The Impact of the COVID-19 Pandemic on the Psychological Well-Being of Caregivers of People with Dementia or Mild Cognitive Impairment: A Systematic Review and Meta-Analysis

The aim of this systematic review was to investigate the effects of the COVID-19 lockdown on the psychological well-being of caregivers of people with dementia or mild cognitive impairment (PwD/MCI). Electronic databases were searched from inception to August 2022 for observational studies investigating the COVID-19 lockdown and psychological well-being of caregivers of PwD/MCI. Summary estimates of standardized mean differences (SMD) in psychological well-being scores pre- versus during COVID-19 were calculated using a random-effects model. Fifteen studies including 1702 caregivers (65.7% female, mean age 60.40 ± 12.9 years) with PwD/MCI were evaluated. Five studies found no change in psychological well-being parameters, including depression, anxiety, distress, caregiver burden, and quality of life. Ten studies found a worsening in at least one parameter: depression (six studies, n = 1368; SMD = 0.40; 95%CI: 0.09–0.71; p = 0.01, I2 = 86.8%), anxiety (seven studies, n = 1569; SMD = 1.35; 95%CI: 0.05–2.65; I2 = 99.2%), caregiver distress (six studies, n = 1320, SMD = 3.190; 95%CI: 1.42–4.95; p < 0.0001; I2 = 99.4%), and caregiver burden (four studies, n = 852, SMD = 0.34; 95%CI: 0.13–0.56; p = 0.001; I2 = 54.1%) (p < 0.05). There was an increase in depression, anxiety, caregiver burden, and distress in caregivers of PwD/MCI during the lockdown in the COVID pandemic. This could have longer term consequences, and it is essential that caregivers’ psychological well-being is assessed and supported, to benefit both themselves and those for whom they care

A European Academy of Neurology guideline on medical management issues in dementia

BACKGROUND AND PURPOSE: Dementia is one of the most common disorders and is associated with increased morbidity, mortality and decreased quality of life. The present guideline addresses important medical management issues including systematic medical follow‐up, vascular risk factors in dementia, pain in dementia, use of antipsychotics in dementia and epilepsy in dementia. METHODS: A systematic review of the literature was carried out. Based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework, we developed a guideline. Where recommendations based on GRADE were not possible, a good practice statement was formulated. RESULTS: Systematic management of vascular risk factors should be performed in patients with mild to moderate dementia as prevention of cerebrovascular pathology may impact on the progression of dementia (Good Practice statement). Individuals with dementia (without previous stroke) and atrial fibrillation should be treated with anticoagulants (weak recommendation). Discontinuation of opioids should be considered in certain individuals with dementia (e.g. for whom there are no signs or symptoms of pain or no clear indication, or suspicion of side effects; Good Practice statement). Behavioral symptoms in persons with dementia should not be treated with mild analgesics (weak recommendation). In all patients with dementia treated with opioids, assessment of the individual risk–benefit ratio should be performed at regular intervals. Regular, preplanned medical follow‐up should be offered to all patients with dementia. The setting will depend on the organization of local health services and should, as a minimum, include general practitioners with easy access to dementia specialists (Good Practice statement). Individuals with dementia and agitation and/or aggression should be treated with atypical antipsychotics only after all non‐pharmacological measures have been proven to be without benefit or in the case of severe self‐harm or harm to others (weak recommendation). Antipsychotics should be discontinued after cessation of behavioral disturbances and in patients in whom there are side effects (Good Practice statement). For treatment of epilepsy in individuals with dementia, newer anticonvulsants should be considered as first‐line therapy (Good Practice statement). CONCLUSION: This GRADE‐based guideline offers recommendations on several important medical issues in patients with dementia, and thus adds important guidance for clinicians. For some issues, very little or no evidence was identified, highlighting the importance of further studies within these areas

Big data and data repurposing – using existing data to answer new questions in vascular dementia research

Introduction: Traditional approaches to clinical research have, as yet, failed to provide effective treatments for vascular dementia (VaD). Novel approaches to collation and synthesis of data may allow for time and cost efficient hypothesis generating and testing. These approaches may have particular utility in helping us understand and treat a complex condition such as VaD. Methods: We present an overview of new uses for existing data to progress VaD research. The overview is the result of consultation with various stakeholders, focused literature review and learning from the group’s experience of successful approaches to data repurposing. In particular, we benefitted from the expert discussion and input of delegates at the 9th International Congress on Vascular Dementia (Ljubljana, 16-18th October 2015). Results: We agreed on key areas that could be of relevance to VaD research: systematic review of existing studies; individual patient level analyses of existing trials and cohorts and linking electronic health record data to other datasets. We illustrated each theme with a case-study of an existing project that has utilised this approach. Conclusions: There are many opportunities for the VaD research community to make better use of existing data. The volume of potentially available data is increasing and the opportunities for using these resources to progress the VaD research agenda are exciting. Of course, these approaches come with inherent limitations and biases, as bigger datasets are not necessarily better datasets and maintaining rigour and critical analysis will be key to optimising data use

Fuzzy oil drop model to interpret the structure of antifreeze proteins and their mutants

Mutations in proteins introduce structural changes and influence biological activity: the specific effects depend on the location of the mutation. The simple method proposed in the present paper is based on a two-step model of in silico protein folding. The structure of the first intermediate is assumed to be determined solely by backbone conformation. The structure of the second one is assumed to be determined by the presence of a hydrophobic center. The comparable structural analysis of the set of mutants is performed to identify the mutant-induced structural changes. The changes of the hydrophobic core organization measured by the divergence entropy allows quantitative comparison estimating the relative structural changes upon mutation. The set of antifreeze proteins, which appeared to represent the hydrophobic core structure accordant with “fuzzy oil drop” model was selected for analysis

Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome

Recently, differences in the levels of various chemokines and cytokines were reported in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as compared with controls. Moreover, the analyte profile differed between chronic ME/CFS patients of long duration versus patients with disease of less than 3 years. In the current study, we measured the plasma levels of 34 cytokines, chemokines and growth factors in 100 chronic ME/CFS patients of long duration and in 79 gender and age-matched controls. We observed highly significant reductions in the concentration of circulating interleukin (IL)-16, IL-7, and Vascular Endothelial Growth Factor A (VEGF-A) in ME/CFS patients. All three biomarkers were significantly correlated in a multivariate cluster analysis. In addition, we identified significant reductions in the concentrations of fractalkine (CX3CL1) and monokine-induced-by-IFN-γ (MIG; CXCL9) along with increases in the concentrations of eotaxin 2 (CCL24) in ME/CFS patients. Our data recapitulates previous data from another USA ME/CFS cohort in which circulating levels of IL-7 were reduced. Also, a reduced level of VEGF-A was reported previously in sera of patients with Gulf War Illness as well as in cerebral spinal fluid samples from a different cohort of USA ME/CFS patients. To our knowledge, we are the first to test for levels of IL-16 in ME/CFS patients. In combination with previous data, our work suggests that the clustered reduction of IL-7, IL-16 and VEGF-A may have physiological relevance to ME/CFS disease. This profile is ME/CFS-specific since measurement of the same analytes present in chronic infectious and autoimmune liver diseases, where persistent fatigue is also a major symptom, failed to demonstrate the same changes. Further studies of other ME/CFS and overlapping disease cohorts are warranted in future

Body mass index and Mini Nutritional Assessment-Short Form as predictors of in-geriatric hospital mortality in older adults with COVID-19

Background & aims: Overweight and obesity have been consistently reported to carry an increased risk for poorer outcomes in coronavirus disease 2019 (COVID-19) in adults. Existing reports mainly focus on in-hospital and intensive care unit mortality in patient cohorts usually not representative of the population with the highest mortality, i.e. the very old and frail patients. Accordingly, little is known about the risk patterns related to body mass and nutrition in very old patients. Our aim was to assess the relationship between body mass index (BMI), nutritional status and in-geriatric hospital mortality among geriatric patients treated for COVID-19. As a reference, the analyses were performed also in patients treated for other diagnoses than COVID-19. Methods: We analyzed up to 10,031 geriatric patients with a median age of 83 years of which 1409 (14%) were hospitalized for COVID-19 and 8622 (86%) for other diagnoses in seven geriatric hospitals in the Stockholm region, Sweden during March 2020–January 2021. Data were available in electronic hospital records. The associations between 1) BMI and 2) nutritional status, assessed using the Mini-Nutritional Assessment - Short Form (MNA-SF) scale, and short-term in-geriatric hospital mortality were analyzed using logistic regression. Results: After adjusting for age, sex, comorbidity, polypharmacy, frailty and the wave of the pandemic (first vs. second), underweight defined as BMI<18.5 increased the risk of in-hospital mortality in COVID-19 patients (odds ratio [OR] = 2.30; confidence interval [CI] = 1.17–4.31). Overweight and obesity were not associated with in-hospital mortality. Malnutrition; i.e. MNA-SF 0–7 points, increased the risk of in-hospital mortality in patients treated for COVID-19 (OR = 2.03; CI = 1.16–3.68) and other causes (OR = 6.01; CI = 2.73–15.91). Conclusions: Our results indicate that obesity is not a risk factor for very old patients with COVID-19, but emphasize the role of underweight and malnutrition for in-hospital mortality in geriatric patients with COVID-19.publishedVersionPeer reviewe

Myeloid Cells Contribute to Tumor Lymphangiogenesis

The formation of new blood vessels (angiogenesis) and lymphatic vessels (lymphangiogenesis) promotes tumor outgrowth and metastasis. Previously, it has been demonstrated that bone marrow-derived cells (BMDC) can contribute to tumor angiogenesis. However, the role of BMDC in lymphangiogenesis has largely remained elusive. Here, we demonstrate by bone marrow transplantation/reconstitution and genetic lineage-tracing experiments that BMDC integrate into tumor-associated lymphatic vessels in the Rip1Tag2 mouse model of insulinoma and in the TRAMP-C1 prostate cancer transplantation model, and that the integrated BMDC originate from the myelomonocytic lineage. Conversely, pharmacological depletion of tumor-associated macrophages reduces lymphangiogenesis. No cell fusion events are detected by genetic tracing experiments. Rather, the phenotypical conversion of myeloid cells into lymphatic endothelial cells and their integration into lymphatic structures is recapitulated in two in vitro tube formation assays and is dependent on fibroblast growth factor-mediated signaling. Together, the results reveal that myeloid cells can contribute to tumor-associated lymphatic vessels, thus extending the findings on the previously reported role of hematopoietic cells in lymphatic vessel formation