Association between inflammatory markers, body composition and frailty in home-dwelling elderly: an 8-year follow-up study.

Frailty has been linked to inflammation and changes in body composition, but the findings are inconsistent. To explore this, we used the Frailty Index (FI) definition to (1) investigate the association between levels of inflammatory markers (baseline) and change in FI score after 8 years of follow-up and (2) investigate the longitudinal associations between inflammatory markers, body composition, and frailty. Home-dwelling elderly (≥ 70 years) were invited to participate in the study and re-invited to a follow-up visit 8 years later. This study includes a total of 133 participants. The inflammatory markers included were high-sensitive C-reactive protein (hs-CRP), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and glycoprotein acetyls (Gp-acetyls). We used the body composition markers fat mass, fat-free mass, and waist circumference. The FI score consisted of 38 variables. Additional clinical assessments such as blood pressure and body mass index (BMI), as well as information about daily medications, were collected at both visits. Linear regression model and Spearman's rank correlation were used to investigate associations. We showed that the FI score increased after 8 years, and participants with higher hs-CRP levels at baseline had the largest change in the FI score. Changes in fat mass were significantly correlated with changes in hs-CRP and IL-6, and changes in waist circumference were significantly correlated with changes in TNF-α. The use of drugs increased during the 8 years of follow-up, which may have attenuated the associations between inflammation and frailty. However, elevated concentrations of hs-CRP in the elderly may be associated with an increased risk of frailty in subsequent years.

Evaluation of Age-Related Changes in Teneligliptin Pharmacokinetics in Japanese and European Descent Subjects Using a Physiologically Based Pharmacokinetic Model.

INTRODUCTION: Drugs often show differing pharmacokinetic (PK) profiles, such as higher plasma concentrations, in older people than in younger people owing to age-related decreases in physiological functions. However, it is difficult to evaluate the PK in older populations. Therefore, we simulated the plasma age-related changes in the PK of teneligliptin, a dipeptidyl peptidase-4 inhibitor, using physiologically based PK (PBPK) models. METHODS: The previously developed PBPK model was revalidated by comparison between simulated data and clinical study data that included older subjects (up to 75 years old). We then simulated the plasma concentration-time profiles for teneligliptin at a dose of 20 mg (single and multiple doses) in virtual Japanese (20-70 years old) and European descent (20-98 years old) subjects. PK parameters were calculated by race and age group. RESULTS: We confirmed the validity of the previous PBPK model by comparison between simulated data and clinical study data. In the evaluation of age-related changes in PK after single and multiple doses using the PBPK model, the area under the plasma concentration-time curve (AUC) of teneligliptin tended to increase slightly with age in both populations up to 70 years old. However, no clear age-related change in the maximum plasma concentration (Cmax) of teneligliptin was observed. In the European descent subjects aged ≥ 70 years, the AUC tended to increase but the ratio of the change in Cmax was smaller than that in AUC. In both populations, there were positive correlations between AUC and age, but not between Cmax and age. CONCLUSION: The simulation using a PBPK model showed a tendency for the AUC of teneligliptin to increase with age, whereas Cmax was less affected by age than AUC.

Plasma levels of neurology-related proteins are associated with cognitive performance in an older population with overweight/obesity and metabolic syndrome.

Cognitive impairment is present in a broad spectrum of medical conditions and in aging. Here, we aimed to identify plasma proteins related to cognitive function in a sample of older adults with overweight/obesity and metabolic syndrome. A total of 129 subjects (mean age 64.7 years; 36% females) were grouped according to low (l-GCF, N=65) or high (h-GCF, N=64) global cognitive function and matched according to education, sex, age, and body mass index. Cognitive performance was assessed using neuropsychological tests. Plasma levels of 92 neurology-related proteins were assessed using a proximity extension assay. An elastic net regression analysis was used to identify proteins more associated with cognitive performance. Additionally, the protein expression levels were compared between the two groups by means of a t-test with false discovery rate correction. Pearson correlations were used to assess associations between the protein levels and scores from the neurocognitive tests. Six proteins (alpha-2-MRAP, HAGH, Siglec-9, MDGA1, IL12, and EDA2R) were identified as potential contributors to cognitive performance, remaining significantly increased in l-GCF compared to h-GCF participants after correction for multiple testing. Negative correlations (r= -0.23 to -0.18, i.e., lower protein levels, higher cognitive function) were found between global cognitive function and Siglec-9, NMNAT1, HAGH, LXN, gal-8, alpha-2-MRAP, IL12, PDGF-R-alpha, NAAA, EDA2R, CLEC1B, and LAT. Mini-mental state examination z scores showed the strongest correlations with protein levels, specifically negative correlations with CLEC1b, LXN, LAT, PLXNB3, NMNAT1, gal-8, HAGH, NAAA, CTSS, EZR, KYNU, MANF (r=-0.38 to -0.26) and a positive correlation with ADAM23 (r= 0.26). In summary, we identified several plasma proteins that were significantly associated with cognitive performance in older adults with obesity and metabolic syndrome, although further research is needed to replicate the results in larger samples and to include a predictive perspective.

[The usefulness of a questionnaire during medical examinations for older subjects in evaluating frailty: Utilization in clinical practice].

AIM: The late-stage medical care system for older people provides medical examinations, including questionnaires for frailty. We examined whether or not this approach is useful in clinical practice. METHODS: We used this questionnaire for the screening of frailty as follows: according to the manual prepared by the Japan Geriatrics Society, each question was classified as concerning oral (Q4, 5), physical (Q6-9), cognitive (Q10, 11), or social (Q13-15) frailty. Each frailty was defined if there was at least one negative answer in each question. The grip power and skeletal muscle index (SMI) according to a bioelectrical impedance analysis were also evaluated. Subjects who showed a reduced grip strength and SMI were defined as having sarcopenia, and those who showed only a reduced grip strength were defined as having possible sarcopenia. RESULTS: One hundred and seventy-one subjects aged 81.0±4.2 years old (63.1% female) were enrolled. A total of 12.3% of subjects showed sarcopenia, and 17.5% showed possible sarcopenia. The prevalence of physical, cognitive, and social frailties was associated with sarcopenia. Oral frailty, defined as having decreased swallowing and mastication functions (Q4 and 5), was significantly related to sarcopenia. Physical frailty was associated with age. In patients with hypertension, a low incidence of cognitive frailty was found. Social frailty was related to a decreased body weight. CONCLUSIONS: A questionnaire during medical examinations for older subjects may be useful for screening various frailties and may lead to promotion of the preventive care activities in the community. Further studies are needed to elucidate the relationship between each type of frailty and background characteristics.

Estimated appendicular skeletal muscle mass using calf circumference and mortality: Results from the aging and longevity study in the Sirente geographic area (ilSIRENTE study).

OBJECTIVE: Low muscle mass is one of the mediators of numerous complications accompanying malnutrition status and sarcopenia and at the same time may have a greater effect on survival than other clinical characteristics. In this study, we evaluated the impact of low appendicular skeletal muscle (ASM) on all-cause mortality risk over 10 years in older community-dwellers. DESIGN: Prospective cohort study. SETTING: Population-based study. PARTICIPANTS: All persons aged 80+ years living in the community of the Sirente geographic area (L'Aquila, Italy) (n = 364). Participants were categorised in low or normal ASM based on the COONUT equation that considered calf circumference, age and gender. PRIMARY OUTCOME: All-cause mortality over 10 years according to the low ASM estimated by calf circumference. RESULTS: Low estimated ASM was identified in 128 participants (37 %). A total of 245 deaths were recorded over 10 years: 110 among participants with low ASM (85.3 %) and 135 among persons with normal ASM (65.1 %; p < 0.001). Participants with low ASM had a higher risk of death than those with normal ASM (HR: 3.38; 95 % CI: 1.93-5.93). This association remained statistically significant after adjusting for a number of potential confounders, such as age, gender, ADL impairment, cognitive impairment, BMI, and plasma CRP and IL6 levels (HR: 1.84; 95 % CI: 1.03-3.28). CONCLUSIONS: Our findings show that low estimated ASM by calf circumference is predictive of 10 years mortality in older community-dwellers. The derived equation used in the present study to estimate ASM, based on calf circumference, may be particularly relevant in clinical practice. Hence, in older persons with low ASM, interventions targeting muscle mass may be effective at preventing or postponing negative health outcomes.

Potential Role of Probiotics for Inflammaging: A Narrative Review.

BACKGROUND AND AIMS: Inflammaging, a chronic, low-grade inflammation (LGI), is one of the mechanisms of adaptation of an organism to aging. Alterations in the composition of gut microbiota and gut permeability are among the main sources of LGI. They may be modulated by supplementation with live microorganisms, i.e. probiotics. This narrative review was performed with the aim to critically examine the current evidence from randomized clinical trials (RCTs) on the effects of probiotics on pro-inflammatory and anti-inflammatory cytokines and C-reactive protein (CRP) in healthy older subjects. METHODOLOGY: RCTs on the effects of probiotics on inflammatory parameters in subjects older than 65 years published in English and Italian from 1990 to October 2020 were searched in PubMed. Studies that were not RCTs, those using probiotics together with prebiotics (synbiotics), and studies performed in subjects with acute or chronic diseases were excluded. The findings of RCTs were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: A total of nine RCTs met the eligibility criteria and were included in this narrative review. Four articles reported that probiotic supplementation significantly affected inflammatory parameters, respectively, by reducing TGF-ß1 concentrations, IL-8, increasing IL-5 and Il-10, and IFN-γ and IL-12. CONCLUSIONS: Based on this narrative review, probiotic supplementation showed a limited effect on inflammatory markers in healthy individuals older than 65 years. Besides being few, the studies analyzed have methodological limitations, are heterogeneous, and provide results which are incomparable.

Association between Food Intake, Clinical and Metabolic Markers and DNA Damage in Older Subjects.

The use of DNA damage as marker of oxidative stress, metabolic dysfunction and age-related diseases is debated. The present study aimed at assessing the level of DNA damage (evaluated as DNA strand-breaks, endogenous and oxidatively-induced DNA damage) in a group of older subjects with intestinal permeability enrolled within the MaPLE (Gut and Blood Microbiomics for Studying the Effect of a Polyphenol-Rich Dietary Pattern on Intestinal Permeability in the Elderly) intervention trial, to evaluate its association with clinical, metabolic and dietary markers. DNA damage in peripheral blood mononuclear cells was assessed by the comet assay in 49 older subjects participating in the study. Clinical and metabolic markers, markers of inflammation, vascular function and intestinal permeability were determined in serum. Food intake was estimated by weighted food diaries. On the whole, a trend towards higher levels of DNA damage was observed in men compared to women (p = 0.071). A positive association between DNA damage and clinical/metabolic markers (e.g., uric acid, lipid profile) and an inverse association with dietary markers (e.g., vitamin C, E, B6, folates) were found and differed based on sex. By considering the importance of DNA stability during aging, the results obtained on sex differences and the potential role of dietary and metabolic factors on DNA damage underline the need for further investigations in a larger group of older adults to confirm the associations found and to promote preventive strategies.

The impact of acute changes of inflammation on appetite and food intake among older hospitalised patients.

The present study aimed to investigate the effect of acute changes in serum C-reactive protein (CRP) on appetite and food intake among older hospitalised patients. A total of 200 patients (age range 65-94 years, 62·5 % women) participated in this prospective longitudinal observational study. Risk of malnutrition was measured according to the Mini Nutritional Assessment Short Form. The Simplified Nutritional Appetite Questionnaire (SNAQ) and Edmonton Symptom Assessment System (ESAS) were used to evaluate patients' appetite at the time of hospital admission (baseline) and after 7 d (follow-up). Food intake was measured according to the plate diagram and serum CRP was analysed at baseline and follow-up. At baseline, 30·5 % of the patients had moderate to severe inflammation, 31·0 % were malnourished and 48·0 % had food intake <75 % of the meals offered. Also, 32·5 and 23·5 % reported poor and very poor appetite or severe loss of appetite according to the SNAQ and ESAS, respectively. Of the patients, 40 % displayed a pronounced reduction in median CRP levels by -1·2 mg/dl and 19 % demonstrated an increase in median CRP levels by +1·2 mg/dl. Appetite significantly improved (P = 0·006) in patients with a decrease in CRP level and deteriorated in those with an increase in CRP level (P = 0·032). Changes in CRP levels did not show any significant impact on food intake. In a regression analysis, changes of inflammation were the major independent predictor for changes of patients' appetite. We conclude that inflammation has a significant impact on appetite and should therefore be considered in the diagnosis and treatment of malnutrition.

Design, Implementation and Preliminary Testing of a Novel Orthosis for Reducing Erector Spinae Muscle Activity, and Improving Balance Control for Hyperkyphotic Elderly Subjects.

BACKGROUND: Aging often results in thoracic kyphosis and adverse postural changes. This may interfere with physiologic activity of paraspinal muscles. Few styles of spinal orthosis have been already used to reduce thoracic kyphosis. This paper describes the development of a novel orthosis, which is designed based on the anatomy of the back muscles. This novel orthosis may potentiate muscle activity and balance control among older hyper kyphotic subjects. OBJECTIVES: The object of this study was to design and preliminary testing of a new orthosis to potentiate muscle activity and balance control among older hyper kyphotic subjects. MATERIAL AND METHODS: In this quasi-experimental study, a new postural control orthosis with a textile band structure was designed to provide an additional support for spine and muscles of the back. The functional impact of this orthosis was evaluated in six older hyper-kyphotic subjects. According to the results, the paraspinal muscles activity and balance control were significantly improved. RESULTS: The RMS sEMG of the lumbar and thoracic erector spinae muscles reduced significantly (p<0.05), and a significant improvement (p<0.05) was observed in the balance test when patients put on the novel orthosis (p<0.05). CONCLUSION: The new orthosis can considerably improve the paraspinal muscles activity at both the upper and lower lumbar levels. It can also recover balance control among elderly subjects.

Cognitive Function in Dementia-Free Subjects and Survival in Old Age: The PROSPER Study.

BACKGROUND: Impairment in domain-specific cognitive function is associated with the increased risk of mortality. We prospectively evaluated the association of executive function and memory with the risk of long-term mortality in dementia-free older subjects. Moreover, we investigated the role of structural brain abnormalities in this association. METHODS: We included 547 dementia-free participants (mean age 78 years, 56.5% male) from the nested magnetic resonance imaging sub-study of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Cox proportional hazard models were used to model 10-year risk of all-cause, cardiovascular, and noncardiovascular mortality in relation to performance in executive function and memory. Moreover, we evaluated the role of total brain parenchymal volume, cerebral blood flow, white matter hyperintensity, and the presence of microbleeds and infarcts in the link between cognitive function and mortality. RESULTS: In the multivariable model, lower performance in executive function was associated with greater risk of all-cause (hazard ratio [HR] 1.49; 95% confidence interval [CI], 1.31-1.70), cardiovascular (HR 1.69; 95% CI, 1.36-2.11), and noncardiovascular (HR 1.36; 95% CI, 1.15-1.62) mortality. Similarly, poorer performance in memory tests associated with higher risk of all-cause (HR 1.47; 95% CI, 1.29-1.68), cardiovascular (HR 1.45; 95% CI, 1.15-1.83), and noncardiovascular (HR 1.49; 95% CI, 1.27-1.76) mortality. The associations were similar in subjects with various levels of brain structural abnormalities and cerebral blood flow (all P for interaction ≫ .05). CONCLUSIONS: Poorer performance in both executive function and memory tests associates with all-cause, cardiovascular, and noncardiovascular mortality in elderly individuals. This association is independent of cardiovascular risk factors and diseases, brain structural abnormalities, and cerebral blood flow.

Predicting Working Memory Capacity in Older Subjects Using Quantitative Electroencephalography.

OBJECTIVE: We utilized a spectral and network analysis technique with an integrated support vector classification algorithm for the automated detection of cognitive capacity using resting state electroencephalogram (EEG) signals. METHODS: An eyes-closed resting EEG was recorded in 158 older subjects, and spectral EEG parameters in seven frequency bands, as well as functional brain network parameters were, calculated. In the feature extraction stage, the statistical power of the spectral and network parameters was calculated for the low-, moderate-, and high-performance groups. Afterward, the highly-powered features were selected as input into a support vector machine classifier with two discrete outputs: low- or high-performance groups. The classifier was then trained using a training set and the performance of the classification process was evaluated using a test set. RESULTS: The performance of the Support Vector Machine was evaluated using a 5-fold cross-validation and area under the curve values of 70.15% and 74.06% were achieved for the letter numbering task and the spatial span task. CONCLUSION: In this study, reliable results for classification accuracy and specificity were achieved. These findings provide an example of a novel method for parameter analysis, feature extraction, training, and testing the cognitive function of elderly subjects based on a quantitative EEG signal.

Hypoglycemic and antioxidant effect of Tai chi exercise training in older adults with metabolic syndrome.

INTRODUCTION: The antioxidant and anti-inflammatory effects of Tai chi (TC) exercise training in healthy older adults has been demonstrated. However, there are no studies on this effect in older adults with metabolic syndrome (MetS). PURPOSE: The aim of this study was to determine the effect of TC exercise on oxidative stress and inflammatory markers in older adults with MetS. METHODS: A quasi-experimental study was carried out with a sample of 110 older sedentary volunteers with clinical diagnoses of MetS: (i) a control group, n = 50, of individuals who do not participate in physical exercise, of which 37 fulfilled the entire study protocol, and (ii) an experimental group, n = 60, of subjects enrolled in a TC exercise training program (eight-form easy), 5 days a week for 6 months, in sessions of 50 min, under the supervision of a qualified instructor, of which 48 fulfilled the entire study protocol. We measured in both groups (pre- and post-intervention) the following cardiovascular parameters: resting heart rate (RHR), diastolic and systolic blood pressure (DBP and SBP), mean arterial pressure (MAP), RHR-SBP product, RHR-MAP product; glycosylated hemoglobin (HbA1c); oxidative stress markers (superoxide dismutase, total antioxidant status, thiobarbituric acid reacting substances, and oxidative stress score); and inflammation markers (TNF-α, IL-6, IL-8, and IL-10). RESULTS: A statistically significant decrease in HbA1c concentration was observed in the TC group compared with the control group (p < 0.05). This group also showed a statistically significant increase in TAS and a decrease in the oxidative stress score (p < 0.05). We did not observe changes in the cardiovascular parameters (RHR, DBP, SBP, MAP, RHR-SBP product, and RHR-MAP product) in the TC experimental group compared to the control group. CONCLUSION: Our findings suggest that the practice of TC exercise has an antioxidative and hypoglycemic effect in the elderly with MetS.

Predicting Working Memory Capacity in Older Subjects Using Quantitative Electroencephalography

OBJECTIVE: We utilized a spectral and network analysis technique with an integrated support vector classification algorithm for the automated detection of cognitive capacity using resting state electroencephalogram (EEG) signals. METHODS: An eyes-closed resting EEG was recorded in 158 older subjects, and spectral EEG parameters in seven frequency bands, as well as functional brain network parameters were, calculated. In the feature extraction stage, the statistical power of the spectral and network parameters was calculated for the low-, moderate-, and high-performance groups. Afterward, the highly-powered features were selected as input into a support vector machine classifier with two discrete outputs: low- or high-performance groups. The classifier was then trained using a training set and the performance of the classification process was evaluated using a test set. RESULTS: The performance of the Support Vector Machine was evaluated using a 5-fold cross-validation and area under the curve values of 70.15% and 74.06% were achieved for the letter numbering task and the spatial span task. CONCLUSION: In this study, reliable results for classification accuracy and specificity were achieved. These findings provide an example of a novel method for parameter analysis, feature extraction, training, and testing the cognitive function of elderly subjects based on a quantitative EEG signal.

Sleep in older adults and in subjects with dementia.

The neuronal structures for the regulation of sleep and wakefulness are located in the brain. This complex network is vulnerable to numerous factors, most importantly neurodegenerative diseases and drugs. The macrostructure and microstructure of sleep change with age. These changes are more pronounced in subjects with dementia. Sleep disorders in subjects with dementia may be independent of dementia or caused by dementia. Furthermore, epidemiological studies reveal that sleep disorders per se may induce dementia by reduction of cerebral clearance of beta-amyloids. The population attributable risk (PAR) of sleep disturbances to the incidence of dementia is estimated to be about 15%; therefore, management of sleep disturbances in older adults and subjects with dementia gives the opportunity of an impact on incidence and course of dementia. Sleep history should be taken from each individual and obvious sleep disturbances, especially sleep apnea, should be managed according to current guidelines. Future studies that concern the incidence and the management of dementia must take into account sleep and sleep disturbances.

Performance Evaluation of State of the Art Systems for Physical Activity Classification of Older Subjects Using Inertial Sensors in a Real Life Scenario: A Benchmark Study.

The popularity of using wearable inertial sensors for physical activity classification has dramatically increased in the last decade due to their versatility, low form factor, and low power requirements. Consequently, various systems have been developed to automatically classify daily life activities. However, the scope and implementation of such systems is limited to laboratory-based investigations. Furthermore, these systems are not directly comparable, due to the large diversity in their design (e.g., number of sensors, placement of sensors, data collection environments, data processing techniques, features set, classifiers, cross-validation methods). Hence, the aim of this study is to propose a fair and unbiased benchmark for the field-based validation of three existing systems, highlighting the gap between laboratory and real-life conditions. For this purpose, three representative state-of-the-art systems are chosen and implemented to classify the physical activities of twenty older subjects (76.4 ± 5.6 years). The performance in classifying four basic activities of daily life (sitting, standing, walking, and lying) is analyzed in controlled and free living conditions. To observe the performance of laboratory-based systems in field-based conditions, we trained the activity classification systems using data recorded in a laboratory environment and tested them in real-life conditions in the field. The findings show that the performance of all systems trained with data in the laboratory setting highly deteriorates when tested in real-life conditions, thus highlighting the need to train and test the classification systems in the real-life setting. Moreover, we tested the sensitivity of chosen systems to window size (from 1 s to 10 s) suggesting that overall accuracy decreases with increasing window size. Finally, to evaluate the impact of the number of sensors on the performance, chosen systems are modified considering only the sensing unit worn at the lower back. The results, similarly to the multi-sensor setup, indicate substantial degradation of the performance when laboratory-trained systems are tested in the real-life setting. This degradation is higher than in the multi-sensor setup. Still, the performance provided by the single-sensor approach, when trained and tested with real data, can be acceptable (with an accuracy above 80%).

Regional specificity of the gut-incretin response to small intestinal glucose infusion in healthy older subjects.

The importance of the region, as opposed to the length, of small intestine exposed to glucose in determining the secretion of the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) remains unclear. We sought to compare the glycemic, insulinemic and incretin responses to glucose administered to the proximal (12-60cm beyond the pylorus), or more distal (>70cm beyond the pylorus) small intestine, or both. 10 healthy subjects (9M,1F; aged 70.3±1.4years) underwent infusion of glucose via a catheter into the proximal (glucose proximally; GP), or distal (glucose distally; GD) small intestine, or both (GPD), on three separate days in a randomised fashion. Blood glucose, serum insulin and plasma GLP-1, GIP and CCK responses were assessed. The iAUC for blood glucose was greater in response to GPD than GP (P<0.05), with no difference between GD and GP. GP was associated with minimal GLP-1 response (P=0.05), but substantial increases in GIP, CCK and insulin (P<0.001 for all). GPD and GD both stimulated GLP-1, GIP, CCK and insulin (P<0.001 for all). Compared to GP, GPD induced greater GLP-1, GIP and CCK responses (P<0.05 for all). Compared with GPD, GD was associated with greater GLP-1 (P<0.05), but reduced GIP and CCK (P<0.05 for both), responses. We conclude that exposure of glucose to the distal small intestine appears necessary for substantial GLP-1 secretion, while exposure of both the proximal and distal small intestine result in substantial secretion of GIP.

Boosting Slow Oscillatory Activity Using tDCS during Early Nocturnal Slow Wave Sleep Does Not Improve Memory Consolidation in Healthy Older Adults.

BACKGROUND: Previous studies have demonstrated an enhancement of hippocampal-dependent declarative memory consolidation, associated slow wave sleep (SWS) and slow wave activity (SWA) after weak slow oscillatory stimulation (so-tDCS) during early non-rapid eye movement sleep (NREM) in young adults. Recent studies in older individuals could not confirm these findings. However, it remained unclear if this difference was due to variations in study protocol or to the age group under study. OBJECTIVE/HYPOTHESIS: Here, we asked if so-tDCS promotes neurophysiological events and associated sleep-dependent memory in the visuo-spatial domain in older adults, using a stimulation protocol that closely resembled the one employed in young adults. METHODS: In a randomized, placebo-controlled single-blind (participant) crossover study so-tDCS (0.75 Hz; max. current density 0.522 mA/cm(2)) vs. sham stimulation was applied over the frontal cortex of 21 healthy older subjects. Impact of stimulation on frequency band activity (linear mixed models), two declarative and one procedural memory tasks (repeated measures ANOVA) and percentage of sleep stages (comparison of means) was assessed. RESULTS: so-tDCS, as compared to sham, increased SWA and spindle activity immediately following stimulation, accompanied by significantly impaired visuo-spatial memory consolidation. Furthermore, verbal and procedural memory remained unchanged, while percentage of NREM sleep stage 4 was decreased over the entire night (uncorrected). CONCLUSION: so-tDCS increased SWA and spindle activity in older adults, events previously associated with stimulation-induced improved consolidation of declarative memories in young subjects. However, consolidation of visuo-spatial (primary outcome) and verbal memories was not beneficially modulated, possibly due to decline in SWS over the entire night that may have prevented and even reversed immediate beneficial effects of so-tDCS on SWA.

Accelerated progression of white matter hyperintensities and subsequent risk of mortality: a 12-year follow-up study.

We examined the association of accelerated progression of white matter hyperintensities (WMH) with mortality outcomes in 534 older subjects at risk for cardiovascular disease. Using brain magnetic resonance imaging, volume of WMH was measured 2 times in an average of 33 months apart. After the second magnetic resonance imaging, occurrence of death was recorded during 12 years of follow-up. In multivariable analyses, each mL/y increase in global WMH was associated with 1.22-fold (95% confidence interval [CI], 1.09-1.37) higher risk of all-cause mortality, 1.29-fold (95% CI, 1.06-1.56) higher risk of cardiovascular mortality, and 1.20-fold (95% CI, 1.02-1.40) higher risk of noncardiovascular mortality. Each mL/y increase in periventricular WMH was associated with 1.22-fold (95% CI, 1.08-37) higher risk of all-cause mortality and 1.24-fold (95% CI, 1.06-1.44) higher risk of noncardiovascular mortality. Conversely, deep cortical WMH was only associated with cardiovascular mortality (1.92-fold, 95% CI, 1.12-3.30). Accelerated progression of WMH is linked with mortality risk in old age. Progression of periventricular WMH associates with noncardiovascular mortality, whereas progression of deep cortical WMH associates with cardiovascular mortality.

DHEA and cognitive function in the elderly.

The adrenal prohormone dehydroepiandrosterone (DHEA) and its sulphate conjugate (DHEAS) steadily decrease with age by 10% per decade reaching a nadir after the age of 80. Both DHEA and DHEAS (DHEA/S) exert many biological activities in different tissues and organs. In particular, DHEA and DHEAS are produced de novo in the brain, hence their classification as neurosteroids. In humans, the brain-to-plasma ratios for DHEA and DHEAS are 4-6.5 and 8.5, respectively, indicating a specific neuroendocrine role for these hormones. DHEA/S stimulates neurite growth, neurogenesis and neuronal survival, apoptosis, catecholamine synthesis and secretion. Together with antioxidant, anti-inflammatory and anti-glucocorticoid properties, it has been hypothesized a neuroprotective effect for DHEA/S. We conducted an accurate research of the literature using PubMed. In the period of time between 1994 and 2013, we selected the observational human studies testing the relationship between DHEA/S and cognitive function in both sexes. The studies are presented according to the cross-sectional and longitudinal design and to the positive or neutral effects on different domains of cognitive function. We also analysed the Clinical Trials, available in the literature, having cognitive domains as the main or secondary outcome. Although the cross-sectional evidence of a positive association between DHEA/S and cognitive function, longitudinal studies and RCTs using DHEA oral treatment (50mg/day) in normal or demented adult-older subjects, have produced conflicting and inconsistent results. In summary, the current data do not provide clear evidence for the usefulness of DHEA treatment to improve cognitive function in adult-older subjects. This article is part of a Special Issue entitled 'Essential role of DHEA'.