Author Affiliation: (1) Department of Morphology, Surgery, and Medical Sciences, University of Ferrara, Ferrara, Italy (2) Department of Cardiology, Santa Maria Della Misericordia Hospital, Rovigo ...General Hospital Viale Tre Martiri, 45100, Rovigo, Italy (d) lorisroncon@gmail.com Article History: Registration Date: 12/02/2020 Accepted Date: 12/02/2020 Online Date: 01/02/2021 Byline:
Late onset Alzheimer disease (LOAD) is traditionally considered as a separate disease from vascular dementia (VAD). However, growing evidence suggests that β-amyloid (Aβ) accumulation, that initiates ...LOAD-related neurodegeneration, is preceded by vascular events. Previous in vitro studies showed that β-secretase 1 (BACE1), the key-enzyme of amyloidogenesis, is upregulated by cerebrovascular insult; moreover, its activity is increased both in brain and serum of LOAD patients. We aimed to investigate whether BACE1 serum activity is altered also in dementias related, or not, to cerebrovascular disease. Thus, we evaluated serum BACE1 activity in a sample of individuals, including patients with LOAD (n. 175), VAD (n. 40), MIXED (LOAD/VAD) dementia (n. 123), other types of dementia (n. 56), and healthy Controls (n. 204). We found that BACE1 was significantly higher not only in LOAD (+ 30%), but also in VAD (+ 35%) and MIXED dementia (+ 22%) (p < 0.001 for all), but not in the other types of dementia (+ 10%). Diagnostic accuracy was 77% for LOAD, 83% for VAD, and 77% for MIXED dementia. In conclusion, we showed for the first time that the increase in peripheral BACE1 activity is a common feature of LOAD and VAD, thus underlying a further pathogenic link between these two forms of dementia.
The prevalence and prognostic implications of metabolic syndrome (MetS) in patients infected by the SARS-CoV-2 remain unclear. We performed a systematic review and meta-analysis of prevalence and ...mortality risk in COVID-19 patients with MetS.
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 every article published up to 1 September 2021, reporting data on MetS among COVID-19 patients. The pooled prevalence of MetS was calculated using a random effects model and presented using 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
statistic.
Six studies, enrolling 209.569 COVID-19 patients mean age 57.2 years, 114.188 males (54.4%) met the inclusion criteria and were included in the final analysis. The pooled prevalence of dyslipidaemia was 20.5% of cases (95% CI: 6.7-47.8%,
= 0.03), with high heterogeneity (I
= 98.9%). Pre-existing MetS was significantly associated with higher risk of short-term mortality (OR: 2.30, 95% CI: 1.52-3.45,
< 0.001), with high heterogeneity (I
= 89.4%). Meta-regression showed a direct correlation with male gender (
= 0.03), hypertension (
< 0.001), DM (
= 0.01) and hyperlipidaemia (
= 0.04), but no effect when considering age (
= 0.75) and chronic pulmonary disease (
= 0.86) as moderators.
MetS represents a major comorbidity in about 20% of COVID-19 patients and it is associated with a 230% increased risk of short-term mortality.
Familial Hypercholesterolemia (FH) is characterized by an increase in Low-Density Lipoprotein Cholesterol (LDL-C) and by premature Cardiovascular Disease (CVD). However, it remains to be fully ...elucidated if FH impairs cholesterol efflux capacity (CEC), and whether CEC is related to lipoprotein subfraction distribution. This study aimed at comparing FH patients and age, sex and BMI matched controls in terms of LDL and HDL subfraction distribution as well as CEC. Forty FH patients and 80 controls, matched for age, sex and BMI, were enrolled in this case-control study. LDL and HDL subfractions were analyzed using the Quantimetrix Lipoprint System. CEC was evaluated as aq-CEC and ABCA1-CEC. FH subjects showed a significantly higher concentration of all LDL subfractions, and a shift from large to small HDL subfraction pattern relative to controls. FH subjects with previous CVD event had smaller LDL lipoproteins than controls and FH subjects without previous CVD event. Both aq-CEC and ABCA1-CEC were increased in FH patients with respect to controls. To conclude, FH subjects had a metabolic profile characterized not only by higher LDL-C but also by shift from large to small HDL subfraction phenotype. However, FH subjects showed an increase CEC than controls.
Objectives
To evaluate the possibility of predicting the risk of progression from mild cognitive impairment (MCI) to dementia using a combination of clinical/demographic parameters.
Methods
A total ...of 462 MCI elderly patients (follow-up: 33 months). Variable measured included cognitive functions, age, gender, MCI type, education, comorbidities, clinical chemistry, and functional status.
Results
Amnestic type (aMCI) represented 63% of the sample, non-amnestic (naMCI) 37%; 190 subjects progressed to dementia, 49% among aMCI, and 28% among naMCI. At Cox multivariate regression analysis, only MMSE (one point increase HR 0.84; 95% CI 0.79–0.90), aMCI (HR 2.35; 95% CI 1.39–3.98), and age (1 year increase HR 1.05; 95% CI 1.01–1.10) were independently associated with progression to dementia. A score was created based on these dichotomized variables (score 0–3): age (≥ or < 78 years), MMSE score (≥ or < 25/30) and aMCI type. The conversion rate progressed from 6% in subjects with score 0 (negative predictive value: 0.94), to 31% in individuals with score 1, to 53% in subjects with score 2, to 72% in individuals with score 3 (positive predictive value: 0.72). ROC curve analysis showed an area under the curve of 0.72 (95% CI 0.66–0.75,
p
0.0001).
Conclusions
We have described a simple score, based on previously recognized predictors such as age, MMSE, and MCI type, which may be useful for an initial stratification of the risk of progression to dementia in patients affected by MCI. The score might help the clinicians to evaluate the need for more expansive/invasive examinations and for a closer follow-up in MCI patients.
Converging lines of evidence suggest that paraoxonase‐1 (PON‐1) may confer protection against inflammatory and oxidative challenge which, in turn, plays a key‐role in the onset and progression of ...dementia. The aim of this study was to evaluate whether serum PON‐1 paraoxonase/arylesterase activities might predict the clinical conversion of mild cognitive impairment (MCI) to late‐onset Alzheimer's disease (LOAD) or vascular dementia (VAD). Serum paraoxonase and arylesterase activities were measured by spectrophotometric assays at baseline in 141 MCI patients (median age: 77 years; interquartile range 71–81) and in 78 healthy controls (median age: 76 years; interquartile range 73–79). After 2 years of follow‐up, 86 MCI remained stable (MCI/MCI), 34 converted to LOAD (MCI/LOAD), whereas 21 converted to VAD (MCI/VAD). Baseline arylesterase activity was lower in all MCI groups compared with controls (all p < 0.01), whereas paraoxonase activity was lower in MCI/VAD group compared to controls (p < 0.05) and MCI/MCI patients (p = 0.009). Low paraoxonase and arylesterase activities (I quartile) were associated to higher risk of conversion to VAD (OR: 3.74, 95% CI: 1.37–10.25 and OR: 3.16, 95% CI: 1.17–8.56, respectively). Our results suggest that in MCI patients low PON‐1 activity might contribute to identify individuals susceptible to develop vascular dementia.
Our study showed that in patients with mild cognitive impairment (MCI) low serum levels of paraoxonase‐1 (PON‐1) activity is associated with a higher likelihood of developing Vascular Dementia, but not Alzheimer's Disease. The observed connection might be explained by the ability of PON‐1 to retard low‐density lipoprotein (LDL) oxidation, decrease oxidative stress, attenuate inflammation, and increase cholesterol efflux.
Our study showed that in patients with mild cognitive impairment (MCI) low serum levels of paraoxonase‐1 (PON‐1) activity is associated with a higher likelihood of developing Vascular Dementia, but not Alzheimer's Disease. The observed connection might be explained by the ability of PON‐1 to retard low‐density lipoprotein (LDL) oxidation, decrease oxidative stress, attenuate inflammation, and increase cholesterol efflux.
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