Pathogenesis of Alzheimer's disease : focus on amyloid â-peptide, homocysteine and metals

Alzheimer's disease (AD) is a complex dementia disorder. It is characterized by the neuronal and synaptic loss, presence of neurofibrillary tangles and senile plaques, composed of amyloid â-peptide (Aâ) in the brain. Biochemical and genetic studies implicate a central role for Aâ in the pathogenesis of AD, however how amyloid leads to neurodegeneration is still unknown. The present work focused on investigating the role of Aâ in AD and other relevant neurological and psychiatric disorders. The study was based on the analysis of Aâ in cell culture media and post-mortem brain tissue. In paper I, we measured Aâ in cell culture media from cells transfected with APP mutations causing familial AD. We could see that mutations in familial AD are primarily pathogenic through their effect on APP processing and not through altered cell signaling. In paper II, we compared the levels of Aâ in the brain of elderly schizophrenics with and without dementia versus controls. We demonstrated that in the brains from people with schizophrenia and dementia there is no increase of Aâ. Thus the pathogenic pathway of dementia in elderly schizophrenics is different from that seen in AD. Additionally, in schizophrenia cases with AD neuropathology, levels of brain Aâ were decreased as compared to 'pure' AD cases. This may be explained by high smoking prevalence among schizophrenics, the use of neuroleptic drugs or could be a result of the disease state per se. In paper III, we further investigated the hypothesis that stimulation of nicotinic receptors may diminish arnyloidosis in the brain. We could prove that deposition of Aâ is attenuated in the cortex of normal elderly people that used to smoke tobacco. However, the mechanism of this attenuation is unknown. Metals have been implicated in AD pathogenesis and some metal chelators have shown therapeutic promise in animal and human studies. In paper IV, we studied the interaction of human brain Aâ with biometals, such as zinc, copper, aluminium, iron and manganese. We extracted and measured cortical Aâ in AD patients and control groups. The levels of the metals were assessed in a parallel set of samples. We found that zinc is strongly elevated in AD brains and is correlated with Aâ and dementia severity. In paper V, we focused on other important factors in AD pathogenesis, such as homocysteine and vitamin B status. We compared plasma homocysteine levels in controls, AD patients and in patients with mild cognitive impairment. We observed hyperhomocysteinemia in AD. We also confirmed that ApoE 4 allele is a risk factor in the development of sporadic AD. We did not find any evidence that polymorphism of the enzyme involved in homocysteine biogenesis, methylenetetrahydrofolate reductase (MTHFR), has a clinical significance in these groups. In summary, these studies suggest a multifactoral pathogenesis of AD, where Aâ, zinc and homocysteine are important factors. They also give insight into targets to develop therapeutic strategies for treatment of dementia. Those include: substances stimulating nicotinic receptors, metals chelators, anti- hyperhomocysteinemia therapies, and anti-Aâ strategies

COVID-19 prevalence and mortality in longer-term care facilities

This essay considers the factors that have contributed to very high COVID-19 mortality in longer-term care facilities (LTCFs). We compare the demographic characteristics of LTCF residents with those of community-dwelling older adults, and then we review the evidence regarding prevalence and infection fatality rates (IFRs), including links to frailty and some comorbidities. Finally, we discuss policy measures that could foster the physical and mental health and well-being of LTCF residents in the present context and in potential future pandemics

Informing patients with acute stroke about their risk of dementia:A survey of UK healthcare professionals

OBJECTIVES: Cognitive problems following stroke are of key concern to stroke survivors. Discussing risk of dementia at the time of stroke could have implications for follow-up care. However, informing someone who has just had a stroke about risk of dementia could cause distress. This survey explored healthcare professionals’ views on discussing risk of post-stroke dementia at the time of stroke. MATERIALS AND METHODS: This online survey was aimed at all UK healthcare professionals who care for patients with stroke. The survey was distributed via the mailing lists of seven professional stroke-related organisations and Twitter. Descriptive statistics were used to summarise findings. RESULTS: Sixty healthcare professionals completed the survey. Healthcare professionals were aware of the main risk factors associated with post-stroke dementia (e.g. previous stroke, age). Most respondents (N=34/60, 57%) thought that patients with acute stroke would benefit from knowing if they are at high risk of dementia, and 75% (N=45/60) agreed that carers would benefit. Despite this, the majority of healthcare professionals (N=47/53, 89%) who cared for patients with acute stroke in the past year said they rarely/never discussed dementia with their patients. Most respondents (N=46/60, 77%) thought risk of dementia should be discussed 1-6 months post-stroke. CONCLUSION: Although healthcare professionals felt it would be helpful to discuss risk of post-stroke dementia, in practice, most said that they rarely or never discussed this with their patients. Stroke survivors could benefit from a healthcare system that offers appropriate follow-up care and support to patients at high risk of dementia

COVID-19 prevalence and mortality in longer-term care facilities

This essay considers the factors that have contributed to very high COVID-19 mortality in longer-term care facilities (LTCFs). We compare the demographic characteristics of LTCF residents with those of community-dwelling older adults, and then we review the evidence regarding prevalence and infection fatality rates (IFRs), including links to frailty and some comorbidities. Finally, we discuss policy measures that could foster the physical and mental health and well-being of LTCF residents in the present context and in potential future pandemics.publishedVersionPeer reviewe

Estudio de prefactibilidad para el Manejo y disposición de aguas grises.

Realiza un estudio de impacto ambiental basado en leyes, reglamentos y normas vigentes para el diseño, planificación y construcción de una planta de tratamiento de aguas residuales y disposición de aguas grises a nivel domiciliar

Dementia and psychotropic medications are associated with significantly higher mortality in geriatric patients hospitalized with COVID-19 : data from the StockholmGeroCovid project

Background: Dementia and psychotropic medications are discussed as risk factors for severe/lethal outcome of the coronavirus disease 2019 (COVID-19). We aimed to explore the associations between the presence of dementia and medication use with mortality in the hospitalized and discharged patients who suffered from COVID-19. Methods: We conducted an open-cohort observational study based on electronic patient records from nine geriatric care clinics in the larger Stockholm area, Sweden, between February 28, 2020, and November 22, 2021. In total, we identified 5122 hospitalized patients diagnosed with COVID-19, out of which 762 (14.9%) patients had concurrent dementia and 4360 (85.1%) were dementia-free. Patients’ age, sex, baseline oxygen saturation, comorbidities, and medication prescription (cardiovascular and psychotropic medication) were registered at admission. The hazard ratios (HRs) with 95% confidence intervals (CIs) of in-hospital, 30-day, 90-day, 365-day post-discharge, and overall mortal- ity during the follow-up were obtained. Then, the associations of dementia and medication use with mortality were determined using proportional hazards regression with time since entry as a time scale. Results: After adjustment, dementia was independently associated with 68% higher in-hospital mortality among COVID-19 patients compared to patients who were dementia-free at admission [HRs (95% CI) 1.68 (1.37–2.06)]. The increase was consistent post-discharge, and the overall mortality of dementia patients was increased by 59% [1.59 (1.40–1.81)]. In addition, the prescription of antipsychotic medication at hospital admission was associated with a 70% higher total mortality risk [1.70 (1.47–1.97)]. Conclusions: The clinical co-occurence of dementia and COVID-19 increases the short- and long-term risk of death, and the antipsychotics seem to further the risk increase. Our results may help identify high-risk patients in need of more specialized care when infected with COVID-19.Swedish Research Council (dnr: 2020-06101 WISER, 2021-013167, 2020-05805)National Institute for Neurological Research, Programme EXCELES (Project No. LX22NPO5107)European Union, Next Generation EUAlzheimerfondenKarolinska InstitutetPublishe

Safety climate perceived by pre-hospital emergency care personnel—an international cross-sectional study

IntroductionImproving patient safety is one of the most critical components of modern healthcare. Emergency medical services (EMS) are, by nature, a challenging environment for ensuring patient safety. It is fast-paced, physically dangerous, and highly stressful, requiring rapid decision-making and action. This can create risks not only for patients but also for employees. We assessed variations in perceptions of safety culture in prehospital emergency care among an international sample of paramedics and nurses.MethodsThe Emergency Medical Services Safety Attitudes Questionnaire (EMS-SAQ) was used for the study. The instrument measures six domains of safety culture in the workplace: teamwork climate, job satisfaction, safety climate, working conditions, stress recognition, and perceptions of management. A total of 1,128 EMS from 9 countries participated in this study.ResultsSafety Climate was 81.32/100 (SD 6.90), Teamwork Climate 84.14/100 (SD 8.74), Perceptions of Management 76.30/100 (SD 10.54), Stress Recognition 89.86/100 (SD 5.70), Working Conditions 81.07/100 (SD 9.75), and Job Satisfaction 70.71/100 (SD 7.21). There was significant variation in safety culture scores across countries for teamwork climate (TWC), working conditions (WC), and job satisfaction (JS). Among the individual variables (age, gender, level of education, and work experience), variations in safety culture scores were unaffected by age, gender, or work experience. Organizational characteristics: employment status and position type were linked to significant variations in safety culture domain scores.ConclusionParticipants’ perceptions of the patient safety climate were not particularly satisfactory, confirming that there is still a need to develop a culture of patient safety in prehospital emergency care

Development of an electronic frailty index for hospitalized older adults in Sweden

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Two Years with COVID-19 : The Electronic Frailty Index Identifies High-Risk Patients in the Stockholm GeroCovid Study

INTRODUCTION: Frailty, a measure of biological aging, has been linked to worse COVID-19 outcomes. However, as the mortality differs across the COVID-19 waves, it is less clear whether a medical record-based electronic frailty index (eFI) that we have previously developed for older adults could be used for risk stratification in hospitalized COVID-19 patients. OBJECTIVES: The aim of the study was to examine the association of frailty with mortality, readmission, and length of stay in older COVID-19 patients and to compare the predictive accuracy of the eFI to other frailty and comorbidity measures. METHODS: This was a retrospective cohort study using electronic health records (EHRs) from nine geriatric clinics in Stockholm, Sweden, comprising 3,980 COVID-19 patients (mean age 81.6 years) admitted between March 2020 and March 2022. Frailty was assessed using a 48-item eFI developed for Swedish geriatric patients, the Clinical Frailty Scale, and the Hospital Frailty Risk Score. Comorbidity was measured using the Charlson Comorbidity Index. We analyzed in-hospital mortality and 30-day readmission using logistic regression, 30-day and 6-month mortality using Cox regression, and the length of stay using linear regression. Predictive accuracy of the logistic regression and Cox models was evaluated by area under the receiver operating characteristic curve (AUC) and Harrell's C-statistic, respectively. RESULTS: Across the study period, the in-hospital mortality rate decreased from 13.9% in the first wave to 3.6% in the latest (Omicron) wave. Controlling for age and sex, a 10% increment in the eFI was significantly associated with higher risks of in-hospital mortality (odds ratio = 2.95; 95% confidence interval = 2.42-3.62), 30-day mortality (hazard ratio [HR] = 2.39; 2.08-2.74), 6-month mortality (HR = 2.29; 2.04-2.56), and a longer length of stay (β-coefficient = 2.00; 1.65-2.34) but not with 30-day readmission. The association between the eFI and in-hospital mortality remained robust across the waves, even after the vaccination rollout. Among all measures, the eFI had the best discrimination for in-hospital (AUC = 0.780), 30-day (Harrell's C = 0.733), and 6-month mortality (Harrell's C = 0.719). CONCLUSION: An eFI based on routinely collected EHRs can be applied in identifying high-risk older COVID-19 patients during the continuing pandemic.publishedVersionPeer reviewe