analysis, and gait speed. They were further aggregated into a score (0-3 points) by counting the numbers of limited components. Multi-nominal logistic regression was applied. RESULTS: Probable sarcopenia (i.e., reduced grip strength) was observed in 9.6% of the patients, and 3.5% were diagnosed with sarcopenia. Patients with faster gait speed showed less likelihood of MCI (odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.06-0.90) and AD (OR: 0.12, 95% CI: 0.03-0.60). One or more limited sarcopenia components was associated with worse cognitive function. After adjusting for potential confounders, the association remained significant only for AD (OR 4.29, 95% CI 1.45-11.92). CONCLUSION: The results indicate a connection between the sarcopenia components and cognitive impairments. Limitations in the sarcopenia measures, especially slow walking speed, were related to poorer cognitive outcomes. More investigationsare required to further verify the causal relationship between sarcopenia and cognitive outcomes.

Background: The World Health Organization claims that rehabilitation is important to meet the needs of persons with dementia. Rehabilitation programmes, however, are not routinely available. Person-centred, multidimensional, and interdisciplinary rehabilitation can increase the opportunities for older adults with dementia and their informal primary caregivers to continue to live an active life and participate in society. To our knowledge, staff team experiences of such rehabilitation programmes, involving older adults with dementia and their informal caregivers has not been previously explored. Methods: The aim of this qualitative focus group study was to explore the experiences of a comprehensive staff team providing person-centred multidimensional, interdisciplinary rehabilitation to community-dwelling older adults with dementia, including education and support for informal primary caregivers. The 13 staff team members comprised 10 professions who, during a 16-week intervention period, provided individualised interventions while involving the rehabilitation participants. After the rehabilitation period the staff team members were divided in two focus groups who met on three occasions each (in total six focus groups) and discussed their experiences. The Grounded Theory method was used for data collection and analysis. Results: The analysis resulted in four categories: Achieving involvement in rehabilitation is challenging, Considering various realities by acting as a link, Offering time and continuity create added value, and Creating a holistic view through knowledge exchange, and the core category: Refining a co-creative process towards making a difference. The core category resembles the collaboration that the staff had within their teams, which included participants with dementia and caregivers, and with the goal that the intervention should make a difference for the participants. This was conducted with flexibility in a collaborative and creative process. Concl

Modifiable lifestyle factors have been shown to promote healthy brain ageing. However, studies have typically focused on a single factor at a time. Given that lifestyle factors do not occur in isolation, multivariable analyses provide a more realistic model of the lifestyle-brain relationship. Here, canonical correlation analyses (CCA) examined the relationship between nine lifestyle factors and seven MRI-derived indices of brain structure. The resulting covariance pattern was further explored with Bayesian regressions. CCA analyses were first conducted on a Danish cohort of older adults (n = 251) and then replicated in a British cohort (n = 668). In both cohorts, the latent factors of lifestyle and brain structure were positively correlated (UK: r =.37, p < 0.001; Denmark: r =.27, p < 0.001). In the cross-validation study, the correlation between lifestyle-brain latent factors was r =.10, p = 0.008. However, the pattern of associations differed between datasets. These findings suggest that baseline characterisation and tailoring towards the study sample may be beneficial for achieving targeted lifestyle interventions.

The ageing process involves several physiological changes that affect both pharmacodynamics and pharmacokinetics and that, in combination with a heavier disease burden and more extensive use of medicines, put older people at higher risk of medication-related problems and associated clinical outcomes. The older population is often treated as a homogenous group, when in fact there are factors that render certain individuals more vulnerable to adverse drug effects and other types of medication-related problems. Older people encountered in the acute medical care setting and/or individuals with varying degrees of cognitive impairment are especially vulnerable in that context. The overall aim of this thesis was to describe and understand medication use in certain vulnerable subgroups of older people, which in turn might identify suitable target populations in which medication-related problems can be prevented or managed through interventions or similar efforts. Paper I presented, in the form of a study protocol, a clinical pharmacist intervention intended to reduce the risk of medication-related readmission to hospital among people aged 75 years or older during transitions of care. Based on 300 participants from the intervention study, approximately 50% had been readmitted to hospital within 180 days of being discharged from the hospital. Both heart failure and cognitive impairment, the latter identified through a four-item test, were predictors of early readmission. Altogether, the study population seems relevant for the purpose of the intervention; whether the intervention model is effective remains to be determined. Based on the same sample of study participants, paper II found that approximately one third of the 300 index hospital admissions were possibly medication related. Moreover, possibly medication-related hospital admissions were negatively associated with the fewest positive/correct answers on the four-item screening tool for cognitive impairment, which sugge

Background: While assessment tools can increase the detection of cognitive impairment, there is currently insufficient evidence regarding clinical outcomes based on screening for cognitive impairment in older adults. Methods: The study purpose was to investigate whether Timed Up and Go dual-task test (TUGdt) results, based on TUG combined with two different verbal tasks (name different animals, TUGdt-NA, and recite months in reverse order, TUGdt-MB), predicted dementia incidence over a period of five years among patients (N = 186, mean = 70.7 years; 45.7% female) diagnosed with Subjective Cognitive Impairment (SCI) and Mild Cognitive Impairment (MCI) following assessment at two memory clinics. Associations between TUG parameters and dementia incidence were examined in Cox regression models. Results: During follow-up time (median (range) 3.7 (0.1–6.1) years) 98 participants converted to dementia. Novel findings indicated that the TUGdt parameter words/time, after adjustment for age, gender, and education, can be used for the prediction of conversion to dementia in participants with SCI or MCI over a period of five years. Among the TUG-related parameters investigated, words/time showed the best predictive capacity, while time scores of TUG and TUGdt as well as TUGdt cost did not produce significant predictive results. Results further showed that the step parameter step length during TUGdt predicts conversion to dementia before adjustment for age, gender, and education. Optimal TUGdt cutoffs for predicting dementia at 2- and 4-year follow-up based on words/time were calculated. The sensitivity of the TUGdt cutoffs was high at 2-year follow-up: TUGdt-NA words/time, 0.79; TUGdt-MB words/time, 0.71; reducing respectively to 0.64 and 0.65 at 4-year follow-up. Conclusions: TUGdt words/time parameters have potential as cost-efficient tools for conversion-to-dementia risk assessment, useful for research and clinical purposes. These parameters may be able to bridge the gap of

Older adults were particularly vulnerable to the COVID-19 pandemic, necessitating significant efforts to avoid contamination. This extraordinary situation posed an increased risk of mental pressure, and the ability to handle stressful situations is affected by several aspects. Therefore, this study aims to explore the coping strategies employed by older adults during the early months of the COVID-19 pandemic. A sample of 41 Swedish older adults aged 70-85 participated in phone interviews regarding their experiences with social distancing due to COVID-19. The interviews were conducted between April and May 2020, with nine follow-up interviews conducted in November and December 2020. The findings revealed results that despite the challenging circumstances, the participants demonstrated a strong mindset and resilience. Strategies utilised to improve their wellbeing and manage the situation included following recommendations, accepting the situation and maintaining a positive outlook. The influence of previous experiences on their coping strategies was evident. Additionally, the participants expressed a longing for their relatives and a need to adopt new technologies to manage their everyday lives. The follow-up interviews indicated no significant changes in worry or behaviour; if anything, participants were less worried at the beginning of the pandemic. This study contributes to the ongoing discussion on vulnerability among older adults by highlighting the diverse range of coping strategies employed during a prolonged crisis such as the COVID-19 pandemic. It demonstrated that though they are medically vulnerable, they are situationally resilient and, in many ways, well set to handle a challenging situation. During crises, older adults might need practical assistance. On the other hand, they can be a resource regarding mental preparedness during crises. Further research should explore the possibilities of balancing the needs of older adults and, at the same time, viewin

Older adults were particularly vulnerable to the COVID-19 pandemic, necessitating significant efforts to avoid contamination. This extraordinary situation posed an increased risk of mental pressure, and the ability to handle stressful situations is affected by several aspects. Therefore, this study aims to explore the coping strategies employed by older adults during the early months of the COVID-19 pandemic. A sample of 41 Swedish older adults aged 70-85 participated in phone interviews regarding their experiences with social distancing due to COVID-19. The interviews were conducted between April and May 2020, with nine follow-up interviews conducted in November and December 2020. The findings revealed results that despite the challenging circumstances, the participants demonstrated a strong mindset and resilience. Strategies utilised to improve their wellbeing and manage the situation included following recommendations, accepting the situation and maintaining a positive outlook. The influence of previous experiences on their coping strategies was evident. Additionally, the participants expressed a longing for their relatives and a need to adopt new technologies to manage their everyday lives. The follow-up interviews indicated no significant changes in worry or behaviour; if anything, participants were less worried at the beginning of the pandemic. This study contributes to the ongoing discussion on vulnerability among older adults by highlighting the diverse range of coping strategies employed during a prolonged crisis such as the COVID-19 pandemic. It demonstrated that though they are medically vulnerable, they are situationally resilient and, in many ways, well set to handle a challenging situation. During crises, older adults might need practical assistance. On the other hand, they can be a resource regarding mental preparedness during crises. Further research should explore the possibilities of balancing the needs of older adults and, at the same time, viewin

Depression is one of the leading causes of disability in older adults worldwide. Many older adults with depression are undetected, and there is a need for brief, scalable psychological treatments for depression that can be delivered remotely. The aims of this thesis were 1) to investigate the diagnostic accuracy of two rating scales (PHQ-9 and GDS-15) for the detection of depression in older adults, and 2) to investigate the feasibility, preliminary efficacy and patients’ experiences of a telephone-based psychological intervention, Behavioral activation with mental imagery (BA-MI), for the treatment of depression in older adults in the context of the covid-19 pandemic. Study I showed that a cutoff of ≥6 on the GDS-15 and ≥5 on the PHQ-9 were optimal to identify major depressive disorder. When identifying both major depressive disorder and subthreshold depression, the optimal cutoff on the GDS-15 was ≥5. Study II was a randomized clinical pilot trial, CoviDep, with a treatment group receiving the BA-MI intervention, and a control group. The drop-out rate was low. Compared to the control group, the treatment group reported a decrease in depressive symptoms throughout the treatment, with a large effect-size at posttreatment. Study III was a long-term follow-up of participants in CoviDep that received the BA-MI intervention. The drop-out rate over time was low, and compared to baseline, decreases in depressive symptoms were observed with a medium effect-size at posttreatment that was maintained 1- and 3 months post-treatment but lower after 6 months. Study IV was a qualitative study. The BA-MI intervention in CoviDep was described as increasing activities and improving mood. Telephone-delivery reduced barriers due to pandemic restrictions but felt less personal and lacking non-verbal communication. Being recognized and talking to a therapist every week was healing, but the manualized mode of treatment seemed to impair the relationship. In sum, this thesis shows that bo

The ageing process involves several physiological changes that affect both pharmacodynamics and pharmacokinetics and that, in combination with a heavier disease burden and more extensive use of medicines, put older people at higher risk of medication-related problems and associated clinical outcomes. The older population is often treated as a homogenous group, when in fact there are factors that render certain individuals more vulnerable to adverse drug effects and other types of medication-related problems. Older people encountered in the acute medical care setting and/or individuals with varying degrees of cognitive impairment are especially vulnerable in that context. The overall aim of this thesis was to describe and understand medication use in certain vulnerable subgroups of older people, which in turn might identify suitable target populations in which medication-related problems can be prevented or managed through interventions or similar efforts. Paper I presented, in the form of a study protocol, a clinical pharmacist intervention intended to reduce the risk of medication-related readmission to hospital among people aged 75 years or older during transitions of care. Based on 300 participants from the intervention study, approximately 50% had been readmitted to hospital within 180 days of being discharged from the hospital. Both heart failure and cognitive impairment, the latter identified through a four-item test, were predictors of early readmission. Altogether, the study population seems relevant for the purpose of the intervention; whether the intervention model is effective remains to be determined. Based on the same sample of study participants, paper II found that approximately one third of the 300 index hospital admissions were possibly medication related. Moreover, possibly medication-related hospital admissions were negatively associated with the fewest positive/correct answers on the four-item screening tool for cognitive impairment, which sugge

BACKGROUND: Sarcopenia and cognitive impairment are two leading causes of disabilities. OBJECTIVE: The objective was to examine the prevalence of sarcopenia and investigate the association between sarcopenia diagnostic components (muscle strength, muscle mass, and physical performance) and cognitive impairment in memory clinic patients. METHODS: 368 patients were included (age 59.0±7.25 years, women: 58.7%), displaying three clinical phenotypes of cognitive impairments, i.e., subjective cognitive impairment (SCI, 57%), mild cognitive impairment (MCI, 26%), and Alzheimer's disease (AD, 17%). Sarcopenia was defined according to diagnostic algorithm recommended by the European Working Group on Sarcopenia in Older People. Components of sarcopenia were grip strength, bioelectrical impedance analysis, and gait speed. They were further aggregated into a score (0-3 points) by counting the numbers of limited components. Multi-nominal logistic regression was applied. RESULTS: Probable sarcopenia (i.e., reduced grip strength) was observed in 9.6% of the patients, and 3.5% were diagnosed with sarcopenia. Patients with faster gait speed showed less likelihood of MCI (odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.06-0.90) and AD (OR: 0.12, 95% CI: 0.03-0.60). One or more limited sarcopenia components was associated with worse cognitive function. After adjusting for potential confounders, the association remained significant only for AD (OR 4.29, 95% CI 1.45-11.92). CONCLUSION: The results indicate a connection between the sarcopenia components and cognitive impairments. Limitations in the sarcopenia measures, especially slow walking speed, were related to poorer cognitive outcomes. More investigationsare required to further verify the causal relationship between sarcopenia and cognitive outcomes.

BACKGROUND: Sarcopenia and cognitive impairment are two leading causes of disabilities. OBJECTIVE: The objective was to examine the prevalence of sarcopenia and investigate the association between sarcopenia diagnostic components (muscle strength, muscle mass, and physical performance) and cognitive impairment in memory clinic patients. METHODS: 368 patients were included (age 59.0±7.25 years, women: 58.7%), displaying three clinical phenotypes of cognitive impairments, i.e., subjective cognitive impairment (SCI, 57%), mild cognitive impairment (MCI, 26%), and Alzheimer's disease (AD, 17%). Sarcopenia was defined according to diagnostic algorithm recommended by the European Working Group on Sarcopenia in Older People. Components of sarcopenia were grip strength, bioelectrical impedance analysis, and gait speed. They were further aggregated into a score (0-3 points) by counting the numbers of limited components. Multi-nominal logistic regression was applied. RESULTS: Probable sarcopenia (i.e., reduced grip strength) was observed in 9.6% of the patients, and 3.5% were diagnosed with sarcopenia. Patients with faster gait speed showed less likelihood of MCI (odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.06-0.90) and AD (OR: 0.12, 95% CI: 0.03-0.60). One or more limited sarcopenia components was associated with worse cognitive function. After adjusting for potential confounders, the association remained significant only for AD (OR 4.29, 95% CI 1.45-11.92). CONCLUSION: The results indicate a connection between the sarcopenia components and cognitive impairments. Limitations in the sarcopenia measures, especially slow walking speed, were related to poorer cognitive outcomes. More investigationsare required to further verify the causal relationship between sarcopenia and cognitive outcomes.

BACKGROUND: Sensitive and interpretable machine learning (ML) models can provide valuable assistance to clinicians in managing patients with heart failure (HF) at discharge by identifying individual factors associated with a high risk of readmission. In this cohort study, we delve into the factors driving the potential utility of classification models as decision support tools for predicting readmissions in patients with HF. OBJECTIVE: The primary objective of this study is to assess the trade-off between using deep learning (DL) and traditional ML models to identify the risk of 100-day readmissions in patients with HF. Additionally, the study aims to provide explanations for the model predictions by highlighting important features both on a global scale across the patient cohort and on a local level for individual patients. METHODS: The retrospective data for this study were obtained from the Regional Health Care Information Platform in Region Halland, Sweden. The study cohort consisted of patients diagnosed with HF who were over 40 years old and had been hospitalized at least once between 2017 and 2019. Data analysis encompassed the period from January 1, 2017, to December 31, 2019. Two ML models were developed and validated to predict 100-day readmissions, with a focus on the explainability of the model's decisions. These models were built based on decision trees and recurrent neural architecture. Model explainability was obtained using an ML explainer. The predictive performance of these models was compared against 2 risk assessment tools using multiple performance metrics. RESULTS: The retrospective data set included a total of 15,612 admissions, and within these admissions, readmission occurred in 5597 cases, representing a readmission rate of 35.85%. It is noteworthy that a traditional and explainable model, informed by clinical knowledge, exhibited performance comparable to the DL model and surpassed conventional scoring methods in predicting readmission amo

Glaucoma is a common retinal disorder characterized by progressive optic nerve damage, resulting in visual impairment and potential blindness. Elevated intraocular pressure (IOP) is a major risk factor, but some patients still experience disease progression despite IOP-lowering treatments. Genome-wide association studies have linked variations in the Caveolin1/2 (CAV-1/2) gene loci to glaucoma risk. Cav-1, a key protein in caveolae membrane invaginations, is involved in signaling pathways and its absence impairs retinal function. Recent research suggests that Cav-1 is implicated in modulating the BDNF/TrkB signaling pathway in retinal ganglion cells, which plays a critical role in retinal ganglion cell (RGC) health and protection against apoptosis. Understanding the interplay between these proteins could shed light on glaucoma pathogenesis and provide potential therapeutic targets.

Non-alcoholic fatty liver disease (NAFLD) is the liver manifestation of the metabolic syndrome with global prevalence reaching epidemic levels. Despite the high disease burden in the population only a small proportion of those with NAFLD will develop progressive liver disease, for which there is currently no approved pharmacotherapy. Identifying those who are at risk of progressive NAFLD currently requires a liver biopsy which is problematic. Firstly, liver biopsy is invasive and therefore not appropriate for use in a condition like NAFLD that affects a large proportion of the population. Secondly, biopsy is limited by sampling and observer dependent variability which can lead to misclassification of disease severity. Non-invasive biomarkers are therefore needed to replace liver biopsy in the assessment of NAFLD. Our study addresses this unmet need. The LITMUS Imaging Study is a prospectively recruited multi-centre cohort study evaluating magnetic resonance imaging and elastography, and ultrasound elastography against liver histology as the reference standard. Imaging biomarkers and biopsy are acquired within a 100-day window. The study employs standardised processes for imaging data collection and analysis as well as a real time central monitoring and quality control process for all the data submitted for analysis. It is anticipated that the high-quality data generated from this study will underpin changes in clinical practice for the benefit of people with NAFLD. Study Registration: clinicaltrials.gov: NCT05479721, Funding Agencies|Innovative Medicines Initiative 2 Joint Undertaking [777377]; European Union; EFPIA; Oxford NIHR Biomedical Research Centre; Newcastle NIHR Biomedical Research Centre; NIHR Senior Investigator

Summary: We assessed the prevalence of hypocalcemia after denosumab injections in a real-world cohort routinely monitored for calcium during up to 7.5 years of treatment. Among 1096 injections in 242 patients, 6.3% resulted in hypocalcemia, and was independent of the injection number. Severe hypocalcemia was rare (1%). Purpose: To assess the prevalence of and risk factors for hypocalcemia after administration of denosumab in a patient cohort routinely monitored for ionized calcium after each dose. Methods: In this retrospective observational study, we analyzed denosumab-induced hypocalcemia in a real-world cohort who were routinely followed up with ionized calcium pre- and post-injection (within 31 days after injection) during the period 2011 to 2020. Results: In total, we included data from 1096 denosumab injections in 242 individuals (1–15 injections per patient). The mean age for the first injection was 74 ± 10 years, and 88% were female. Post-injection hypocalcemia occurred after 6.3% of all injections (4.6% mild, 0.6% moderate, and 1.1% severe) and was independent of the number of injections (rate of hypocalcemia varied from 3–8%). Risk factors for hypocalcemia were male sex, severe renal failure, pre-injection hypocalcemia, hypomagnesemia, hypophosphatemia, and vitamin D insufficiency. Furthermore, older age was not associated with an increased hypocalcemia risk. Conclusions: Denosumab-induced hypocalcemia is a prevalent adverse event, which occurs independently of the number of injections. However, severe hypocalcemia is a rare occurrence, and severe renal failure and nutritional status appear to be important predictive factors. Magnesium and phosphate might add value in the pre-injection risk assessment; however, this observation needs to be confirmed in larger cohorts., Funding: Linkoping University

Background In order to improve detection of suspected infections in frail elderly there is an urgent need for development of decision support tools, that can be used in the daily work of all healthcare professionals for assessing non-specific and specific changes. The aim was to study non-specific signs and symptoms and fever temperature for early detection of ongoing infection in frail elderly, and how these correlates to provide the instrument, the Early Detection Infection Scale (EDIS), which is used to assess changes in health condition in frail elderly. Methods This was an explorative, prospective cohort study, including 45 nursing home residents, 76 to 99 years, in Sweden. Nursing assistants measured morning ear body temperature twice a week and used the EDIS to assess individual health condition daily for six months. The outcome comprised events of suspected infection, compiled from nursing and medical patient records. Factor analysis and multivariate logistic regression analysis were performed to analyse data. Results Fifteen residents were diagnosed with at least one infection during the six-month follow-up and 189 observations related to 72 events of suspected infection were recorded. The first factor analysis revealed that the components, change in cognitive and physical function, general signs and symptoms of illness, increased tenderness, change in eye expression and food intake and change in emotions explained 61% of the variance. The second factor analysis, adding temperature assessed as fever to > 1.0 degrees C from individual normal, resulted in change in physical function and food intake, confusion and signs and symptoms from respiratory and urinary tract, general signs and symptoms of illness and fever and increased tenderness, explaining 59% of the variance. In the first regression analysis, increased tenderness and change in eye expression and food intake, and in the second change in physical function and food intake, general signs and sy, Funding Agencies|We thank the residents, the nursing assistants and the nurses who contributed to the study.

Background: Allostatic load (AL) is defined as the cumulative dysregulation of neuroendocrine, immunological, metabolic, and cardiovascular systems that increases the susceptibility to stress-related health problems. Several dementia and Alzheimers disease (AD) risk factors have been identified, yet little is known about the role of AL and its associations with AD biomarkers (e.g., beta-amyloid (A & beta;) or tau) and cognitive function among memory clinic patients. Hence, this study aims to assess the association between AL and AD biomarkers, cognitive performance, and cognitive decline after 3-years of follow-up.Methods: Data from 188 memory clinic patients were derived from the Cortisol and Stress in AD (Co-STAR) study in Sweden. Participants underwent baseline assessments including blood tests for AL measures (including cortisol, thyroid stimulating hormone, cobalamin, homocysteine, leukocytes, glycated hemoglobin, albumin, high-density and low-density lipoprotein cholesterol, triglycerides, and creatinine), cerebrospinal fluid (CSF) sampling for AD biomarkers and neuropsychological tests including five cognitive domains. Linear regressions were conducted, adjusting for age, sex, and education.Results: Higher AL was associated with lower CSF A & beta;1-42 levels (& beta; =-0.175, p = 0.025), reflecting higher brain levels of A & beta;1-42. Stratified analyses suggested a significant association among women but not men, although the AL-sex interaction was not statistically significant. AL was not significantly associated with T-tau level (& beta; =-0.030, p = 0.682) and P-tau level (& beta; = 0.091, p = 0.980). There were no significant associations between AL and cognition or cognitive decline after 3 years.Conclusion: This study showed that higher AL was associated with increased brain amyloid accumulation. This suggests that AL may play a role in AD/dementia pathophysiology. Potential sex-related differences should be assessed in furthe, Funding Agencies|Fonds de Recherche du Quebec Sante; Alzheimerfonden; Hjarnfonden; Center for Innovative Medicine (CIMED) at Karolinska Institutet South Campus; Knut and Alice Wallenberg Foundation; Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse; Joint Program of Neurodegenerative Disorders - prevention (EURO-FINGERS); Region Stockholm; Stiftelsen Stockholms sjukhem; Swedish Research Council; NordForsk NJ-FINGERS; European Research Council; Rut and Arvid Wolff Memorial Foundation; Center for Medical Innovation (CIMED) Network Grant (Karolinska Institutet); Foundation for Geriatric Diseases at Karolinska Institutet; Erik Ronnbergs Stipend -Riksbankens Jubileumsfond [804371]; Loo and Hans Osterman Foundation for Medical Research [2020-02325]; Demensforbundet [119886]

More women have Alzheimer disease (AD) than men, but the reasons for this phenomenon are still unknown. Including women in clinical research and studying their biology is key to understand not just their increased risk but also their resilience against the disease. In this sense, women are more affected by AD than men, but their reserve or resilience mechanisms might delay symptom onset. The aim of this review was to explore what is known about mechanisms underlying womens risk and resilience in AD and identify emerging themes in this area that merit further research. We conducted a review of studies analyzing molecular mechanisms that may induce neuroplasticity in women, as well as cognitive and brain reserve. We also analyzed how the loss of steroid hormones in aging may be linked to AD. We included empirical studies with human and animal models, literature reviews as well as meta-analyses. Our search identified the importance of 17-b-estradiol (E2) as a mechanism driving cognitive and brain reserve in women. More broadly, our analysis revealed the following emerging perspectives: (1) the importance of steroid hormones and their effects on both neurons and glia for the study of risk and resilience in AD, (2) E2s crucial role in womens brain reserve, (3) womens verbal memory advantage as a cognitive reserve factor, and (4) E2s potential role in linguistic experiences such as multilingualism and hearing loss. Future directions for research include analyzing the reserve mechanisms of steroid hormones on neuronal and glial plasticity, as well as identifying the links between steroid hormone loss in aging and risk for AD., Funding Agencies|Joyce Posluns Chair in Womens Brain Health and Aging from the Posluns Family Foundation; Canadian Institutes of Health Research (CIHR); Ontario Brain Institute; Alzheimer Society of Canada [WJP-150643]; Canadian Consortium on Neurodegeneration in Aging [CCNA 049-04]; CIHR [CNA 163902]; Jacqueline Ford Gender and Health Fund

BackgroundTo quantify cardiovascular health (CVH), the American Heart Association (AHA) recently launched an updated construct of the "Lifes Simple 7" (LS7) score, the "Lifes Essential 8" (LE8) score. This study aims to analyse the association between both CVH scores and carotid artery plaques and to compare the predictive capacity of such scores for carotid plaques.MethodsRandomly recruited participants aged 50-64 years from the Swedish CArdioPulmonary bioImage Study (SCAPIS) were analysed. According to the AHA definitions, two CVH scores were calculated: i) the LE8 score (0, worst CVH; 100, best CVH) and two different versions of the LS7 score [(0-7) and (0-14), 0 indicating the worst CVH]. Ultrasound-diagnosed carotid plaques were classified as no plaque, unilateral, and bilateral plaques. Associations were studied by adjusted multinomial logistic regression models and adjusted (marginal) prevalences, while comparison between LE8 and LS7 scores was performed through receiver operating characteristic (ROC) curves.ResultsAfter exclusions, 28,870 participants remained for analysis (50.3% women). The odds for bilateral carotid plaques were almost five times higher in the lowest LE8 (<50 points) group [OR: 4.93, (95% CI: 4.19-5.79); adjusted prevalence 40.5%, (95% CI: 37.9-43.2)] compared to the highest LE8 (& GE;80 points) group [adjusted prevalence 17.2%, (95% CI: 16.2-18.1)]. Also, the odds for unilateral carotid plaques were more than two times higher in the lowest LE8 group [OR: 2.14, (95% CI: 1.82-2.51); adjusted prevalence 31.5%, (95% CI: 28.9-34.2)] compared to the highest LE8 group [adjusted prevalence 29.4%, (95% CI: 28.3-30.5)]. The areas under ROC curves were similar between LE8 and LS7 (0-14) scores: for bilateral carotid plaques, 0.622 (95% CI: 0.614-0.630) vs. 0.621 (95% CI: 0.613-0.628), P = 0.578, respectively; and for any carotid plaque, 0.602 (95% CI: 0.596-0.609) vs. 0.600 (95% CI: 0.593-0.607), P = 0.194, respectively.ConclusionThe new

Sarcopenia - from the Greek words 'sarx' (flesh) and 'penia' (loss) - was, when coined in 1989, a term denoting the decline in muscle mass and strength that occurs with aging. Such definition implies everyone suffers from sarcopenia to varying degrees, which naturally makes studying sarcopenia challenging. Early (practical) definitions of sarcopenia focused on identification of low muscle mass, while later definitions also include criteria of low muscle strength. Use of such definitions to study sarcopenia has shown that wasting is intensified in those suffering from metabolic diseases, and even more rapid in end-stage diseases. Although it is unknown whether sarcopenia accelerate disease or the other way around, detection of sarcopenia concurrent with other diseases clearly identifies a vulnerable subgroup of patients who may need more extensive care. In severe stages of liver disease, poor muscle health has been linked to higher morbidity and mortality, and may affect the outcome of liver transplantation. Sarcopenia is therefore recognized as an important factor that should affect both clinical decision-making and intervention in patients being evaluated for liver transplantation. However, sarcopenia is poorly understood (and commonly overlooked) in earlier stages of disease, where the potential of preventative care is greater. One challenge has been the prevalence of obesity in diseases that may precede more advanced disease, such as non-alcoholic fatty liver disease (NAFLD). Due to their larger body size, individuals with obesity need more muscle mass to maintain mobility function. Therefore, the threshold for what is considered ‘low muscle mass’ needs to be higher, or somehow adjusted for body size. This thesis started by applying the European definition of sarcopenia in 10,000 individuals aged 44-78 years volunteering for the UK Biobank imaging study. It was identified that current body size adjustments used to detect 'low muscle mass' were ineffective. The co, Sarkopeni - från grekiskans 'sarx' (kött) och 'penia' (förlust) - syftade, när uttrycket myntades 1989, till förlust av muskelmassa och funktion i samband med åldrande. En sådan definition är inte speciellt praktiskt för studerandet av sarkopeni då den innebär att alla har (till olika grad) sarkopeni. Tidiga (praktiskt tillämpbara) definitioner av sarkopeni fokuserade på identifiering av låg muskelmassa men senare inkluderar även krav på låg muskelstyrka. Studier av sarkopeni som använt dessa definitioner har visat att muskelförtvining är intensifierad inom metabola sjukdomar och än mer aggressiv vid terminal sjukdom. Trots detta är det fortfarande okänt om sarkopeni accelererar utvecklingen av andra sjukdomar eller tvärt om. Det är dock tydligt att individer med sarkopeni och samsjuklighet är mer sårbara än andra och har större vårdbehov. Hos individer med svår leversjukdom har nedsatt muskelhälsa bland annat kopplats till högre sjuklighet och dödlighet samt visats påverka resultatet efter levertransplantation. Därför anses sarkopeni vara en viktig faktor som bör övervägas vid patientbeslut och interventioner för patienter som utvärderas för levertransplantation. Vid tidigare faser av leversjukdom är förståelsen för sarkopeni mer begränsad och tillståndet är sällan uppmärksammat inom vården. En utmaning är den höga förekomsten av obesitas inom sjukdomar (så som fettlever eller diabetes) som kan föregå mer avancerad sjukdom. På grund av större kroppsstorlek, behöver individer med obesitas mer muskelmassa för att bibehålla rörlighet. Därför behövs en högre tröskel för vad som anses vara 'låg muskelmassa', eller alternativt ett mått på muskelmassa som är korrigerat för kroppsstorlek. Den här avhandlingen börjar med att tillämpa den europeiska definitionen av sarkopeni på 10,000 frivilliga deltagare från UK Biobank med åldern 44-78. Det visades att dagens metoder för korrigering av kroppsstorlek inte fungerade, vilket ledde till underdiagnostisering av sarkopeni hos in

BackgroundAdverse drug reactions (ADR), both preventable and non-preventable, are frequent and pose a significant burden. This study aimed to produce up-to-date estimates for ADR rates in hospitals, in Portugal, from 2010 to 2018. In addition, it explores possible pitfalls when crosswalking between ICD-9-CM and ICD-10-CM code sets for ADR identification.MethodsThe Portuguese Hospital Morbidity Database was used to identify hospital episodes (outpatient or inpatient) with at least one ICD code of ADR. Since the study period spanned from 2010 to 2018, both ICD-9-CM and ICD-10-CM codes based on previously published studies were used to define episodes. This was an exploratory study, and descriptive statistics were used to provide ADR rates and summarise episode features for the full period (2010-2018) as well as for the ICD-9-CM (2010-2016) and ICD -10-CM (2017-2018) eras.ResultsBetween 2010 and 2018, ADR occurred in 162,985 hospital episodes, corresponding to 1.00% of the total number of episodes during the same period. Higher rates were seen in the oldest age groups. In the same period, the mean annual rate of episodes related to ADR was 174.2/100,000 population. The episode rate (per 100,000 population) was generally higher in males, except in young adults (aged '15-20', '25-30' and '30-35' years), although the overall frequency of ADR in hospital episodes was higher in females.ConclusionsDespite the ICD-10-CM transition, administrative health data in Portugal remain a feasible source for producing up-to-date estimates on ADR in hospitals. There is a need for future research to identify target recipients for preventive interventions and improve medication safety practices in Portugal.

Background & aims Prior studies have shown an association between malnutrition and mortality. However, it is uncertain whether malnutrition assessed with the Mini Nutritional Assessment (MNA) instrument is suitable for providing long-term prognostic information regarding older adults admitted to hospital. The aim of the present study was to examine if MNA-assessed malnutrition was associated with long-term mortality in older adults admitted to hospital and for how long the association persisted. Methods 1768 older adults (≥65 years old) admitted to a Swedish hospital were assessed with the 18-item MNA during 2008–2009 and followed-up after 10 years. All-cause mortality (ACM) was analyzed separately for the five follow-up periods 0 to ≤2 years, >2 to ≤4 years, >4 to ≤6 years, >6 to ≤8 years, and >8 to ≤10 years using Cox regression models adjusted for important demographic, nutritional, and clinical confounders. Results The participants were on average 78.1 years old at baseline, with 56.0% being females. At 10 years follow-up, 174 (94.1%) malnourished patients, 757 (75.9%) patients at risk of malnutrition, and 297 (50.7%) well-nourished patients had died. For all follow-up periods, malnourished patients and patients at risk of malnutrition had significantly higher risks of early death in the adjusted regression analyses when compared with well-nourished patients (all P < 0.05), with the highest risk observed for malnourished patients. For patients still alive at 8 years, the risk of death during the following two years was 2.7 times higher for patients being malnourished at baseline (P = 0.013) and 1.9 times higher for patients being at risk of malnutrition at baseline (P = 0.001), compared with patients being well-nourished at baseline. Conclusions MNA-assessed malnutrition is an important independent predictor of long-term mortality in older adults admitted to hospital and the association is consistent over 10 years of follow-up. In clinical pra, The authors contributed equally

Background Depression is commonly experienced by people with dementia, and associated with lower quality of life and functional decline. However, access to evidence-based psychological interventions for people with dementia and depression is limited. One potential solution is guided low-intensity behavioral activation. Following the new Medical Research Council Framework, considering factors such as potential barriers and facilitators to implementation is recommended during the development of new interventions. Aims of this study were to: (1) develop an understanding of existing healthcare and community support in the Swedish context for people with dementia and their informal caregivers; and (2) identify barriers and facilitators to intervention uptake informed by Normalization Process Theory. Methods Semi-structured interviews and focus groups were held with healthcare (n = 18) and community (n = 7) stakeholders working with people with dementia and/or informal caregivers. Interview questions were informed by Normalization Process Theory. Data was analysed utilizing a two-step deductive analysis approach using the Normalization Process Theory coding manual, with inductive categories applied to data related to the main mechanisms of the theory, but not captured by its sub-constructs. Results Twelve deductive and three inductive categories related to three Normalization Process Theory primary mechanisms (Coherence, Cognitive Participation, and Collective Action) were identified. Identified barriers to intervention uptake included: (1) additional burden for informal caregivers; (2) lack of appropriate workforce to provide guidance; (3) lack of time and financial resources; (4) people with dementia not recognising their diagnosis of dementia and/or a need for support; and (5) stigma. Identified facilitators to intervention uptake included: (1) intervention has potential to fill a large psychological treatment gap in Sweden; (2) objectives and potential benefits unders, De två sista författarna delar sistaförfattarskapet

Depression is one of the leading causes of disability in older adults worldwide. Many older adults with depression are undetected, and there is a need for brief, scalable psychological treatments for depression that can be delivered remotely. The aims of this thesis were 1) to investigate the diagnostic accuracy of two rating scales (PHQ-9 and GDS-15) for the detection of depression in older adults, and 2) to investigate the feasibility, preliminary efficacy and patients’ experiences of a telephone-based psychological intervention, Behavioral activation with mental imagery (BA-MI), for the treatment of depression in older adults in the context of the covid-19 pandemic. Study I showed that a cutoff of ≥6 on the GDS-15 and ≥5 on the PHQ-9 were optimal to identify major depressive disorder. When identifying both major depressive disorder and subthreshold depression, the optimal cutoff on the GDS-15 was ≥5. Study II was a randomized clinical pilot trial, CoviDep, with a treatment group receiving the BA-MI intervention, and a control group. The drop-out rate was low. Compared to the control group, the treatment group reported a decrease in depressive symptoms throughout the treatment, with a large effect-size at posttreatment. Study III was a long-term follow-up of participants in CoviDep that received the BA-MI intervention. The drop-out rate over time was low, and compared to baseline, decreases in depressive symptoms were observed with a medium effect-size at posttreatment that was maintained 1- and 3 months post-treatment but lower after 6 months. Study IV was a qualitative study. The BA-MI intervention in CoviDep was described as increasing activities and improving mood. Telephone-delivery reduced barriers due to pandemic restrictions but felt less personal and lacking non-verbal communication. Being recognized and talking to a therapist every week was healing, but the manualized mode of treatment seemed to impair the relationship. In sum, this thesis shows that bo

BACKGROUND: Participatory research approaches can potentially empower older adults and improve their quality of life and care. These include research designs, methods, and conceptual frameworks in collaboration with people directly involved and invested in the research and research outcomes. However, participatory research approaches have rarely been explored in long-term care facilities for older adults, such as nursing homes or residential care facilities. We aimed to provide increased understanding and recommendations about how participatory research approaches can be conceptualised and used in long-term care facilities for older adults. METHODS: Inspired by Noblit and Hare (1988) and the seven phases of the eMERGe guidelines (2019), we performed a meta-ethnography (synthesis of qualitative research). We searched MEDLINE, CINAHL, ERIC, Sociological Abstracts, and Web of science in July 2021 and June 2022 for studies published between Jan 1, 2001, and June 27, 2022 (see appendix for search terms). We included peer-reviewed qualitative publications on participatory research approaches with older adults or staff in long-term care facilities, written in English. To promote rigour, a protocol was used with two authors independently screening the articles, reaching consensus through critical discussions with a third author, and using the Critical Appraisal Skills Programme (CASP) checklist. We extracted data regarding types of participatory research approaches and themes. This study is registered with PROSPERO, CRD42021275187. FINDINGS: Ten of 1445 articles screened were included in the analysis. Using seven types of participatory research approaches, the included studies investigated experiences of approximately 153 residents and 99 staff from seven countries (Australia, Belgium, England, Guyana, Ireland, Sweden, and the Netherlands). We identified five themes, expressed as a conceptual model with recommendations: (1) participatory backdrop; (2) collaborative places