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A recent study by Ding et al. explores the integration of artificial intelligence (AI) in predicting dementia risk over a 10-year period using a multimodal approach. While revealing the potential of machine learning models in identifying high-risk individuals through neuropsychological testing, MRI imaging, and clinical risk factors, the imperative of dynamic frailty assessment emerges for accurate late-life dementia prediction. The commentary highlights challenges associated with AI models, including dimensionality and data standardization, emphasizing the critical need for a dynamic, comprehensive approach to reflect the evolving nature of dementia and improve predictive accuracy. [ABSTRACT FROM AUTHOR]

Simple Summary: The Comprehensive Geriatric Assessment is a multidimensional and multidisciplinary evaluation designed for elderly patients with the goal of structuring tailored care and follow-up. Despite the known benefits of this approach, the Comprehensive Geriatric Assessment is not universally applied to elderly cancer patients due to economic and practical barriers. This narrative review aims to investigate the cost-effectiveness of the Comprehensive Geriatric Assessment adopted in geriatric oncology. The results revealed a lack of research on the topic, but recurrent cost-saving effects of this approach in geriatric oncology settings were highlighted—suggesting a positive cost-effectiveness ratio. Further structured research with comprehensive economic evaluations is needed to confirm these findings. The Comprehensive Geriatric Assessment (CGA) and the corresponding geriatric interventions are beneficial for community-dwelling older persons in terms of reduced mortality, disability, institutionalisation and healthcare utilisation. However, the value of CGA in the management of older cancer patients both in terms of clinical outcomes and in cost-effectiveness remains to be fully established, and CGA is still far from being routinely implemented in geriatric oncology. This narrative review aims to analyse the available evidence on the cost-effectiveness of CGA adopted in geriatric oncology, identify the relevant parameters used in the literature and provide recommendations for future research. The review was conducted using the PubMed and Cochrane databases, covering published studies without selection by the publication year. The extracted data were categorised according to the study design, participants and measures of cost-effectiveness, and the results are summarised to state the levels of evidence. The review conforms to the SANRA guidelines for quality assessment. Twenty-nine studies out of the thirty-seven assessed for eligibility met the inclusion criteria. Although there is a large heterogeneity, the overall evidence is consistent with the measurable benefits of CGA in terms of reducing the in-hospital length of stay and treatment toxicity, leaning toward a positive cost-effectiveness of the interventions and supporting CGA implementation in geriatric oncology clinical practice. More research employing full economic evaluations is needed to confirm this evidence and should focus on CGA implications both from patient-centred and healthcare system perspectives. [ABSTRACT FROM AUTHOR]

Delirium is commonly seen in older adults with multimorbidity, during a hospitalization, resulting from the interplay between predisposing factors such as advanced age, frailty, and dementia, and a series of precipitating factors. The association between delirium and specific multimorbidity is largely unexplored so far although of potential key relevance for targeted interventions. The aim of the study was to check for a potential association of multimorbidity with delirium in a large cohort of older patients hospitalized for an acute medical or surgical condition. This is a cross-sectional study nested in the 2017 Delirium Day project. The study includes 1829 hospitalized patients (age: 81.8, SD: 5.5). Of them, 419 (22.9%) had delirium. Sociodemographic and medical history were collected. The 4AT was used to assess the presence of delirium. The Charlson Comorbidity index was used to assess multimorbidity. The results identified neurosensorial multimorbidity as the most prevalent, including patients with dementia, cerebrovascular diseases, and sensory impairments. In light of the highest co-occurrence of 3 neurosensorial chronic conditions, we could hypothesize that a baseline altered brain functional and neural connectivity might determine the vulnerability signature for incipient overall system disruption in presence of acute insults. Eventually, our findings moved a step forward in supporting the key importance of routine screening for sensory impairments and cognitive status of older patients for the highest risk of in-hospital delirium. In fact, preventive interventions could be particularly relevant and effective in preventing delirium in such vulnerable populations and might help refining this early diagnosis. [ABSTRACT FROM AUTHOR]

Alzheimer's disease may mimic frontotemporal dementia. We describe a case of presenile dementia who presented with peudo-psychotic symptoms carrying a PSEN1 mutation (P355 S), which was not known to be pathogenic. PET-FDG showed bilateral frontotemporal hypometabolism, but at MRI, multiple microbleeds were detected, suggestive of amyloid angiopathy. [ABSTRACT FROM AUTHOR]

Background: Hip fracture is a major health problem and a patient's biological age, comorbidity, and cognitive vulnerability have an impact on its related outcomes. Length of stay (LOS) for these highly vulnerable patients is rather long and the possible causes have not been clearly identified yet.Objective: We aimed to assess the main clinical factors associated with protracted LOS, focusing on delirium with or without dementia in older age hip fractured patients.Methods: 218 subjects (mean age 86.70±6.18 years), admitted to the Orthogeriatric Unit of the Ospedale Policlinico San Martino (Italy), were recruited. All patients received physical and comprehensive geriatric assessment. Days to surgery, days from surgery to rehabilitation, and LOS were recorded. In-hospital and three months' mortality were reported.Results: Prevalent delirium at hospital admission was of 3.1%. 35% of patients developed incident delirium. 56.4% were affected by dementia of Alzheimer-type. In addition, 52% of patients developed delirium superimposed to dementia. Mean LOS was 13.5±4.99 days. Namely, delirium, time to surgery, and complication rate disproportionally affected LOS. The analysis with 3 months mortality, based on cognitive vulnerability profiles, showed how delirium mainly affect short-term mortality in patients with dementia.Conclusion: Our exploratory study originally pointed out the high incidence of delirium superimposed to dementia in orthogeriatric wards and how delirium turns to be a moderator of LOS. The results meet the need for additional research by virtue of a deeper understanding of the impact of delirium and dementia on orthogeriatric clinical management and outcomes. [ABSTRACT FROM AUTHOR]

Objective. Acute pain is frequent and underestimated in older persons, especially when they suffer from cognitive impairment. Algoplus is an observational scale for acute pain evaluation, validated in French in older persons with communication disorders. We present the validation by an international expert team of the Algoplus scale in five languages: English, Spanish, Italian, Portuguese, and Turkish. Methods. A total of 181 older consecutive patients were included in five countries (Spain, Australia, Italy, Portugal, and Turkey). Test-retest and interrater reliabilities were determined by weighted kappa coefficient for each item and internal consistency by Kuder-Richardson-20 (KD). Results. Regarding test-retest reliability, the kappa coefficient for the five items ranged from 0.68 to 0.84. Inter-rater reliability kappa values ranged from 0.64 to 0.82. Internal consistency was indicated at a KD-greater than 0.6. Satisfaction was good to excellent for all teams. Results show that reliability tests are good to excellent for all items of Algoplus. Conclusions. This study shows evidence that Algoplus is an acceptable, reproducible, reliable, and easy-to-use tool. It provides a unique opportunity to include the translated Algoplus scale in daily assessment of older persons with communication disorders in many countries. [ABSTRACT FROM AUTHOR]

The addiction of tumors to elevated nicotinamide adenine dinucleotide (NAD+) levels is a hallmark of cancer metabolism. Obstructing NAD+ biosynthesis in tumors is a new and promising antineoplastic strategy. Inhibitors developed against nicotinamide phosphoribosyltransferase (NAMPT), the main enzyme in NAD+ production from nicotinamide, elicited robust anticancer activity in preclinical models but not in patients, implying that other NAD+-biosynthetic pathways are also active in tumors and provide sufficient NAD+ amounts despite NAMPT obstruction. Recent studies show that NAD+ biosynthesis through the so-called "Preiss-Handler (PH) pathway", which utilizes nicotinate as a precursor, actively operates in many tumors and accounts for tumor resistance to NAMPT inhibitors. The PH pathway consists of three sequential enzymatic steps that are catalyzed by nicotinate phosphoribosyltransferase (NAPRT), nicotinamide mononucleotide adenylyltransferases (NMNATs), and NAD+ synthetase (NADSYN1). Here, we focus on these enzymes as emerging targets in cancer drug discovery, summarizing their reported inhibitors and describing their current or potential exploitation as anticancer agents. Finally, we also focus on additional NAD+-producing enzymes acting in alternative NAD+-producing routes that could also be relevant in tumors and thus become viable targets for drug discovery. [ABSTRACT FROM AUTHOR]

Background/Aims: Postoperative delirium (POD) is more frequent in elderly patients undergoing major cancer surgery. The interplay between individual clinical vulnerability and a series of perioperative factors seems to play a relevant role. Surgery is the first-line treatment option for cancer, and fast-track surgery (FTS) has been documented to decrease postoperative complications. The study sought to assess, after comprehensive geriatric assessment (CGA) and frailty stratification (Rockwood 40 items index), which perioperative parameters were predictive of POD development in elderly patients undergoing FTS for colorectal cancer. Methods: A total of 107 consecutive subjects admitted for elective colorectal FTS were enrolled. All patients underwent CGA, frailly stratification, Timed up & go (TUG) test, 4AT test for delirium screening, anesthesiologists physical status classification, and Dindo-Clavien classification. Results: The incidence of POD was 12.3%. Patients’ prevalent clinical phenotype was pre-frail. The multivariate analysis indicated physical performance (TUG in seconds) as the most significant predictor of POD for each second of increase. Conclusions: Only few procedure-specific studies have examined the impact of FTS for colorectal cancer on POD. This is the first study to investigate the risk factors for POD, in a vulnerable octogenarian oncogeriatric population submitted to FTS surgery and frailty stratification. [ABSTRACT FROM AUTHOR]

Aim Prognosis informs the physician's decision-making process, especially for frail older adults. So far, any non-disease-specific index has proven full evidence for routine use in clinical practice. Here, we aimed at assessing, prospectively, the calibration and discriminating accuracy of validated prognostic indices in a cohort of elderly hospitalized patients. Methods This was a prospective observational study that enrolled elderly patients ( n = 100). The patients' assessment included clinical variables, as well as the following five prognostic indices of mortality: (i) Levine index (2007); (ii) Walter index (2001); (iii) CARING (C, primary diagnosis of cancer; A, ≥ 2 admissions to the hospital for a chronic illness within the last year; R, resident in a nursing home; I, intensive care unit admission with multiorgan failure, NG, noncancer hospice guidelines [meeting ≥ 2 of the National Hospice and Palliative Care Organization's guidelines]) criteria of Fischer (2006-2011); (iv) Silver Code of Di Bari (2010); and (v) Burden of Illness Score for Elderly Persons of Inouye (2003). Results Patients' clinical characteristics: 70% women (age 86.20 ± 0.69 years), 30% men (age 85.40 ± 1.07 years), Comorbidity Illness rating scale (CIRS) 4.3 ± 0.61 and Barthel Index 28 ± 0.54. Walter and Burden of Illness Score for Elderly Persons scores showed similar prediction rates when compared with the expected validated values ( ancova: F = 14.00, P < 0.008). Burden of Illness Score for Elderly Persons was the most calibrated and accurate index (receiver operating characteristic curve 0.72; P < 0.02). Conclusions None of the assessed prognostic indices, in a 'real world' scenario, afforded the optimal predictive accuracy (receiver operating characteristic curve 0.90); all these indices are still far from a robust answer to the prognosis in older age, reflecting a poor ability to encompass the spectrum of frailty. Effort should be made to tailor the prognostication in geriatrics, moving from a disease-centered model to a precision model, tailored to the frail phenotype. Geriatr Gerontol Int 2017; 17: 1015-1021. [ABSTRACT FROM AUTHOR]

Pain is still a neglected clinical issue in elderly people with dementia and/or communicative disorders, with an unacceptable higher rate of under diagnosis and under treatment. Cognitive deficit and emotional and psychological disturbances entangle pain symptoms, affecting patient self-report. So far, observational pain tools do not have fully adequate clinimetric properties and quality requirements for easy-to-use daily rating. Older patients with dementia represent a clinical challenge. The assessment of pain is important for improving clinical outcomes, such as functional status, frailty trajectories, comorbidity, and quality of life. The PAINAID scale appears to be the most accurate pain tool in people with dementia along with the Algoplus® scale, a recently developed tool to rapidly assess acute pain in hospitals settings. The present study aimed to assess the clinimetric properties of the Algoplus®, as compared to PAINAID, for detecting acute pain in a real-world cohort of hospitalized older patients with dementia. [ABSTRACT FROM AUTHOR]

In spite of in depth investigations in the field of the amyloid cascade hypothesis, so far, no disease modifying therapy has been developed for Alzheimer's disease (AD). The pathophysiology provides some evidence of the inverse correlation between cancer and AD. Both AD and cancer are characterized by abnormal cellular behaviors; trigger factors along with a meta synchronously action is expected to drive cancer or neurodegeneration, supporting, respectively, progressive neuronal loss or uncontrolled cell proliferation in cancer cells. So far, cancer and AD are seemingly two opposite ends of the same biological spectrum. Basic science increasingly indicates shared molecular mechanisms between cancer and AD and gives weight to key relevant biological theories; according to them, the inverse tuning of clustered gene expression, the sharing of mutual independent pathway or the deregulated unfolded proteins system (UPR) may count for this inverse association. Additionally, the common biological background gave credibility to the recent discovery of a repurposing role for cancer drugs in AD. It refers to the development of new uses for existing pharmaceuticals having the same role as the original mechanism or to the discovery of a new drug action with disease modifying effects. The present review summarizes the most important biological theories that link neurodegeneration and cancer and provides an up-to-date revision of the repurposing cancer agents for AD. The review also addresses the gap of knowledge, since drug cancer repositioning holds an important promise but further investigations are warranted to ascertain the clinical relevance of such attractive clinical candidate compounds for AD. [ABSTRACT FROM AUTHOR]

Autopsy studies have indicated brain accumulation of amyloid-β peptides as a common pathogenetic hallmark of amnestic cognitive impairment (aMCI) and overt Alzheimer's disease (AD). The pathogenesis of AD is still debated but recent reports have even designated AD as type III diabetes. This study aims to assess plasma levels of malondialdehyde, pentosidine, and insulin resistance in a group of aMCI patients, AD subjects, and age- and gender-matched controls, to confirm, beyond the accumulation of amyloid-β, the presence of a metabolic disorder, as a causative/contributive factor for AD. Patients were recruited and diagnosed as aMCI (n = 180), AD (n = 84), and age- and gender-matched controls (n = 62) at three different Italian memory clinics. Plasma insulin and glucose, plasma pentosidine and malondialdehyde (MDA), HOMA-IR and QUICKI score for insulin sensitivities indexes were collected at the basal visit. Plasma MDA levels were higher in the aMCI group who converted to AD compared to controls, stable aMCI subjects, and AD subjects (p < 0.01) respectively, while plasma pentosidine was higher compared to controls. The aMCI group showed a significant correlation between HOMA-IR, QUICKI, insulin, and MDA (p < 0.02). aMCI might be considered the early biochemical active disease stage where glycoxidation, hyperinsulinemia, and pro-amyloidogenic status are at the highest rate while overt AD might indicate the glycoxidative cascade dwindling, ending a process possibly started two decades earlier. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is a life shortening disease, and the lack of disease modifying therapy implies a huge impact on life expectancy as well as an outgrowing financial and socioeconomic burden. Cholinesterase inhibitors (ChEIs) represent the first line symptomatic therapy, whose benefit to harm ratio is still a matter of debate. Acetylcholinesterase enzyme is a core interest for pharmacological and toxicological research to unmask the fine balance between therapeutic drug efficacy, tolerability, safety, and detrimental effects up to adverse drug reaction. So far, a body of evidence advocated that an increased vagal tone was associated to an increased risk of gastrointestinal and cardiac side effects (negative chronotropic, arrhytmogenic, hypotensive effects), able to hamper ChEIs effects on cognition, reducing administration feasibility and compliance, especially in older and comorbid patients. Conversely, a growing body of evidence is indicating a protective role of ChEIs on overall cardiovascular mortality in patients with dementia, through a series of in vitro and in vivo investigations. The present review is aimed to report the up to date literature in the controversial field of ChEIs and cardioprotection in dementia, offering a state of the art, which may constitute the conceptual framework to be enlarged in order to build higher evidence. Chronic vagal nerve stimulation acted upon by donepezil might improve long term survival through pharmacological properties apart from cholinesterase inhibition, able to offer cardioprotection, abating the overall cardiovascular risk, and, thus profiling a new line of therapeutic intervention for ChEI drug class. [ABSTRACT FROM AUTHOR]

Background: The histopathological hallmarks in Alzheimer's disease (AD) include neuronal cell death, formation of amyloid plaques and neurofibrillary tangles. Glycoxidation plays a crucial role in AD pathogenesis, as pentosidine and Nε- carboxymethyl-lysine (CML), were detected in AD hallmarks, and in vivo cerebrospinal fluid (CSF). However, the definitive role of AGEs in the neuropathology of AD is inconclusive. The aim of this preliminary study was to assess the level of pentosidine in CSF of patients affected by neurological disorders, including probable AD, in order to assess the feasibility of AGEs detection in CSF and to explore pentosidine as a potential biomarker in AD. Methods: Twenty-five patients diagnosed with AD (NINCDS ADRDA criteria) and different neurological disorders were enrolled. Diabetic patients were excluded. Pentosidine, CML, amyloid β1-42 were assessed by high performance liquid chromatography (HPLC) by Odetti modified method,and by sandwich ELISA respectively. Results: Our data showed the presence of pentosidine in all CSF samples, a significant increase in CSF pentosidine levels with age (p<0.05) and a significant decreased concentration of pentosidine in four AD subjects (p<0.01), after normalization to CSF protein concentration. Conclusions: The study showed that AGEs concentration in CSF might benefit from age correction, at least for pentosidine, originally addressing a potential systemic age-dependent AGEs accumulation. The significant decrease of CSF pentosidine in AD, even in 4 patients, might conceive that different AGEs inform specific types of neurodegeneration, depending on oxidative stress levels, blood - brain barrier permeability, brain localization and systemic risk factors. [ABSTRACT FROM AUTHOR]

The aim of this work was to evaluate the ability of oxidative and glycative stressors to modify properties of human serum albumin (HSA) by analyzing markers of glycation (pentosidine) and oxidation (advanced oxidative protein products (AOPPs)) and assessing fluorescence and circular dichroism. HSA was incubated for up to 21 days with ribose, ascorbic acid (AA) and diethylenetriamine pentacetate (DTPA) in various combinations in order to evaluate influences of these substances on the structure of HSA. Ribose was included as a strong glycative molecule, AA as a modulator of oxidative stress, and DTPA as an inhibitor of metal-catalyzed oxidation. Ribose induced a significant increase in pentosidine levels. AA and DTPA prevented the accumulation of pentosidine, especially at later time points. Ribose induced a mild increase in AOPP formation, while AA was a strong inducer of AOPP formation. Ribose, in combination with AA, further increased the formation of AOPP. DTPA prevented the AA-induced generation of AOPP. Ribose was also a potent inducer of fluorescence at 335nm ex/385nm em, which is typical of pentosidine. AA and DTPA prevented this fluorescence. Circular dichroism showed complex results, in which AA and DTPA were strong modifiers of the percentages of the alpha-helical structure of HSA, while ribose affected the structure of HSA only at later time points. [ABSTRACT FROM AUTHOR]

A growing body of evidence claims there is a pivotal role of heat temperatures and summer hot spells in the pathogenesis of exceeding morbidity and mortality among older people. The European well-known “2003 killer hot summer” has boosted many epidemiological and clinical investigations to clarify the pathogenetic correlation between hot spells and elderly mortality with new acquirements in terms of pathophysiology, preventive measures, and therapeutic approaches. However, a quite controversial issue arises: overall elderly mortality is higher in the cold winter compared with summer. The progressive development of preventive, therapeutic, and environmental measures, if targeted with promptness, has generally proven effective in coping with heat temperature, restraining elderly mortality. However, few investigations have been performed dealing with cold, with pioneeristic as well as simplistic approaches, without any conclusiveness or effectiveness in terms of prevention or therapy. Data from recent literature enlist various clinical and environmental approaches in counteracting cold-related mortality in elderly, but lack evidence-based results; a recent European collaborative study reported cold-related elderly mortality as non-negligible, deserving the growing attention of public authorities. We conducted a 4-year survey among 6 different nursing homes located in a seaside city of northern Italy so as to collect epidemiological data on stressful weather spells and elderly mortality. Our results showed that overall elderly mortality in the cold season displayed as significantly high rates as in summer, and the monthly deaths per year of observation showed higher rates in the cold season, addressing it as the most prevalent time period related to mortality in older people. Thus, research in the field is mandatory so as to draw a broader conceptual framework for the stratification of specific population risk profiling and the assessment of adequate preventive and therapeutic measures. To the present knowledge, the lack of pathophysiological understanding, the missing evidence-based data in coping with cold weather-related elderly mortality, together with policy makers'' misconceptions is mounting the controversy on this emerging clinical issue. [Copyright &y& Elsevier]

In this cross-sectional study, we assessed palliative care (PC) needs in older adults with dementia. Using the NECPAL CCOMS-ICO© 3.1 tool and comprehensive geriatric assessment, 16.25% of the 554 evaluated patients required PC, which had clinical frailty and a moderate stage of dementia. Advanced frailty was associated with the poorest prognosis, according to the PC-based stratification. Our findings support the use of PC assessment in dementia care, which focuses on a person-centered approach while minimizing unnecessary or ineffective treatments and meeting the real-world patient's needs. PC care may fulfill the multidimensional nature of dementia, shifting towards personalized palliative approaches. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck squamous cell carcinoma (HNSCC) is a common cancer in older adults, but treatment decisions for these patients can be challenging due to age-related factors, such as frailty. This study aimed to evaluate how pre-treatment frailty assessment can help predict survival outcomes and treatment-related side effects in older patients with HNSCC who undergo radiotherapy, with or without chemotherapy. We found that frailty plays a significant role in determining overall survival, but it was not directly related to acute radiation toxicity. Our findings suggest that incorporating frailty assessment into treatment planning could help personalize therapy for older patients, improving decision-making and potentially enhancing long-term outcomes. Background/Objectives: Over 60% of diagnoses of head and neck squamous cell carcinoma (HNSCC) occur in patients aged over 65. The benefits of radiotherapy (RT) combined with chemotherapy remain controversial in geriatric patients. Frailty stratification is underutilized in clinical practice despite evidence suggesting its predictive power. We aimed to assess the impact of pre-treatment frailty stratification on overall survival (OS) and acute radiation-related toxicity in a cohort of older patients with HNSCC. Methods: A prospective cohort of 117 patients aged ≥65 years with newly diagnosed HNSCC was enrolled between 2017 and 2022. Patients received RT with or without chemotherapy. Frailty was assessed using the 40-item Frailty Index (FI) as part of a comprehensive geriatric assessment. The primary outcomes were OS and acute RT toxicity, defined as a grade ≥ 3 based on CTCAE 5.0. Cox proportional hazard models and logistic regression models, adjusted for age, tumor stage, and chemotherapy, were used. Results: After a median follow-up of 819 days, FI (HR 1.478, 95% CI 1.182–1.848, p < 0.001) was an independent predictor of OS. Grade ≥ 3 toxicities were observed in 38% of patients, but frailty was not significantly associated with toxicity. A sub-analysis of oropharyngeal carcinoma patients demonstrated improved OS in HPV-positive patients (HR 0.231, 95% CI 0.078–0.686, p = 0.008). Conclusions: the standardized introduction of frailty assessment in the evaluation of older HNSCC patients holds great promise for predicting long-term survival. This approach could be crucial in tailoring treatment protocols that account for the biological heterogeneity of older adults. [ABSTRACT FROM AUTHOR]

Pharmacological pain treatment in older persons is presented by a multi-disciplinary group of European pain experts. Drugs recommended for acute or chronic nociceptive pain, also for neuropathic pain and the routes of administration of choice are the same as those prescribed for younger persons but comorbidities and polypharmacy in older persons increase the risk of adverse effects and drug interactions. Not all drugs are available or authorised in all European countries. For mild-to-moderate pain, non-opioids including paracetamol and non-steroidal anti-inflammatory drugs are first-line treatments, followed by nefopam and metamizole. Codeine, dihydrocodeine and tramadol are prescribed for moderate to severe pain and 'strong' opioids, including morphine, hydromorphone, oxycodone, fentanyl, buprenorphine, methadone and tapentadol, for severe pain. Chronic neuropathic pain treatment relies on coanalgesics, including anti-epileptics (gabapentinoids) and anti-depressants with additional option of topical lidocaine and capsaicine. The choice of analgesic(s) and the route of administration should be guided by the pain characteristics, as well as by the patient's comorbidities, organ function and medications. Several directions have been highlighted to optimise pharmacological pain management in older individuals: (1) before starting pain treatment adequately detect and assess pain and always perform a full geriatric assessment, (2) consider kidney function systematically to adjust the doses of analgesics and avoid the risks of overdose, (3) start with the lowest dose of an analgesic and increase it gradually under the control of the effect, (4) involve the older persons and family in their treatment, (5) reevaluate pain regularly during treatment and (6) combine pharmacological treatment with non-pharmacological approaches. [ABSTRACT FROM AUTHOR]

Neuronal senescence is a major risk factor for the development of many neurodegenerative disorders. The mechanisms that drive neurons to senescence remain largely elusive; however, dysregulated mitochondrial physiology seems to play a pivotal role in this process. Consequently, strategies aimed to preserve mitochondrial function may hold promise in mitigating neuronal senescence. For example, dietary restriction has shown to reduce senescence, via a mechanism that still remains far from being totally understood, but that could be at least partially mediated by mitochondria. Here, we address the role of mitochondrial inorganic polyphosphate (polyP) in the intersection between neuronal senescence and dietary restriction. PolyP is highly present in mammalian mitochondria; and its regulatory role in mammalian bioenergetics has already been described by us and others. Our data demonstrate that depletion of mitochondrial polyP exacerbates neuronal senescence, independently of whether dietary restriction is present. However, dietary restriction in polyP‐depleted cells activates AMPK, and it restores some components of mitochondrial physiology, even if this is not sufficient to revert increased senescence. The effects of dietary restriction on polyP levels and AMPK activation are conserved in differentiated SH‐SY5Y cells and brain tissue of male mice. Our results identify polyP as an important component in mitochondrial physiology at the intersection of dietary restriction and senescence, and they highlight the importance of the organelle in this intersection. [ABSTRACT FROM AUTHOR]

Background: As the population ages, the concept of frailty becomes increasingly relevant and may be considered a precursor between aging and the development of dementia in later life. Similarly, the construct of cognitive reserve (CR) is an accepted model of cognitive resilience that may account for individual differences in trajectories of brain aging, mitigating the clinical expression of dementia. Objective: We aim to estimate the role of CR and frailty in moderating the prediction of dementia in the population aged over 80 who are attending an Italian outpatient memory clinic. Methods: Comprehensive Geriatric Assessment, Clinical Frailty Scale (CFS) to screen for frailty, and Cognitive Reserve Index questionnaire (CRIq) to evaluate CR, were used to assess patients systematically. We performed multivariate logistic regression to assess associations with dementia. Model performance and interaction between frailty and cognitive reserve were then evaluated. Results: 166 patients were consecutively enrolled (mean age was 85.7 years old, females composed 68%); 25% had a diagnosis of amnestic mild cognitive impairment, and 75% had a diagnosis of dementia. Multivariate regression analysis showed that CRIq and CFS were the main clinical assessment tools associated with the presence of dementia, even after collinearity adjustment. No significant interaction of CFS*CRIq was found. Conclusions: To our knowledge, this is the first study to investigate the association between CR, frailty, dementia, and their related interacting terms in a real-world population of very old patients. Our findings may suggest that both CR and frailty shape an individual's resilience throughout their lifetime. This may potentially counteract the effects of brain neuropathology, in line with the hypothesis that meaningful associations exist between CR, frailty, and cognition in later life. [ABSTRACT FROM AUTHOR]

Background: As the population ages, the concept of frailty becomes increasingly relevant and may be considered a precursor between aging and the development of dementia in later life. Similarly, the construct of cognitive reserve (CR) is an accepted model of cognitive resilience that may account for individual differences in trajectories of brain aging, mitigating the clinical expression of dementia. Objective: We aim to estimate the role of CR and frailty in moderating the prediction of dementia in the population aged over 80 who are attending an Italian outpatient memory clinic. Methods: Comprehensive Geriatric Assessment, Clinical Frailty Scale (CFS) to screen for frailty, and Cognitive Reserve Index questionnaire (CRIq) to evaluate CR, were used to assess patients systematically. We performed multivariate logistic regression to assess associations with dementia. Model performance and interaction between frailty and cognitive reserve were then evaluated. Results: 166 patients were consecutively enrolled (mean age was 85.7 years old, females composed 68%); 25% had a diagnosis of amnestic mild cognitive impairment, and 75% had a diagnosis of dementia. Multivariate regression analysis showed that CRIq and CFS were the main clinical assessment tools associated with the presence of dementia, even after collinearity adjustment. No significant interaction of CFS*CRIq was found. Conclusions: To our knowledge, this is the first study to investigate the association between CR, frailty, dementia, and their related interacting terms in a real-world population of very old patients. Our findings may suggest that both CR and frailty shape an individual's resilience throughout their lifetime. This may potentially counteract the effects of brain neuropathology, in line with the hypothesis that meaningful associations exist between CR, frailty, and cognition in later life. [ABSTRACT FROM AUTHOR]

Background: Discrepancy between caregiver and patient assessments of apathy in mild cognitive impairment (MCI) is considered an index of apathy unawareness, independently predicting progression to AD dementia. However, its neural underpinning are uninvestigated. Objective: To explore the [18F]FDG PET-based metabolic correlates of apathy unawareness measured through the discrepancy between caregiver and patient self-report, in patients diagnosed with MCI. Methods: We retrospectively studied 28 patients with an intermediate or high likelihood of MCI-AD, progressed to dementia over an average of two years, whose degree of apathy was evaluated by means of the Apathy Evaluation Scale (AES) for both patients (PT-AES) and caregivers (CG-AES). Voxel-based analysis at baseline was used to obtain distinct volumes of interest (VOIs) correlated with PT-AES, CG-AES, or their absolute difference (DISCR-AES). The resulting DISCR-AES VOI count densities were used as covariates in an inter-regional correlation analysis (IRCA) in MCI-AD patients and a group of matched healthy controls (HC). Results: DISCR-AES negatively correlated with metabolism in bilateral parahippocampal gyrus, posterior cingulate cortex, and thalamus, PT-AES score with frontal and anterior cingulate areas, while there was no significant correlation between CG-AES and brain metabolism. IRCA revealed that MCI-AD patients exhibited reduced metabolic/functional correlations of the DISCR-AES VOI with the right cingulate gyrus and its anterior projections compared to HC. Conclusions: Apathy unawareness entails early disruption of the limbic circuitry rather than the classical frontal-subcortical pathways typically associated with apathy. This reaffirms apathy unawareness as an early and independent measure in MCI-AD, marked by distinct pathophysiological alterations. [ABSTRACT FROM AUTHOR]

The article presents a case study on the association between premorbid personality traits and behavioral disturbances in dementia patients. It describes the patients' clinical characteristics such as age, disease duration, and mental state. It shows some indications that support how premorbid personality might influence critical behavior disturbances including emotional stability, impulse control and energy/extroversion and increased neuropsychiatric inventory.

Background and aim. During ageing, the prevalence of dementia, and especially of Alzheimer's disease (AD) and cardiovascular disease (CVD), increases. The aim of this review is to investigate the relationship between AD and CVD and its risk factors, with a view to explain the underlying mechanisms of this association. Methods. This review is based on the material obtained via MEDLINE (PubMed), EMBASE, and Clinical Trials databases, from January 1980 until May 2019. The search term used was "Alzheimer's disease," combined with "cardiovascular disease," "hypertension," "dyslipidaemia," "diabetes mellitus," "atrial fibrillation," "coronary artery disease," "heart valve disease," and "heart failure." Out of the 1,328 papers initially retrieved, 431 duplicates and 216 records in languages other than English were removed. Among the 681 remaining studies, 98 were included in our research material on the basis of the following inclusion criteria: (a) the community-based studies; (b) using standardized diagnostic criteria; (c) reporting raw prevalence data; (d) with separate reported data for sex and age classes. Results. While AD and CVD alone may be considered deleterious to health, the study of their combination constitutes a clinical challenge. Further research will help to clarify the real impact of vascular factors on these diseases. It may be hypothesized that there are various mechanisms underlying the association between AD and CVD, the main ones being hypoperfusion and emboli, atherosclerosis, and the fact that, in both the heart and brain of AD patients, amyloid deposits may be present, thus causing damage to these organs. Conclusions. AD and CVD are frequently associated. Further studies are needed in order to understand the effect of CVD and its risk factors on AD in order to better comprehend the effects of subclinical and clinical CVD on the brain. Finally, we need to clarify the impact of the underlying hypothesized mechanisms of this association and to investigate gender issues. [ABSTRACT FROM AUTHOR]

Background: The containment measures linked to the COVID‐19 pandemic negatively affected the phyco‐physical well‐being of the population, especially older adults with neurocognitive disorders (NCDs). This study aims to evaluate whether the frailty of NCD patients was associated with different changes in multiple health domains, in particular in relation to loneliness and social isolation, pre‐ and post‐lockdown. Materials and Methods: Patients were recruited from 10 Italian Centers for Cognitive Disorders and Dementia. Data were collected in the pre‐pandemic period (T0), during the pandemic lockdown (T1), and 6–9 months post‐lockdown (T2). The UCLA Loneliness Scale‐3, Activities of Daily Living (ADL), Instrumental ADL (IADL), Mini‐Mental State Examination, and Neuropsychiatric Inventory (NPI) were administered. Caregivers' burden was also tested. Patients were categorized as non‐frail, pre‐frail, and frail according to the Fatigue, Resistance, Ambulation, Illness, and Loss of Weight scale. Results: The sample included 165 subjects (61.9% women, mean age 79.5 ± 4.9 years). In the whole sample, the ADL, IADL, and NPI scores significantly declined between T0 and T2. There were no significative variations in functional and cognitive domains between the frail groups. During lockdown we recorded higher Depression Anxiety Stress Scales and Perceived Stress Scale scores in frail people. In multivariable logistic regression, frailty was associated with an increase in social isolation, and a loss of IADL. Conclusions: We observed a global deterioration in functional and neuro‐psychiatric domains irrespective of the degree of frailty. Frailty was associated with the worsening of social isolation during lockdown. Frail patients and their caregivers seemed to experience more anxiety and stress disorders during SARS‐CoV‐2 pandemic. [ABSTRACT FROM AUTHOR]

Optimizing the functional status of patients of any age is a major global public health goal. Rehabilitation is a process in which a person with disabilities is accompanied to achieve the best possible physical, functional, social, intellectual, and relational outcomes. The Intermediate Care Unit within the O.U. of Geriatrics and Gerontology of the San Martino Hospital in Genoa is focused on the treatment and motor reactivation of patients with geriatric pathologies. The objective of this study was to identify which factor, among the characteristics related to the patient and those identified by the geriatric evaluation, had the greatest impact on rehabilitation outcomes. Our findings revealed significant correlations between the Barthel Index delta, the 4AT Screening Test, and the number of drugs taken. This association highlights the potential benefits of medication management in enhancing the overall well-being and functional abilities of frail older adults, despite the literature suggesting that polypharmacotherapy is associated with a reduction in functional status and an increase in mortality. These findings underscore the significance of a multidimensional geriatric assessment. Refining and optimising these multidisciplinary approaches is the objective of a more effective geriatric rehabilitation strategy. [ABSTRACT FROM AUTHOR]

Background: Major affective conditions are associated with significant disability and psychosocial impairment. Whether specific socio-demographic and clinical characteristics may distinguish subgroups of patients in terms of prognosis and illness trajectories is a matter of debate.Methods: The sample of this naturalistic cohort study included 675 currently euthymic patients with major affective disorders of which 428 (63.4%) were diagnosed with unipolar and 247 (36.6%) with bipolar disorders.Results: Younger adults with a longer duration of untreated illness and residual inter-episodic symptoms were more likely to be single or divorced, students, with an earlier age of first treatment/hospitalization, longer duration of substance abuse and duration of illness than older patients who were, conversely, more likely to be widowed and retired. Multivariate analyses showed a significant positive contribution to age at illness onset by marital status, nonpsychiatric medications, substance abuse, psychiatric diagnosis (bipolar vs. unipolar), age at first treatment/hospitalization, duration of illness, and current age. According to a further analysis, we also found a significant positive contribution to duration of illness by marital status, educational level, positive history of psychiatric conditions in family, substance abuse, psychiatric diagnosis (bipolar vs. unipolar), age at illness onset, age at first treatment, and certain cardiovascular disorders.Conclusions: There are substantial socio-demographic and clinical differences that may help to distinguish specific subgroups of patients; however, additional studies are requested to replicate these results and further investigate the main factors underlying our findings. [ABSTRACT FROM AUTHOR]

Background: Apathy is a frequent behavioral symptom of Alzheimer's disease (AD). The Apathy Evaluation Scale (AES) is a tool exploring the perception of apathy by both caregivers (CG-AES) and patients (PT-AES), and the discrepancy in their ratings is a proxy of patients' disease unawareness. Objective: To assess in a cohort study of patients with amnesic mild cognitive impairment (aMCI) whether apathy and awareness of apathy predict progression to dementia and timing. Methods: From the global AES scores of 110 patients with aMCI and their caregivers, we obtained two principal indices for analysis: 1) 'Apathy', the mean of PT-AES and CG-AES, and 2) 'Discrepancy', obtained by subtracting CG-AES from PT-AES. Patients were followed with visits every six months for three years or until dementia. AES indices and the principal demographical/neuropsychological variables were filtered from multicollinearity. The most robust variables entered a logistic regression model and survival analyses (Cox regression, log-rank test of Kaplan-Meier curves) to estimate which predicted the risk and timing of progression, respectively. Results: Sixty patients (54.5%) developed dementia (57 AD) after 6.0–36.0 months, 22 (20%) remained in an MCI stage, and 28 (25.5%) dropped out. 'Discrepancy' was a robust and accurate predictor of the risk of progression (AUC = 0.73) and, after binarization according to a computed cutoff, of timing to dementia. Conclusion: A structured evaluation of apathy, both self-assessed and estimated by caregivers, can provide useful information on the risk and timing of progression from aMCI to dementia. The discrepancy between the two estimates is a fairly reliable index for prediction purposes as a proxy of disease unawareness. [ABSTRACT FROM AUTHOR]

Depriving cancer cells of sufficient NAD levels, mainly through interfering with their NAD-producing capacity, has been conceived as a promising anti-cancer strategy. Numerous inhibitors of the NAD-producing enzyme, nicotinamide phosphoribosyltransferase (NAMPT), have been developed over the past two decades. However, their limited anti-cancer activity in clinical trials raised the possibility that cancer cells may also exploit alternative NAD-producing enzymes. Recent studies show the relevance of nicotinic acid phosphoribosyltransferase (NAPRT), the rate-limiting enzyme of the Preiss–Handler NAD-production pathway for a large group of human cancers. We demonstrated that the NAPRT inhibitor 2-hydroxynicotinic acid (2-HNA) cooperates with the NAMPT inhibitor FK866 in killing NAPRT-proficient cancer cells that were otherwise insensitive to FK866 alone. Despite this emerging relevance of NAPRT as a potential target in cancer therapy, very few NAPRT inhibitors exist. Starting from a high-throughput virtual screening approach, we were able to identify and annotate two additional chemical scaffolds that function as NAPRT inhibitors. These compounds show comparable anti-cancer activity to 2-HNA and improved predicted aqueous solubility, in addition to demonstrating favorable drug-like profiles. [ABSTRACT FROM AUTHOR]

Background: Information on prevalence, pathophysiology, and clinical assessment of paratonia are scarce. In a previous study, we suggested that surface electromyography (EMG) can be used to assess paratonia.Objective: To assess clinical and EMG features of paratonia in both patients with cognitive impairment and healthy subjects.Methods: We examined 18 patients with Alzheimer's disease (AD), 21 patients with mild cognitive impairment (MCI), 30 healthy seniors (seniors), and 30 healthy juniors (juniors). Paratonia was assessed using the "Paratonia Scale". EMG bursts were recorded from biceps and triceps during manually applied passive movements of elbow joint. Continuous (sinusoidal) and discontinuous (linear) movements were applied at 2 different velocities (fast and slow).Results: In comparison to juniors, seniors had higher clinical scores. In comparison to seniors, AD had higher oppositional scores, while MCI had higher facilitatory scores. EMG activity during passive movements correlated with paratonia clinical scores, was velocity-dependent and increased with movement repetition, most effectively for sinusoidal movements. Similar EMG activity was detected in not paratonic muscles.Conclusion: Paratonia increases with normal aging and cognitive decline progression. While facilitatory paratonia is due to involuntary contraction of the shortening muscle, oppositional paratonia is due, at least partially, to involuntary contraction of the lengthening muscle. Most characteristic feature of this muscle contraction is the progressive increase with movement repetition, that helps distinguish oppositional paratonia from spasticity and rigidity. A similar EMG activity is detected in not paratonic muscles, showing that, during tone assessment, the descending motor system is incompletely inactivated also in normotonic muscles. [ABSTRACT FROM AUTHOR]

People affected by dementia experienced decreased life expectancy with a 2-4 times higher risk of death at a given age compared to non-demented people. Dementia represents a major cost to health care and society in the Western world and, particularly in Italy, is projected to become a high-resource demanding chronic disease. The present study aimed to estimate the average survival rate of a group of community dwelling elderly affected by dementia in Italy, and to assess the predictive variables associated with survival length. This retrospective study collected the data of patients (n = 290) who died from 2008 to 2012. The data were extracted from a cohort of over 2,000 patients from three outpatient Dementia Clinics of Genoa (Italy). Demographic data and other clinical parameters listed in the patients' clinical records were collected. The mean survival rate after dementia diagnosis was 3.3 ± 0.1 years, lower compared to the age-matched healthy population. The survival rate of these patients showed a significant correlation with age (n = 290; r = -0.16: p < 0.006), with the cognitive status (n = 285; r = 0.16: p < 0.007), with education (n = 204; r = 0.23: p < 0.001), with comorbidity (n = 138; r = -0.41: p < 0.0001), with depressive mood (n = 74; r = 0.44: p < 0.0001), and with the functional status (ADL: n = 242, r = 0.29: p < 0.0001; IADL: n = 243; r = 0.25: p < 0.0001). Multivariate regression revealed age, gender, and functional status as the main determinants informing patient survival. The study provides interesting and reliable data on the pivotal value of early dementia diagnosis in predicting longer survival and addresses comprehensive geriatric assessment, which encompasses most of the predictive variables provided by the study, as a remarkable tool in estimating life expectancy of patients with dementia. [ABSTRACT FROM AUTHOR]

Osteoporosis, a multifactorial and progressive skeletal metabolic disease, is characterized by low-mass density and structural deterioration of bone micro-architecture that leads to enhanced bone fragility and increased susceptibility to fractures. Recently, it has been proposed that age-related bone loss could be correlated with the glycoxidative process. The aim of the present study was to investigate the in vitro effects of pentosidine, a glycoxidative end product, on human osteoblasts (HOb). The mineralization rate, the specific bone markers (alkaline phosphatase [ALP], collagen Iα1 [COL Iα1], osteocalcin [BGP]), and the human receptor for advanced glycation end products (RAGE) gene expression have been evaluated. Pentosidine incubation of HOb caused a significant decrease in ALP, Col Iα1, and RAGE mRNA levels, but only the RAGE gene expression decreased with no dose dependency. Moreover, pentosidine incubation of osteoblasts hampered the formation of bone nodules. No effect was observed on BGP gene expression under all experimental conditions. Our data gives further support to a detrimental effect of AGEs on bone that leads to functional alterations of osteoblasts. This study addresses a crucial role of protein glycoxidation in the bone mineralization process. AGEs formation and accumulation in bone may be one of the first pathogenetic steps of bone remodeling in aging and in age-related diseases, leading to enhanced bone mass loss. [ABSTRACT FROM AUTHOR]

Uraemic subjects undergoing chronic haemodialysis show increased oxidative stress. The use of non-biocompatible filters and reduced antioxidative defences are important sources of reactive oxygen species (ROS) release. The highly oxidative environment accelerates the onset and progression of tissue damage and atherosclerotic cardiovascular disease. The aldehyde 4-hydroxyl-2-nonenal (HNE) is probably the best marker of oxidative stress. In this study, the concentration of plasma HNE was evaluated in eight uremic subjects during two sessions of haemodialysis: the first using a standard biocompatible filter and the second using a filter coated with vitamin E. Baseline plasma levels of HNE were elevated, and dropped during haemodialysis. At the end of the session, however, low levels were maintained only when the vitamin E-modified filter was used. By contrast, a marked increase in HNE was recorded at the end of the session in all subjects who underwent haemodialysis with the conventional filter. This study provides evidence that the vitamin E-coated filter plays a role in counteracting oxidative stress. The chronic use of vitamin E-modified filters in haemodialysed subjects might help to counterbalance oxidative attack and, consequently, contribute to preventing cardiovascular disease. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BD) is a chronic and disabling psychiatric condition that is linked to significant disability and psychosocial impairment. Although current neuropsychological, molecular, and neuroimaging evidence support the existence of neuroprogression and its effects on the course and outcome of this condition, whether and to what extent neuroprogressive changes may impact the illness trajectory is still poorly understood. Thus, this selective review was aimed toward comprehensively and critically investigating the link between BD and neurodegeneration based on the currently available evidence. According to the most relevant findings of the present review, most of the existing neuropsychological, neuroimaging, and molecular evidence demonstrates the existence of neuroprogression, at least in a subgroup of BD patients. These studies mainly focused on the most relevant effects of neuroprogression on the course and outcome of BD. The main implications of this assumption are discussed in light of specific shortcomings/limitations, such as the inability to carry out a meta-analysis, the inclusion of studies with small sample sizes, retrospective study designs, and different longitudinal investigations at various time points. [ABSTRACT FROM AUTHOR]

• Antidepressant drugs continue to be commonly prescribed in bipolar disorder. • After regression analyses, factors associated with antidepressant use by were reduced personal autonomy, and hopelessness levels. • A better understanding of patterns/correlates related to antidepressant use may improve the management of different BD subtypes. Given that the patterns and clinical correlates related to antidepressant drugs (ADs) prescription for Bipolar Disorder (BD) remain generally unclear, this study aimed to compare socio-demographic and clinical features of BD patients treated vs. not treated with ADs. The sample consists of 287 currently euthymic bipolar patients. Among participants (mean age=51.9±15.02), 157 54.7% were receiving ADs. Based on the main findings, subjects given ADs were older and more frequently retired than those without receiving ADs. Moreover, patients given ADs were more likely to have had a first major depressive episode. Lifetime substance abuse/dependence history was less frequently reported among patients given ADs. Furthermore, ADs given patients had a higher number of affective episodes, and longer duration of their illness. Additionally, subjects treated with ADs reported higher hopelessness levels, and lower positive reinterpretations than those who were not treated with ADs. Factors associated with ADs-use by multivariate modeling were reduced personal autonomy (OR=.070), and hopelessness levels (OR=1.391). These results may help clinicians to better understand the clinical correlates of BD subtypes and improve their differential management. Additional studies are needed to replicate these findings, and facilitate the differential trajectories of BD patients based on socio-demographic/clinical profiles. [ABSTRACT FROM AUTHOR]

Background: The primary aim of the study was determining the validation of the modified 19‐item Frailty Index (mFI‐19), based on the standard procedure for creating a frailty index scoring in the accumulation deficit theory of Rockwood and comparing it with the gold standard comprehensive geriatric assessment (CGA) in old age patients with hip fracture. As a secondary aim, we compared prognostic accuracies of mFI‐19 and CGA in predicting long‐term mortality after surgery. Materials and Methods: A total of 364 older patients with hip fractures, each a candidate for surgery, were consecutively enrolled. All were subjected to CGA and mFI‐19 at baseline and time to death (years from hip surgery) were collected prospectively. Results: Mean patient age was 86.5 (SD: 5.65) years. The most common clinical phenotype (77%) was frail. Both CGA and mFI‐19 performed similarly in predicting long‐term mortality (Harrell's C‐index: 0.66 and 0.68, respectively). Conclusions: The mFI‐19 was validated, compared to the gold standard CGA, based on a systematic process for creating a frailty index in relation to the accumulation deficit. This is one of few prospective studies addressing long‐term mortality in older adults with hip fractures, invoking a methodologically robust frailty screening assessment. [ABSTRACT FROM AUTHOR]

Introduction: Optimizing the approach to older adults with cancer is now a priority given the increasing frequency of new cancer diagnoses that are made in the older population. The comprehensive geriatric assessment (CGA) represents the gold‐standard for (1) defining prognosis and ability to withstand cancer treatments, (2) exploring the multiple aspects that define the complexity of frail older persons, and (3) designing person‐tailored interventions. Materials and methods: In this document, based on a comprehensive revision of the literature, the Italian Society for Geriatrics and Gerontology proposes a CGA model (ONCOGER CGA) to be adopted by oncology centers for their routine approach to older patients with cancer. Results and discussion: A widespread use of this standardized CGA format will facilitate comparisons across institutions, promote studies based on a multidimensional patient assessment, and foster the inclusion of geriatric endpoints in oncological clinical trials. Furthermore, we predict that the use of a standardized CGA approach will increase the integration of geriatricians into oncology care teams with the final result of improving therapeutic choices and clinical outcomes. [ABSTRACT FROM AUTHOR]

Dementia is an age-related clinical condition, with higher incidence rates in older ages. However, there is some evidence that a reverse epidemiology is also observed. Namely, the cohort analysis of dementia incidence rates by birth in selected populations demonstrated a decreased incidence of dementia in late life across the last twenty years, possibly due to decreased incidence of cardiovascular disorders and increased education and cognitive reserve. In line with that, age is probably a proxy for other pathophysiological processes rather than a strictly causative factor for the onset of dementia, especially in oldest old persons. The present narrative review provides an update on the clinical interplay between the spectrum of brain aging, cardiovascular morbidity, dementia pathologies, and their clinical expression in the oldest old patients. Available evidence suggests that vascular prevention in the perspective of dementia largely involve middle ages, with an apparent reverse epidemiology in oldest old. Similarly, the present findings underline how cognitive resilience and frailty may be key relevant mediators in the modulation of the clinical expression of brain mixed neuropathologies in persons over 85 years old, providing a new integrated conceptual framework. [ABSTRACT FROM AUTHOR]

Background: Older adults face radical changes in their social life during ageing, dealing with several age‐related social adaptations. The aim of this review is to systematically explore the literature on social vulnerability (SV) and its association with functional decline activity of daily living (ADL)/instrumental activities of daily living (IADL) as an endpoint in older adults. Methods: We searched for relevant studies in three different databases: PubMed, Ovid Medline and PsychInfo. Inclusion criteria included: prospective cohort studies assessing SV correlation; studies in English, Italian, French and Spanish to the end of March 2018; a general population aged >65 years living in a community setting and/or studies including younger participants if the mean age was >65 years; and basic ADL and/or IADL by Katz and Lawton, respectively, as functional decline and clinical outcomes. Results: We identified 65 manuscripts that assessed the role of SV in functional decline. Our systematic analysis showed that 26, 36 and 19 studies observed a correlation between Basic Social Needs, Social Resources and Social Behaviour and Activity, respectively, and the onset of ADL/IADL functional decline. Twenty‐six studies explored the correlation between General Social Resources and the onset of ADL/IADL functional decline. Conclusions: When examining a wide set of social variables, the "quality," rather than just structure, and "type" of social relationship represents the core feature of SV that predicts functional decline in older adults. By defining individual SV, its measurement and evaluation, we can plan effective social interventions aimed at preventing or delaying functional decline or death. [ABSTRACT FROM AUTHOR]

Highlights • Major affective disorders are associated with significant psychosocial impairment. • Unipolar differ from bipolar inpatients according to specific clinical characteristics. • Higher lifetime psychotic symptoms and illness episodes were significant predictors of bipolarity. Abstract Major affective conditions including both unipolar (UD) and bipolar disorders (BD) are associated with significant disability throughout the life course. We aimed to investigate the most relevant socio-demographic/clinical differences between UD and BD subjects. Our sample included 180 inpatients, of which 82 (45.5%) participants were diagnosed with UD and 98 (54.5%) with BD. Relative to UD patients, BD individuals were more likely to report prior psychoactive medications, lifetime psychotic symptoms, nicotine abuse, a reduced ability to provide to their needs, gambling behavior, and fewer nonsuicidal self-harm episodes. Moreover, BD patients were more likely to report severe side effects related to medications, a younger age at illness onset and first hospitalization, higher illness episodes, and longer illness duration in years than UD subjects. In a multivariate logistic analysis accounting for age, gender, and socio-demographic characteristics, a significant positive contribution to bipolarity was found only for higher lifetime psychotic symptoms (β = 1.178; p ≤.05) and number of illness episodes (β =.155; p ≤.05). The present findings suggest that specific clinical factors may be used in order to better distinguish between UD and BD subgroups. Further studies are required to replicate these findings in larger samples. [ABSTRACT FROM AUTHOR]

Background: Novel pectin-honey hydrogels have been developed and characterized as medical device. Ideally, a wound dressing should maintain optimal fluid affinity, permit moisture evaporation, protect the wound from microbes, and have shape-conformability, biocompatibility, and antibacterial activity. Objective: A novel, simple and fast method to produce pectin-honey wound dressings is described. Methods: The properties of these pectin-honey hydrogels were investigated, including swelling ability, water vapour transmission rate, hydrogen peroxide production, methylglyoxal content and antibacterial activity. Biocompatibility was assessed by proliferation assays using cultured fibroblast cells and by in vivo study with subcutaneous and intraperitoneal implantation in rats. Results: Hydrogel showed a good water vapour transmission rate, fluid uptake and were not cytotoxic for fibroblasts. The hydrogel demonstrated good antibacterial activity toward clinically relevant pathogens, including S. aureus and E. coli. Biocompatibility was confirmed by the measurement of plasma levels of interleukin (IL)1 beta, IL-6, tumour necrosis factor (TNF) alpha, and prostaglandin (PG)E2. No histological changes were observed. Conclusions: The presence of a natural active component, conformability, and complete resorbability are the main characteristics of this new biocompatible biomaterial that is well tolerated by the body, possibly improves healing, may be used for surgical complications prevention, with a simple and inexpensive production process. [ABSTRACT FROM AUTHOR]

Aims and objectives To assess the effects of a texture-modified food program for dysphagia on the nutritional, biochemical and functional profile in a cohort of institutionalised older people in Italy. Background Dysphagic institutionalised older people, often also affected by dementia, are frequently exposed to malnutrition. Malnutrition in older people has negative effects on mortality, days of hospitalisation, infection, wound healing and risk of pressure injuries. Therefore, it is very important to prevent malnutrition in this frail population. Design A pre-post study without a control group. Methods The study included 479 dysphagic institutionalised older people from 20 nursing homes. Anthropometrical, biochemical, nutritional and functional parameters were collected retrospectively, 6 months before the study intervention, at time zero and, prospectively for 6 months after implementing the NUTRICARE food programme, for a total of nine evaluations. The NUTRICARE programme includes meals without nutritional supplementation, and personalised levels of density, viscosity, texture and particle size. Results The total mean body mass index of our sample passed from 17.88-19.00; body weight averagely improved by 7.19%, as well as their nutritional and biochemical profiles. There was a progressive improvement of total protein and serum albumin values. Nutritional parameters (serum transferrin and lymphocytes) displayed similar changes. Plasma lymphocytes reached normal levels in 98.23% of the sample. Plasma creatinine levels remained steady throughout the study and within the normal range. No side effects were reported. Conclusion The NUTRICARE food programme with a adequate proteins, calories, balanced nutritional and bromatological properties, and appropriate texture and palatability significantly improved the nutritional, biochemical and functional profile in a cohort of institutionalised dysphagic older people. Relevance to clinical practice The introduction of a balanced nutritional programme, using high-quality natural ingredients, appropriate texture and palatability can significantly improve health and quality of life in dysphagic older people. [ABSTRACT FROM AUTHOR]

In the last decade, substantial efforts have been made to identify NAD+ biosynthesis inhibitors, specifically against nicotinamide phosphoribosyltransferase (NAMPT), as preclinical studies indicate their potential efficacy as cancer drugs. However, the clinical activity of NAMPT inhibitors has proven limited, suggesting that alternative NAD+ production routes exploited by tumors confer resistance. Here, we show the gene encoding nicotinic acid phosphoribosyltransferase (NAPRT), a second NAD+-producing enzyme, is amplified and overexpressed in a subset of common types of cancer, including ovarian cancer, where NAPRT expression correlates with a BRCAness gene expression signature. Both NAPRT and NAMPT increased intracellular NAD+ levels. NAPRT silencing reduced energy status, protein synthesis, and cell size in ovarian and pancreatic cancer cells. NAPRT silencing sensitized cells to NAMPT inhibitors both in vitro and in vivo; similar results were obtained with the NAPRT inhibitor 2-hydroxynicotinic acid. Reducing NAPRT levels in a BRCA2-deficient cancer cell line exacerbated DNA damage in response to chemotherapeutics. In conclusion, NAPRT-dependent NAD+ biosynthesis contributes to cell metabolism and to the DNA repair process in a subset of tumors. This knowledge could be used to increase the efficacy of NAMPT inhibitors and chemotherapy. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is characterized by a highly unstable genome, with aneuploidy observed in nearly all patients. The mechanism causing this karyotypic instability is largely unknown, but recent observations have correlated these abnormalities with dysfunctional DNA damage response. Here, we show that the NAD+-dependent deacetylase SIRT6 is highly expressed in MM cells, as an adaptive response to genomic stability, and that high SIRT6 levels are associated with adverse prognosis. Mechanistically, SIRT6 interacts with the transcription factor ELK1 and with the ERK signaling-related gene. By binding to their promoters and deacetylating H3K9 at these sites, SIRT6 downregulates the expression of mitogen-activated protein kinase (MAPK) pathway genes, MAPK signaling, and proliferation. In addition, inactivation of ERK2/p90RSK signaling triggered by high SIRT6 levels increases DNA repair via Chk1 and confers resistance to DNA damage. Using genetic and biochemical studies in vitro and in human MM xenograft models, we show that SIRT6 depletion both enhances proliferation and confers sensitization to DNA-damaging agents. Our findings therefore provide insights into the functional interplay between SIRT6 and DNA repair mechanisms, with implications for both tumorigenesis and the treatment of MM. [ABSTRACT FROM AUTHOR]

To determine the effect of geriatric comanagement on clinical outcomes of older patients undergoing surgery for gastrointestinal cancer. This was a single-center, nonrandomized, before-and-after study, which compared patient outcomes before and after the implementation of geriatric comanagement in an oncological surgery division. The study included patients aged 70 or older, who were treated for a gastrointestinal cancer at the Oncological Surgery Division of the Policlinico San Martino Hospital (Genoa, Italy). Patients from the control group were treated between January 2015 and October 2018, and the patients who received geriatric comanagement during their stay in the surgical ward were treated between November 2018 and December 2019. Patients from both groups received a preoperative comprehensive geriatric assessment in the preoperative phase and were followed according to the Enhanced Recovery After Surgery model in the perioperative period. In the geriatric comanagement group, targeted interventions during daily geriatrician-led ward rounds were performed. Inverse probability weighting was used to adjust estimates for potential baseline confounders. A total of 207 patients were included: 107 in the control group and 90 who received geriatric comanagement. Overall, patients from both groups had similar demographic and clinical characteristics with a median [interquartile range (IQR)] age of 80.0 (77.0, 84.0) years and a pre-frail phenotype [median (IQR) 40-item Frailty Index 0.15 (0.10, 0.26)]. In the geriatric comanagement group, a significant reduction in grade I–V complications (adjusted odds ratio 0.29; 95% CI 0.21–0.40); P <.001) and in 1-year readmissions (adjusted hazard ratio 0.53; 95% CI 0.28–0.98; P <.044) was observed. No difference between the 2 groups in terms of 1-year mortality was detected. Our study supports the implementation of geriatric comanagement in the care of older patients undergoing surgery for gastrointestinal cancer. [ABSTRACT FROM AUTHOR]