Undernutrition, cognitive decline and dementia: The collaborative PROMED-COG pooled cohorts study.

BACKGROUND & AIMS: Undernutrition may negatively impact cognitive function, but evidence of this relationship is not yet consolidated. Under the "PROtein enriched MEDiterranean diet to combat undernutrition and promote healthy neuroCOGnitive ageing" (PROMED-COG) project, we evaluated the association between undernutrition, and cognitive decline and incident dementia in older adults. METHODS: Retrospective data harmonization was performed on three Italian population-based studies: the Italian Longitudinal Study of Ageing (ILSA), the Progetto Veneto Anziani (Pro.V.A.), and the Bollate Eye Study-Follow-Up (BEST-FU). The associations between undernutrition, operationalized using the Global Leadership Initiative on Malnutrition (GLIM) criteria, and decline on the Mini-Mental State Examination (MMSE) or dementia incidence follow-up were evaluated with Cox proportional hazard regression models. RESULTS: The pooled cohort comprised 9071 individuals (52% females) aged between 42 and 101 years. The prevalence of undernutrition at the baseline was 14.3%, significantly higher among females (15.4% vs 13%) and in older age, ranging from 3.5% in those aged <60 years to 28.8% in those 85+ years. Undernutrition was associated with both cognitive decline over a median 8.3-year follow-up (Hazard Ratio (HR) 1.20, 95% Confidence Interval (CI) 1.02-1.41, p = 0.028) and incidence of dementia over a median 8.6-year follow-up (HR = 1.57, 95%CI 1.01-2.43, p = 0.046). For cognitive decline, the association with undernutrition was more marked in males than females (HR = 1.36, 95%CI 1.05-1.77, p = 0.019 vs HR = 1.10, 95% CI 0.89-1.36, p = 0.375). CONCLUSION: Undernutrition is prevalent among older people and is associated with an increased risk of experiencing cognitive decline and dementia. The prevention and early identification of undernutrition could be an important nonpharmacologic strategy to counteract neurodegeneration.

Food insecurity and body mass index among older people: A systematic review and meta-analysis.

Food insecurity, characterized by inadequate access to sufficient and nutritious food, poses a significant challenge to the health and well-being of older adults. This systematic review and meta-analysis was aimed to examine the association between food insecurity and body mass index (BMI) in older people, i.e., aging 60 and above. PRISMA 2020 guidelines were followed. The protocol was registered in PROSPERO in advance (ID CRD 42024543271). PubMed/MEDLINE, and Scopus were searched up to February 2024. Out of 5834 retrieved article, a total of 13 studies met the inclusion criteria, encompassing diverse geographic regions and socioeconomic contexts. The meta-analysis revealed a significant association between food insecurity and higher BMI (both obesity and overweight) in older adults. Pooled estimates indicated that food-insecure older individuals were more likely to be overweight or obese (combined) compared to their food-secure counterparts [OR= 1.29 (95% CI= 1.28-1.30), p<0.001; I2= 94.92]. Results were also confirmed for overweight or obesity alone. Notably, food insecurity was linked to increased consumption of energy-dense, nutrient-poor foods, contributing to higher BMI. These findings underscore the complex relationship between food insecurity and BMI among older adults, emphasizing the need for targeted interventions to address food access and nutritional quality.

Association between Glycosylated Hemoglobin Levels and Vaccine Preventable Diseases: A Systematic Review.

People with diabetes are at higher risk of serious complications from many vaccine-preventable diseases (VPDs). Some studies have highlighted the potential impact of glycosylated hemoglobin levels (HbA1c), but no systematic review has synthesized these findings. Of the 823 identified studies, 3 were included, for a total of 705,349 participants. Regarding the incidence of herpes zoster (HZ), one study found that higher HbA1c levels at the baseline (>10.3%) were associated with a significantly higher risk of HZ of 44%, compared to those with a good HbA1c control (6.7%). On the contrary, the second one reported that when compared to the reference group (HbA1c of 5.0-6.4%), participants with a HbA1c less than 5.0% were at higher risk of HZ of 63%, whilst participants with a HBA1c more than 9.5% had a similar risk. Finally, the third study observed that diabetes, defined using a value of HbA1c more than 7.5%, was associated with an increased risk of mortality in men with COVID-19. In conclusion, both high and low HBA1c levels appear to be associated with a higher risk of HZ. Regarding COVID-19, a value of HbA1c more than 7.5% was associated with a higher risk of death in COVID-19, but only in men.

The impact of the Mediterranean diet on immune function in older adults.

Diet is one of the lifestyle factors that is most amenable to intervention, and has a substantial effect on the potential for successful aging and mitigation of the risk of disease. Good nutrition is a pillar of healthy aging, and a large body of evidence attests to the benefits of the Mediterranean diet on the quality of the aging process. The Mediterranean diet comprises a wide range of nutrients which, both individually and collectively, exert positive effects on immunity, in large part mediated by the gut microbiota. In this article, we review the effect of the Mediterranean diet on immunity, and how its beneficial effects are mediated by the gut microbiota. We review the effects of certain key components of the Mediterranean dietary pattern, including vitamins, zinc, selenium, and polyphenols. Overall, the existing body of evidence convincingly demonstrates that the Mediterreanean diet affects immune health by maintaining a healthy body weight and reducing the risk of metabolic and cardiovascular diseases; by reducing inflammation and by promoting a healthy gut microbiota profile.

Changes in Sleep Duration and Sleep Timing in the General Population from before to during the First COVID-19 Lockdown: A Systematic Review and Meta-Analysis.

BACKGROUND: The COVID-19 lockdown had a profound effect on everyday life, including sleep health. This systematic review and meta-analysis evaluated changes in quantitative sleep parameters during the first lockdown compared with pre-lockdown in the general population. METHODS: A search in scientific databases was performed to identify eligible observational studies from inception to 8 February 2023. We performed a random effects meta-analysis of those studies reporting (a) means of sleep duration, time in bed (TIB), and sleep timing (bedtime and wake-up time); (b) the percentages of atypical sleep duration before and during the lockdown; (c) the percentages of change in sleep duration and sleep timing. RESULTS: A total of 154 studies were included. A small increase in sleep duration (0.25 standardized mean difference, 95% CI 0.180-0.315) was found, with 55.0% of the individuals reporting changes, predominantly an increase (35.2%). The pooled relative risk for sleeping more than 8/9 h per night was 3.31 (95% IC 2.60-4.21). There was a moderately significant delay in sleep timing and a surge in napping. CONCLUSION: An increase in sleep duration and napping, and delayed sleep timing were observed. High-quality studies should evaluate whether these parameters have now become chronic or have returned to pre-lockdown values.

Interventions to prevent and treat delirium: An umbrella review of randomized controlled trials.

Delirium is a common condition across different settings and populations. The interventions for preventing and managing this condition are still poorly known. The aim of this umbrella review is to synthesize and grade all preventative and therapeutic interventions for delirium. We searched five databases from database inception up to March 15th, 2023 and we included meta-analyses of randomized controlled trials (RCTs) to decrease the risk of/the severity of delirium. From 1959 records after deduplication, we included 59 systematic reviews with meta-analyses, providing 110 meta-analytic estimates across populations, interventions, outcomes, settings, and age groups (485 unique RCTs, 172,045 participants). In surgery setting, for preventing delirium, high GRADE evidence supported dexmedetomidine (RR=0.53; 95%CI: 0.46-0.67, k=13, N=3988) and comprehensive geriatric assessment (OR=0.46; 95%CI=0.32-0.67, k=3, N=496) in older adults, dexmedetomidine in adults (RR=0.33, 95%CI=0.24-0.45, k=7, N=1974), A2-adrenergic agonists after induction of anesthesia (OR= 0.28, 95%CI= 0.19-0.40, k=10, N=669) in children. High certainty evidence did not support melatonergic agents in older adults for delirium prevention. Moderate certainty supported the effect of dexmedetomidine in adults and children (k=4), various non-pharmacological interventions in adults and older people (k=4), second-generation antipsychotics in adults and mixed age groups (k=3), EEG-guided anesthesia in adults (k=2), mixed pharmacological interventions (k=1), five other specific pharmacological interventions in children (k=1 each). In conclusion, our work indicates that effective treatments to prevent delirium differ across populations, settings, and age groups. Results inform future guidelines to prevent or treat delirium, accounting for safety and costs of interventions. More research is needed in non-surgical settings.

Podcast: Need for Quality Evidence for Decision-Making on Seasonal Influenza Vaccines.

Seasonal influenza is usually considered an acute respiratory infection with a full recovery within a week. In addition to the traditional outcomes, there is now evidence of indirect effects in terms of neurological and functional complications. Major organ systems can be affected, underlining the need for preventative measures against infection. The aim of this podcast, featuring Dr. Ann Falsey, Dr. Stefania Maggi, and Dr. Tor Biering-Sørensen, is to outline influenza complications beyond acute respiratory disease, as well as discussing the need for quality of evidence when evaluating influenza vaccines. Assessing the benefits of vaccination can be challenging. To ensure a high quality of evidence, the innovative randomization of patients within the study design to avoid bias and the assessment of additional outcomes beyond immunogenicity as well as the inclusion of a broad population-including frail or vulnerable individuals-are essential. Studies leveraging nationwide registries such as the DANFLU-2 trial in Denmark highlight the advantages of a digitalized healthcare system for conducting large-scale randomized trials. Furthermore, large-scale trials such as the Gravenstein study have supplied a sizable body of evidence supporting the use of high-dose influenza vaccine in older adults. In conclusion, achieving a high quality of evidence is key for decision-making on seasonal influenza vaccines.

Evidence-Based Guideline for the management of osteoporosis in men.

Historically, osteoporosis has been viewed as a disease of women, with research, trials of interventions and guidelines predominantly focused as such. It is apparent, however, that this condition causes a substantial health burden in men also, and that its assessment and management must ultimately be addressed across both sexes. In this article, an international multidisciplinary working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases presents GRADE-assessed recommendations for the diagnosis, monitoring and treatment of osteoporosis in men. The recommendations are based on a comprehensive review of the latest research related to diagnostic and screening approaches for osteoporosis and its associated high fracture risk in men, covering disease burden, appropriate interpretation of bone densitometry (including the use of a female reference database for densitometric diagnosis in men) and absolute fracture risk, thresholds for treatment, and interventions that can be used therapeutically and their health economic evaluation. Future work should specifically address the efficacy of anti-osteoporosis medications, including denosumab and bone-forming therapies.

SARS-CoV-2 vaccination and risk of infectious diseases in hospitalized older patients.

PURPOSE: Vaccinations, for example flu vaccine, may be a cause of cross-reactive immunostimulation that prevents a larger spectrum of infections. However, whether SARS-CoV-2 vaccinations may also determine this effect is unclear. This study aims, first, to assess the incidence of infections at hospital admission and during the hospitalization in older inpatients vaccinated and unvaccinated against SARS-CoV-2; second, to compare length of hospital stay and in-hospital mortality between vaccinated and unvaccinated individuals. METHODS: This retrospective study included 754 older inpatients admitted to the Geriatrics and Orthogeriatrics Units of the University Hospital of Ferrara (Italy) between March 2021 and November 2021. Sociodemographic and health-related data, and the diagnosis of infections at hospital admission and during hospitalization were collected from medical records. RESULTS: The sample's mean age was 87.2 years, 59.2% were females, and 75.5% were vaccinated against SARS-CoV-2. Vaccinated individuals had 36% lower odds of intra-hospital infections (OR = 0.64, 95%CI 0.44-0.94) and 39% lower in-hospital death (HR = 0.61, 95%CI 0.39-0.95), also after adjusting for potential confounders, while no significant results emerged about infections at hospital admission. Considering the hospitalization's endpoints, SARS-CoV-2 vaccination was associated with a lower probability of being transferred to long-term care or other hospital departments than returning home (OR = 0.63, 95%CI 0.40-0.99). CONCLUSIONS: In older inpatients, SARS-CoV-2 vaccination seems to be associated with a lower likelihood of intra-hospital infectious diseases not caused by SARS-CoV-2 and all-cause in-hospital mortality. The vaccination coverage in the older population could limit not only the onset and severity of COVID-19 but also the occurrence of other infectious diseases.

Sleep disorders during the COVID-19 pandemic: Results from the second phase of web-based EPICOVID19 study.

The COVID-19 pandemic has induced significant impairments, including sleep disturbances. The present study aimed to explore the impact of fear in relation to stress on sleep disorders among Italian adults and older participants in the second phase of the EPICOVID19 web-based survey (January-February 2021). Sleep disturbances during the pandemic were evaluated using the Jenkins Sleep Scale, perceived stress through the 10-item Perceived Stress Scale and fear of contagion and about economic and job situation with four ad hoc items. The strength of the pathways between stress, sleep disturbances and fear was explored using structural equation modelling, hypothesising that stress was related to sleep disturbances and that fear was associated with both stress and sleep problems. Out of 41,473 participants (74.7% women; mean age 49.7 ± 13.1 years), 8.1% reported sleep disturbances and were more frequently women, employed in a work category at risk of infection or unemployed, and showed higher deprivation scores. Considering an a priori hypotheses model defining sleep and stress scores as endogenous variables and fear as an exogenous variable, we found that fear was associated with sleep problems and stress, and stress was associated with sleep problems; almost half of the total impact of fear on sleep quality was mediated by stress. The impact of stress on sleep quality was more evident in the younger age group, among individuals with a lower socioeconomic status and healthcare workers. Fear related to COVID-19 seem to be associated with sleep disturbances directly and indirectly through stress.

Podcast: Influenza-Associated Complications and the Impact of Vaccination on Public Health.

Influenza is primarily considered an acute respiratory infection but can lead to a myriad of medium and long-term sequelae across every major organ system in the body. Increasing awareness, gaining broader understanding of its mechanistic pathways, identifying at-risk individuals, and determining how to better protect them could help minimize its impact. The aim of this podcast, featuring Dr Stefania Maggi, Dr Annemarijn de Boer, and Dr Melissa K. Andrew, is to outline the main influenza complications and their impact beyond acute respiratory disease, as well as highlighting vaccination as a tool at our disposal. Both physical and cognitive function can be affected as a result of influenza infection, notably in frailer individuals, which in turn may lead to a loss of independence. Observational studies have identified beneficial effects of vaccination for cardioprotection as well as preventing dementia, but more evidence is required. In conclusion, influenza can cause a wide array of complications, which vaccination may help prevent.Podcast available for this article.

Polypharmacy and Antibody Response to SARS-CoV-2 Vaccination in Residents of Long-Term Care Facilities: The GeroCovid Vax Study.

BACKGROUND AND OBJECTIVE: Polypharmacy is common in older adults, particularly among those living in long-term care facilities. This condition represents a marker of clinical complexity and might directly affect the immunological response. However, there are limited data on the association of polypharmacy with vaccine immunogenicity. This study evaluated the immune response to anti-SARS-CoV-2 vaccines in older residents of long-term care facilities as a function of the number of medications used. METHODS: In 478 long-term care facility residents participating in the GeroCovid Vax study, we assessed SARS-CoV-2 trimeric S IgG levels through chemiluminescent assays before the vaccination and after 2, 6, and 12 months. A booster dose was administered between 6- and 12-month assessments. Sociodemographic information and data on chronic diseases and medications were derived from medical records. Based on the number of daily medications, residents were classified into the no polypharmacy (zero to four medications), polypharmacy (five to nine medications), and hyperpolypharmacy (ten or more medications) groups. RESULTS: In the sample (mean age 82.1 years, 69.2% female), 200 (41.8%) residents were taking five or fewer medications/day (no polypharmacy), 229 (47.9%) had polypharmacy, and 49 (10.3%) had hyperpolypharmacy. Using linear mixed models adjusted for potential confounders, we found that hyperpolypharmacy was associated with a steeper antibody decline after 6 months from the first vaccine dose administration (ß = - 0.29, 95% confidence interval - 0.54, - 0.03, p = 0.03) than no polypharmacy, while no significant differences were observed at 12 months. CONCLUSIONS: The humoral immune response to SARS-CoV-2 vaccination of older residents showed only slight changes as a function of the number of medications taken. Although it seemed less durable among older residents with hyperpolypharmacy, the booster dose administration equalized such a difference.

Influenza vaccination for elderly, vulnerable and high-risk subjects: a narrative review and expert opinion.

Influenza is associated with a substantial health burden, especially in high-risk subjects such as older adults, frail individuals and those with underlying chronic diseases. In this review, we summarized clinical findings regarding the impact of influenza in vulnerable populations, highlighted the benefits of influenza vaccination in preventing severe illness and complications and reviewed the main evidence on the efficacy, effectiveness and safety of the vaccines that are best suited to older adults among those available in Italy. The adverse outcomes associated with influenza infection in elderly and frail subjects and those with underlying chronic diseases are well documented in the literature, as are the benefits of vaccination (mostly in older adults and in patients with cardiovascular diseases, diabetes and chronic lung disease). High-dose and adjuvanted inactivated influenza vaccines were specifically developed to provide enhanced immune responses in older adults, who generally have low responses mainly due to immunosenescence, comorbidities and frailty. These vaccines have been evaluated in clinical studies and systematic reviews by international immunization advisory boards, including the European Centre for Disease Prevention and Control. The high-dose vaccine is the only licensed influenza vaccine to have demonstrated greater efficacy versus a standard-dose vaccine in preventing laboratory-confirmed influenza in a randomized controlled trial. Despite global recommendations, the vaccination coverage in high-risk populations is still suboptimal. All healthcare professionals (including specialists) have an important role in increasing vaccination rates.

Effects of PROtein enriched MEDiterranean Diet and EXercise on nutritional status and cognition in adults at risk of undernutrition and cognitive decline: the PROMED-EX Randomised Controlled Trial.

INTRODUCTION: Undernutrition leading to unplanned weight loss is common in older age and has been linked to increased dementia risk in later life. Weight loss can precede dementia by a decade or more, providing a unique opportunity for early intervention to correct undernutrition and potentially prevent or delay cognitive impairment. The combined effects of diet and exercise on undernutrition have not yet been evaluated. The objective of this trial is to determine the effect of a protein-enriched Mediterranean diet, with and without exercise, on nutritional status and cognitive performance in older adults at risk of undernutrition and cognitive decline. METHODS: One hundred and five participants aged 60 years and over at risk of undernutrition and with subjective cognitive decline will be recruited to participate in a 6-month, single-blind, parallel-group randomised controlled trial. Participants will be block randomised into one of three groups: group 1-PROMED-EX (diet+exercise), group 2-PROMED (diet only) and group 3-standard care (control). The primary outcome is nutritional status measured using the Mini Nutritional Assessment. Secondary outcomes include cognitive function, nutritional intake, body composition, physical function and quality of life. Mechanistic pathways for potential diet and exercise-induced change in nutritional status and cognition will be explored by measuring inflammatory, metabolic, nutritional and metabolomic biomarkers. ETHICS AND DISSEMINATION: The study is approved by the UK Office for Research Ethics Committee (ref: 21/NW/0215). Written informed consent will be obtained from participants prior to recruitment. Research results will be disseminated to the public via meetings and media and the scientific community through conference presentations and publication in academic journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05166564).

Physical activity and exercise for the prevention and management of mild cognitive impairment and dementia: a collaborative international guideline.

BACKGROUND: Physical activity and exercise have been suggested as effective interventions for the prevention and management of mild cognitive impairment (MCI) and dementia, but there are no international guidelines. OBJECTIVES: To create a set of evidence- and expert consensus-based prevention and management recommendations regarding physical activity (any bodily movement produced by skeletal muscles that results in energy expenditure) and exercise (a subset of physical activity that is planned, structured, repetitive), applicable to a range of individuals from healthy older adults to those with MCI/dementia. METHODS: Guideline content was developed with input from several scientific and lay representatives' societies. A systematic search across multidisciplinary databases was carried out until October 2021. Recommendations for prevention and management were developed according to the GRADE and complemented by consensus statements from the expert panels. RECOMMENDATIONS: Physical activity may be considered for the primary prevention of dementia. In people with MCI there is continued uncertainty about the role of physical activity in slowing the conversion to dementia. Mind-body interventions have the greatest supporting evidence. In people with moderate dementia, exercise may be used for maintaining disability and cognition. All these recommendations were based on a very low/low certainty of evidence. CONCLUSIONS: Although the scientific evidence on the beneficial role of physical activity and exercise in preserving cognitive functions in subjects with normal cognition, MCI or dementia is inconclusive, this panel, composed of scientific societies and other stakeholders, recommends their implementation based on their beneficial effects on almost all facets of health.

Poverty and Influenza/Pneumococcus Vaccinations in Older People: Data from The Survey of Health, Ageing and Retirement in Europe (SHARE) Study.

Vaccine acceptance seems to be lower in poor people. The determinants of the lower vaccine coverage in poor people are not established. Therefore, we aimed to explore the association between poverty and influenza/pneumococcus vaccinations and the factors potentially associated with vaccination's coverage in poor people. The data of the Survey of Health, Ageing and Retirement in Europe (SHARE), an ongoing longitudinal, multi-disciplinary, and cross-national European study where used. Poverty was defined using information on income and household size. Among 47,370 participants initially included in the SHARE study, 12,442 were considered poor. In the multivariable logistic regression analysis, "Household size" was associated with a significantly lower vaccination probability, meanwhile "Age", "Years of education", "Regularly taking prescription drugs", and the level of income were significantly associated with higher probabilities of both influenza and pneumonia vaccinations. The "Number of illnesses/health conditions" was significantly associated with a higher probability of getting vaccination against influenza and against pneumococcus. In conclusion, among poor older people, several specific factors could be identified as barriers for the vaccinations against influenza or pneumococcus that are unique to this segment of the population, such as living with the family and having a job.

Immune microenvironment dynamics in breast cancer during pregnancy: impact of gestational age on tumor-infiltrating lymphocytes and prognosis.

Background: Breast cancer during pregnancy (PrBC) is a rare condition known for its aggressive clinical behavior. The presence of tumor-infiltrating lymphocytes (TILs) has been shown to have a significant impact on the prognosis of these patients. Despite some biological characteristics of the tumor that may differ depending on the gestational age, little is known about the dynamics of the immune landscape within the tumor microenvironment (TME) in PrBC. Therefore, in this study, our objective was to gain comprehensive insights into the relationship between gestational age at breast cancer diagnosis and the composition of the TME. Methods: n = 108 PrBC were selected from our institutional registry and categorized based on the gestational age by trimester. For all cases, TILs were profiled according to the International TILs Working Group recommendations, and subtyped by CD4, CD8, and forkhead box P3 (FOXP3) immunohistochemistry. PD-L1 was tested according to the combined positive score (CPS) using the IHC 22C3 pharmDx assay, with a cutoff value of ≥10 for positivity. The statistical approach encompassed Fisher's and Chi-squared tests, with appropriate adjustments for multiple comparisons, logistic regression models, and survival analyses based on the Kaplan-Meier method. Results: The proportion of patients with poorly differentiated (G3) neoplasms increased as the gestational age advanced (first trimester, n = 25, 56.8%; second trimester, n = 27, 69.2%; third trimester, n = 21, 87.5%; p = 0.03). The histologic subtypes as well as the hormone receptor (HR) and HER2 status did not show significant changes across different pregnancy trimesters. In the HR+/HER2- subtype, there was a higher proportion of tumors with high/moderate TILs in the early phases of pregnancy, similar to FOXP3 expression (TILs: first trimester, n = 10, 35.7%; second trimester, n = 2, 10.5%; third trimester, n = 0; p = 0.02; FOXP3: first trimester, n = 10, 40%; second trimester, n = 3, 15.8%; third trimester, n = 0; p = 0.03). The median follow-up for our cohort was 81 months. Patients who relapsed after a breast cancer diagnosis during the first trimester were more frequently PD-L1-negative, unlike those with no disease recurrence (n = 9, 100% vs. n = 9, 56.3%; p = 0.03; hormone therapy and n = 9, 100% vs. n = 7, 53.9%; p = 0.02; chemotherapy). No statistically significant differences were seen among the three trimesters in terms of survival outcome. Conclusion: The TME dynamics of HR+/HER2- PrBC vary based on gestational age, suggesting that immune tolerance expression during later gestational age could explain the increased aggressiveness of tumors diagnosed at that stage.