Metabolic and nutritional approach to older frail people

Frailty is a common clinical syndrome in older adults that carries an increased risk for poor health outcomes including falls, incident disability, hospitalization, and mortality. It is characterized by multisystem dysregulations, leading to a loss of dynamic homeostasis, decreased physiologic reserve, and increased vulnerability to stressors. A large body of literature suggests several important multisystem pathophysiologic processes in the pathogenesis of the frailty syndrome, including chronic inflammation and immune activation, insulin resistance and those in musculoskeletal and endocrine systems. Currently, no effective pharmaceutical interventions have been developed for the prevention and treatment of the frailty syndrome. Conversely, epidemiological and intervention studies suggest that adequate nutrition and physical exercise might prevent or postpone the onset of frailty and related clinical manifestations

Acetyl-cholinesterase-inhibitors slow cognitive decline and decrease overall mortality in older patients with dementia

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 (Delta-MMSE:-10.8 vs. -5.7 points; p < 0.001), although a similar effect was observed in VD (Delta-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

Lipoprotein-Associated Phospholipase A2 Activity as Potential Biomarker of Vascular Dementia

A wealth of evidence suggests that Lipoprotein-associated phospholipase A2 (Lp-PLA2) plays a relevant role in atherogenesis and inflammation, which in turn are associated with the risk of developing dementia. The aim of this study was to evaluate whether serum Lp-PLA2 activity might be an early and/or late biomarker for different forms of dementia. Serum Lp-PLA2 activity was assessed in older patients with mild cognitive impairment (MCI, n = 166; median clinical follow-up = 29 months), Late-Onset Alzheimer's disease (LOAD, n = 176), vascular dementia (VAD, n = 43), dementia characterized by an overlap between LOAD and VAD (AD-VAD MIXED dementia) (n = 136), other dementia subtypes (n = 45), and cognitively normal controls (n = 151). We found a significant trend towards higher levels of Lp-PLA2 activity in VAD compared with the other groups (ANOVA, p = 0.028). Similarly, Lp-PLA2 activity was greater in MCI converting to VAD compared with those that did not or did convert to the other types of dementia (ANOVA, p = 0.011). After adjusting for potential confounders, high levels of Lp-PLA2 activity were associated with the diagnosis of VAD (O.R. = 2.38, 95% C.I. = 1.06-5.10), but not with other types of dementia. Our data suggest that increased serum Lp-PLA2 activity may represent a potential biomarker for the diagnosis of VAD

Dyslipidaemia and mortality in COVID-19 patients - a meta-analysis

Background: The prevalence and prognostic implications of pre-existing dyslipidaemia in patients infected by the SARS-CoV-2 remain unclear. Aim: To assess the prevalence and mortality risk in COVID-19 patients with pre-existing dyslipidaemia. Design: Systematic review and meta-Analysis. 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 31 January 2021, reporting data on dyslipidaemia among COVID-19 survivors and non-survivors. The pooled prevalence of dyslipidaemia 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-effect models with odds ratio (OR) and related 95% CI. Statistical heterogeneity was measured using the Higgins I2 statistic. Results: Of about 18 studies, enrolling 74 132 COVID-19 patients (mean age 70.6 years), met the inclusion criteria and were included in the final analysis. The pooled prevalence of dyslipidaemia was 17.5% of cases (95% CI: 12.3-24.3%, P < 0.0001), with high heterogeneity (I2 = 98.7%). Pre-existing dyslipidaemia was significantly associated with higher risk of short-Term death (OR: 1.69, 95% CI: 1.19-2.41, P = 0.003), with high heterogeneity (I2 = 88.7%). Due to publication bias, according to the Trim-And-Fill method, the corrected random-effect ORs resulted 1.61, 95% CI 1.13-2.28, P < 0.0001 (one studies trimmed). Conclusion: Dyslipidaemia represents a major comorbidity in about 18% of COVID-19 patients but it is associated with a 60% increase of short-Term mortality risk

Targeted lipidomics distinguishes patient subgroups in mild cognitive impairment (MCI) and late onset Alzheimer's disease (LOAD)

AbstractBackgroundDiverse research approaches support the concept that a clinical diagnosis of Late-Onset Alzheimer's Disease (LOAD) does not distinguish between subpopulations with differing neuropathologies, including dementia patients with amyloid deposition and dementia patients without amyloid deposition but with cortical thinning. Mild cognitive impairment (MCI) is generally considered the prodromal phase for LOAD, however, while a number of studies have attempted to define plasma biomarkers for the conversion of MCI to LOAD, these studies have not taken into account the heterogeneity of patient cohorts within a clinical phenotype.MethodsStudies of MCI and LOAD in several laboratories have demonstrated decrements in ethanolamine plasmalogen levels in plasma and brain and increased levels of diacylglycerols in plasma and brain. To further extend these studies and to address the issue of heterogeneity in MCI and LOAD patient groups we investigated the levels of diacylglycerols and ethanolamine plasmalogens in larger cohorts of patients utilizing, high-resolution (0.2 to 2ppm mass error) mass spectrometry.ResultsFor the first time, our lipidomics data clearly stratify both MCI and LOAD subjects into 3 different patient cohorts within each clinical diagnosis. These include i) patients with lower circulating ethanolamine plasmalogen levels; ii) patients with augmented plasma diacylglycerol levels; and iii) patients with neither of these lipid alterations.ConclusionsThese represent the first serum biochemical data to stratify MCI and LOAD patients, advancing efforts to biochemically define patient heterogeneity in cognitive disorders.General significanceLipidomics offers a new approach for identifying biomarkers and biological targets in cognitive disorders

serum soluble tumor necrosis factor related apoptosis inducing ligand levels in older subjects with dementia and mild cognitive impairment

Background: The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been involved in both physiological and pathological conditions, including va

Lipoprotein profile in older patients with vascular dementia and Alzheimer's disease

BACKGROUND: Some alterations of the lipoprotein profile have been associated with cerebrovascular disease. Recently, it has been suggested that cerebrovascular disease might play a role in the pathogenesis of both vascular dementia (VD) and Alzheimer's disease (AD). Nevertheless, the possible association of dyslipidemias with VD or AD is still a controversial issue. METHODS: We investigated the lipoprotein profile in 100 older patients with vascular dementia (VD; n°: 60) or Late Onset Alzheimer's Disease (LOAD; n°: 40). The patients were compared with 54 community dwelling non-demented older controls. RESULTS: After adjustment for functional status, blood sedimentation rate, and serum albumin levels, no differences in lipoprotein profile emerged between the three groups, with the exception of HDL-C that was lower in VD compared with controls. Low HDL-C (< 45 mg/dL) was associated with VD (O.R.: 6.52, C.I. 95%: 1.42–30.70 vs controls, and 4.31, C.I. 95%: 0.93–19.82 vs LOAD), after multivariate adjustment. No differences in plasma lipid levels emerged between the three groups after stratification for apo E4 genotype. CONCLUSIONS: In this cross-sectional study low HDL-C levels are associated with VD, but not with LOAD, in a sample of older subjects

PPARγ Pro12Ala and ACE ID polymorphisms are associated with BMI and fat distribution, but not metabolic syndrome

<p>Abstract</p> <p>Background</p> <p>Metabolic Syndrome (MetS) results from the combined effect of environmental and genetic factors. We investigated the possible association of peroxisome proliferator-activated receptor-γ2 (PPARγ2) Pro12Ala and Angiotensin Converting Enzyme (ACE) I/D polymorphisms with MetS and interaction between these genetic variants.</p> <p>Methods</p> <p>Three hundred sixty four unrelated Caucasian subjects were enrolled. Waist circumference, blood pressure, and body mass index (BMI) were recorded. Body composition was estimated by impedance analysis; MetS was diagnosed by the NCEP-ATPIII criteria. A fasting blood sample was obtained for glucose, insulin, lipid profile determination, and DNA isolation for genotyping.</p> <p>Results</p> <p>The prevalence of MetS did not differ across PPARγ2 or ACE polymorphisms. Carriers of PPARγ2 Ala allele had higher BMI and fat-mass but lower systolic blood pressure compared with Pro/Pro homozygotes. A significant PPARγ2 gene-gender interaction was observed in the modulation of BMI, fat mass, and blood pressure, with significant associations found in women only. A PPARγ2-ACE risk genotype combination for BMI and fat mass was found, with ACE DD/PPARγ2 Ala subjects having a higher BMI (p = 0.002) and Fat Mass (p = 0.002). Pro12Ala was independently associated with waist circumference independent of BMI and gender.</p> <p>Conclusions</p> <p>Carriers of PPARγ2 Ala allele had higher BMI and fat-mass but not a worse metabolic profile, possibly because of a more favorable adipose tissue distribution. A gene interaction exists between Pro12Ala and ACE I/D on BMI and fat mass. Further studies are needed to assess the contribution of Pro12Ala polymorphism in adiposity distribution.</p

Autophagy and mitophagy biomarkers are reduced in sera of patients with Alzheimer's disease and mild cognitive impairment

Dementia is a neurocognitive disorder characterized by a progressive memory loss and impairment in cognitive and functional abilities. Autophagy and mitophagy are two important cellular processes by which the damaged intracellular components are degraded by lysosomes. To investigate the contribution of autophagy and mitophagy in degenerative diseases, we investigated the serum levels of specific autophagic markers (ATG5 protein) and mitophagic markers (Parkin protein) in a population of older patients by enzyme-linked immunosorbent assay. Two hundred elderly (≥65 years) outpatients were included in the study: 40 (20 F and 20 M) with mild-moderate late onset Alzheimer's disease (AD); 40 (20 F and 20 M) affected by vascular dementia (VAD); 40 with mild cognitive impairment (MCI); 40 (20 F and 20 M) with "mixed" dementia (MD); 40 subjects without signs of cognitive impairment were included as sex-matched controls. Our data indicated that, in serum samples, ATG5 and Parkin were both elevated in controls, and that VAD compared with AD, MCI and MD (all p &lt; 0.01). Patients affected by AD, MD, and MCI showed significantly reduced circulating levels of both ATG5 and Parkin compared to healthy controls and VAD individuals, reflecting a significant down-regulation of autophagy and mitophagy pathways in these groups of patients. The measurement of serum levels of ATG5 and Parkin may represent an easily accessible diagnostic tool for the early monitoring of patients with cognitive decline

Depressive symptoms and cognitive/functional status in a sample of elderly subjects referring to a memory clinic

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