Mitochondrial genome study in blood of maternally inherited ALS cases.

BACKGROUND: ALS is a heterogeneous disease in which different factors such as mitochondrial phenotypes act in combination with a genetic predisposition. This study addresses the question of whether homoplasmic (total mitochondrial genome of a sample is affected) and/or heteroplasmic mutations (wildtype and mutant mitochondrial DNA molecules coexist) might play a role in familial ALS. Blood was drawn from familial ALS patients with a possible maternal pattern of inheritance according to their pedigrees, which was compared to blood of ALS patients without maternal association as well as age-matched controls. In two cohorts, we analyzed the mitochondrial genome from whole blood or isolated white blood cells and platelets using a resequencing microarray (Affymetrix MitoChip v2.0) that is able to detect homoplasmic and heteroplasmic mitochondrial DNA mutations and allows the assessment of low-level heteroplasmy. RESULTS: We identified an increase in homoplasmic ND5 mutations, a subunit of respiratory chain complex I, in whole blood of ALS patients that allowed maternal inheritance. This effect was more pronounced in patients with bulbar onset. Heteroplasmic mutations were significantly increased in different mitochondrial genes in platelets of patients with possible maternal inheritance. No increase of low-level heteroplasmy was found in maternal ALS patients. CONCLUSION: Our results indicate a contribution of homoplasmic ND5 mutations to maternally associated ALS with bulbar onset. Therefore, it might be conceivable that specific maternally transmitted rather than randomly acquired mitochondrial DNA mutations might contribute to the disease process. This stands in contrast with observations from Alzheimer's and Parkinson's diseases showing an age-dependent accumulation of unspecific mutations in mitochondrial DNA.

Prevalence of Sarcopenia in Chronic Heart Failure and Modulating Role of Chronic Kidney Disease.

INTRODUCTION: Sarcopenia, heart failure (HF), and chronic kidney disease (CKD) are common among the older people. Our objective was to evaluate the frequency of sarcopenia, among community-dwelling older adults with HF, possible causative factors, and the additive factor of CKD. METHODS: A cross-sectional analysis of 1,420 older people living in the community was carried out. Participants (aged 75 years and more) came from a European multicenter prospective cohort (SCOPE study). Global geriatric assessment including short physical performance battery, handgrip strength test, and bioelectrical impedance analysis was performed. Previous known HF was defined as physician-diagnosed HF registered in the patient's medical record or the use of HF-related medications, regardless of left ventricular ejection fraction (LVEF). Sarcopenia was defined by the updated criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). Estimated glomerular filtration rate was calculated using Berlin Initiative Study (BIS) to define the stages of CKD. Two-year mortality was also collected. RESULTS: A total of 226 (15.9%) participants had a prior chronic HF diagnosis, with a median age of 80.0 (5.0), and 123 (54.4%) were women. Using EWGSOP2 definition, 11.5% HF and 10.7% in non-HF participants met diagnostic criteria for sarcopenia. In multivariate analyses, only a lower body mass index (BMI) (odds ratios [OR], 0.82; 95% confidence interval [CI], 0.73-0.93) and lower short physical performance battery score (OR, 0.81; 95% CI, 0.69-0.96) were associated with sarcopenia. Patients with HF and sarcopenia have a similar all-cause mortality risk but higher 2-year cardiovascular mortality risk (p = 0.047). DISCUSSION/CONCLUSION: One out of ten community-dwelling older adults with concurrent clinical stable chronic HF, without considering LVEF, have sarcopenia. Lower BMI and poor physical performance are associated with sarcopenia in this population, but not CKD.

Association between low values of mean arterial pressure and impaired cognitive performance in older patients with mild cognitive impairment: cross-sectional preliminary findings from the STRENGTH Project.

BACKGROUND: Uncontrolled blood pressure (BP) is a risk factor for Mild Cognitive Impairment (MCI) and dementia. AIMS: This study examined the relationship between BP and clinical/cognitive/neuropsychological aspects in MCI individuals. METHODS: MCI patients underwent clinical, functional, cognitive and metacognitive, as well as psychological assessments. Social network, lifestyle characteristics, and medication prescriptions were also evaluated. Each patient underwent BP measurements. RESULTS: Lower values of systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP) were associated with poorer cognitive performance. Notably, MAP showed greater capability in detecting impairments in attention and visuospatial abilities compared to SBP and DBP. DISCUSSION: These findings support the notion that in older individuals with MCI excessively low BP values, particularly MAP, might represent a risk and suggest that cerebral hypoperfusion may play a key role. CONCLUSIONS: Routine assessment of MAP could aid clinicians in adjusting antihypertensive treatment and closely monitoring cognitive function in MCI patients.

Diabetes and factors associated with cognitive and functional decline. The screening for CKD among older people across Europe (SCOPE) study.

BACKGROUND: Type 2 diabetes mellitus (DM) in older people is a heterogeneous condition that exhibits differential characteristics in comparison with younger adults. DM increases the risk of disability, is associated with dementia and loss of function, and cognition may often be interrelated and more pronounced in older patients with DM than in those without. AIMS: Our aim was to evaluate the incidence of functional and/or cognitive impairment in older adults with and without DM, and its associated factors in DM participants. METHODS: A 2-year prospective analysis was conducted in a European multicenter prospective cohort (SCOPE study). Older community-dwelling adults (aged ≥ 75 years) underwent a comprehensive geriatric assessment. New functional and/or cognitive decline was explored. RESULTS: Of 1611 participants, 335 (22.0%) had DM at baseline. The percentage of participants scoring at least one ADL impairment and/or cognitive impairment (MMSE < 24) was similar in both groups (9.6%). Factors associated with any new disability in participants with DM in the multivariate analysis were female sex (OR 3.28, 95% CI 1.42-7.56), history of stroke (OR 4.58, 95% CI 1.64-12.7), and greater IADL dependency (OR 1.08 95% CI 1.02-1.15). DISCUSSION: Association between DM and cognitive or functional decline in outpatients of 75 years and older was not found, but factors such as female gender, history of stroke, and IADL dependency could be related. CONCLUSION: Decline in functional and cognitive status of community-dwelling older adults with DM was similar to participants without DM in a short period of 2 years of follow-up, though several clinical factors may increase its risk in this population.

Structural Analysis of Social Behavior: Using Cluster Analysis to Examine Intrapsychic Personality Traits Associated With Depression in Women With Breast Cancer.

BACKGROUND: This study aimed to investigate personality traits associated with depression in breast cancer women (BCW). METHODS: Sample: 236 BCW recently diagnosed (early stages). Tests: SASB-Structural-Analysis of Social-Behavior; IPAT-CDQ-Depression. Statistical analysis: cluster K-Means analysis to explore SASB personality-traits considering the 8 SASB clusters (Cl); CDQ scores dichotomized by 50th percentile cutoff (high/low); Pearson's chi square test to compare CDQ levels and SASB traits. RESULTS: Cluster analysis results supported two distinguishable SASB personality traits (for all SASB Cl-Scales P < .001) classified as "Love and Autonomy" (62.2%) and "Control and Hate" (37.8%). Patients with Love/Autonomy traits are spontaneous, accept their deepest feelings and desire to be close to other people (Cl1, Cl2, Cl3, Cl4). They show a medium value of self-control and a low tendency to self-abusive and self-critical behaviors (Cl5, Cl6). They pay attention to themselves and to their needs at emotional and physical levels also if may be occasionally engaged in self-destructive behaviors (Cl7, Cl8). Women with Control/Hate traits are not spontaneous and do not always express emotions (C1, Cl2, Cl3, Cl4) and flexibility in their relationship with others (Cl5, Cl6). In stressful situations, they may ignore the option of choices for self-growth and neglect their needs and those of others (Cl7, Cl8). BCWs with Control/Hate traits scored higher in depression (P <.001) than those with the Love/Autonomy profile. CONCLUSIONS: Healthcare professionals should be aware of these personality traits and their association with depression to identify the psychologically most vulnerable BCW and improve the care they provide them. The psychotherapeutic intervention should be planned to face on the personality problems.

Transient versus stable nature of fear of falling over 24 months in community-older persons with falls- data of the EU SCOPE project on Kidney function.

BACKGROUND: Fear of falling (FoF) is an important risk factor for falls among older people. The objectives of our investigations were: a.) to present characteristics of older community-dwelling (CD) fallers with persistent or transient FoF (P-FoF or T-FoF) over 12 months, and b.) to investigate clinical predictors of P-FoF and T-FoF and c.) to explore differences between P-FoF and T-FoF. METHODS: Our series consisted of 389 older people reporting a fall or injurious fall at baseline and during 24 months follow-up participating in a multicenter prospective study. T-FoF was defined as participants reported "not at all" at baseline and "somewhat/fairly/very concerned" at follow-up, or "not at all" at follow-up, and "somewhat/fairly/very concerned" at baseline, and P-FoF was defined as participants answered "somewhat/fairly/very concerned" in both assessments at baseline and at follow-up. The association between risk factors and T-FoF or P-FoF was investigated by logistic regression analysis. RESULTS: The mean age of fallers in our sample was 79.0 years (SD 6.0), and 54.2% were females. Out of 389 older adults with a fall history at baseline, 83 participants (21.3%) did not report any FoF over time, P-FoF and T-FoF were observed in 42.7% and 35.9% of participants, respectively. After adjusting for potential confounders (e.g. age, gender), osteoporosis (OR = 2.04, 95%CI = 1.03-4.05) and impaired physical performance (OR = 2.38, 95%CI = 1.12-5.03) were significant predictors of T-FoF vs No-FoF. Osteoporosis (OR = 2.68, 95%CI = 1.31-5.48), depressive symptoms (OR = 3.54, 95%CI = 1.23-10.1) and living alone (OR = 2.44, 95%CI = 1.17-5.06) were significantly associated with P-FoF vs No-FoF. When comparing T-FoF and P-FoF, female gender (OR = 1.95, 95%CI = 1.16-3.27), BMI (OR = 1.08, 95%CI = 1.02-1.14), overall comorbidity (OR = 1.07, 95%CI = 1.02-1.13) and depression (OR = 2.55, 95%CI = 1.33-4.88) were significant predictors of P-FoF. CONCLUSIONS: T-FoF and P-FoF may be predicted by different sets of risk factors among older fallers. Thus, fallers should be screened for FoF especially when carrying specific risk factors, including female gender, osteoporosis, depression, living alone, impaired physical performance, BMI, comorbidity. These findings may be helpful in designing tailored intervention to blunt the risks related to consequence of FoF among older people experiencing falls. TRIAL REGISTRATION: The SCOPE study was registered prospectively at clinicaltrials.gov (NCT02691546; 25/02/2016).

Study of the effects of mindfulness training on quality of life of patients with Alzheimer's disease and their caregivers (Dyad Mindfulness Project).

BACKGROUND: The training of mindfulness enhances the emotive and cognitive equilibrium and well-being in older adults. So some authors hypothesize it is an appropriate approach to cultivating these benefits and a good quality of life in Alzheimer's patients (AD-P) at early stage and in their caregivers (Cg) (Dyad). AIM: Our main hypothesis is that AD-P and Cg who completed the program of Mindfulness-Based Interventions (MBIs) training would experience improvements in well-being and mood and cognitive performance (AD-P: attention and memory). METHODS: The perspective randomized controlled will enroll the Dyad of 80 Alzheimer's patients (age ≥ 60) and 80 caregivers (age > 18) who will be randomly assigned to 6 months MBI training in groups and to control group study. All outcome will be analyzed before intervention (baseline), after follow-up 1 (at the end of treatment), after 6 months (follow-up 2) and after 1 year (follow-up 3) from the end of treatment. DISCUSSION: AD-P-expected outcomes: (a) improvement of the quality of life (QoL-AD); (b) decrease of depression (BDI); (c) improvement of spiritual well-being (Facit SWB Index); (d) improvement of attention and good cognitive performance Rey Memory Test (MFIT); (e) decrease of neuropsychiatric symptoms. (NPI)-Cg-expected outcomes: (a) improvement of the quality of life (SF36); (b) decrease of the care burden (CBI); (c) decrease of depression (BDI); (d) improvement of self-awareness (FFMQ); (e) increase in spiritual-well-being (Facit SWB). CONCLUSIONS: This study could provide a clues on multidisciplinary interventions as secondary prevention of Alzheimer's dementia and on stress reduction in family caregivers.

Contribution of clinical severity and geriatric risk factors in predicting short-term mortality of older hospitalized pneumonia patients: the Pneumonia in Italian Acute Care for Elderly units (PIACE) study.

BACKGROUND: Clinical severity of pneumonia in older persons increases the risk for short-term mortality. Comprehensive geriatric assessment (CGA) may provide further insight in prognostic stratification. AIMS: To investigate whether CGA may improve prognostic stratification among older patients with pneumonia admitted to hospital. METHODS: Our series consisted of 318 consecutive patients hospitalized for pneumonia in a multicenter observational study. Disease severity was assessed by Sequential Organ Failure Assessment (SOFA) and Pneumonia Severity Index (PSI). CGA included the occurrence of delirium, Basic Activities of Daily Living (BADL) disability, cognitive impairment at Short Portable Mental Status Questionnaire (SPMSQ) and overall comorbidity assessed by Cumulative Illness Rating Scale (CIRS). The outcomes were in-hospital and post-discharge 3 month mortality. Statistical analysis was carried out by Cox regression, area under receiver operating curve (AUC) and net reclassification index (NRI). RESULTS: Overall, 53 patients died during hospitalization and 52 after discharge. Delirium, SOFA score and admission BADL disability were significant predictors of in-hospital mortality. SOFA score, CIRS, previous long-term oxygen therapy and discharge BADL dependency significantly predicted post-discharge mortality. The accuracy of SOFA in predicting in-hospital and post-discharge mortality was fair (AUC = 0.685, 95% CI = 0.610-0.761 and AUC = 0.663, 95% CI = 0.593-0.734, respectively). BADL dependency and delirium improved predictive accuracy for in-hospital mortality (ΔAUC = 0.144, 95% CI = 0.062-0.227, p < 0.001), while pre-admission oxygen therapy, CIRS and BADL dependency improved predictivity for 3 month mortality (ΔAUC = 0.177, 95% CI = 0.102-0.252, p < 0.001). DISCUSSION: Among older pneumonia patients, prognostic stratification obtained by clinical severity indexes is significantly improved by CGA risk factors. CONCLUSIONS: CGA provides important information for prognostic stratification and clinical management of older pneumonia patients.

"The Community That Takes Care of Itself": A Feasibility Study to Support Families Caring for a Loved One With Alzheimer Disease.

This pilot project was aimed at supporting those families caring at home for loved ones suffering from Alzheimer dementia. Fourteen dyads of "caregivers-loved ones with dementia" were recruited and assigned either to the experimental group (n = 7) or to the control group (n = 7). The experimental group attended a training course, an Alzheimer Café, a self-help group for caregivers, and the support from a volunteer and professional nurse in-home visits, while the control group's dyads attended a standard intervention. To investigate the effects of this integrated and interprofessional model of care, caregivers completed the Caregiver Burden Inventory and 2 ad hoc structured questions to evaluate whether quality of life of the dyads was changed. Moreover, the caregivers of the experimental group completed the Self-Assessment Single Questionnaire, version 6 (Q-UAV6). Only caregivers of the experimental group reported a significant reduction in burden and an improved quality of life of the dyad. They also showed a greater acceptance of the disease, became experts in the care of their loved ones, and improved their relationship. The creation of a service integration network of professionals, volunteers, and families has been shown to be useful in supporting those families caring at home for loved ones suffering from Alzheimer dementia.

Elderly Helping Other Elderly: A Comparative Study of Family Caregiver Burden Between Patients With Dementia or Cancer at the End of Life.

A new reality is being observed around the world as the population ages: family caregivers, who are themselves older adults helping their ill older relatives. The aim of this study is to assess the burden of the older family caregiver assisting older patients in his or her end-of-life who are suffering from dementia or cancer. In this context, the elderly person is involved in the dual role of patient and caregiver. In this comparative study, a total of 87 older family caregivers (age ≥ 65 years) completed the Caregiver Burden Inventory (CBI) measurement. The sample was divided into 2 subgroups based on the individuals' advanced disease: Alzheimer's disease (AD) or cancer. Compared to cancer caregivers, the AD subgroup reported significantly higher scores in the CBI-emotional subscale (P = 0.006), confirmed by the evaluation of the generalized linear model (multivariate). There were no significant differences in the other CBI subscales and overall scores. According to the findings of this study, elderly who help elderly with AD are at a higher risk of experiencing an emotional burden than cancer caregivers. This data could be considered in designing interventions to reduce the caregiver burden of older family caregivers as they provide informal end-of-life care.

Does trail making test predict long-term prognosis in older patients with COPD?

Executive abilities are frequently impaired in patients with chronic obstructive pulmonary disease (COPD). We aimed at investigating the association between trail making test (TMT) and survival. Our series consisted of 68 stable COPD outpatients followed-up every 6 months for 52.6 ± 27.6 months. Enrolled patients underwent a baseline comprehensive neuropsychological assessment, including mini-mental state exam, attentional matrices, digit span, Rey auditory verbal learning, Rey-Osterrieth complex figure, copy drawing, tokens test, verbal fluency, category fluency, frontal assessment battery, Raven's progressive matrices, TMT-A, -B and -B-A. The association between neuropsychological deficits and overall mortality was investigated by Cox regression. During follow-up period, 41 patients (60.3%) died. After adjusting for potential confounders, TMT-B was significantly associated with mortality (HR = 2.42, 95% CI = 1.10-5.31), along with age (HR = 1.06, 95% CI = 1.0-1.13), overall comorbidity (HR = 1.29, 95% CI = 1.02-1.62) and use of noninvasive ventilation (HR = 2.16, 95% CI = 1.05-4.45). Defective TMT-B may be associated with long-term mortality in patients with stable COPD.

Design and methodology of the chronic kidney disease as a dysmetabolic determinant of disability among older people (CKD-3D) study: a multicenter cohort observational study.

BACKGROUND: Chronic kidney disease (CKD) is a common condition in older people and represents a global health issue since it increases the risk of associated comorbidities and all-cause mortality. Furthermore, older people with reduced renal function might be at higher risk for developing functional limitation and disability. Moreover, the current creatinine-based measures of renal function are influenced by several factors in older population. The aims of the CKD-3D project are to perform an observational study to expand the knowledge about CKD-disability relationship and to investigate the use of novel biomarkers of kidney function. METHODS: An observational, multicenter, prospective cohort study will be conducted in 75 + old patients consecutively admitted to acute care wards of geriatric medicine at participating hospitals. The study planned to enroll 440 patients undergoing clinical and laboratory evaluations at baseline and after 12 months. Face-to-face follow-up at 6 months and telephone follow-up at 3 and 9 months will be carried out. Comprehensive Geriatric Assessment (CGA) and the measurement of Cystatin C, Beta-Trace Protein and Beta2-Microglobulin levels will be included. DISCUSSION: This study will provide useful information to prevent CKD-related disability by collecting real-life data over 1-year period. The combined approach of CGA and the investigation of innovative existing biomarkers will make it possible to develop new recommendations and guidelines for a patient-centered approach. It is believed that such a study may lead to an improvement of knowledge on CKD in elderly patients and may also have implications in daily clinical practice and in decision-making process.

Chronic kidney disease in the context of multimorbidity patterns: the role of physical performance : The screening for CKD among older people across Europe (SCOPE) study.

BACKGROUND: Chronic kidney disease (CKD) is known to be associated with several co-occurring conditions. We aimed at exploring multimorbidity patterns associated with CKD, as well as the impact of physical performance and CKD severity on them in a population of older outpatients. METHODS: Our series consisted of 2252 patients enrolled in the Screening of CKD among Older People across Europe multicenter observational study. Hypertension, stroke, transient ischemic attack, cancer, hip fracture, osteoporosis, Parkinson's disease, asthma, chronic obstructive pulmonary disease, congestive heart failure, angina, myocardial infarction, atrial fibrillation, anemia, CKD (defined as GFR < 60, < 45 or < 30 ml/min/1.73 m2), cognitive impairment, depression, hearing impairment and vision impairment were included in the analyses. Physical performance was assessed by the Short Physical Performance Battery (SPPB) and used as stratification variable. Pairs of co-occurring diseases were analyzed by logistic regression. Patterns of multimorbidity were investigated by hierarchical cluster analysis. RESULTS: CKD was among the most frequently observed conditions and it was rarely observed without any other co-occurring disease. CKD was significantly associated with hypertension, anemia, heart failure, atrial fibrillation, myocardial infarction and hip fracture. When stratifying by SPPB, CKD was also significantly associated with vision impairment in SPPB = 5-8 group, and hearing impairment in SPPB = 0-4 group. Cluster analysis individuated two main clusters, one including CKD, hypertension and sensory impairments, and the second including all other conditions. Stratifying by SPPB, CKD contribute to a cluster including diabetes, anemia, osteoporosis, hypertension and sensory impairments in the SPPB = 0-4 group. When defining CKD as eGFR< 45 or 30 ml/min/1.73 m2, the strength of the association of CKD with hypertension, sensory impairments, osteoporosis, anemia and CHF increased together with CKD severity in pairs analysis. Severe CKD (eGFR< 30 ml/min/1.73 m2) contributed to a wide cluster including cardiovascular, respiratory and neurologic diseases, as well as osteoporosis, hip fracture and cancer. CONCLUSIONS: CKD and its severity may contribute significantly to specific multimorbidity patterns, at least based on the cluster analysis. Physical performance as assessed by SPPB may be associated with not negligible changes in both co-occurring pairs and multimorbidity clusters. TRIAL REGISTRATION: The SCOPE study is registered at clinicaltrials.gov ( NCT02691546 ).

Impaired kidney function is associated with lower quality of life among community-dwelling older adults : The screening for CKD among older people across Europe (SCOPE) study.

BACKGROUND: Quality of life (QoL) refers to the physical, psychological, social and medical aspects of life that are influenced by health status and function. The purpose of this study was to measure the self-perceived health status among the elderly population across Europe in different stages of Chronic Kidney Disease (CKD). METHODS: Our series consisted of 2255 community-dwelling older adults enrolled in the Screening for Chronic Kidney Disease (CKD) among Older People across Europe (SCOPE) study. All patients underwent a comprehensive geriatric assessment (CGA), including included demographics, clinical and physical assessment, number of medications taken, family arrangement, Geriatric Depression Scale (GDS), Cumulative Illness Rating Scale, History of falls, Lower urinary tract symptoms, and Short Physical Performance Battery (SPPB). Estimated glomerular filtration rate (eGFR) was calculated by Berlin Initiative Study (BIS) equation. Quality of life was assessed by Euro Qol questionnaire (Euro-Qol 5D) and EQ-Visual Analogue Scale (EQ-VAS). The association between CKD (eGFR < 60, < 45 ml or < 30 ml/min/1.73m2) and low EQoL-VAS was investigated by multivariable logistic regression models. RESULTS: CKD was found to be significantly associated with low EQoL-VAS in crude analysis (OR = 1.47, 95%CI = 1.16-1.85 for eGFR< 60; OR = 1.38, 95%CI = 1.08-1.77 for eGFR< 45; OR = 1.57, 95%CI = 1.01-2.44). Such association was no longer significant only when adjusting for SPPB (OR = 1.20, 95%CI = 0.93-1.56 for eGFR< 60; OR = 0.87, 95%CI = 0.64-1.18 for eGFR< 45; OR = 0.84, 95%CI = 0.50-1.42), CIRS and polypharmacy (OR = 1.16, 95%CI = 0.90-1.50 for eGFR< 60; OR = 0.86, 95%CI = 0.64-1.16 for eGFR< 45; OR = 1.11, 95%CI = 0.69-1.80) or diabetes, hypertension and chronic obstructive pulmonary disease (OR = 1.28, 95%CI = 0.99-1.64 for eGFR< 60; OR = 1.16, 95%CI = 0.88-1.52 for eGFR< 45; OR = 1.47, 95%CI = 0.92-2.34). The association between CKD and low EQoL-VAS was confirmed in all remaining multivariable models. CONCLUSIONS: CKD may significantly affect QoL in community-dwelling older adults. Physical performance, polypharmacy, diabetes, hypertension and COPD may affect such association, which suggests that the impact of CKD on QoL is likely multifactorial and partly mediated by co-occurrent conditions/risk factors.

Kidney function and other factors and their association with falls : The screening for CKD among older people across Europe (SCOPE) study.

BACKGROUND: Reduced kidney function has become a major public health concern, especially among older people, as Chronic Kidney Disease (CKD) is associated with increased risk of end stage renal disease and mortality. Falls are a serious negative health outcome in older persons with one third of people aged 65 years experiencing a fall per year and increasing fall rates with increasing age. The impact of CKD on falls in older community-dwelling persons is not well investigated. Additionally, lower urinary tract symptoms (LUTS) may also increase the risk of falls. Therefore, our aim was to investigate the impact of CKD and LUTS on falls as well as on injurious falls. METHODS: The SCOPE study is an observational, multinational, multicenter, prospective cohort study involving community-dwelling older persons aged 75 years and more recruited from August 2016 to March 2018 in seven European countries. The main outcomes of the present study were any falls and any injurious falls during the 12 months before enrolment. The cross-sectional association of estimated glomerular filtration rate (eGFR) and LUTS with study outcomes was investigated by logistic regression analysis adjusted for baseline characteristics of enrolled subjects. RESULTS: Our series consisted of 2256 SCOPE participants (median age = 79.5 years, 55.7% female). Of them, 746 participants experienced a fall and 484 reported an injurious fall in the 12 months prior to baseline assessment. CKD was not significantly associated with falls (OR = 0.95, 95%CI = 0.79-1.14 for eGFR< 60; OR = 1.02, 95%CI = 0.81-1.28 for eGFR< 45; OR = 1.08, 95%CI = 0.74-1.57 for eGFR< 30) or injurious falls (OR = 0.91, 95%CI = 0.67-1.24 for eGFR< 60; OR = 0.93, 95%CI = 0.63-1.37 for eGFR< 45; OR = 1.19, 95%CI = 0.62-2.29 for eGFR< 30). LUTS were found significantly associated with both falls (OR = 1.56, 95%CI = 1.29-1.89) and injurious falls (OR = 1.58, 95%CI = 1.14-2.19), and such associations were confirmed in all multivariable models. CONCLUSIONS: Cross-sectional data suggest that CKD may not be associated with history of falls or injurious falls, whereas LUTS is significantly associated with the outcomes. TRIAL REGISTRATION: This study was registered on 25th February 2016 at clinicaltrials.gov ( NCT02691546 ).

Association between kidney function, nutritional status and anthropometric measures in older people : The Screening for CKD among Older People across Europe (SCOPE) study.

BACKGROUND: Different mechanisms connect the nutritional status with the occurrence and the course of chronic kidney disease (CKD). The end-stage renal disease is complicated by catabolic inflammatory reactions and cachexia which leads to malnutrition (undernutrition). On the other hand, obesity is an important risk factor for the development and acceleration of CKD. METHODS: In the SCOPE study, community-dwelling persons aged 75 years and over, from 6 European countries and Israel were examined at the baseline phase. We assessed the relationship between anthropometric measures (Body Mass Index (BMI), circumferences of arm (AC), waist (WC), hip (HC), and calf (CC), waist-to-hip ratio - WHR, waist-to-height ratio - WHtR, risk of malnutrition (Mini Nutritional Assessment - MNA), serum albumin) and estimated glomerular filtration rate (eGFR) calculated by Berlin Initiative Study (BIS) equation. RESULTS: We studied 2151 subjects (932 men and 1219 women) with a mean age of 79.5 ± 5.9 years. A total of 1333 (62%) participants had CKD (GRF < 60 ml/min/1.73 m2). Negative correlations between eGFR and weight, AC, WC, HC, CC, BMI, WHtR were observed. Positive correlation occurred between eGFR and MNA score (Spearman's rho = 0.11) and albumin concentration (rho = 0.09). Higher weight, AC, WC, HC, CC, BMI and WHtR increased the odds ratio of CKD; higher MNA (OR = 0.98, 95% CI 0.94-1.0) and higher serum albumin (OR = 0.73, 95% CI 0.53-1.0) were weakly associated with reduced odds. The risk of malnutrition was the highest with eGFR < 30 as compared to eGFR > 60 (OR = 2.95, 95%CI = 1.77-4.94 for MNA < 24; OR = 5.54, 95%CI = 1.66-18.5 for hypoalbuminemia < 3.5 g/dL). CONCLUSION: The population of community dwelling people aged 75+ with CKD shows general features of overweight and obesity with a small prevalence of malnutrition. For anthropometric measures, the strongest association with eGFR and the highest odds of CKD were identified using WC, HC, CC and WHtR. Albumin level and MNA, but not MNA Short Form, indicated an increased odds of malnutrition with a decrease in eGFR.

Prevalence of sarcopenia in community-dwelling older adults using the updated EWGSOP2 definition according to kidney function and albuminuria : The Screening for CKD among Older People across Europe (SCOPE) study.

BACKGROUND: Loss of muscle mass and function may be more pronounced in older adults with chronic kidney disease (CKD) and with albuminuria. Thus, we investigated the prevalence of sarcopenia among community-dwelling older adults according to kidney function and grade of albuminuria. We also explored differences in the prevalence of sarcopenia according to three different equations for the estimation of glomerular filtration rate (eGFR). METHODS: A cross-sectional analysis of 1420 community-dwelling older adults (≥75 years old) included in the SCOPE study, a multicenter prospective cohort study, was conducted. Comprehensive geriatric assessment including short physical performance battery (SPPB), handgrip strength test and bioelectrical impedance analysis (BIA) was performed. Sarcopenia was defined using the updated criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). eGFR was calculated using Berlin Initiative Study (BIS), Chronic Kidney Disease Epidemiological Collaboration (CKD-EPI) and Full Age Spectrum (FAS) equations, and urinary albumin-to-creatinine ratio (ACR) was collected to categorize CKD according to Kidney Disease Improving Global Outcomes guidelines. RESULTS: Median age was 79.5 years (77.0-83.0), 804 (56.6%) were women. Using EWGSOP2 definition, 150 (10.6%) participants met diagnostic criteria for sarcopenia. Moreover, 85 (6%) participants had severe sarcopenia. Sarcopenia was more prevalent in participants with more advanced stages of CKD according to BIS eq. (9.6% in stages 1 and 2 and 13.9% in stages 3a, 3b and 4, p = 0.042), and also according to CKD-EPI (9.8% vs. 14.2%, p = 0.042) and FAS although not reaching statistical signification (9.8% vs. 12.7%, p = 0.119). Thus, differences in prevalence are observed among CKD categories as estimated by different equations. Prevalence of sarcopenia was also higher with increasing albuminuria categories: 9.3% in normoalbuminuric, 13.2% in microalbuminuric and 16.8% in macroalbuminuric participants, (p = 0.019). CONCLUSIONS: Sarcopenia is common among community-dwelling older adults, especially among those with more advanced CKD categories, with prevalence estimates differing slightly depending on the equation used for the estimation of eGFR; as well as among those with higher albuminuria categories.

Is kidney function associated with cognition and mood in late life? : The Screening for CKD among Older People across Europe (SCOPE) study.

BACKGROUND: Chronic kidney disease (CKD), cognitive impairment and depression share common risk factors. Previous studies did not investigate the possible association between kidney function and cognitive and mood disorders in older persons in a broad range of kidney function. The present study explored associations between kidney function, cognition and mood in outpatients of 75 years and over. METHODS: Baseline data of 2252 participants of the SCOPE study, an international multicenter cohort observational study,were used in which community-dwelling persons of 75 years and over were enrolled to screen for CKD Kidney function was estimated with the BIS1-eGFR equation, cognition was assessed with the Mini-Mental State Examination (MMSE) and mood with the Geriatric Depression Scale 15 items (GDS-15). Characteristics were compared across stages of CKD. Mean eGFR values were also compared across categories of MMSE (< 24, 24-26, ≥27) and between groups with high and low score on the GDS-15 (> 5/≤5). RESULTS: In total, 63% of the population had an eGFR < 60 mL/min. In advanced stages of CKD, participants were older and more often men than in earlier stages (p < 0.001). Cardiovascular diseases and diabetes mellitus were more often found in those in advanced stages of CKD (p < 0.001), and also cumulative comorbidity scores were higher than in those in earlier stages (p < 0.001). Median MMSE was 29 in CKD stage 1-2 and 3, and 30 in CKD stage 4, whereas median GDS-15 score was 2 in all stages of CKD. Mean values of eGFR did not differ across categories of MMSE or between groups with high and low score on the GDS-15. Stratification for albuminuria did not change these results. CONCLUSIONS: Older persons in more advanced stages of CKD did not have lower cognitive scores or higher rates of depressive symptoms than older persons in earlier stages. Future longitudinal studies might give information on the possible effect of kidney function on cognition and mood in late life. TRIAL REGISTRATION: This study was registered prospectively on 25th February 2016 at clinicaltrials.gov ( NCT02691546 ).

Analysis of mitochondrial DNA allelic changes in Parkinson's disease: a preliminary study.

BACKGROUND: Mitochondrial DNA (mtDNA) mutations are considered as a possible primary cause of age-associated neurodegenerative disorders like Parkinson's disease (PD). AIMS: To analyze, along the whole mtDNA sequence of PD patients, the presence of non-reference alleles compared to reference alleles, as defined in the revised Cambridge Reference Sequence (rCRS). METHODS: mtDNA was extracted from whole blood of PD and control groups, and was sequenced using a chip-based resequencing system. RESULTS: 58 nucleotide positions (np) exhibited a different allelic distribution in the two groups; in 81% of them the non-reference alleles were over-represented in PD patients, similar to findings reported in patients with Alzheimer's disease, albeit in reduced proportion. Closer analysis of the 58 np in PD group showed that they were characterized by low-level heteroplasmy, and that the nucleotide substitutions determined an amino acid change in 84% of cases. CONCLUSIONS: These results suggest that mtDNA allelic changes are increased in PD and that age-related neurodegenerative diseases could share a common mechanism involving mtDNA.

Study of the effects of adapted Tango and multidimensional intervention in pREvention of dementia in agiNG: developing healTHy lifestyle programs (STRENGTH Project)-the experimental protocol of a prospective randomised controlled trial.

BACKGROUND: Dementia represents a key health issue for older adults, with negative consequences on psycho-social and functional status. Treatments that counteract cognitive deficits in mild cognitive impairment (MCI) are needed to prevent or delay it. AIM: To describe the experimental protocol of the STRENGTH Project. This study investigates a multimodal intervention in older adults with MCI to improve cognitive, functional, biochemical and psycho-social aspects. METHODS: The prospective randomised controlled trial will enrol 300 subjects with MCI (age ≥ 60 years). Participants will be randomly assigned to: (a) the experimental group, which will undergo sessions of adapted tango, music therapy, engagement in social activities, cognitive intervention and psycho-education for 6 months or (b) the control group, which will receive psycho-education and advice on healthy lifestyle for 6 months. All outcomes will be analysed before intervention (baseline), immediately after termination (follow-up 1), after 6 months (follow-up 2) and after 2 years (follow-up 3). DISCUSSION: We expect that the findings of this multidisciplinary study will be useful to optimize clinical and psycho-social interventions for improving cognitive and functional status of subjects with MCI. CONCLUSIONS: This project could have a meaningful impact on National Health Systems by providing clues on multidisciplinary management of older adults affected by cognitive decline to prevent dementia.