Physical Performance and Falling Risk Are Associated with Five-Year Mortality in Older Adults: An Observational Cohort Study.

Background: Falls in older people have a significant impact on public health. The scientific literature has provided evidence about the necessity for older adults to be physically active, since it reduces the incidence of falls, several diseases, and deaths, and can even slow down some effects of aging. The primary aim of our study is to identify if physical performances and risk of falling are related to 1-, 2-, 3-, 4-, and 5-year mortality. Its secondary aim is to establish if people with both severely impaired physical performance and a high risk of falling also present impairment in other geriatric domains. Methods: In this prospective study, we enrolled subjects aged 65 years or more, subjected them to comprehensive assessment (including assessment of risk of falling, physical capacities, comorbidities, autonomies in daily living, cognitive abilities, mood, and nutritional status), and followed them for 5 years. Results: We included 384 subjects, 280 of whom were women (72.7%), with a median age of 81 years. Our results showed that physical performances and risk of falling are highly correlated to each other (rho = 0.828). After divided the sample into three groups (people without augmented risk of falling and able to perform adequate physical activity; people with moderate risk of falling and/or disability; people with severe risk of falling and/or disability), we found that the more severe the disability and risk of falling were, the more compromised the other geriatric domains were. Moreover, the survival probability progressively increased following the same trend, amounting to only 41% in severely compromised people, 51.1% in moderately compromised people, and 62.8% in people without physical compromise nor an augmented falling risk (p = 0.0124). Conclusions: Poor physical performance combined with a high risk of falling, correlated with each other, are associated with higher mortality and impairment in multiple domains in older adults.

The Repeatable Battery for the Assessment of Neuropsychological Status as a screening strategy for HIV-Associated Neurocognitive Disorders.

HIV-infected people are at risk for neurocognitive impairment (HIV-Associated Neurocognitive Disorders - HAND). To evaluate whether the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), a widely used neurocognitive screening tool, could be a valid instrument for HAND identification, we evaluated 166 HIV-infected subjects. Our results showed that 96 (57.8%) HIV-infected scored RBANS Total Index Score <85 (at least one SD below the normal), 12 (7.2%) of them scored RBANS Total Index Score <70 (at least 2 SD below the normal, indicating a possible HIV-Associated Dementia). The more compromised areas were Immediate and Delayed Memory, and Attention. In the group with RBANS Total Index Score <85, there were significantly lower scores of Mini Mental State Examination (P = 0.0008), Clock Drawing Test (P = 0.0015) and higher score of Geriatric Depression Scale (P = 0.02) compared to the RBANS Total Index Score ≥85 group. Using a stepwise logistic regression, considering RBANS Total Index Score as dependent variable, we found a positive interaction with tenofovir/emtricitabine assumption (P = 0.027), Clock Drawing Test (P = 0.0125) and educational level (P = 0.0054). Being the viro-immunological markers not capable of predicting cognitive decline in HIV-infected individuals, our data suggest that RBANS may be a valid tool for the early identification of HIV-related cognitive impairment.

How to evaluate Quality of Life.

In medical terminology, it has become more and more common the use of the expression "Quality of Life" (QoL) to define a series of aspects that go beyond the traditional, clinical and "objective" evaluation of the medical intervention. The attention to QoL comes from the need to find tools that are able to reveal important aspects of the life of the patient that cannot be measured by a laboratory exam and/or a radiological procedure. The QoL is measured through multidimensional questionnaires on, at the very least, the domains of physical, psychological and social health. The improvement of the health care standards and the technological progress in medical matters have brought about an increase in the average age of the population, and as a consequence, an increase of the chronic and degenerative disease, which can negatively influence the patient's quality of life. Amongst these pathologies, heart failure (HF) has a high prevalence in patients who are at least 70 years old, and it's the cause of frequent and repeated hospitalizations. The estimate of the QoL becomes then a very important piece of the puzzle to figure out, as important as the clinical parameters, to allow the patient to become an integral part of the physician's decisions and to reach more quickly and with better results the therapeutic objectives.

The venous thromboembolic risk and the clot wave analysis: a useful relationship?

BACKGROUND: Hospitalized patients with acute medical conditions have higher venous thromboembolism (VTE) risk. A patient with a final Padua Prediction Score (PPS) of ≥4 is considered to be at high risk for VTE. The aim of this study was to investigate on a possible relationship between PPS, the dynamics of the clot formation, i.e. the clot waveform analysis (CWA) of aPTT, fibrinogen and D-Dimer in a large group of medical patients. METHODS: CWA in terms of velocity (first derivative), acceleration (second derivative), density (Delta) of aPTT, fibrinogen, D-Dimer and PPS for VTE were determined in 801 medical patients divided in three groups (without antithrombotic prophylaxis and high PPS, without antithrombotic prophylaxis and low PPS, with antithrombotic prophylaxis and high PPS) and a group of healthy subjects. RESULTS: CWA, fibrinogen and D-Dimer values were higher in the medical patients with high PPS with or without antithrombotic prophylaxis when compared with patients without antithrombotic prophylaxis with low PPS and healthy subjects. The second derivative, fibrinogen and D-Dimer were significantly associated with a high PPS score (≥4): odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.03-2.28; OR = 1.91, 95% CI = 1.3-2.79; OR = 3.16, 95% CI = 2.29-4.36, respectively. Interactions between first derivative and D-Dimer (OR = 2.14, 95% CI = 1.23-3.72) and first derivative and fibrinogen (OR = 1.75, 95% CI = 1.02-2.98) were found. CONCLUSIONS: CWA could give useful information to recognize a hypercoagulable state in patients admitted to a medical ward with high and low PPS. First and second derivative aPTT, D-Dimer and fibrinogen levels could be added to PPS to better assess the global thromboembolic risk of these patients.

Cholesterol esterification as a mediator of proliferation of vascular smooth muscle cells and peripheral blood mononuclear cells during atherogenesis.

BACKGROUND/AIMS: We determined growth rates, cholesterol esterification and mRNA levels for caveolin-1 (Cav-1), neutral cholesterol esters hydrolase (n-CEH) and ATP-binding cassette transporter (ABCA-1), in quiescent and growth-stimulated peripheral blood mononuclear cells (PBMCs) and intimal vascular smooth muscle cells (VSMCs) from blood and primary atherosclerotic plaques, respectively. These cells were cultured in the presence or absence of the mTOR inhibitor 40-O-(2-hydroxyethyl) rapamycin (RAD). METHODS: The rate of cell proliferation was determined by 3H-thymidine incorporation into DNA and that of lipid metabolism by utilizing 14C-acetate and 14C-oleate as precursors. Lipid deposit in the vascular cells was evaluated by Oil Red O staining and lipid mass by thin layer chromatography-linked enzymatic assay. RESULTS: Growth stimulation of PBMCs and VSMCs caused a rapid increase in intracellular cholesterol esterification and an accumulation of cholesterol esters (CEs) accompanied by a reduction of free cholesterol (FC) and Cav-1, ABCA-1 and n-CEH mRNAs. RAD reduced intracellular lipid accumulation in growth-stimulated cells and also increased expression of Cav-1, n-CEH and ABCA-1 genes. CONCLUSION: Collectively, these data provide evidence that the determination of CEs in PBMCs may be an easy prescreening test to identify subjects at risk for vascular proliferative disease and that FC, CE, Cav-1, n-CEH and ABCA-1 may be suitable targets for antiproliferative therapies.

Age-related macular degeneration and cognitive impairment show similarities in changes of neutral lipids in peripheral blood mononuclear cells.

Starting from previous studies showing that patients with cognitive deficit present neutral lipids (NLs) accumulation in cytoplasm of their peripheral blood mononuclear cells (PBMCs) and considering that there is epidemiological evidence linking age-related macular degeneration (AMD) to cognitive deficit, the first purpose of this study was to test whether neutral lipids also accumulated in PBMCs from AMD subjects. Moreover, the impact of statin use on AMD was explored and whether such use in AMD subjects was associated with NLs accumulation in PBMCs. The study was conducted on 222 subjects: 136 AMD (36 of which - 26.5% - using statins], 48 cognitive deficit (20 of which - 41.7% - using statins) and 38 healthy controls (4 of which -10.1% - using statins), AMD lesions were assessed from color fundus photographs. Mini-mental state examination (MMSE), demographics, lifestyle factors and medical history were collected at interview. MMSE score was categorized as normal (24-30), and impaired (<24), NLs content was evaluated by oil red 0 (ORO) staining method. ORO determination showed that neutral lipids were generally absent or very low (score between 0 and 1) in healthy controls while most of PBMCs from cognitive deficit and AMD had ORO staining levels scoring 2-4. Post hoc analysis (Bonferroni) in a one-way ANOVA revealed that ORO score was significantly higher in cognitive deficit and AMD subjects compared to healthy controls and in cognitive deficit compared to AMD. Bonferroni-test also showed that AMD subjects had significantly lower total cholesterol (TC) levels compared to healthy controls while high density lipoprotein-cholesterol (HDL-C) did not reach statistical significance. The results also revealed a significant higher number of statin-users in AMD compared to healthy controls. Likewise when cognitive deficit vs healthy controls was analyzed, the number of statin users were found to be significant higher in cognitive deficit than in healthy controls. There were no significant differences in statin use between AMD and cognitive deficit. Compared to healthy controls, statin use in cognitive deficit and AMD groups was significantly associated with ORO scores of 2-4. This data supports the hypothesis that AMD and cognitive deficit share similar complex pathophysiology and risk factors including NLs accumulation in their PBMCs, although this does not necessarily imply that one disease causes the other. In addition, they provide further evidence that statin use may increase the risk of AMD.

Association between Depressive Mood, Antidepressant Therapy and Neuropsychological Performances: Results from a Cross-Sectional Study on Elderly Patients.

BACKGROUND: Currently, the global demographic landscape is undergoing a transformative shift towards an increasingly aging population. This leads to an increase in chronic pathologies, including depression and cognitive impairment. This study aimed to evaluate the association between depressive mood, whether in treatment or not, and cognitive capacities, assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). METHODS: This study included 259 subjects, aged 65 years or older, evaluated at the Geriatric Outpatient Service of the University Hospital of Monserrato, Cagliari, between July 2018 and May 2022, who experienced subjective depressive mood and/or cognitive deficits. RESULTS: Only 25.1% of the sample showed no cognitive impairment on the RBANS. Education was a significant regressor of the RBANS Total Scale scores (p < 0.0001) and was negatively associated with mood deflection (r = -0.15, p = 0.0161). Subjects with depressive mood had more impaired attention and visuospatial/constructional abilities compared to untreated euthymic patients. Post-hoc analysis, conducted with the Conover test, showed that untreated euthymic patients (GDS-15 ≤ 5, group 2) had a higher score on the RBANS total scale than patients with mood deflection (GDS-15 > 5, group 1), and treated euthymic patients (GDS-15 ≤ 5, group 3). Finally, different logistic regression analyses revealed a significant negative coefficient for GDS as a regressor of the RBANS total scale (coefficient: -0.04, p = 0.0089), visuospatial/constructional abilities (coefficient: -0.03, p = 0.0009), language (coefficient: -0.05, p = 0.0140), and attention (coefficient: -0.05, p < 0.0001). CONCLUSIONS: Our analysis demonstrated that "naturally" euthymic people show better cognitive performances than people with depressive mood and subjects with acceptable mood due to antidepressants. Furthermore, the gender-based difference observed in the language domain suggests the potential utility of incorporating an alternative category for male patients in the Semantic Fluency test.

Cognitive Impairment in People Living with HIV and the Impact of Mood: Results from a Cross-Sectional Study.

Background: Human Immunodeficiency Virus (HIV) infection represents a significant public health concern and, consequently, the incidence of HIV-Associated Neurocognitive Disorder (HAND) has grown over the years. The present study aims to assess HAND with the Montreal Cognitive Assessment (MoCA) in People Living With HIV/AIDS (PLWHA) to find significant associations with cognitive impairment. Methods: The study included 210 PLWHA, aged from 30 to 81 years, of whom, 137 (65.2%) were males. They were assessed at the Immunology Service of the University Hospital of Monserrato, Cagliari, Italy, between November 2022 and April 2023. Results: The sample showed an overall optimal response to antiretroviral therapy, as shown by the excellent levels of CD4+ lymphocytes and HIV RNA copies. A sum of 115 subjects (54.8%) were considered cognitively impaired and the multivariate analysis demonstrated that it was independently associated with duration of infection (OR: 0.96), age (OR: 1.12), alanine aminotransferase (ALT) (OR: 1.02), and depression (OR: 1.33). By dichotomizing the variables, the significance of the association was confirmed for age (65-year threshold) (χ2: 5.142, p = 0.0233) and depression (χ2: 7.834, p = 0.0051). Conclusions: Our study demonstrates that it is hard to find both statistically and clinically significantly associated variables with cognitive impairment in PLWHA, and that the strongest independent association is with depressed mood.

Mini-Mental State Examination: Optimal Cut-Off Levels for Mild and Severe Cognitive Impairment.

Considering the need to intercept neurocognitive damage as soon as possible, it would be useful to extend cognitive test screening throughout the population. Here, we propose differential cut-off levels that can be used to identify mild and severe cognitive impairment with a simple and widely used first-level neurocognitive screening test: the Mini-Mental State Examination (MMSE). We studied a population of 262 patients referred for cognitive impairment testing using the MMSE and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), a neuropsychological battery. The sample consisted of 262 participants with mean age 73.8 years (60-87), of whom 154 (58.8%) women. No significant gender-related differences in cognitive ability were identified. The two tests (MMSE and RBANS) showed a moderate correlation in identifying cognitive deficit. We used RBANS as a categorial variable to identify different degrees of cognitive impairment. Youden's J indexes were used to consider the better sensitivity/specificity balance in the 24-point cut-off score for severe cognitive deficit, 29.7-point score for mild cognitive deficit, and 26.1-point score for both mild and severe cognitive deficit. The study shows that the MMSE does not identify early cognitive impairment. Though different cut-offs are needed to discriminate different impairment degrees, the 26.1-point score seems to be preferable to the others.

Anemia in Elderly Patients-The Impact of Hemoglobin Cut-Off Levels on Geriatric Domains.

Background: The primary aim of this study was to evaluate the impact of anemia­according to the WHO criteria­on cognitive performances, mood, functional and nutritional status, and comorbidities in a population of subjects aged 65 years or older. The secondary aim of this study was to understand if different hemoglobin cut-off levels are associated with a variation of the mentioned domains' impairment. Methods: We designed a cross-sectional study, including subjects aged 65 or more consecutively evaluated in an outpatient setting from July 2013 to December 2019. A sum of 1698 subjects met the inclusion criteria. They were evaluated with: MMSE and CDT (cognitive assessment), GDS (mood), BADL, IADL, PPT, and POMA (autonomies), MNA (nutritional status), and CIRS (comorbidities). Results: According to the WHO criteria, non-anemic patients reported significantly better performances than the anemics in BADL (p < 0.0001), IADL (p = 0.0007), PPT (p = 0.0278), POMA (p = 0.0235), MNA, CIRS TOT, CIRS ICC, and CIRS ISC (p < 0.0001). The same tendency has been found by considering the 12 g/dL- and the 13 g/dL-cut-off level in the whole population. The multivariate analysis showed that, considering the 12 g/dL-cut-off level, age (OR: 1.03, p = 0.0072), CIRS (OR: 1.08, p < 0.0001), and gender (OR: 0.57, p = 0.0007) were significant regressors of anemia, while considering the 13 g/dL-cut-off level, age (OR: 1.04, p = 0.0001), POMA (OR: 1.03, p = 0.0172), MNA (OR = 0.95, p = 0.0036), CIRS (OR: 1.17, p < 0.0001), ICC (OR = 0.83, p = 0.018), and gender (OR = 0.48, p < 0.0001) were significant regressors of anemia, while the other CGA variables were excluded by the model (p > 0.01). Conclusions: Our study showed that anemia negatively impact on geriatric people's general status, regardless of which hemoglobin cut-off level is considered. It also highlighted that hemoglobin concentrations < 13 g/dL, regardless of gender, have an association with the impairment of the affective-functional-nutritional state as well as an increase in comorbidities; therefore, it should be pursuable to consider the elderly person "anemic" if Hb < 13 g/dL regardless of gender.

STOPP/START Anti-aggregation and Anticoagulation Alerts in Atrial Fibrillation.

BACKGROUND: Atrial Fibrillation (AF) is common in the elderly. A key component of AF management is Oral Anticoagulant Therapy (OAT), consisting of Vitamin K Antagonists (VKAs) or Direct Oral Anticoagulants (DOACs). The aim of the present study is to check, using STOPP (Screening Tool of Older Persons' Prescriptions)/START (Screening Tool to Alert to Right Treatment) Criteria, if such drugs are potentially inappropriately prescribed/omitted in an elderly population with AF, and to determine their impact on mortality. METHODS: This study included patients (n = 427) with nonvalvular AF consecutively evaluated between 2013 and 2019 at the Geriatric Outpatient Service, University Hospital of Monserrato, Cagliari, Italy, and followed up for 36 months. The OAT group included 330 patients; the other 97 patients constituted the non-OAT group. The sample was assessed for STOPP/START criteria. RESULTS: We found no difference (p > 0.1) in comorbidity burden, frailty, and cardio-cerebro-vascular disease prevalence in the two groups, which also did not present a difference in 36-month mortality (p = 0.97). OAT was overall appropriately taken, and 62.4% of OAT-group presented the START criterion to take antiplatelets but also the STOPP criterion not to take them, because of the simultaneous anticoagulant intake. In the non-OAT group, 69.1% presented the START criterion to take anticoagulants, and 21.6% the START criterion to take antiplatelets. CONCLUSION: Patients with AF are often prone to under or over-prescription, particularly of antithrombotic drugs. The STOPP/START criteria are a valid tool to assess and correct wrong therapeutic choices. In frail and comorbid subjects, survival is not correlated with the assumption of OAT.

Six-item cognitive impairment test (6-CIT)'s accuracy as a cognitive screening tool: best cut-off levels in emergency department setting.

Background: Nowadays, elderly patients represent a significant number of accesses to the Emergency Department (ED). Working rhythms do not allow to perform complete cognitive analysis, which would, however, be useful for the health care. This study aims to define the optimal cut-off values of the six-item Cognitive Impairment Test (6-CIT) as a cognitive screening tool in ED. Methods: This study included 215 subjects, evaluated at the Emergency Department of the University Hospital of Monserrato, Cagliari, Italy, from July to December 2021. The accuracy of 6-CIT as a cognitive screening tool was assessed by comparison with Mini Mental State Examination (MMSE). Results: The correlation coefficient between the two tests was -0.836 (CI: -0.87 to -0.79; p < 0.0001), and 6-CIT showed AUC = 0.947 (CI: 0.908-0.973; p < 0.0001). The 8/9 6-CIT cut-off score presented 86.76% sensitivity (CI: 76.4-93.8) and 91.84% specificity (CI: 86.2-95.7), and Youden index for this score was 0.786. Conclusion: Our study demonstrates that 6-CIT is a reliable cognitive screening tool in ED, offering excellent sensitivity and specificity with a 8/9 points cut-off score.

Frailty and comorbidity burden in Atrial Fibrillation.

Background: With the aging of the population, the characterization of frailty and comorbidity burden is increasingly taking on particular importance. The aims of the present study are to analyze such conditions in a population affected by Atrial Fibrillation (AF), matching it with a population without AF, and to recognize potential independent factors associated with such common cardiovascular disease. Methods: This study included subjects consecutively evaluated over 5 years at the Geriatric Outpatient Service, University Hospital of Monserrato, Cagliari, Italy. A sum of 1981 subjects met the inclusion criteria. The AF-group was made up of 330 people, and another 330 people were randomly selected to made up the non-AF-group. The sample was subjected to Comprehensive Geriatric Assessment (CGA). Results: In our sample, severe comorbidity burden (p = 0.01) and frailty status (p = 0.04) were significantly more common in patients with AF than without AF, independently on gender and age. Furthermore, the 5-years follow-up demonstrated that survival probability was significantly higher in AF-group (p = 0.03). The multivariate analysis (AUC: 0.808) showed that the presence of AF was independently positively associated with a history of coronary heart disease (OR: 2.12) and cerebrovascular disease (OR: 1.64), with the assumption of Beta Blockers (OR: 3.39), and with the number of drugs taken (OR: 1.12), and negatively associated with the assumption of antiplatelets (OR: 0.09). Conclusions: Elderly people with AF are frailer, have more severe comorbidities, and take more drugs, in particular beta blockers, than people without AF, who conversely have a higher survival probability. Furthermore, it is necessary to pay attention to antiplatelets, especially in AF-group, in order to avoid dangerous under- or over-prescriptions.

Orthogeriatric Assessment of the Elderly Patient with Fragility Hip Fracture: Preliminary Results of a Prospective Study.

Nowadays, more studies deal with "OrthoGeriatrics", for the co-management of elderly patients suffering fractures, from the admission to the discharge and beyond. For the first time at Cagliari University Hospital, we introduced an orthogeriatric service, in which trained geriatricians stay in orthopedic unit alongside trained orthopedics. The primary aim of the study was to analyze the rate of death and rehospitalization in elderly femur-fractured people of 65 or more years of age, identifying possible predictive factors. The secondary aim of the study was to analyze the recovery of daily living autonomies during the months following surgery. To reach the aim, we designed a prospective study, which is currently ongoing. We evaluated femur-fractured patients aged 65 years or more with a comprehensive geriatric assessment before surgery. The most common fractures were lateral hip ones, treated with osteosynthesis. Cognitive-affective, functional, and nutritional status, mood, and comorbidities were less impaired than in the outpatient service of the same hospital devoted to frail elderly. Pain control was excellent. A significantly low delirium incidence was found. More than a third of the sample were recognized as frail (according to the Survey of Health, Ageing and Retirement in Europe-Frailty Instrument (SHARE-FI)), and over a third of the sample were identified as a moderate-high risk of hospitalization and death (according to Multidimensional Prognostic Index (MPI)). Overall mortality rate was 13.87%, and rehospitalization rate was 11.84%. Frail people were more likely to die than non-frail (HR: 5.64), and pre-frail ones (HR: 3.97); similarly, high-risk patients were more likely to die than low-risk (HR: 8.04), and moderate-risk ones (HR: 5.46). Conversely, neither SHARE-FI nor MPI predicted rehospitalization. Creatinine (OR: 2.66, p = 0.003) and folate (OR: 0.75, p = 0.03) levels were independently associated with death and rehospitalization, respectively. Finally, the patients did recover the lost autonomies later, 6 months after surgery. Our study demonstrated that SHARE-FI and MPI are reliable tools to predict mortality in an orthogeriatric setting, and that creatinine and folate levels should also be measured given their independent association with negative outcomes.

Diabetes mellitus, malnutrition, and sarcopenia: The bond is not explained by bioelectrical impedance analysis in older adults.

As people age, their risk of diabetes mellitus (DM) and sarcopenia increases due to the decline in muscle mass and strength. Bioelectrical impedance analysis (BIA) is a method used to detect changes in body composition. The primary aim of the study was to determine the distribution of BIA variables among a group of non-DM people and two groups of patients with controlled and uncontrolled DM. The secondary aim was to establish the independent association between BIA-derived data, lipidic assets, and the prevalence of metabolic syndromes with DM. This study included a total of 235 participants who were categorized into three groups based on the presence of diabetes mellitus (DM) and their glycated hemoglobin (HbA1c) levels: non-DM, controlled DM (HbA1c≤7.0%), and uncontrolled DM (HbA1c>7.0%). Waist circumference (p=0.005), bone (p<0.001), muscular (p<0.001), and appendicular skeletal mass (p<0.001) were lower in the non-DM group, while sarcopenic risk (p<0.001), total cholesterol (p<0.001), and LDL (p<0.001), were higher. Grip strength (p<0.001), visceral fat (p=0.01), and phase angle (p=0.04) were significantly lower in non-DM than uncontrolled DM patients, as well as the number of drugs taken (p=0.014). A multivariate analysis highlighted that LDL (coefficient -0.006, p=0.01) was negatively associated, while bone mass (coefficient 0.498, p=0.0042) was positively associated with DM uncontrol. Our study shows that BIA may not be the ideal tool for distinguishing between elderly individuals with and without DM, as it can be affected by numerous covariates, including potential differences in glucometabolic and cardiovascular control.

Changes in cholesterol metabolism-related gene expression in peripheral blood mononuclear cells from Alzheimer patients.

BACKGROUND: Cholesterol homeostasis dysfunction has been reported to have role in the pathogenesis of Alzheimer disease (AD). Therefore, changes in cholesterol metabolism in blood components may help to develop new potential AD biomarkers. In this study changes in cholesterol metabolism-related gene expression genes were evaluated in peripheral blood mononuclear cells (PBMCs) from AD subjects, their first degree relatives (FDR) and two groups of age matched controls (C1 > 80 years, C2 < 60 years). The expression of three genes related to APP processing was also determined. RESULTS: Results showed significantly different behavior (P = 0.000) in the expression of all analyzed genes among the 4 groups. An inverse correlation emerged between the age of controls and the propensity of their PBMCs to express selected genes. Moreover, when gene expression was evaluated in PBMCs from AD patients and compared with that of PBMCs from healthy subjects of the same age, LDL-R and APP mRNAs were most abundant in AD as compared C1 whereas SREBP-2 and particularly nCEH were present at much lower mRNA levels in AD-PBMCs. This study describes for the first time a differential expression profile of cholesterol and APP related genes in PBMCs from AD patients and their FDR. CONCLUSIONS: We suggest that the expressions of cholesterol homeostasis and APP processing related genes in PBMC could be proposed as possible biomarkers to evaluate AD risk. In addition, gene expression in PBMC could be also used for diagnosis and development of therapeutic strategies as well as for personalized prediction in clinical outcome of AD.

Nutritional Status and Potentially Inappropriate Medications in Elderly.

(1) Background: The association between polypharmacy and malnutrition has been investigated in several studies; however, few of these specifically deepened the relationship between potentially inappropriate medication and malnutrition. With a descriptive approach, the primary aim of our study was to evaluate the impact of the nutritional status, assessed with the Mini Nutritional Assessment (MNA), on potentially inappropriate medications (PIM), estimated 10-year survival, and the risk of adverse drug reactions in elderly patients; the secondary aim was to evaluate how the Screening Tool of Older People's Prescriptions (STOPP), Screening Tool to Alert to Right Treatment (START), and BEERS 2019 criteria identify PIM compared to nutritional status. (2) Methods: In this study, 3091 subjects were enrolled, of whom 2748 (71.7%) were women; the median age was 80 years, with an interquartile range between 75 and 85 years of age. The subjects were assessed at the outpatient service for frail older people of the University Hospital of Cagliari. The study population was evaluated for their: MNA, Charlson Comorbidity Index, 10-year survival estimation, BEERS 2019, STOPP and START criteria, and ADR Risk scores. (3) Results: We divided the study population into three groups: MNA1 (MNA score ≥ 24), MNA2 (23.5−17), and MNA3 (<17): the severity of comorbidities, STOPP and START alerts, and BEERS 2019 criteria were significantly worse in both MNA2 and MNA3 compared to MNA1­with the exception of BEERS "non-anti-infective medications that should be avoided or have their dosage reduced with varying levels of kidney function in older adults". Moreover, the estimated 10-year survival was significantly higher in MNA1 than in MNA2 and MNA3, and also in MNA2 compared to MNA3. Finally, the ADR risk scores were significantly lower in MNA1 than in MNA2 and MNA3. (4) Conclusions: Our study demonstrated the association between nutritional status and PIM checked with the BEERS 2019 criteria, and, for the first time, with the STOPP and START criteria.

Comprehensive Geriatric Assessment: Application and correlations in a real-life cross-sectional study.

Background: The assessment process of elderly people considers all aspects of an individual's life, including physical, mental, and social aspects. Frailty refers to a decline in physiological functions or strengths leading to increased vulnerability to stressors and decreased ability to cope with them. Comprehensive Geriatric Assessment (CGA) is a validated and useful tool in this context to holistically study elderly people. The primary aim of this study was to determine the prevalence of impaired health status in a large geriatric population turning to outpatient service, based on the components of the CGA, and thus to describe its usefulness in real-life clinical practice. The secondary aim of this study was the evaluation of the association between nutritional status, assessed with Mini Nutritional Assessment (MNA)-within the CGA-and cognitive-affective and functional capacities, and multimorbidity. Materials and methods: This real-life, retrospective cross-sectional study included subjects consecutively evaluated from January 2009 to December 2020 at the Geriatric Outpatient Service, University Hospital of Monserrato, Cagliari, Italy. A sum of 3,260 patients were subjected to CGA. Results: Only a small proportion of the sample (2.24%) showed an absence of impairment in cognitive-affective, functional, and nutritional domains. Moderate correlations were found between MNA and several other CGA variables, namely, Geriatric Depression Scale (GDS; ϱ = -0.41, p < 0.0001), Barthel Index of Independence in Activities of Daily Living (ADL) (ϱ = 0.51, p < 0.0001), Instrumental Activities of Daily Living (IADL) (ϱ = 0.43, p < 0.0001), and Performance-Oriented Mobility Assessment (ϱ = 0.44, p < 0.0001). A multiple regression also highlighted these variables as significant regressors of MNA. Finally, malnutrition showed a significant association with depression (odds ratio [OR]: 4.97), dependence on ADL (OR: 19.8) and IADL (OR: 7.04), and falling risk (OR: 5.16). Conclusion: This study has figured out the complex situation in which geriatric care finds itself the complexity and severe impairment of elderly people. The possibilities of intervention are often limited, but the literature confirms the benefits of good nutritional status on the general health status. The data that emerged from our study fit into this assumption, highlighting the close association between the nutritional domain and the other CGA domains.

Thalassemia intermedia is associated with a proatherogenic biochemical phenotype.

OBJECTIVE: Unlike beta thalassemia major (ß-TM) in which cardiac siderosis represents the leading cause of mortality and morbidity, in beta thalassemia intermedia (ß-TI), pulmonary hypertension (PHT) and thrombosis seems to be the major cardiovascular complications. However, the mechanism underlying these complications in ß-TI is still unclear. Endothelial dysfunction, the key early event in atherogenesis, is now emerging as an important cardiovascular risk determiner in ß-TI patients. Among the factors known to affect endothelial function, iron and cholesterol merit particular consideration in ß-TI patients. Therefore, with the aim to extend our knowledge on the mechanisms connecting atherosclerosis to ß-TI, in this study, we compared lipid and iron metabolism in serum and in peripheral blood mononuclear cells (PBMCs) from ß-TI and ß-TM patients and controls. METHODS AND RESULTS: In this study the iron status and the lipid profile in serum and in peripheral blood mononuclear cells (PBMCs) of 22 adult ß-TI patients were examined, and compared with 70 adult ß-TM, and 50 age-matched controls. Despite the great variability, levels of serum iron and transferrin saturation were significantly higher in ß-TI compared to both controls and ß-TM. By contrast, transferrin and hepcidin levels were lower in ß-TI patients. Changes in serum indicators in ß-TI patients were associated with altered expressions in PBMCs of hepcidin and IL-1α, involved in some way in the regulation of iron homeostasis. In addition ß-TI exhibited a reduction of total and high density lipoprotein cholesterol in serum and of neutral cholesterol ester hydrolase in PBMCs, and an increase of cytoplasmic neutral lipids and mRNA levels of acetyl-coenzymeA:cholesterol acyltransferase. CONCLUSIONS: Taken together, these findings provide experimental support for the idea that ß-TI patients exhibit a proatherogenic biochemical phenotype which may contribute to enhance cardiovascular risk in these subjects.

Evidence for a proatherogenic biochemical phenotype in beta thalassemia minor and intermedia.

The purpose of this study was to focus on pathophysiological mechanisms linking ß-thalassemia intermedia (ß-TI) and minor (ß-TMI) with cardiovascular risk. Iron status, prooxidant-antioxidant balance and lipid profiles in serum, and lipid content in peripheral blood mononuclear cells (PBMCs) were evaluated in 20 ß-TMI subjects, 22 ß-TI patients and in 30 nonthalassemic blood donors. The mRNA levels of some genes involved in the regulation of iron and cholesterol metabolism were also determined. In ß-TI and in ß-TMI, serum iron, prooxidant-antioxidant ratio, transferrin saturation and erythropoietin levels were higher, while transferrin and hepcidin were lower compared to controls. Hepcidin and interleukin-1α mRNA levels were found to be reduced in ß-TI- and ß-TMI-PBMCs, while those of tumor necrosis factor alpha were increased. A reduction in high-density lipoprotein cholesterol in serum and an accumulation of neutral lipids coupled with increased mRNA levels of acetyl-coenzyme A:cholesterol acyltransferase and decreased neutral cholesterol ester hydrolase in PBMCs were also observed in ß-TI and ß-TMI compared to controls. Taken together, these findings provide experimental support for the idea that not only ß-TI patients but also ß-TMI have a proatherogenic biochemical phenotype which may contribute to increase their cardiovascular disease risk.