Severe AD Research Articles

Assessing Disease Control in Patients with Atopic Dermatitis by Using the Atopic Dermatitis Control Tool in Daily Practice

Plain Language SummaryAtopic dermatitis (AD) is a common chronic skin disease that affects up to 10% of adults. The burden of AD is not only limited to skin symptoms but also sleep disturbances, mental health effects, declined work productivity, which leads to a general decrease in quality of life. Recently, the Atopic Dermatitis Control Tool (ADCT) was recommended for comprehensively assessing disease control in adults with AD. However, little is known about the use of ADCT in daily practice. In this study, by sending questionnaires to 2,066 adult patients with previously physician-diagnosed AD, we evaluated disease control in adult AD patients using the ADCT in daily practice and assessed its association with age, sex, disease severity, quality of life, itch, and treatment. It was found that around 60% of the patients perceived their AD as controlled. Uncontrolled AD was associated with more severe AD, worse quality of life, increased itchiness, and was more likely to be treated with topical anti-inflammatory agents only. Females were more likely to report uncontrolled AD than males, probably due to their limited use of systemic treatments. Additionally, the ADCT could contribute to switching patients with uncontrolled AD from topical to systemic treatment.

Mild atopic dermatitis is characterized by increase in non-staphylococcus pathobionts and loss of specific species

Atopic dermatitis is the most common inflammatory skin condition with a severe negative impact on patients’ quality of life. The etiology of AD is complex and depends on age, genetics, the immune system, environmental factors, and the skin microbiome, with a key role for pathogenic Staphylococcus aureus in the development of severe AD. However, the composition of the skin microbiome in mild AD is understudied. Here, using metagenomic shallow shotgun sequencing, we showed that mild AD lesions did not show a significant difference in the diversity of the skin microbiome compared to samples from non-AD patients and that the relative abundance of S. aureus did not differ in these mild AD lesions. However, when we assessed other taxa, Mycobacterium ostraviense, Pedobacter panaciterrae_A and four Streptomyces species were identified with higher abundances in mild AD lesions and species of 15 genera were decreased in abundance. The highest fold decreases were observed for Paracoccus marcusii, Microbacterium lacticum, Micrococcus luteus, and Moraxella sp002478835. These microbiome compositional insights are a first step towards novel microbiome-based diagnostics and therapeutics for early intervention at the stage of mild AD and provide a path forward for the functional study of species involved in this often-overlooked patient population.

Disease burden, clinical management and unmet treatment need of patients with moderate to severe atopic dermatitis; consensus statements, insights and practices from CERTADE (Central/Eastern EU, Russia, Turkiye AD Experts) Delphi panel.

There is limited insight into the current disease burden and everyday clinical management of moderate-to- severe AD in Poland, Czechia, Russia, and Turkiye. Therefore, this study aimed to get information-driven insights regarding the current disease burden and clinical management of patients with moderate-to-severe AD with common and differentiating aspects of the patient journey and establish a consensus. In this modified 2-round Delphi panel, 133 questions were asked in total to 27 dermatologists. A consensus was achieved when 70% of the panel members strongly agreed or agreed (or strongly disagreed or disagreed) with an item. Statements with <40% agreement dropped from the Delphi rounds and were not repeated. The results state that AD has a significant impact on the quality of life for both patients and their families with social and economic consequences in these countries. While there were significant dissimilarities regarding the current treatment approach by preference order and treatment duration among participants, there was also a high percentage of consensus on literature and guideline-based statements. Current topical therapies and the immune response modifiers were not found to be sufficient by panelists to cover the therapeutic needs of patients with moderate-to-severe AD. Moreover, panelists highlighted the significant burden of adverse events with the off-label use of currently available immunosuppressants. These results underlined that there is a significant disease burden with an unmet treatment need for patients with moderate-to-severe AD in Poland, Czechia, Russia, and Turkiye.

IL-4-induced decrease in both the number and CTLA-4 expression of Treg impairs suppression of Th2 type inflammation in severe atopic dermatitis

BackgroundTreg plays a pivotal role in the suppression of Th2 cell and the maintenance of immune homeostasis. The precise molecular mechanism underlying the disruption of Treg suppression of Th2 cell and the promotion of Th2 type inflammation in allergic diseases remains elusive. ObjectiveThis study aims to investigate the molecular mechanism underlying quantitative and functional changes of Treg in AD. MethodsThe molecular mechanism was investigated using flow cytometry, mRNA sequencing, co-culture experiments, co-immunoprecipitation, chromatin immunoprecipitation, and bisulfite sequencing in vitro or in AD mice model and patients with AD. ResultsIncreased proportion of Treg was detected in mild and moderate AD. Conversely, characteristic decrease in both the number and CTLA-4 expression of Treg was relevant to serum IL-4 level in severe AD patients, which was verified under a high concentration of IL-4 treatment in vitro. The underlying mechanism is that IL-4/pSTAT6 pathway recruits DNMT1 and HDAC2 to inhibit transcriptional regulation of Foxp3 and CTLA-4 loci. High level of IL-4 impaired the suppression of Treg against Th2 cell differentiation mediated by CTLA-4, and blockade of IL-4Rα signaling in Treg restored Treg number and suppression of Th2 cell in AD model mice and patients with AD. ConclusionThe number of Treg is relevant to stratification of severity and serum IL-4 level in patients with AD. Abnormal high level of IL-4 epigenetically triggers a decrease in both the number and CTLA-4 expression of Treg. The reduced expression of CTLA-4 on Treg induced by IL-4 impairs suppression of Th2 cell differentiation.

Management of Patients Affected by Moderate-to-Severe Atopic Dermatitis with JAK Inhibitors in Real-World Clinical Practice: An Italian Delphi Consensus.

Several systemic therapies have been approved for the treatment of severe AD. In particular, Janus kinase inhibitors (JAKi), including abrocitinib, baricitinib, and upadacitinib, recently received approval for the treatment of patients with severe AD after being evaluated in several clinical trials. However, a few concerns have been raised regarding their long-term safety and the management of these drugs in real-world clinical practice. In this article we described the results of a Delphi consensus aimed at describing the knowledge on JAKi and focusing, in particular, on providing clinical recommendations for dermatologists in daily practice regarding the use of these drugs. Twelve Italian dermatologists reviewed the most recent literature regarding the efficacy and safety profiles of JAKi and proposed 24 statements. Agreement was reached for statements focusing on three main topics: (1) place in therapy of JAKi in patients with moderate-to-severe AD; (2) effectiveness and safety of JAK inhibitors in different phenotypes; (3) different approaches to the management of patients treated with JAKi in clinical practice. The panel proposed several recommendations regarding all the statements. Given the wide use of JAKi in clinical practice, it is crucial to establish a specific follow-up for each patient's phenotype in order to achieve the best possible clinical outcome and minimize potential adverse events.

Phenotypes, endotypes and genotypes of atopic dermatitis and allergy in populations of African ancestry on the continent and diaspora.

Atopic dermatitis is a complex inflammatory condition characterized by synergist interactions between epidermal and immune related genotypes, skin barrier defects and immune dysregulation as well as microbial dysbiosis. Ethnicity-specific variations in clinical presentation, immune endotypes and genetic susceptibility have been described in diverse populations. We summarize available data with specific consideration of AD in populations of African ancestry. Some highlights include the observation of AD lesions on extensor surfaces, lichen planus-like AD, prurigo type AD and follicular AD in African populations. In addition, a consistent absence of dominant filaggrin gene defects has been reported. The detection of normal filaggrin protein content in AD skin implicates the contribution of alternative mechanisms in the pathogenesis of AD in African patients. Markedly high IgE has been described in paediatric and adult African AD. While Th2, Th22 and Th17 activation in African AD skin shares the same direction as with other populations, it has been noted that the magnitude of activation is dissimilar. Reduced Th17 cytokines have been observed in the circulation of moderate to severe paediatric AD.

The circadian metabolome of atopic dermatitis

BackgroundAtopic dermatitis (AD) is a chronic inflammatory skin disease characterized by dry, pruritic skin. Several studies have described nocturnal increases in itching behavior, suggesting a role for the circadian rhythm in modulating symptom severity. However, the circadian rhythm of metabolites in the skin and serum of patients with AD has yet to be described. ObjectiveThis study sought to assess circadian patterns of skin and serum metabolism in patients with AD. Methods12 patients with moderate to severe AD and 5 healthy volunteers were monitored for 28 hours in a controlled environment. Serum was collected every 2 hours and tape strips every 4 hours from both lesional and non-lesional skin in participants with AD and location-, sex-, and age-matched, healthy skin of controls. We then performed an untargeted metabolomics analysis, examining the circadian peaks of metabolism in AD. ResultsDistinct metabolic profiles were observed in AD vs. control samples. When accounting for time of collection, the greatest differences in serum metabolic pathways were observed in the arachidonic acid, steroid biosynthesis, and terpenoid backbone biosynthesis. We identified 42 circadian peaks in AD or control serum and 17 in the skin. Pathway enrichment and serum-skin metabolite correlation varied throughout the day. Differences were most evident in the late morning and immediately after sleep onset. ConclusionAlthough limited by a small sample size and observational design, our findings suggest that accounting for sample collection time could improve biomarker detection studies in AD and highlight that metabolic changes may be associated with nocturnal differences in symptom severity.

Injection site reactions after dupilumab or tralokinumab for atopic dermatitis

Background: Injection site reaction (ISR) is a local phenomenon defined as a constellation of symptoms, including swelling, erythema, pruritus, and pain around the site of injection. Objective: ISR is reported as a frequent adverse event after subcutaneous injection (SCI) of several biologics. Methods: We performed an observational real-life study to compare dupilumab and tralokinumab as regards ISR, analysing frequency, duration and intensity of symptoms related to SCI. From January 2023 to June 2023, we enrolled adult patients affected by moderate to severe AD and being on dupilumab or tralokinumab treatment. A 12 items questionnaire was administered to all enrolled patients. Results and conclusions: Three hundred and ninety-two patients were included. ISR was a frequent occurrence in both the treatment groups, with tralokinumab causing ISR more frequently than dupilumab. However, the reactions were generally mild and no patient stopped therapy.

Measuring “What Matters Most™” to individuals living with Alzheimer’s disease and care partners: A conceptual model of Alzheimer’s Disease

AbstractBackgroundThe Alzheimer’s Disease Patient and Caregiver Engagement™ Initiative‘s What Matters Most™ (WMM) Research Program includes seminal studies to identify and measure treatment‐related needs, preferences, and priorities of people living with Alzheimer’s disease (PLWAD) and their informal care partners (CPs). WMM research identified 42 concepts deemed to be of highest relevance and importance in treatment related needs across the AD spectrum (preclinical – severe AD). Now, the WMM Next Generation Studies (WMM NG) are generating data to contextualize findings through a conceptual model of disease, verify previously identified concepts, and learn of new emerging concepts from a more diverse and inclusive study sample. Results will be used to broaden the context of an online survey to inform additional studies, including health economic evaluations, across the Alzheimer’s research field.MethodA draft conceptual model of disease was developed building on an existing model (Hartry, 2018) after careful examination of previously collected WMM data (DiBenedetti, 2020; Hauber, 2023). A cross‐sectional, observational qualitative research study was conducted, comprised of a series of individual, in‐depth interviews of those with clinically confirmed PLWAD and their CPs. Analyses of these data include qualitative content analysis and thematic analysis methods (Hsiu‐Fang, 2005).ResultThe 42 WMM concepts were categorized across thought processing (14), communication (3), mood/emotions (6), daily activities (12), social life/activities, (3) and independence (4) domains to form a draft conceptual model of disease. A total of 64 PLWAD and CPs of diverse ethnic and cultural backgrounds participated in in‐depth, web‐based interviews. Results reaffirmed the 42 WMM concepts, informed the model structure, and added missing concepts. Further, cognitive debriefing approaches elucidated participant perception of the terms “bother” and “interference” describing emotional connotation of these words, compared to the assessment of “impact”, to inform development of AD burden survey items.ConclusionWMM concepts contextualized by domains offer a roadmap to support future clinical trials seeking to measure clinically meaningful outcomes and patient‐centric endpoints. WMM NG data collection will enhance robustness of the findings to evaluate the impact of disease symptoms and inform health economic evaluation. The conceptual model will be refined continuously over the WMM research.

Strategies for managing patients with moderate to severe Alzheimer’s disease: high‐dose donepezil vs. memantine combination

AbstractBackgroundsWhen dementia patients who took already a maintenance dose of 10mg donepezil get worse to advanced stage, clinicians would consider and select which one is better between higher‐dose donepezil (23 mg/day) and memantine combination.ObjectivesTo compare the clinical benefits between high‐dose donepezil and memantine (20 mg/day) combination in moderate to severe Alzheimer’s diseaseMethodsA single center, retrospective, observational study was conducted. Patients with moderate to severe AD who were treated with a stable dose of donepezil were included. They started further treatments such as higher‐dose donepezil or memantine combination because they showed poor or waning response to a maintenance dose. After 6 months follow‐up, clinical efficacy and safety were compared between two groups, higher‐dose donepezil and memantine combination.ResultsA total of 108 patients, 35 with higher‐dose donepezil and 75 with memantine combination, were included. Baseline characteristics such as age, sex, education, MMSE, and CDR were similar between groups. After follow‐up, changes of MMSE and CDR were not different. Treatment responses measured as CGI‐C were as follows: 41.3% (improved 31, not changed 25, and worse 9) of patients improved after memantine combination and 22.9% (improved 8, not changed 12, and worse 15) improved after higher‐dose donepezil (p = 0.069). Adverse events were not different. Among patients with memantine combination, those who had no benefits to the initial donepezil showed better responses (27 vs. 48). Patients who had benefits to lower dose of donepezil showed better responses (24 vs. 11) after higher‐dose.ConclusionBoth of higher‐dose donepezil and memantine combination, which are approved as effective in moderate to severe AD, were not different in clinical benefits and safety. Although not statistically significant, treatment responses showed some differences. Patients who had shown good response at the time of the initial therapy of donepezil preferred higher‐dose donepezil over memantine combination, whereas those who did not respond to the initial donepezil had more effective after memantine was added. Further studies including randomized blind trials could strengthen these findings.

Influence of drugs of protocol therapy on the production of pro-inflammatory cytokines of t-lymphocytes of children with bronchial asthma

ABSTRACT. At the current stage of solving the problem in the pathogenesis of atopic BA in moderate-severe and severe course of the disease, the leading role is played by pro-inflammatory cytokines of T-lymphocytes and factors of the late phase of allergic inflammation. Goal. To determine the effect of the drugs of the therapy protocol recommended by GINA (2021) and the Ministry of Health of Ukraine No. 2856 on the production of pro-inflammatory cytokines in children with AD. Materials and methods. The study was conducted in 106 patients with BA and 20 healthy children aged 5 to 14 years in the period of disease remission before and after therapy. The impact of the protocol therapy scheme on the production of pro-inflammatory cytokines and their antibody control in children with different degrees of severity of the course of the disease was evaluated. The results. In asthma in children with a mild persistent course, protocol therapy reduces the release of mediators of the early phase of the allergic disease and the partial production of pro-inflammatory cytokines, which leads to clinical remission of the disease. With a moderately severe persistent course of AD, the influence of protocol therapy drugs reduce the level of production of pro-inflammatory cytokines to weakly positive values, which indicates incomplete control of therapy and unstable clinical remission. In severe persistent AD, protocol therapy partially reduces the production of pro-inflammatory cytokines, but does not affect the late phase of allergic inflammation and the autoimmune component of the pathogenesis of the disease. Conclusions. The recommended GINA protocol therapy (2021) eliminates the early phase and does not affect the late phase of allergic inflammation and the autoimmune component. This requires the development of additional therapy for moderate and severe asthma in children.

METHOTREXATE IN THE MANAGEMENT OF MODERATE TO SEVERE ATOPIC DERMATITIS

The retrospective study was conducted in the Department of Dermatology from June 2021 to June 2022 to analyze the complication profile, adverse effects, and efficacy of methotrexate in patients with moderate to severe AD. The patients with moderate to severe AD were included in the study. The demographic data, clinical records, and response to MTX were analyzed. The clinical response was assessed as a decrease in itching, improvement in skin lesions, lesser use of topical CS, and assessment by the dermatologist. During the treatment, the patient's renal function, liver function, and complete blood count were assessed every month for three months. The study was conducted on 40 patients (17 female, 23 male). The mean starting dose was 13.8mg. The mean maintenance dose was 17.8 mg. The dose was gradually tapered after control of symptoms. 28 (70%) patients had clear responses, 7 (17.5%) had excellent, 3 (7.5%) had good, and 2(5%) patients had partial response. The mean duration of MTX therapy was 36.9 months. Due to disease control, MTX was discontinued in 8 (17.5%) patients. 4 (10%) patients remained clear, and treatment was restarted in 3 (7.5%) patients due to flare. Thirty-two patients were still on treatment at the time of the study. Nausea occurred in 4(10%) patients, fatigue in 3 (7.5%) and a transient increase in transaminases in 7 (17.5%) patients. 1 (2.5%)patient had a transient decrease in hemoglobin and platelet level; Hb was maintained at 106-120 g/L, and platelet level became normal. Methotrexate is safe and effective for the treatment of moderate to severe AD. Lower doses can control disease in the long term without posing any significant risks.

Economic Burden of Alzheimer’s Disease: A Systematic Review

ObjectivesAlzheimer’s disease (AD) has become one of the most prevalent neurodegenerative disorders among the elderly. The global cost of dementia is expected to reach US $2 trillion in 2030. In this systematic review, existing evidence on the cost of dementia specific to AD is appraised. MethodsA comprehensive search was done on 3 databases, namely PubMed, ScienceDirect, and Web of Science, to identify original cost-of-illness studies that only evaluate the economic burden of AD up to August 2022. The risk of bias in the studies was assessed using Consolidated Health Economic Evaluation Reporting Standards 2022 criteria. Cost articles without specifying etiology of AD or those in non-English were excluded. ResultsTwelve of 5536 studies met the inclusion criteria. The total annual cost of AD per capita ranged from US $468.28 in mild AD to US $171 283.80 in severe AD. The cost of care raised nonlinearly with disease severity. Indirect caregiving cost represented the main contributor to societal cost in community-dwelling patients. When special caregiving accommodation was opted in daily care, it results in cost shifting from indirect cost to direct nonmedical cost. Formal caregiving accommodation caused increase in direct cost up to 67.3% of overall economic burden of the disease. ConclusionsAD exerts a huge economic burden on patients and caregivers. Overall rise of each cost component could be anticipated with disease deterioration. Choice of special caregiving accommodation could reduce caregiver’s productivity loss but increase the direct nonmedical expenditure of the disease from societal perspective.

Evaluating Elements of the Care Partner Experience in Individuals Who Care for People with Alzheimer's Disease Across the Severity Spectrum.

Non-professional care partners play an important and often evolving role in the care of persons living with Alzheimer's disease (PLWAD). We investigated two elements of the care partner experience, namely time and strain incurred by care partners providing care to PLWAD across the severity spectrum. Data gathered from the Alzheimer's Disease Patient and Caregiver Engagement (AD PACE) What Matters Most (WMM) study series were analyzed to determine how much time care partners spent providing care to PLWAD based on where the care recipients lived. Additionally, quantitative assessments of weekly hours providing care and the strain experienced by care partners were conducted using the UsAgainstAlzheimer's A-LIST Insights Series survey, which included the Modified Caregiver Strain Index (MCSI). Finally, a targeted literature review was conducted to contextualize findings and characterize the existing literature landscape. Care partners in the AD PACE WMM studies (n = 139) spent significantly more hours providing care for recipients who lived with someone (mean ± standard deviation [SD], 57.3 ± 44.3h/week) than for recipients who lived alone (26.0 ± 12.0h/week) (P = 0.0096) or lived in assisted living/nursing home (23.6 ± 14.4h/week) (P = 0.0002). In the A-LIST Insights Series survey, care partners provided an overall mean (± SD) 58.1 ± 53.0h of direct care each week, with caregiving hours increasing with increasing severity of AD/AD-related dementias(AD/ADRD). Additionally, care partners for recipients with mild (n = 14), moderate (n = 111), and severe AD/ADRD (n = 91) had overall mean MCSI scores of 9.0 ± 3.8 (range 2-14), 13.3 ± 4.8 (range 4-23), and 17.5 ± 5.3 (range 4-26), respectively, with higher scores suggesting greater care partner strain. Persons living with AD require increasing levels of care along the spectrum of disease, and even individuals with early disease need care from partners. Early interventions that slow progression of AD and programs that improve family function may have beneficial impact on the experiences of care partners for recipients with mild, moderate, or severe AD.

Correlation of serum complement factor 5a level with inflammatory response and cognitive function in patients with Alzheimer’s disease of different severity

BackgroundAlzheimer’s disease (AD) is a common cause of dementia. Serum complement factor 5a (C5a) is exceedingly implicated in AD. We explored the role of C5a levels in AD patients of different severity.MethodsMild, moderate, and severe AD patients, and healthy controls were included. C5a and pro-inflammatory factor (TNF-α, IL-1β, IL-6, CRP) levels were assessed by ELISA, and cognitive function was evaluated by Mini-Mental state examination (MMSE) score. The correlations between C5a, inflammatory factor levels, MMSE score, and plasma Aβ42/Aβ40 ratio were analyzed by Pearson tests. Independent risk factors for AD aggravation were assessed by logistic multivariate regression analysis. According to the cut-off value of receiver operating characteristic (ROC) curve analysis of C5a level, AD patients were assigned into low/high expression groups, and severe AD incidence was compared. Severe AD cumulative incidence was analyzed by Kaplan-Meier curve.ResultsSerum C5a, TNF-α, IL-1β, IL-6 and CRP levels were raised, and MMSE score was lowered in AD. Serum C5a, TNF-α, IL-1β, IL-6 and CRP levels in severe AD patients were higher than those in mild/moderate AD patients, but there were no significant differences in these cytokines between moderate and mild AD groups. The MMSE score of severe AD patients was lower than that of mild/moderate AD patients. Serum C5a level was positively correlated with serum TNF-α, IL-1β, IL-6, and CRP levels, and negatively correlated with MMSE score, with no obvious correlation with plasma Aβ42/Aβ40 ratio. Serum C5a level was one of the independent risk factors for AD aggravation. The occurrence of severe AD might be related to an increase in serum C5a level.ConclusionSerum C5a level increased with AD severity, and its expression was positively correlated with serum pro-inflammatory factor levels, and negatively correlated with cognitive function.

Artículo traducido] Consenso de la Sociedad Española de Farmacia Hospitalaria sobre el manejo fármacoterapéutico óptimo de la dermatitis atópica

AimThis study’s aims are: 1) To use the Delphi method to determine the level of consensus among HPs as regards the factors involved in the current approach to patients with AD; 2) To identify potential areas for improvement in hospital pharmacy in terms of dealing with patients with severe AD; and 3) To contribute to adequate pharmaceutical care for patients with AD by drawing up recommendations. MethodsA two-round Delphi survey with participation from HPs from all over Spain. Three theme-based blocks were set out: 1) AD; 2) Management of patients with severe AD in the Hospital Pharmacy setting; and 3) Unmet needs (pathology, patient, treatment and management). ResultsThe 42 HPs participating reached a consensus in recognizing the impact of severe AD on the patients suffering from it, the need to encourage adherence and the recommendations to use scales that take into account the patient's quality of life and indicators of the patient’s experience. It has also been demonstrated that it is worthwhile evaluating the results in real clinical practice in consensus with other specialists from the multidisciplinary team. Finally, it is advisable to use drugs that have demonstrated long-term effectiveness and safety for patients with severe AD, given the disease´s chronic nature. ConclusionsThis Delphi consensus highlights the impact of severe AD on patients, the importance of a multidisciplinary and holistic approach, in which HP play a major role. It also highlights the importance of increased access to new drugs to improve health outcomes.

Relationship Between Nasal Cavity Microbial Colonization and Atopic Dermatitis Severity: A Systematic Review and Meta-analysis

Context: Atopic dermatitis is among the most common chronic diseases in children, with increasing prevalence. Objectives: This study evaluated the relationship between the microbial composition of nasal nares and atopic dermatitis severity. Study Selection: This meta-analysis included all types of studies (experimental and observational) on nasal colonization of pediatrics (age ≤ 19 years old) with a diagnosis of AD confirmed by a physician. The following search strategy was used in the databases: Atopic dermatitis AND (nasal OR nares). Results: Twenty-two studies were included in our analysis. Nine studies compared the odds of Staphylococcus aureus nasal colonization between AD pediatrics and non-AD healthy controls. In 13 studies, there was no control group. Subgroup analysis was performed on eight studies regarding AD severity in pediatrics with positive nasal colonization of S. aureus. Pooled analysis showed that S. aureus was colonized in 38% of the pediatrics with mild AD, 50% with moderate AD, and 22% with severe AD. The random-effects model showed that the odds of nasal colonization of S. aureus were significantly higher in AD pediatrics than in non-AD healthy controls (OR: 2.52; 95% CI (1.60, 3.97); I2 = 72%). Conclusions: The nasal cavity of pediatric AD patients was more colonized with S. aureus than in healthy children. More studies on children with severe AD are needed to accurately prove the role of S. aureus colonization in the severity of atopic dermatitis.

Assessing awareness in severe Alzheimer’s disease

AbstractBackgroundThere is an urgent need to understand the nature of awareness in severe AD to ensure effective person‐centred care. Transcranial Magnetic Stimulation (TMS) combined with Electroencephalography (EEG), Event Related Potentials (ERPs) and functional Magnetic Resonance Imaging (fMRI) are robust techniques for assessing awareness in clinical populations who are unable to communicate. We present novel feasibility and preliminary data on using these methods to assess capacity for consciousness and contents of awareness in severe AD.Method a) TMS‐EEG was performed in 6 healthy older controls and 3 people with severe AD. The perturbational complexity index (PCIST) was calculated as a measure of capacity for conscious awareness. b) ERPs were recorded during a masked visual perception paradigm and analysed for the presence of visual awareness negativity and P400 components, previously identified as associated with conscious visual perception. c) An fMRI movie‐viewing task, validated in previous studies to demonstrate activation in a fronto‐parietal network during conscious engagement with the film was also conducted.Result a) Participants with severe AD demonstrated a PCIST around the previously identified threshold for consciousness, suggesting reduced capacity for consciousness. b) In response to viewing faces, two patients with severe AD provisionally demonstrated similar visual awareness negativity to healthy controls. c) Healthy controls and one person with severe AD revealed spatially, but not temporally similar activation in a fronto‐parietal network, suggesting differences in conscious engagement with the movie.ConclusionThese biomarkers provide experimental approaches to assess awareness and improve understanding and care for people with severe AD.

Prevalence of anti‐egg albumin antibodies in cerebrospinal fluid of patients with mild and severe Alzheimer’s Disease. Correlation with gender and incidence of anti‐casein antibodies and AGEs.

AbstractBackgroundAlzheimer’s Disease (A.D.) is a multifactorial process. Advanced glycation end products (AGEs) have been correlated with disease development1. Additionally, high concentrations of antibodies against the food derived antigens egg‐albumin and bovine casein, have been detected in patients with Alzheimer’s disease in preliminary research presented by our team, previously (AAIC 2018).In the present study, antibodies against egg‐albumin and bovine casein as well as AGEs were detected in the cerebrospinal fluid of 36 patients with mild and 35 patients with severe Alzheimer’s Disease and 13 healthy individuals and a correlation between the measured parameters and sample properties was attempted.MethodELISA plates pre‐treated with highly hydrophilic microlon resin were used for the purpose of this study2. Egg‐albumin or bovine casein antigens were attached at the ELISA plates for the measurement of antibodies. Additionally, polyclonal antibodies against multiple AGE products were used to detect attached sample CSF AGEs.ResultAccording to the results, 48,6% of of the samples of patients with severe AD had anti‐egg albumin concentration higher than mean concentration of healthy idividuals+2SD (characterized as positive) compared to 8.3% of positive samples in patients with mild disease. An overall 265% increase in mean concentration was observed in severe compared to mild patients, indicating association with severity. The observed difference was significant at p = 0.01 according to mann witney U test. Lower anti‐egg albumin concentrations were observed in female samples of either mild or severe disease (Figure 1). Much lower incidence of anti‐casein antibody positive samples was found in in severe AD (5.7% positive in severe versus 0% in mild AD). A slight, not statisticaly significant, increase in mean anti‐casein antibodies concentration (23.7%) and AGEs (16.2%) was observed in severe compared to mild disease with the higher concentrations also detected in the most positive to anti‐egg albumin samples.ConclusionThe results indicated a potential correlation of antibodies against egg‐albumin with the severity of Alzheimer’s disease with increased incidence in male patients. A lower correlation was observed in case of anti‐casein antibodies and AGEs.

Burden of Illness in People with Alzheimer’s Disease: A Systematic Review of Epidemiology, Comorbidities and Mortality

BackgroundAlzheimer’s disease (AD) is the most common neurodegenerative disease worldwide, and an updated quantification of its impact on morbidity, disability, and mortality is warranted. We conducted a systematic literature review, focusing on the past decade, to characterize AD and assess its impact on affected individuals.MethodsSearches of Embase, MEDLINE, and the Cochrane Library were conducted on August 7, 2020 and updated on November 10, 2021. Observational studies from any country reporting incidence, prevalence, comorbidities, and/or outcomes related to disability and mortality/life expectancy, in people with mild cognitive impairment (MCI) due to AD, or mild, moderate, or severe AD dementia, were considered relevant.ResultsData were extracted from 88 studies (46 incidence/prevalence; 44 comorbidities; 25 mortality-/disability-related outcomes), mostly from Europe, the USA, and Asia. AD dementia diagnosis was confirmed using biomarkers in only 6 studies. Estimated 5-year mortality in AD was 35%, and comorbidity prevalence estimates varied widely (hypertension: 30.2–73.9%; diabetes: 6.0–24.3%; stroke: 2.7–13.7%). Overall, people with AD dementia were more likely to have cardiovascular disease or diabetes than controls, and 5-year mortality in people with AD dementia was double that in the age- and year-matched general population (115.0 vs 60.6 per 1,000 person-years).ConclusionsAD is associated with excess morbidity and mortality. Future longitudinal studies of population aging, incorporating biomarker assessment to confirm AD diagnoses, are needed to better characterize the course of MCI due to AD and AD dementia.