Different patterns of white matter degeneration using multiple diffusion indices and volumetric data in mild cognitive impairment and Alzheimer patients

Alzheimeŕs disease (AD) represents the most prevalent neurodegenerative disorder that causes cognitive decline in old age. In its early stages, AD is associated with microstructural abnormalities in white matter (WM). In the current study, multiple indices of diffusion tensor imaging (DTI) and brain volumetric measurements were employed to comprehensively investigate the landscape of AD pathology. The sample comprised 58 individuals including cognitively normal subjects (controls), amnestic mild cognitive impairment (MCI) and AD patients. Relative to controls, both MCI and AD subjects showed widespread changes of anisotropic fraction (FA) in the corpus callosum, cingulate and uncinate fasciculus. Mean diffusivity and radial changes were also observed in AD patients in comparison with controls. After controlling for the gray matter atrophy the number of regions of significantly lower FA in AD patients relative to controls was decreased; nonetheless, unique areas of microstructural damage remained, e.g., the corpus callosum and uncinate fasciculus. Despite sample size limitations, the current results suggest that a combination of secondary and primary degeneration occurrs in MCI and AD, although the secondary degeneration appears to have a more critical role during the stages of disease involving dementia

Interventions for preventing delirium in older people in institutional long-term care

BACKGROUND: Delirium is a common and distressing mental disorder. It is often caused by a combination of stressor events in susceptible people, particularly older people living with frailty and dementia. Adults living in institutional long-term care (LTC) are at particularly high risk of delirium. An episode of delirium increases risks of admission to hospital, development or worsening of dementia and death. Multicomponent interventions can reduce the incidence of delirium by a third in the hospital setting. However, it is currently unclear whether interventions to prevent delirium in LTC are effective. This is an update of a Cochrane Review first published in 2014. OBJECTIVES: To assess the effectiveness of interventions for preventing delirium in older people in institutional long-term care settings. SEARCH METHODS: We searched ALOIS (www.medicine.ox.ac.uk/alois), the Cochrane Dementia and Cognitive Improvement Group (CDCIG) 's Specialised Register of dementia trials (dementia.cochrane.org/our-trials-register), to 27 February 2019. The search was sufficiently sensitive to identify all studies relating to delirium. We ran additional separate searches in the Cochrane Central Register of Controlled Trials (CENTRAL), major healthcare databases, trial registers and grey literature sources to ensure that the search was comprehensive. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cluster-randomised controlled trials (cluster-RCTs) of single and multicomponent, non-pharmacological and pharmacological interventions for preventing delirium in older people (aged 65 years and over) in permanent LTC residence. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Primary outcomes were prevalence, incidence and severity of delirium; and mortality. Secondary outcomes included falls, hospital admissions and other adverse events; cognitive function; new diagnoses of dementia; activities of daily living; quality of life; and cost-related outcomes. We used risk ratios (RRs) as measures of treatment effect for dichotomous outcomes, hazard ratios (HR) for time-to-event outcomes and mean difference (MD) for continuous outcomes. For each outcome, we assessed the overall certainty of the evidence using GRADE methods. MAIN RESULTS: We included three trials with 3851 participants. All three were cluster-RCTs. Two of the trials were of complex, single-component, non-pharmacological interventions and one trial was a feasibility trial of a complex, multicomponent, non-pharmacological intervention. Risk of bias ratings were mixed across the three trials. Due to the heterogeneous nature of the interventions, we did not combine the results statistically, but produced a narrative summary.It was not possible to determine the effect of a hydration-based intervention on delirium incidence (RR 0.85, 95% confidence interval (CI) 0.18 to 4.00; 1 study, 98 participants; very low-certainty evidence downgraded for risk of bias and very serious imprecision). This study did not assess delirium prevalence, severity or mortality.The introduction of a computerised system to identify medications that may contribute to delirium risk and trigger a medication review was probably associated with a reduction in delirium incidence (12-month HR 0.42, CI 0.34 to 0.51; 1 study, 7311 participant-months; moderate-certainty evidence downgraded for risk of bias) but probably had little or no effect on mortality (HR 0.88, CI 0.66 to 1.17; 1 study, 9412 participant-months; moderate-certainty evidence downgraded for imprecision), hospital admissions (HR 0.89, CI 0.72 to 1.10; 1 study, 7599 participant-months; moderate-certainty evidence downgraded for imprecision) or falls (HR 1.03, CI 0.92 to 1.15; 1 study, 2275 participant-months; low-certainty evidence downgraded for imprecision and risk of bias). Delirium prevalence and severity were not assessed.In the enhanced educational intervention study, aimed at changing practice to address key delirium risk factors, it was not possible to determine the effect of the intervention on delirium incidence (RR 0.62, 95% CI 0.16 to 2.39; 1 study, 137 resident months; very low-certainty evidence downgraded for risk of bias and serious imprecision) or delirium prevalence (RR 0.57, 95% CI 0.15 to 2.19; 1 study, 160 participants; very low-certainty evidence downgraded for risk of bias and serious imprecision). There was probably little or no effect on mortality (RR 0.82, CI 0.50 to 1.34; 1 study, 215 participants; moderate-certainty evidence downgraded for imprecision). The intervention was probably associated with a reduction in hospital admissions (RR 0.67, CI 0.57 to 0.79; 1 study, 494 participants; moderate-certainty evidence downgraded due to indirectness). AUTHORS' CONCLUSIONS: Our review identified limited evidence on interventions for preventing delirium in older people in LTC. A software-based intervention to identify medications that could contribute to delirium risk and trigger a pharmacist-led medication review, probably reduces incidence of delirium in older people in institutional LTC. This is based on one large RCT in the US and may not be practical in other countries or settings which do not have comparable information technology services available in care homes. In the educational intervention aimed at identifying risk factors for delirium and developing bespoke solutions within care homes, it was not possible to determine the effect of the intervention on delirium incidence, prevalence or mortality. This evidence is based on a small feasibility trial. Our review identified three ongoing trials of multicomponent delirium prevention interventions. We identified no trials of pharmacological agents. Future trials of multicomponent non-pharmacological delirium prevention interventions for older people in LTC are needed to help inform the provision of evidence-based care for this vulnerable group

Prevention and Management of Frailty

It is important to prevent and manage the frailty of the elderly because their muscle strength and physical activity decrease in old age, making them prone to falling, depression, and social isolation. In the end, they need to be admitted to a hospital or a nursing home. When successful aging fails and motor ability declines due to illness, malnutrition, or reduced activity, frailty eventually occurs. Once frailty occurs, people with frailty do not have the power to exercise or the power to move. The functions of the heart and muscles are deteriorated more rapidly when they are not used. Consequently, frailty goes through a vicious cycle. As one’s physical fitness is deteriorated, the person has less power to exercise, poorer cognitive functions, and inferior nutrition intake. Consequently, the whole body of the person deteriorates. Therefore, in addition to observational studies to identify risk factors for preventing aging, various intervention studies have been conducted to develop exercise programs and apply them to communities, hospitals, and nursing homes for helping the elderly maintain healthy lives. Until now, most aging studies have focused on physical frailty. However, social frailty and cognitive frailty affect senile health negatively just as much as physical frailty. Nevertheless, little is known about social frailty and cognitive frailty. This special issue includes original experimental studies, reviews, systematic reviews, and meta-analysis studies on the prevention of senescence (physical senescence, cognitive senescence, social senescence), high-risk group detection, differentiation, and intervention

Gender roles and physical function in old age

Contexte : Les différences de fonctionnement physique entre les hommes et les femmes ne sont pas bien comprises. Les chercheurs ont porté attention aux différences biologiques entre les hommes et les femmes mais ne se sont pas concentrés sur les différences de fonctionnement physique et de mobilité qui pourraient être reliées au sexe et au genre. En particulier, les effets de la masculinité et de la féminité sur le fonctionnement physique des personnes âgées n’ont pas été examinés. Objectifs : L’objectif principal de cette recherche est d’évaluer l’association entre fonctionnement physique et rôles de genre. Pour atteindre cet objectif, nous avons examiné : 1) la validité de la version courte (12 items) de l’Inventaire des rôles sexués de Bem (IRSB) ; 2) les associations transversales et longitudinales entre l’IRSB et des indicateurs de mobilité et de performance physique, et finalement 3) les variables jouant un rôle de médiation entre l’IRSB et la performance physique. Méthodes : Les données de l’étude internationale sur la mobilité au cours du vieillissement (IMIAS) recueillies en 2012 et 2014 ont été utilisées dans cette recherche. Cette étude s’est déroulée dans 5 villes : Saint-Hyacinthe (Québec) and Kingston (Ontario) au Canada, Tirana (Albanie), Manizales (Colombie) et Natal (Brésil), avec un échantillon approximatif à chaque site de 200 hommes et 200 femmes âgés de 65 à 74 ans vivant dans la communauté (N=2004). Deux aspects du fonctionnement physique ont été examinés dans cette thèse : la mobilité et la performance physique. La mobilité a été mesurée par deux questions sur la difficulté à marcher un Km et à monter un étage d’escaliers. La performance physique a été objectivée par le Short Physical Performance Battery (SPPB). Cette batterie inclut des mesures de la marche, de l’équilibre et de la force musculaire et elle mesure le temps requis pour exécuter trois tests : marcher quatre mètres, se tenir début en position de tandem et se lever d’une chaise cinq fois. Pour la validation psychométrique de l’instrument IRSB, des analyses factorielles exploratoires et confirmatoires ont été réalisées. Pour les études d’associations transversales, des analyses de régression de Poisson ont permis l’estimation des ratios de prévalence pour les incapacités de mobilité et la mauvaise performance physique, comparant les rôles masculins, féminins et indifférenciés. Pour l’étude de l’incidence de la mauvaise performance physique, les estimations de risque relatif ont été obtenues à l’aide de la régression de Poisson. L’étude des variables de médiation entre les rôles de genre et la performance physique a inclus le tabagisme, l’inactivité physique, la consommation d’alcool, l’index de masse corporelle élevé, le nombre de maladies chroniques et la dépression. Finalement, une méta-analyse a été effectuée pour examiner l’homogénéité des associations entre les rôles de genre et la performance physique dans les cinq sites de recherche. Résultats : Les résultats des analyses factorielles pour l’instrument de mesure IRSB ont révélé qu’une solution à deux facteurs (instrumentalité-expression) donne une validité conceptuelle satisfaisante, ainsi qu’un ajustement aux données supérieur par rapport à une solution à trois facteurs. La solution à deux facteurs permet d’assigner un score de masculinité et un score de féminité à chaque participant et de classifier les personnes âgées dans quatre catégories selon leur typologie de rôle de genre : masculin, féminin, androgyne et indifférencié. En ce qui concerne les associations avec les indicateurs de mobilité et de fonctionnement physique, les rôles féminins et indifférenciés sont des facteurs indépendants associés à la prévalence des incapacités dans la mobilité et à la mauvaise performance après ajustement avec des variables de confusion potentielle. Les rôles féminins et indifférenciés sont des facteurs de risque associés à une détérioration plus rapide du fonctionnement des extrémités inferieures. Nous avons rapporté une incidence de mauvaise performance physique plus élevée pour ceux qui adoptent un rôle féminin (IRR ajusté=2.36, intervalle de confiance de 95% 1.55-3.60) ou le rôle indifférencié (IRR ajusté=2.19, 95% Intervalle de confiance de 95% 1.45-3.30) comparé au rôle androgyne. Le score de masculinité est associé à la performance physique, alors que le score de féminité ne l’est pas. Une augmentation d’une unité sur le score de masculinité est associée à une incidence de mauvais fonctionnement physique plus faible (IRR ajusté=0.76, 95% intervalle de confiance de 95% 0.67-0.87). Les rôles de genre agissent sur les comportements de santé (tabagisme et inactivité physique), sur l’index de masse corporelle et sur les maladies chroniques et la dépression, tous des facteurs de risque pour la performance physique. Les effets des rôles de genre ne sont que partiellement expliqués par ces facteurs de médiation et un effet direct des rôles de genre sur le fonctionnement physique reste toujours significatif. Conclusion : Les rôles de genre sont présents dans tous les cinq sites de recherche. La mobilité et la performance physique des personnes âgées sont associées au type de rôle de genre avec un possible effet protecteur pour les personnes androgynes, indépendamment du fait qu’ils soient un homme ou une femme. Les rôles de genre semblent influencer les comportements de santé et les risques de développer une maladie chronique et de souffrir de dépression, ce qui peut avoir des effets sur la fonction physique au cours du vieillissement. Cette étude est la première sur le sujet et nos résultats devraient être confirmés par des études futures avant d’être traduits en interventions concrètes de santé publique.Background: Gender differences in mobility disability among older adults are not well understood. Studies have focused on the biological differences between men and women, but not on the mobility differences due to interrelationships of sex and gender. The associations between masculinity, and femininity on physical function in old age have never been examined. Objective: The main objective of this dissertation is to study the relationships between physical function and gender roles in old age. To accomplish this objective, I have: 1) assessed the psychometric properties and construct validity of the 12-items short form Bem Sex Roles Inventory (BSRI), 2) examined the cross-sectional associations between BSRI and mobility and physical performance, and 3) examined mediating pathways between BSRI and physical performance. Methods: A total of 2004 community-dwelling older adults from the International Mobility in Aging Study (IMIAS) aged 65 to 74 years were recruited in Natal (Brazil), Manizales (Colombia), Tirana (Albania), Kingston (Ontario, Canada), and Saint-Hyacinthe (Quebec, Canada). Two aspects of mobility loss will be assessed in this dissertation: first, Mobility disability is a self-reported measure of the difficulty to walk half a mile or climb one flight of stairs without assistance. Second, poor physical function or performance of the lower extremities which is assessed by an objective tool and defined as inability to perform physical action in the manner considered normal in the short physical performance battery (SPPB). This battery includes three timed tests of lower extremity function: a hierarchical test of standing balance, a four-meter walk, and five repetitive chair stands. To assess the validity of BSRI in old age as a measure of gender roles. The psychometric properties of the 12- items short form BSRI were assessed by means of exploratory (EFA) and confirmatory factor analysis (CFA). To assess the cross-sectional associations between gender roles and both measures of mobility loss, I used Poisson regression analysis to estimate prevalence rate ratios of gender role types using the androgynous type as reference category. To calculate the incidence of poor physical performance after two years of follow up, Poisson regression was conducted for the estimation of relative risks. Body mass index, smoking, alcohol consumption, physical activity, chronic diseases, and depression were tested as potential mediators in the pathway between gender roles and physical performance in old age. Finally, taking account the possible differences in associations between countries, I have conducted a meta-analysis to estimate overall effects of masculinity and femininity scores on physical performance based on five distinct studies representing each research site of IMIAS. Results: The results of Exploratory Factor Analysis revealed a three-factor model. This model was further confirmed by CFA and compared with the original two-factor structure model. CFA results revealed that a two-factor solution (instrumentality-expressiveness) has satisfactory construct validity and superior fit to data compared to the three-factor solution. These factor analysis findings allowed to calculate scores of masculinity and femininity and classify participants into four categories according to gender roles: Masculine, feminine, androgynous and undifferentiated. Feminine and undifferentiated gender roles are independent risk factors associated with the prevalence of mobility disability and low physical performance in older adults. Consistent with cross sectional analysis, higher incidence of poor physical performance was observed among participants endorsing the feminine role or the undifferentiated role compared to the androgynous role. Higher masculinity but not femininity scores predicted good physical performance two years later. Gender roles predicted poor physical performance through statistically significant direct and indirect pathways. Cumulative smoking, BMI, physical activity, multimorbidity, and depression were serial mediators explaining the indirect effect of gender roles on physical performance. These intermediate behavioral and pathological pathways only partially mediated the observed associations. None of the potential serial mediators in the present study could completely account for the association between gender roles and physical performance. Conclusions: Traditional gender roles are existent in the five research sites of IMIAS. Gender roles influence physical function in old age with a possible protective effect of androgyny in old age independent of biological sex. Gender roles influence health behaviors which in turn contribute to chronic conditions and faster decline of lower extremities physical function. This study adds to the scant literature on this topic and the findings obtained from this dissertation need to be confirmed by future longitudinal studies for the appropriate translation into public health actions

Deprescribing tool for STOPPFall (screening tool of older persons prescriptions in older adults with high fall risk) items

Background: Health care professionals are often reluctant to deprescribe fall-risk-increasing drugs (FRIDs). Lack of knowledge and skills form a significant barrier. To support clinicians in the management of FRIDs and to facilitate the deprescribing process, a deprescribing tool was developed by a European expert group for STOPPFall (Screening Tool of Older Persons Prescriptions in older adults with high fall risk) items. Methods: STOPPFall was created using an expert Delphi consensus process in 2019 and in 2020, 24 panellists from EuGMS SIG on Pharmacology and Task and Finish on FRIDs completed deprescribing tool questionnaire. To develop the questionnaire, a Medline literature search was performed. The panellists were asked to indicate for every medication class a possible need for stepwise withdrawal and strategy for withdrawal. They were asked in which situations withdrawal should be performed. Furthermore, panellists were requested to indicate those symptoms patients should be monitored for after deprescribing and a possible need for follow-ups. Results: Practical deprescribing guidance was developed for STOPPFall medication classes. For each medication class, a decision tree algorithm was developed including steps from medication review to symptom monitoring after medication withdrawal. Conclusion: STOPPFall was combined with a practical deprescribing tool designed to optimize medication review. This practical guide can help overcome current reluctance towards deprescribing in clinical practice by providing an up-to-date and straightforward source of expert knowledge

Association between number of medications and mortality in geriatric inpatients : a Danish nationwide register-based cohort study

Purpose: To explore the association between the number of medications and mortality in geriatric inpatients taking activities of daily living and comorbidities into account. Methods: A nationwide population-based cohort study was performed including all patients aged C65 years admitted to geriatric departments in Denmark during 2005-2014. The outcome of interest was mortality. Activities of daily living using Barthel-Index (BI) were measured at admission. National health registers were used to link data on an individual level extracting data on medications, and hospital diseases. Patients were followed to the end of study (31.12.2015), death, or emigration, which ever occurred first. Kaplan-Meier survival curves were used to estimate crude survival proportions. Univariable and multivariable analyses were performed using Cox regression. The multivariable analysis adjusted for age, marital status, period of hospital admission, BMI, and BI (model 1), and further adding either number of diseases (model 2) or Charlson comorbidity index (model 3). Results: We included 74603 patients (62.8% women), with a median age of 83 (interquartile range [IQR] 77-88) years. Patients used a median of 6 (IQR 4-9) medications. Increasing number of medications was associated with increased overall, 30-days, and 1-year mortality in all 3 multivariable models for both men and women. For each extra medication the mortality increased by 3% in women and 4% in men in the fully adjusted model. Conclusion: Increasing number of medications was associated with mortality in this nationwide cohort of geriatric inpatients. Our findings highlight the importance of polypharmacy in older patients with comorbidities

Coffee and Caffeine Consumption for Human Health

Caffeine is present in coffee and many other beverages and is the most widely used central nervous system stimulant. Coffee drinking or caffeine supplementation may have a role in preventing cardiometabolic and endocrine disease, neuroinflammation, cancer, and even all-cause mortality. Other aspects are either less known or controversial, including the effects on the brain–gut axis, neurodevelopment, behavior, pain, muscle–skeletal health, skin or sexual function. Studies focusing on special populations (neonates, children, adolescents, athletes, elderly, pregnant and nonpregnant women), or interactions with other drugs and foods, are relatively scarce but of obvious interest. Other compounds present in coffee and other caffeinated food stuffs may affect caffeine´s physiological effects with a tremendous impact on health. This Special Issue, which contains twenty-one manuscripts, has focused on some of these varied topics, providing further evidence of the multiple health benefits that coffee/caffeine intake may exert in humans, at least in specific populations (with a particular genetic profile or suffering from specific diseases). However, the specific effects in the different organs and systems, as well as the mechanisms involved are not yet clear. Furthermore, within the current context aiming to sustainable development, the coffee plant Coffee sp. and its so-far relatively neglected by-products are expected to become soon a source of ingredients for new functional foods whose properties will need to be precisely determined. We hope the readers of this Special Issue will find inspiration for new studies on the topic