Frontier on Alzheimer's Disease Cervellati, Carlo; Zuliani, Giovanni
International journal of molecular sciences,
04/2023, Letnik:
24, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Although substantial progress has been made in the last two decades, there are still important unfilled gaps in the understanding of the pathomechanism of Alzheimer's disease (AD) ....
Current demographic and epidemiological trends highlight a growing task in surgical departments by elderly patients, characterized by high prevalence of comorbidity, complexity, and functional ...disability. Of consequence, discharge of an elderly patient must be considered in a new cultural perspective and should be imagined as a well-structured process starting from admission to surgical department and finishing with the patient discharge in a setting able to support her/him in the best possible way. The lack of a suitable discharge planning and of a proper transition program in the elderly subjects increases the risk of quick re-admission and may negatively affect the functional and the status quality of life of patients and caregivers. To reduce the risk of negative outcome it is essential a hospital organization dedicated to the discharge of frail older patients considering: (1) adequate attention to assess the comprehensive clinical/social/care conditions; (2) respect of the expectations of the patient and her/his relatives; (3) formalization of institutional roles or teams designated to the planning and coordination of discharge; (4) good knowledge of management programs of transitional care, and (5) strong communication/information ability in patients transition between hospital, home care and community settings.
We evaluated the effect of Acetyl-cholinesterase-inhibitors (AChEIs) on cognitive decline and overall survival in a large sample of older patients with late onset Alzheimer's disease (LOAD), vascular ...dementia (VD) or Lewy body disease (LBD) from a real world setting. Patients with dementia enrolled between 2005 and 2020 by the "Alzheimer's Disease Research Centers" were analysed; the mean follow-up period was 7.9 years. A 1:1 propensity score matching was performed generating a cohort of 1.572 patients (786 treated AChEIs + and 786 not treated AChEIs- with AChEIs. The MMSE score was almost stable during the first 6 years of follow up in AChEIs + and then declined, while in AChEIs- it progressively declined so that at the end of follow-up (13.6 years) the average decrease in MMSE was 10.8 points in AChEIs- compared with 5.4 points in AChEIs + (p < 0.001). This trend was driven by LOAD (Δ-MMSE:-10.8 vs. -5.7 points; p < 0.001), although a similar effect was observed in VD (Δ-MMSE:-11.6 vs. -8.8; p < 0.001). No effect on cognitive status was found in LBD. At multivariate Cox regression analysis (adjusted for age, gender, dependency level and depression) a strong association between AChEIs therapy and lower all-cause mortality was observed (H.R.:0.59; 95%CI: 0.53-0.66); this was confirmed also in analyses separately conducted in LOAD, VD and LBD. Among older people with dementia, treatment with AChEIs was associated with a slower cognitive decline and with reduced mortality, after a mean follow-up of almost eight years. Our data support the effectiveness of AChEIs in older patients affected by these types of dementia.
Purpose
The impacts of pre-existing atrial fibrillation (AF) on COVID-19-associated outcomes are unclear. We conducted a systematic review and meta-analysis to investigate the pooled prevalence of ...pre-existing AF and its short-term mortality risk in COVID-19 patients.
Methods
Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in abstracting data and assessing validity. We searched MEDLINE and Scopus to locate all the articles published up to January 31, 2021, reporting data on pre-existing AF among COVID-19 survivors and non-survivors. The pooled prevalence of pre-existing AF was calculated using a random effects model and presenting the related 95% confidence interval (CI), while the mortality risk was estimated using the Mantel-Haenszel random effects models with odds ratio (OR) and related 95% CI. Statistical heterogeneity was measured using the Higgins I
2
statistic.
Results
Twelve studies, enrolling 15.562 COVID-19 patients (mean age 71.6 years), met the inclusion criteria and were included in the final analysis. The pooled prevalence of pre-existing AF was 11.0% of cases (95% CI: 7.8–15.2%,
p
< 0.0001) with high heterogeneity (
I
2
= 95.2%). Pre-existing AF was associated with higher risk of short-term death (OR 2.22, 95% CI 1.47–3.36,
p
< 0.0001), with high heterogeneity (
I
2
= 79.1%).
Conclusion
Pre-existing AF is present in about 11% of COVID-19 cases but results associated with an increased risk of short-term mortality.
Older people with type 2 diabetes are at high risk of mobility disability. We investigated the association of diabetes with lower-limb muscle mass and muscle quality to verify whether ...diabetes-related muscle impairments mediate the association between diabetes and low walking speed.
We performed a cross-sectional analysis of 835 participants (65 years old and older) enrolled in the InCHIANTI (Invecchiare in Chianti, aging in the Chianti area) population-based study. Total, muscular, and fat cross-sectional areas of the calf and relative muscle density were measured using peripheral quantitative computerized tomography. Indicators of muscle performance included knee-extension torque, ankle plantar flexion and dorsiflexion strength, lower-extremity muscle power, and ankle muscle quality (ratio of ankle strength to the muscle area kilograms per centimeters squared). Gait performance was assessed by 4- and 400-m walking speed. Diabetes was ascertained by standard American Diabetes Association criteria.
Prevalence of diabetes was 11.4%. After adjustment for age and sex, participants with diabetes had lower muscle density, knee and ankle strength, and muscle power and worse muscle quality (all P < 0.05). Diabetic participants were also slower on both 4-m (β: -0.115 ± 0.024 m/s, P < 0.001) and 400-m (β:-0.053 ± 0.023 m/s, P < 0.05) walking tests. In multivariable linear regression models, lower-limb muscle characteristics accounted for 24.3 and 15.1% of walking speed difference comparing diabetic and nondiabetic subjects in the 4- and 400-m walks, respectively.
In older persons, diabetes is associated with reduced muscle strength and worse muscle quality. These impairments are important contributors of walking limitations related to diabetes.
Sarcopenia is associated with increased risk of adverse outcomes in older people. Aim of the study was to explore the predictive value of the European Working Group on Sarcopenia in Older People ...(EWGSOP) diagnostic algorithm in terms of disability, hospitalization, and mortality and analyze the specific role of grip strength and walking speed as diagnostic criteria for sarcopenia.
Longitudinal analysis of 538 participants enrolled in the InCHIANTI study. Sarcopenia was defined as having low muscle mass plus low grip strength or low gait speed (EWGSOP criteria). Muscle mass was assessed using bioimpedance analysis. Cox proportional and logistic regression models were used to assess risk of death, hospitalization, and disability for sarcopenic people and to investigate the individual contributions of grip strength and walking speed to the predictive value of the EWGSOP's algorithm.
Prevalence of EWGSOP-defined sarcopenia at baseline was 10.2%. After adjusting for potential confounders, sarcopenia was associated with disability (odds ratio 3.15; 95% confidence interval CI 1.41-7.05), hospitalization (hazard ratio HR 1.57; 95% CI 1.03-2.41), and mortality (HR 1.88; 95% CI 0.91-3.91). The association between an alternative sarcopenic phenotype, defined only by the presence of low muscle mass and low grip strength, and both disability and mortality were similar to the association with the phenotypes defined by low muscle mass and low walking speed or by the EWGSOP algorithm.
The EWGSOP's phenotype is a good predictor of incident disability, hospitalization and death. Assessment of only muscle weakness, in addition to low muscle mass, provided similar predictive value as compared to the original algorithm.
The human oral microbiome (HOM) is the second largest microbial community after the gut and can impact the onset and progression of several localized and systemic diseases, including those of viral ...origin, especially for viruses entering the body via the oropharynx. However, this important aspect has not been clarified for the new pandemic human coronavirus SARS-CoV-2, causing COVID-19 disease, despite it being one of the many respiratory viruses having the oropharynx as the primary site of replication. In particular, no data are available about the non-bacterial components of the HOM (fungi, viruses), which instead has been shown to be crucial for other diseases. Consistent with this, this study aimed to define the HOM in COVID-19 patients, to evidence any association between its profile and the clinical disease. Seventy-five oral rinse samples were analyzed by Whole Genome Sequencing (WGS) to simultaneously identify oral bacteria, fungi, and viruses. To correlate the HOM profile with local virus replication, the SARS-CoV-2 amount in the oral cavity was quantified by digital droplet PCR. Moreover, local inflammation and secretory immune response were also assessed, respectively by measuring the local release of pro-inflammatory cytokines (L-6, IL-17, TNFα, and GM-CSF) and the production of secretory immunoglobulins A (sIgA). The results showed the presence of oral dysbiosis in COVID-19 patients compared to matched controls, with significantly decreased alpha-diversity value and lower species richness in COVID-19 subjects. Notably, oral dysbiosis correlated with symptom severity (
= 0.006), and increased local inflammation (
< 0.01). In parallel, a decreased mucosal sIgA response was observed in more severely symptomatic patients (
= 0.02), suggesting that local immune response is important in the early control of virus infection and that its correct development is influenced by the HOM profile. In conclusion, the data presented here suggest that the HOM profile may be important in defining the individual susceptibility to SARS-CoV-2 infection, facilitating inflammation and virus replication, or rather, inducing a protective IgA response. Although it is not possible to determine whether the alteration in the microbial community is the cause or effect of the SARS-CoV-2 replication, these parameters may be considered as markers for personalized therapy and vaccine development.
The most frequent form of monogenic hypercholesterolemia, also known as Familial Hypercholesterolemia (FH), is characterized by plasma accumulation of cholesterol transported in Low Density ...Lipoproteins (LDLs). FH has a co-dominant transmission with a gene-dosage effect. FH heterozygotes have levels of plasma LDL-cholesterol (LDL-C) twice normal and present xanthomas and coronary heart disease (CHD) in adulthood. In rare FH homozygotes plasma LDL-C level is four times normal, while xanthomas and CHD are present from infancy. Most FH patients are carriers of mutations of the LDL receptor (LDLR); a minority of them carry either mutations in the Apolipoprotein B (ApoB), the protein constituent of LDLs which is the ligand for LDLR, or gain of function mutations of PCSK9, the protein responsible for the intracellular degradation of the LDLR. From 1970 to the mid 90s some publications described children with the clinical features of homozygous FH, who were born from normocholesterolemic parents, strongly suggesting a recessive transmission of FH. In these patients the involvement of LDLR and APOB genes was excluded. Interestingly, several patients were identified in the island of Sardinia (Italy), whose population has a peculiar genetic background due to geographical isolation. In this review, starting from the early descriptions of patients with putative recessive hypercholesterolemia, we highlight the milestones that led to the identification of a novel gene involved in LDL metabolism and the characterization of its encoded protein. The latter turned out to be an adaptor protein required for the LDLR-mediated endocytosis of LDLs in hepatocytes. The loss of function of this protein is the cause of Autosomal Recessive Hypercholesterolemia (ARH).
•Description of rare patients with Autosomal Recessive Hypercholesterolemia (ARH)•Exclusion of mutations of LDL-receptor and Apolipoprotein B in ARH patients•Discovery of a defect in the internalization of the LDL-receptor in ARH lymphocytes•Identification of ARH gene and characterization of its mutations in ARH patients•Demonstration of the functional role of ARH protein in LDL-receptor endocytosis
Inflammation plays a major role in the onset of cardiovascular disease (CVD). Interleukine-6 (IL-6) is a multifunctional cytokine involved both in the beneficial acute inflammatory response and in ...the detrimental chronic low-grade systemic inflammation. Large genetic human studies, using Mendelian randomization approaches, have clearly showed that IL-6 pathway is causally involved in the onset of myocardial infarction. At the same time, IL-6 pathway is divided into two arms: classic signaling (effective in hepatocytes and leukocytes) and trans-signaling (with ubiquitous activity). Trans-signaling is known to be inhibited by the circulating soluble glycoprotein 130 (sgp130). In animal and in vitro models, trans-signaling inhibition with sgp130 antibody clearly shows a beneficial effect on inflammatory disease and atherosclerosis. Conversely, epidemiological data report inconsistent results between sgp130 levels and CV risk factors as well as CV outcome. We have reviewed the literature to understand the role of sgp130 and to find the evidence in favor of or against a possible clinical application of sgp130 treatment in the prevention of cardiovascular disease.
We conducted a systematic review and meta-analysis to investigate the possible difference in the SARS-CoV-2 viral load between asymptomatic and symptomatic COVID-19 patients. Preferred Reporting ...Items for Systematic Reviews and Meta-Analyses guidelines were followed in abstracting data and assessing validity. We searched MEDLINE, Scopus, Web of Science and Google Scholar for all investigations in the English language, reporting data on the threshold cycle (Ct) from real-time RT-PCR assays for the RNA-dependent RNA polymerase (RdRp), envelope (E) and nucleocapsid (N) SARS-CoV-2 genes in asymptomatic and symptomatic COVID-19 patients. Results: Overall, 703 COVID-19 patients (553 symptomatic and 150 asymptomatic) were analyzed. Five investigations reported the mean age of patients, evidencing that asymptomatic patients were younger than symptomatic patients (34.0 vs. 40.3 years, respectively). Pooled data regarding the levels of expression of the RdRp gene revealed no significant difference between symptomatic and asymptomatic subjects. Similarly, no differences were observed comparing the mean Ct values for the E and N genes. Based on real-time RT-PCR data, no differences exist in the viral load between symptomatic and asymptomatic COVID-19 subjects considering Ct values for RdRp, E and N genes’ expression. Asymptomatic subjects may represent a reservoir of the infection and significantly contribute to the maintenance of the pandemic.
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