Whole-brain histogram and voxel-based analyses of Diffusion Tensor Imaging in patients with Leukoaraiosis. Correlation with motor and cognitive impairment

BACKGROUND AND PURPOSE: Cerebral white matter changes, termed leukoaraiosis (LA), appearing as areas of increased signal intensity in T2-weighted MR images, are common in elderly subjects, but the possible correlation of LA with cognitive or motor deficit has not been established. We hypothesized that histogram and voxel-based analyses of whole-brain mean diffusivity (MD) and fractional anisotropy (FA) maps calculated from diffusion tensor imaging (DTI) could be more sensitive tools than visual scales to investigate the clinical correlates of LA. MATERIALS AND METHODS: Thirty-six patients of the Leukoaraiosis and Disability Study were evaluated with fluid-attenuated inversion recovery for LA extension, T1-weighted images for volume, and DTI for MD and FA. The extent of LA was rated visually. The normalized total, gray, and white matter brain volumes were computed, as well as the 25th percentile, 50th percentile, kurtosis, and skewness of the MD and FA maps of the whole brain. Finally, voxel-based analysis on the maps of gray and white matter volume, MD, and FA was performed with SPM2 software. Correlation analyses between visual or computerized data and motor or neuropsychologic scale scores were performed using the Spearman rank test and the SPM2 software. RESULTS: The visual score correlated with some MD and FA histogram metrics (P<.01). However, only the 25th and 50th percentiles, kurtosis, and skewness of the MD and FA histograms correlated with motor or neuropsychologic deficits. Voxel-based analysis revealed a correlation (P<.05 corrected for multiple comparisons) between a large cluster of increased MD in the corpus callosum and pericallosal white matter and motor deficit. CONCLUSIONS: These results are consistent with the hypothesis that histogram and voxel-based analyses of the whole-brain MD and FA maps are more sensitive tools than the visual evaluation for clinical correlation in patients with LA

Determinants of Mobility Disability in Older Adults: Evidence from Population-Based Epidemiologic Studies

Gait and mobility are cardinal to maintain autonomy and independency in daily life, also for older persons. Changes in these functions might be critical in the transition towards disability and loss of autonomy during the aging process. The aim of the present work, which collects three years of research conducted between Italy and the United States, was to assess some of the main risk factors for the progressive impairment of mobility and gait in older adults living in the community. According to our results, abnormalities in the nervous and cardiovascular systems, even subtle, are associated with a subsequent worsening of these functions. These data might help to better understand the progressive development of disability in the elderly, and in the future might also have practical implications for prevention

Impact of supplementation with vitamins B6, B12, and/or folic acid on the reduction of homocysteine levels in patients with mild cognitive impairment: A systematic review

Àcid fòlic; Hhomocisteïna; Deteriorament cognitiu lleuÁcido fólico; Homocisteína; Deterioro cognitivo leveFolic acid; Homocysteine; Mild cognitive impairmentHyperhomocysteinemia is an independent predictor of the risk for cognitive decline and may be a result of low levels of vitamins B12, B6, and folate. Previous findings suggest that adequate intake of these vitamins may reduce homocysteine levels. This review aimed to assess the effects of treatment with vitamins B6, B12, and/or folic acid in the homocysteine levels in patients with mild cognitive impairment (MCI). A systematic literature review was conducted in EMBASE, MEDLINE®, PsycINFO, and Cochrane Central Register of Controlled Trials. The research question was formulated using the Population, Intervention, Comparison, and Outcome (PICO) framework: in patients with MCI (P); what is the efficacy of vitamins B6, B12, and/or folic acid intake (I); compared with baseline values, and/or compared with controls (C); in reducing homocysteine levels from baseline (O). A total of eight primary studies with a total of 1,140 participants were included in the review. Four were randomized controlled trials, one was a quasi-controlled trial, and three were observational studies. All studies included folic acid in their intervention, seven vitamin B12, and four vitamin B6. Mean (SD) length of the intervention period was 18.8 (19.3) months, ranging from 1 to 60 months. All studies showed a statistically significant decrease in homocysteine levels in groups treated with vitamins B6, B12, and/or folic acid compared to controls, with a mean decline of homocysteine concentration of 31.9% in the intervention arms whereas it increased by 0.7% in the control arm. This review identified evidence of a reduction of plasma homocysteine levels in MCI patients taking vitamins B6, B12, and/or folic acid supplements, with statistically significant declines being observed after 1 month of supplementation. Findings support that supplementation with these vitamins might be an option to reduce homocysteine levels in people with MCI and elevated plasma homocysteine.Nestlé Health Science, Switzerlan

Dual-task related frontal cerebral blood flow changes in older adults with mild cognitive impairment: A functional diffuse correlation spectroscopy study

Cerebral blood flow; Mild cognitive impairment; SpectroscopyFlux sanguini cerebral; Deteriorament cognitiu lleu; EspectroscòpiaFlujo sanguíneo cerebral; Deterioro cognitivo leve; EspectroscopiaIntroduction: In a worldwide aging population with a high prevalence of motor and cognitive impairment, it is paramount to improve knowledge about underlying mechanisms of motor and cognitive function and their interplay in the aging processes. Methods: We measured prefrontal cerebral blood flow (CBF) using functional diffuse correlation spectroscopy during motor and dual-task. We aimed to compare CBF changes among 49 older adults with and without mild cognitive impairment (MCI) during a dual-task paradigm (normal walk, 2- forward count walk, 3-backward count walk, obstacle negotiation, and heel tapping). Participants with MCI walked slower during the normal walk and obstacle negotiation compared to participants with normal cognition (NC), while gait speed during counting conditions was not different between the groups, therefore the dual-task cost was higher for participants with NC. We built a linear mixed effects model with CBF measures from the right and left prefrontal cortex. Results: MCI (n = 34) showed a higher increase in CBF from the normal walk to the 2-forward count walk (estimate = 0.34, 95% CI [0.02, 0.66], p = 0.03) compared to participants with NC, related to a right- sided activation. Both groups showed a higher CBF during the 3-backward count walk compared to the normal walk, while only among MCI, CFB was higher during the 2-forward count walk. Discussion: Our findings suggest a differential prefrontal hemodynamic pattern in older adults with MCI compared to their NC counterparts during the dual-task performance, possibly as a response to increasing attentional demand.This work was supported by the Instituto de Salud Carlos III (MEDPHOTAGE, DTS 16/00099 and DTS 16/00087, 2017, and FRONT STAGE, PI 19/00734, 2020) and co-funded by European Regional Development Fund/European Social Fund “Investing in your future,” the European Union’s Horizon 2020 Research and Innovation Program under the Marie Skłodowska-Curie (Grant No. 713729), Fundació CELLEX Barcelona, Fundació Mir-Puig, Agencia Estatal de Investigación (PHOTOMETABO, PID2019-106481RB-C31/10.13039/501100011033), FEDER EC and LASERLAB-EUROPE V (EC H2020 number 871124) and “Severo Ochoa” Programme for Centres of Excellence in R&D (CEX2019-000910-S)

Is loneliness a predictor of the modern geriatric giants? Analysis from the survey of health, ageing, and retirement in Europe

Background: The modern Geriatric Giants have evolved to encompass four new syndromes, of frailty (linked to fatigue and physical inactivity), sarcopenia, anorexia of ageing, and cognitive impairment. In parallel, loneliness has been established as a risk factor for adverse mental and physical health outcomes among older adults. Objective: To analyse loneliness as a predictor of the modern Geriatric Giants in European older adults, using a longitudinal design of nationally representative data. Design: Longitudinal population-based cohort study. Subjects: Data from countries that participated in waves 5 and 6 of the Survey of Health, Ageing, and Retirement in Europe project. The sizes of the subsamples analysed ranged from 17,742 for physical inactivity to 24,524 for anorexia of ageing. Methods: Loneliness (measured from wave 5) was the independent variable of interest. The dependent variables were incidence of fatigue, physical inactivity, sarcopenia, anorexia of ageing, and cognitive impairment from wave 5 (baseline) to wave 6. Poisson regression models were used for multivariable analysis, obtaining Relative Risk (RR) and 95 % confidence intervals (CI). Results: The prevalence of loneliness ranged from 9.2%–12.4% at wave 5. The 2-year incidence of fatigue was 16 % (95 % CI: 15.5–16.5), physical inactivity 9.8 % (95 % CI: 9.4–10.3), sarcopenia 5.6 % (95 % CI: 5.3–5.9), anorexia of aging 5.4 % (95 % CI: 5.1–5.7), and cognitive impairment 10.3 % (95 % CI: 9.9–10.8). The multivariable analysis showed that loneliness was a predictive factor for fatigue (30 %, CI: 17–45 % higher risk), physical inactivity (24 %, CI: 7–43 % higher risk) and cognitive impairment (26 %, CI: 9–46 % higher risk), adjusted by age, sex, number of chronic diseases, education level, region and depression. Conclusions: Loneliness is an independent risk factor for fatigue, physical inactivity, and cognitive impairment in older adults. The incidence of anorexia of ageing and sarcopenia was not associated with loneliness over the 2- year observation period

Experience, facilitators, and barriers to the implementation of a multicomponent programme in older people living in the community, +AGIL Barcelona: A qualitative study

Exercise; Exercise implementation programme; FrailtyEjercicio; Programa de ejecución de ejercicios; FragilidadExercici; Programa d'execució d'exercicis; FragilitatIntroduction: The +AGIL Barcelona programme is a multicomponent care intervention for frail older adults (FOAs) living in the community. To improve the programme, it is essential to investigate the experience of all participants. Our objective was to explore the perspective of FOA and professionals about the barriers, facilitators, and improvement elements of the development of the +AGIL Barcelona programme. Qualitative descriptive approach. Were included FOA and professionals who participated in the +AGIL Barcelona programme. Methods: Three focus groups and four interviews were conducted. These were analyzed following the qualitative method of content analysis. The criteria of scientific rigor of credibility, dependence, and transferability were ensured throughout the study. Results: Three themes and seven sub-themes were developed: facilitators (positive experience and perceived benefits), barriers (self-perceived health status, digital divide, and continuity of the programme at home), and improvements elements (programme continuity and adaptation of technology). All the participants felt satisfied, highlighting aspects such as interpersonal relationships and social contact, face-to-face sessions guided by a physiotherapist, and the functional improvement achieved. Some of the difficulties were the self-perception of frailty, the need for technological support, and continuing the exercise programme at home. Conclusion: The FOA who participated in the +AGIL Barcelona programme perceived direct benefits for their health and physical condition due to the development of self-confidence by being able to perform physical exercise despite their baseline condition, and the professionals experienced an improvement in the quality of care due to work in a multidisciplinary team.This study was partially supported by Subvencions de L'institut de Cultura de Barcelona per a Projectes de Recerca i Innovació del Pla Barcelona Ciència 2019 (ID 19S01576-006)

Exercise-based interventions to enhance long-term sustainability of physical activity in older adults: a systematic review and meta-analysis of randomized clinical trials

Older adults; Physical activity; AdherenceAdultos mayores; Actividad física; AdherenciaAdults majors; Activitat física; AdherènciaExercise is a form of physical activity (PA). PA is an important marker of health and quality of life in older adults. The purpose of this study was to conduct a systematic review of the literature to assess the effect of exercise-based interventions on an at least six-month follow up PA measure, and to describe the specific strategies implemented during the intervention to strengthen the sustainability of PA in community-dwelling 65+ year-old adults. We registered and conducted a systematic review and meta-analysis (PROSPERO: CRD42017070892) of randomized clinical trials (RCT). We searched three electronic databases during January 2018 to identify RCT assessing any type of exercise-based intervention. Studies had to report a pre-, post-, and at least 6-month post-intervention follow-up. To be included, at least one PA outcome had to be assessed. The effect of exercise-based interventions was assessed compared to active (e.g., a low-intensity type of exercise, such as stretching or toning activities) and non-active (e.g., usual care) control interventions at several time points. Secondary analyses were conducted, restricted to studies that reported specific strategies to enhance the sustainability of PA. The intervention effect was measured on self-reported and objective measures of time spent in PA, by means of standardized mean differences. Standardized mean differences of PA level were pooled. Pooled estimates of effect were computed with the DerSimonian–Laird method, applying a random effects model. The risk of bias was also assessed. We included 12 studies, comparing 18 exercise intervention groups to four active and nine non-active control groups. Nine studies reported specific strategies to enhance the long-term sustainability of PA. The strategies were mostly related to the self-efficacy, self-control, and behavior capability principles based on the social cognitive theory. Exercise interventions compared to active control showed inconclusive and heterogeneous results. When compared to non-active control, exercise interventions improved PA time at the six-months follow up (standardized mean difference (SMD) 0.30; 95%CI 0.15 to 0.44; four studies; 724 participants; I2 0%), but not at the one- or two-years follow-ups. No data were available on the mid- and long-term effect of adding strategies to enhance the sustainability of PA. Exercise interventions have small clinical benefits on PA levels in community-dwelling older adults, with a decline in the observed improvement after six months of the intervention cessation.The present study was funded by United States Department of Health & Human Services National Institutes of Health (NIH), USA, and NIH National Institute on Aging (NIA), USA, (K24 AG057728)

Operationalization of a frailty index among older adults in the InCHIANTI study: predictive ability for all-cause and cardiovascular disease mortality

Background The frailty index (FI) is a sensitive instrument to measure the degree of frailty in older adults, and is increasingly used in cohort studies on aging. Aims To operationalize an FI among older adults in the "Invecchiare in Chianti" (InCHIANTI) study, and to validate its predictive capacity for mortality. Methods Longitudinal data were used from 1129 InCHIANTI participants aged >= 65 years. A 42-item FI was operationalized following a standard procedure using baseline data (1998/2000). Associations of the FI with 3- and 6-year all-cause and cardiovascular disease (CVD) mortality were studied using Cox regression. Predictive accuracy was estimated by the area under the ROC curve (AUC), for a continuous FI score and for different cut-points. Results The median FI was 0.13 (IQR 0.08-0.21). Scores were higher in women, and at advanced age. The FI was associated with 3- and 6-year all-cause and CVD mortality (HR range per 0.01 FI increase = 1.03-1.07, all p < 0.001). The continuous FI score predicted the mortality outcomes with moderate-to-good accuracy (AUC range 0.72-0.83). When applying FI cut-offs between 0.15 and 0.35, the accuracy of this FI for predicting mortality was moderate (AUC range 0.61-0.76). Overall, the predictive accuracy of the FI was higher in women than in men. Conclusions The FI operationalized in the InCHIANTI study is a good instrument to grade the risk of all-cause mortality and CVD mortality. More measurement properties, such as the responsiveness of this FI when used as outcome measure, should be investigated in future research

Sleep disturbances and the speed of multimorbidity development in old age : results from a longitudinal population-based study

Sleep disturbances are prevalent among older adults and are associated with various individual diseases. The aim of this study was to investigate whether sleep disturbances are associated with the speed of multimorbidity development among older adults. Data were gathered from the Swedish National study of Aging and Care in Kungsholmen (SNAC-K), an ongoing population-based study of subjects aged 60+ (N = 3363). The study included a subsample (n = 1189) without multimorbidity at baseline (< 2 chronic diseases). Baseline sleep disturbances were derived from the Comprehensive Psychiatric Rating Scale and categorized as none, mild, and moderate-severe. The number of chronic conditions throughout the 9-year follow-up was obtained from clinical examinations. Linear mixed models were used to study the association between sleep disturbances and the speed of chronic disease accumulation, adjusting for sex, age, education, physical activity, smoking, alcohol consumption, depression, pain, and psychotropic drug use. We repeated the analyses including only cardiovascular, neuropsychiatric, or musculoskeletal diseases as the outcome. Moderate-severe sleep disturbances were associated with a higher speed of chronic disease accumulation (ß /year = 0.142, p = 0.008), regardless of potential confounders. Significant positive associations were also found between moderate-severe sleep disturbances and neuropsychiatric (ß /year = 0.041, p = 0.016) and musculoskeletal (ß /year = 0.038, p = 0.025) disease accumulation, but not with cardiovascular diseases. Results remained stable when participants with baseline dementia, cognitive impairment, or depression were excluded. The finding that sleep disturbances are associated with faster chronic disease accumulation points towards the importance of early detection and treatment of sleep disturbances as a possible strategy to reduce chronic multimorbidity among older adults. The online version contains supplementary material available at 10.1186/s12916-020-01846-w

The challenge of clinical complexity in the 21st century: could Frailty Indexes be the answer?

The number of older people with complex clinical conditions and complex care needs continues to increase in the population. This is presenting many challenges to healthcare professionals and healthcare systems. In the face of these challenges, approaches are required that are practical and feasible. The frailty paradigm may be an excellent opportunity to review and establish some of the principles of comprehensive Geriatric Assessment in specialties outside Geriatric Medicine. The assessment of frailty using Frailty Indexes provides an aid to the 'situational diagnosis' of complex clinical situations, and may help in tackling uncertainty in a person-centred approach.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.regg.2016.07.00