Healthy Middle-aged Participants Research Articles

Daily Dynamics of Resting-State Electroencephalographic Theta and Gamma Fluctuations Are Associated With Cognitive Performance in Healthy Aging.

Healthy age-related cognitive changes are highly heterogeneous across individuals. This variability is increasingly explained through the lens of spontaneous fluctuations of brain activity, now considered a powerful index of age-related changes. However, brain activity is a biological process modulated by circadian rhythms, and how these fluctuations evolve throughout the day is under investigation. We analyzed data from 101 healthy late middle-aged participants from the Cognitive Fitness in Aging study (68 women and 33 men; aged 50-69 years). Participants completed 5 electroencephalographic (EEG) recordings of spontaneous resting-state activity on the same day. We used weighted phase-lag index (wPLI) analyses as an index of the functional synchrony between brain regions couplings, and we computed daily global PLI fluctuation rates of the 5 recordings to assess the association with cognitive performance and β-amyloid and tau/neuroinflammation pathological markers. We found that theta and gamma daily fluctuations in the salience-control executive internetwork (SN-CEN) are associated with distinct mechanisms underlying cognitive heterogeneity in aging. Higher levels of SN-CEN theta daily fluctuations appear to be deleterious for memory performance and were associated with higher tau/neuroinflammation rates. In contrast, higher levels of gamma daily fluctuations are positively associated with executive performance and were associated with lower rate of β-amyloid deposition. Thus, accounting for daily EEG fluctuations of brain activity contributes to a better understanding of subtle brain changes underlying individuals' cognitive performance in healthy aging. Results also provide arguments for considering the time of day when assessing cognition for old adults in a clinical context.

The effects of resistance training on denervated myofibers, senescent cells, and associated protein markers in middle-aged adults.

Denervated myofibers and senescent cells are hallmarks of skeletal muscle aging. However, sparse research has examined how resistance training affects these outcomes. We investigated the effects of unilateral leg extensor resistance training (2 days/week for 8 weeks) on denervated myofibers, senescent cells, and associated protein markers in apparently healthy middle-aged participants (MA, 55 ± 8 years old, 17 females, 9 males). We obtained dual-leg vastus lateralis (VL) muscle cross-sectional area (mCSA), VL biopsies, and strength assessments before and after training. Fiber cross-sectional area (fCSA), satellite cells (Pax7+), denervated myofibers (NCAM+), senescent cells (p16+ or p21+), proteins associated with denervation and senescence, and senescence-associated secretory phenotype (SASP) proteins were analyzed from biopsy specimens. Leg extensor peak torque increased after training (p < .001), while VL mCSA trended upward (interaction p = .082). No significant changes were observed for Type I/II fCSAs, NCAM+ myofibers, or senescent (p16+ or p21+) cells, albeit satellite cells increased after training (p = .037). While >90% satellite cells were not p16+ or p21+, most p16+ and p21+ cells were Pax7+ (>90% on average). Training altered 13 out of 46 proteins related to muscle-nerve communication (all upregulated, p < .05) and 10 out of 19 proteins related to cellular senescence (9 upregulated, p < .05). Only 1 out of 17 SASP protein increased with training (IGFBP-3, p = .031). In conclusion, resistance training upregulates proteins associated with muscle-nerve communication in MA participants but does not alter NCAM+ myofibers. Moreover, while training increased senescence-related proteins, this coincided with an increase in satellite cells but not alterations in senescent cell content or SASP proteins. These latter findings suggest shorter term resistance training is an unlikely inducer of cellular senescence in apparently healthy middle-aged participants. However, similar study designs are needed in older and diseased populations before definitive conclusions can be drawn.

Submaximal, Low-Dose Eccentric vs Traditional Cycling Exercise: Reduced Oxygen Uptake and Pulmonary Artery Pressure Assessed by Echocardiography in Healthy Middle-aged Adults. A Randomized Controlled, Crossover Trial

ObjectiveTo investigate the ventilatory and circulatory differences between eccentric (ECC) and concentric (CON) cycling exercise at submaximal, low-dose intensity from onset to end-exercise in healthy middle-aged participants. DesignRandomized controlled crossover trial. SettingThe participants underwent 1 ECC and 1 CON test according to stepwise incremental exercise protocols at identical, submaximal intensities. Breath-by-breath analyses of ventilatory gas exchange and echocardiography were used to assess cardiopulmonary function during exercise. Participants24 healthy middle-aged, untrained participants (14 women, 10 men, 50±14 years) were included. Interventions1 ECC and 1 CON test at submaximal intensities. Main Outcome MeasureThe main outcome was oxygen uptake (V'O2). ResultsThe V'O2 increase was reduced by -422 mL/min (-52%, 95% confidence interval: -513 to -292, P<.001) during ECC, as well as the ventilatory drive. Echocardiographic parameters, heart rate (-14%), cardiac output (-21%), stroke volume (-15%), and pulmonary artery pressure by tricuspid regurgitation pressure gradient (TRPG) (-26%) were also significantly reduced during ECC compared with CON at identical intensities. Participants reported significantly less dyspnea and unchanged perceived leg fatigue in ECC. ConclusionECC was well tolerated, and significant reductions were observed in V'O2, ventilation, and right ventricular load compared with CON, even at low intensity levels. This study, conducted on healthy middle-aged participants, did not raise concerns that would hinder further investigation of the effects of ECC in patients with severely limited cardiopulmonary disease, and it calls for further research on this topic.

Acute Treatment with the Nootropic CILTEP® Does Not Improve Cognitive Performance in Healthy Middle-Aged Participants

This study investigated the acute effects of the dietary nootropic stack CILTEP®. It contains a combination of ingredients that have been individually reported to improve cognitive performance. Especially, the ingredients luteolin, which is considered a phosphodiesterase type 4 (PDE4) inhibitor, and forskolin, an adenylate cyclase stimulator, were of interest since they can increase the second messenger cAMP and thus also intracellular signaling. Numerous studies have shown that inhibition of PDE4 can improve memory in animals and humans. We examined whether acute dosing of 3 capsules of CILTEP® would improve cognitive function in healthy participants aged 30 to 40 (n = 33). We used a randomized, double-blind, placebo-controlled, two-way cross-over design. Our test battery was aimed at measuring memory performance, attention, and sensorimotor speed. The primary outcome measures were the performance on the verbal learning task and the spatial pattern separation task. Secondary outcomes included other cognitive tests, event-related potentials (ERPs), and assessment of the activity of the enzyme beta-glucuronidase and its effect on the bioavailability of luteolin, heart rate, and blood pressure. No relevant effects of acute CILTEP® treatment were found on any measure of the test battery or ERPs. Blood plasma concentrations of luteolin increased, yet about 2000 times too low to likely exert any PDE4 inhibition. CILTEP® treatment did neither affect heart rate nor blood pressure. In summary, there is no evidence that a single standardized dose of 3 capsules of CILTEP® can improve cognitive function in healthy middle-aged participants.

Functional connectivity mediates the relationship between cardiorespiratory fitness and stress in midlife.

BackgroundIncreasing evidence suggests that the relation between mental health and physical health is bidirectional and underpinned by complex neural systems. Cardiovascular fitness is a key measure of physical health but its relation to mental health is insufficiently examined. Characterizing the neural mechanisms by which cardiovascular fitness influences mental health could inform the development of strategies to promote mental health and minimize the risk of mental disorders. Methods and resultsThe relation between cardiorespiratory fitness, functional brain connectivity and mental health was studied in 418 healthy middle-aged (aged 40–65 years) adult participants of the Barcelona Brain Health Initiative (BBHI). Higher cardiorespiratory fitness, measured by VO₂ peak, was associated with lower symptoms of anxiety (β = −0.111, p = 0.017) and stress (β = −0.242, p = 0.002) scores, evaluated by the Depression Anxiety and Stress Scale (DASS-21) and its three subscales (stress, anxiety, and depression). Higher within-network functional connectivity of the Default Mode Network (DMN) was associated with higher VO₂ peak (β = 0.195, p = 0.002), and lower stress scores (β = −0.126, p = 0.011). In addition, higher functional connectivity between the Frontoparietal Network (FPN) and Salience Network (SN) was associated with higher VO₂ peak (β = 0.187, p = 0.002), and lower stress scores (β = −0.123, p = 0.016). Both within-DMN [ACME = −0.02 (-0.04,-0.00), p = 0.040] and between FPN-SN [ACME = −0.01 (-0.04,-0.00), p = 0.036] functional connectivity mediated the relationship between cardiorespiratory fitness and stress. ConclusionsThe relationship between the cardiorespiratory fitness and stress in middle-aged adults is mediated by functional connectivity of several intrinsic resting-state networks. These results highlight a potential mechanistic pathway through which higher cardiorespiratory fitness can positively impact brain health in midlife.

Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial

Many animal studies have shown that oral administration of the nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide mononucleotide (NMN) prevents the reduction of NAD+ levels in organs and tissues, helping alleviate aging-related diseases. However, there are very few clinical reports of NMN supplementation in humans. Thus, this study aimed to investigate the influence of a 12-week NMN oral supplementation on biochemical and metabolic health parameters. A 12-week randomized, double-blind, placebo-controlled, parallel-group clinical trial was conducted. A total of 36 healthy middle-aged participants received one capsule of either 125 mg NMN or placebo twice a day. Among the NAD+ metabolites, the levels of nicotinamide in the serum were significantly higher in the NMN intake group than in the placebo group. Pulse wave velocity values indicating arterial stiffness tended to decrease in the NMN intake group. However, no significant difference was found between the two groups. Long-term NMN supplementation at 250 mg/day was well tolerated and did not cause adverse events. NMN safely and effectively elevated NAD+ metabolism in healthy middle-aged adults. Additionally, NMN supplementation showed potential in alleviating arterial stiffness.

Age- and sex-related differences in cortical morphology and their relationships with cognitive performance in healthy middle-aged and older adults.

The impacts of age and sex on brain structures related to cognitive function may be important for understanding the role of aging in Alzheimer disease for both sexes. We intended to investigate the age and sex differences of cortical morphology in middle-aged and older adults and their relationships with the decline of cognitive function. In this cross-sectional study, we examined the cortical morphology in 204 healthy middle-aged and older adult participants aged 45 to 89 years using structural magnetic resonance imaging (sMRI) data from the Dallas Lifespan Brain Study data set. Brain cortical thickness, surface complexity, and gyrification index were analyzed through a completely automated surface-based morphometric analysis using the CAT12 toolbox. Furthermore, we explored the correlation between cortical morphology differences and test scores for processing speed and working memory. There were no significant interactions of age and sex with cortical thickness, fractal dimension, or gyrification index. Rather, we found that both males and females showed age-related decreases in cortical thickness, fractal dimension, and gyrification index. There were significant sex differences in the fractal dimension in middle-aged participants and the gyrification index in older adult participants. In addition, there were significant positive correlations between the cortical thickness of the right superior frontal gyrus and Wechsler Adult Intelligence Scale (WAIS)-III Letter-Number Sequencing test scores in males (r=0.394; P<0.001; 95% CI for r values 0.216-0.577) and females (r=0.344; P<0.001; 95% CI for r values 0.197-0.491), respectively. Furthermore, a significant relationship between the gyrification index of the right supramarginal gyrus (SupraMG) and WAIS-III Digit Symbol test scores was observed in older adult participants (r=0.375; P<0.001; 95% CI for r values 0.203-0.522). The results suggest that, compared with males, females have more extensive differences in cortical morphology. The gyrification index of the right SupraMG can be used as an imaging marker of sexual cognitive differences between males and females in older adults. This study helps to further understand sex differences in the aging of the brain and cognition.

Adaptive working memory training does not produce transfer effects in cognition and neuroimaging

Despite growing interest in cognitive interventions from academia and industry, it remains unclear if working memory (WM) training, one of the most popular cognitive interventions, produces transfer effects. Transfer effects are training-induced gains in performance in untrained cognitive tasks, while practice effects are improvements in trained task. The goal of this study was to evaluate potential transfer effects by comprehensive cognitive testing and neuroimaging. In this prospective, randomized-controlled, and single-blind study, we administered an 8-week n-back training to 55 healthy middle-aged (50–64 years) participants. State-of-the-art multimodal neuroimaging was used to examine potential anatomic and functional changes. Relative to control subjects, who performed non-adaptive WM training, no near or far transfer effects were detected in experimental subjects, who performed adaptive WM training. Equivalently, no training-related changes were observed in white matter integrity, amplitude of low frequency fluctuations, glucose metabolism, functional and metabolic connectivity. Exploratory within-group comparisons revealed some gains in transfer tasks, which, however, cannot be attributed to an increased WM capacity. In conclusion, WM training produces transfer effects neither at the cognitive level nor in terms of neural structure or function. These results speak against a common view that training-related gains reflect an increase in underlying WM capacity. Instead, the presently observed practice effects may be a result of optimized task processing strategies, which do not necessarily engage neural plasticity.

The Role of Working Memory, Short-Term Memory, Speed of Processing, Education, and Locality in Verb-Related Morphosyntactic Production: Evidence From Greek.

This study investigates the relationship between verb-related morphosyntactic production (VRMP) and locality (i.e., critical cue being adjacent to the target or not), verbal Working Memory (vWM), nonverbal/visuospatial WM (nvWM), verbal short-term memory (vSTM), nonverbal/visuospatial STM (nvSTM), speed of processing, and education. Eighty healthy middle-aged and older Greek-speaking participants were administered a sentence completion task tapping into production of subject–verb Agreement, Time Reference/Tense, and grammatical Aspect in local and nonlocal configurations, and cognitive tasks tapping into vSTM, nvSTM, vWM, nvWM, and speed of processing. Aspect elicited worse performance than Time Reference and Agreement, and Time Reference elicited worse performance than Agreement. There were main effects of vSTM, vWM, education, and locality: the greater the participants’ vSTM/vWM capacity, and the higher their educational level, the better their VRMP; nonlocal configurations elicited worse performance on VRMP than local configurations. Moreover, vWM affected Aspect and Time Reference/Tense more than Agreement, and education affected VRMP more in local than in nonlocal configurations. Lastly, locality affected Agreement and Aspect (with nonlocal configurations eliciting more agreement and aspect errors than local configurations) but not Time Reference. That vSTM/vWM (but not nvSTM/nvWM) were found to subserve VRMP suggests that VRMP is predominantly supported by domain-specific, not by domain-general, memory resources. The main effects of vWM and vSTM suggest that both the processing and storage components of WM are relevant to VRMP. That vWM (but not vSTM) interacts with production of Aspect, Time Reference, and Agreement suggests that Aspect and Time Reference are computationally more demanding than Agreement. These findings are consistent with earlier findings that, in individuals with aphasia, vWM interacts with production of Aspect, Time Reference, and Agreement. The differential effect of education on VRMP in local vs. nonlocal configurations could be accounted for by assuming that education is a proxy for an assumed procedural memory system that is sensitive to frequency patterns in language and better supports VRMP in more frequent than in less frequent configurations. In the same vein, the interaction between locality and the three morphosyntactic categories might reflect the statistical distribution of local vs. nonlocal Aspect, Agreement, and Time Reference/Tense in Greek.

Abstract WMP20: Association Of Periventricular And Deep White Matter Hyperintensity With Cognitive Performance In A Middle-aged Population

Introduction: White matter hyperintensity (WMH) has been associated with manual dexterity performance in apparently healthy middle-aged population. However, the relative effect of WMH topographic distribution on cognition remains unknown. We hypothesized that periventricular WMH (PVWMH) is more strongly associated with manual dexterity and cognitive measures compared to deep WMH (DWMH) given its proximity to the white matter tracts involved in motor and executive functions. Methods: Apparently healthy middle-aged participants in the Genetic Study of Atherosclerosis Risk with brain MRI and cognitive measurements were selected. Cognitive measures included delayed word recall short (DWRS) and long (DWRL), digit symbol substitution (DSS), word fluency (WF), digit span forward test (DSFT), backward (DSBT) and total (DSTS), and grooved peg board test (GPBT) including the dominant and non-dominant hand (GPBTD, GPBTnD). PVWMH and DWMH volumes were measured using semi-automated segmentation paradigm. The relative associations of these measurements with PVWMH and DWMH volumes as multiple measurements within the same individual further nested within families were determined using multilevel linear models adjusting for intracranial volume, age, sex and cardiovascular risk factors. Results: 782 subjects were included (age 51.1±10.6, 58.4% female and 39% African American, PVWMH volume 437.4 [0-1646] mm 3 , DWMH volume 273.5 [76-665] mm 3 ). Within the same subject, PVWMH showed greater association than DWMH with worse performance on GPBT, GPBTD, GPBTnD, DWRS, and DWRL (P=0.006, 0.01, 0.01, 0.01 and 0.03, respectively) after adjusting for age and other cardiovascular risk factors. There was no difference in the association of PVWMH versus DWMH volumes with DSS, WF, DSFT, DSBT, DSTS (P=0.19, 0.52, 0.13, 0.6, and 0.6, respectively). Conclusions: PVWMH shows greater association than DWMH with cognitive measures of manipulative manual dexterity and recall suggesting that PVWMH and DWMH may have different cognitive phenotypes in middle-aged population with cerebral small vessel disease.

Vitamin D Deficiency Is a Potential Risk for Blood Pressure Elevation and the Development of Hypertension.

Background and objectives: Hypertension is a global health problem and a major risk factor for cardiovascular diseases. Vitamin D deficiency is closely related to high blood pressure and the development of hypertension. This study investigated the relationship between the vitamin D and blood pressure status in healthy adults, and their 8-year follow-up was added. Materials and Methods: A total of 491 healthy middle-aged participants without any chronic illness, ages 21 to 67 at baseline, were divided into two groups as non-optimal blood pressure (NOBP) and optimal blood pressure (OBP). NOBP group was divided into two subgroups: normal (NBP) and high normal blood pressure (HNBP). Serum 25-hydroxy vitamin D levels were measured with the immunoassay method. 8-year follow-up of the participants was added. Results: The average vitamin D level was detected 32.53 ± 31.50 nmol/L in the OBP group and 24.41 ± 14.40 nmol/L in the NOBP group, and a statistically significant difference was found (p < 0.001). In the subgroup analysis, the mean vitamin D level was detected as 24.69 ± 13.74 and 24.28 ± 14.74 nmol/L in NBP and HNBP, respectively. Together with parathyroid hormone, other metabolic parameters were found to be significantly higher in the NOBP. During a median follow-up of 8 years, higher hypertension development rates were seen in NOBP group (p < 0.001). Conclusions: The low levels of vitamin D were significantly associated with NBP and HNBP. The low levels of vitamin D were also associated with the development of hypertension in an 8-year follow-up.

Plasma trimethylamine N-oxide (TMAO) levels predict future risk of coronary artery disease in apparently healthy individuals in the EPIC-Norfolk prospective population study

BackgroundRecent studies show a mechanistic link between gut microbiota-dependent formation of the atherosclerosis- and thrombosis-promoting metabolite trimethylamine N-oxide (TMAO) and cardiovascular disease (CVD). The clinical utility of TMAO in apparently healthy subjects for predicting incident CVD risks is unclear. Methods and ResultsIn the EPIC-Norfolk community-based study, we examined baseline fasting levels of TMAO and two of its nutrient precursors, choline and betaine, in a case:control design study comparing apparently European healthy middle-aged participants who subsequently develop CVD (Cases, n = 908) vs those who did not (Controls, n = 1,273) over an ensuing average follow-up period of 8 years. In participants who developed CVD vs controls, higher plasma TMAO (3.70 [IQR 2.50-6.41]μM vs 3.25 [IQR 2.19-52,1.15]μM; P < .001) and choline levels (9.09 [IQR 7.87-10.53]μM vs 8.89 [IQR 7.66-10.13]μM; P = .001) were observed. Following adjustments for traditional risk factors, elevated TMAO (adjusted odds ratio (OR) 1.58 [95% confidence interval (CI) 1.21-2.06], P < .001) and choline levels (adjusted OR 1.31 [95%CI 1.00-1.72], P < .05) remained predictive of incident CVD development. The clinical prognostic utility of TMAO remained significant and essentially unchanged regardless of the level of cutoff chosen between 1.5 uM (10%ile) to 10.5 uM (90%ile). ConclusionIn apparently healthy participants of the community-based middle-aged EPIC-Norfolk population, elevated plasma levels of the gut microbe-dependent metabolite TMAO, and its nutrient precursor choline, predict incident risk for CVD development independent of traditional risk factors.

Higher midlife CAIDE score is associated with increased brain atrophy in a cohort of cognitively healthy middle-aged individuals

BackgroundStructural brain changes associated with Alzheimer’s disease (AD) can occur decades before the onset of symptoms. The Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) score has been suggested to be associated with accelerated brain atrophy in middle-aged subjects but the regional specificity of atrophic areas remains to be elucidated.Methods3T T1-weighted magnetic resonance imaging scans of 160 cognitively healthy middle-aged participants (mean age = 52) in the PREVENT-Dementia cohort, from baseline and from follow-up after 2 years, were examined. Images were preprocessed using Computational Anatomy Toolbox 12. Voxel-based morphometry was performed in FSL 6.0.1 to identify areas of grey matter (GM) volume differences both cross-sectionally and longitudinally between subjects with high and low baseline CAIDE score (CAIDE score was dichotomized at cohort-median). A GM percentage of change map was created for each subject for evaluation of atrophy over 2 years. Analyses were adjusted for age, gender, education and total intracranial volume.ResultsCompared to subjects with CAIDE score ≤ 6 (low risk), subjects with CAIDE score > 6 (high risk) showed lower GM volume in the temporal, occipital, and fusiform cortex and lingual gyrus at baseline, and greater percentage of GM loss over 2 years in the supramarginal gyrus, angular gyrus, precuneus, lateral occipital cortex, superior parietal lobule and cingulate gyrus (corrected P < 0.05).ConclusionThis study demonstrated accelerated GM atrophy concentrated in several AD signature cortical regions in healthy middle-aged subjects with high CAIDE scores.

Adoption of a new gait system to evaluate the clinical effects of minimally invasive needle-knife scope therapy for the treatment of rheumatoid arthritis of the knee joint.

The purpose of this study was to use kinematic gait analysis, to evaluate the clinically curative effects of minimally invasive needle-knife scope therapy in the treatment of rheumatoid arthritis (RA) of the knee joint. A total of 32 patients with RA of the knee joint were treated with minimally invasive needle-knife scope therapy. All patients were assessed with a kinematic gait analysis system, and then analyzed and compared the measurements with the kinematic gait performances of 28 healthy middle-aged and elderly participants. Before receiving the therapy, the ranges of motion (ROMs) of the patients' tibial inward and outward rotation, flexion and extension, anterior and posterior displacement of the tibia, and tibial upward and downward movement were all smaller than those of the healthy middle-aged and elderly group (P<0.05). After receiving the therapy, the patients' knees had a remarkably larger ROM. After one month of this therapy, they had a noticeably greater ROM in flexion and extension, tibial inward and outward rotation, and upward and downward movement of the tibia (P<0.05). After 1 month of therapy, the patients' maximum flexion angle and tibial posterior displacement angle were noticeably greater than beforehand (P<0.01). After 1 year of therapy, the patients' flexion and extension range became remarkably greater than it was after 1 month of the therapy (P<0.01). Their ranges of DOF reflected no apparent difference to the healthy middle-aged and elderly group, which remained smaller than the latter (P<0.05). After 1 year of therapy, the maximum values of the patients' flexion angle, tibial internal rotation angle, tibial posterior displacement angle, and tibial downward movement angle were remarkably higher than before commencing treatment (P<0.05). Minimally invasive needle-knife scope therapy enables a good recovery of function for patients with RA and remarkably improves the DOF of knees. Gait analyses are more objective, accurate, and quantitative than other indexes, and thus may become a new means to assess the changes in knee joint functions.

Association of sleep spindle characteristics with executive functioning in healthy sedentary middle-aged and older adults.

To determine the relationship between sleep spindle characteristics (density, power and frequency), executive functioning and cognitive decline in older adults, we studied a convenience subsample of healthy middle-aged and older participants of the Brain in Motion study. Participants underwent a single night of unattended in-home polysomnography with neurocognitive testing carried out shortly afterwards. Spectral analysis of the EEG was performed to derive spindle characteristics in both central and frontal derivations during non-rapid eye movement (NREM) Stage 2 and 3. Multiple linear regressions were used to examine associations between spindle characteristics and cognitive outcomes, with age, body mass index (BMI), periodic limb movements index (PLMI) and apnea hypopnea index (AHI) as covariates. NREM Stage 2 total spindle density was significantly associated with executive functioning (central: β=.363, p=.016; frontal: β=.408, p=.004). NREM Stage 2 fast spindle density was associated with executive functioning (central: β=.351, p=.022; frontal: β=.380, p=.009) and Montreal Cognitive Assessment score (MoCA, central: β=.285, p=.037; frontal: β=.279, p=.032). NREM Stage 2 spindle frequency was also associated with MoCA score (central: β=.337, p=.013). Greater spindle density and fast spindle density were associated with better executive functioning and less cognitive decline in our study population. Our cross-sectional design cannot infer causality. Longitudinal studies will be required to assess the ability of spindle characteristics to predict future cognitive status.

Cognitive efficiency in late midlife is linked to lifestyle characteristics and allostatic load.

We investigated whether cognitive fitness in late midlife is associated with physiological and psychological factors linked to increased risk of age-related cognitive decline. Eighty-one healthy late middle-aged participants (mean age: 59.4 y; range: 50-69 y) were included. Cognitive fitness consisted of a composite score known to be sensitive to early subtle cognitive change. Lifestyle factors (referenced below as cognitive reserve factors; CRF) and affective state were determined through questionnaires, and sleep-wake quality was also assessed through actimetry. Allostatic load (AL) was determined through a large range of objective health measures. Generalized linear mixed models, controlling for sex and age, revealed that higher cognitive reserve and lower allostatic load are related to better cognitive efficiency. Crystallized intelligence, sympathetic nervous system functioning and lipid metabolism were the only sub-fields of CRF and AL to be significantly associated with cognition. These results show that previous lifestyle characteristics and current physiological status are simultaneously explaining variability in cognitive abilities in late midlife. Results further encourage early multimodal prevention programs acting on both of these modifiable factors to preserve cognition during the aging process.

Comparative Effect of a Balance Training Program and Core Stabilization Program on Factors Related to the Prevention of Falling in Healthy Middle-Aged Individuals: A Double-Blind Randomized Controlled Clinical Trial

Objectives: The aim of this study to compare the effectiveness of the balance training program (BTP), and the corestabilization program (CSP), on dynamic balance in healthy middle-aged individuals.Material and Methods: This study was a single-blind randomized controlled trial design. Forty-two healthy middle-aged participants were randomly assigned to the BTP group (n=21), or the CSP group (n=21). Participants in both groups received an intervention program (balance training or core stabilization) 3 times a week, for 60 minutes, over 6 weeks. The primary outcome was the dynamic balance measured by the timed up and go test. The other outcomes were: core muscle endurance, muscle strength of the lower extremities, the flexibility of the lower back and hamstring muscles, and gait variables. The measurements included: the prone bridge endurance test, 5 times sit to stand test, sit and reach test and a wireless movement monitoring inertial sensor system, respectively. All outcomes were measured at baseline, and then after 6 weeks. The data were analyzed by the Independent Sample t-test between groups, and the paired t-test within either group.Results: After 6 weeks, there was no statistically significant difference between the groups in either dynamic balance,or other variables, however, a statistically significant difference was found in core muscle endurance (p-value=0.003). In so saying, the BTP group, statistically significant improvements were found only in core muscle endurance, the flexibility of the lower back and hamstring muscles, and gait variables from pre- to post-test. Moreover, in the CSP group, there was a statistically significant difference from pre- to post-test in all measured outcomes. Conclusion: The Core stabilization program is not superior to a balance training program, for the improvement of dynamic balance. Although, after 6 weeks of training, the study found that the Core stabilization program was effective for improving dynamic balance. This finding may point out that the Core stabilization program helps improve balance in a middle-aged person

The effects of low-volume high-intensity interval training and circuit training on maximal oxygen uptake

PurposeHigh-intensity interval training (HIIT) and circuit training (CT) are popular methods of exercise, eliciting improvements in cardiorespiratory fitness (CRF). However, direct comparisons of these two training methods are limited. We investigated the effects of HIIT and CT on CRF.MethodsThirty-nine apparently healthy middle-aged participants [HIIT; mean age: 42.5 ± 12.3; dot{V}{text{O}}_{2hbox{max} } 31.5 ± 7.1 (ml kg−1 min−1); 52% males; CT; mean age: 41.2 ± 12.9; dot{V}{text{O}}_{2hbox{max} } 31.4 ± 6.8 (ml kg−1 min−1); 57% males] were randomly allocated to two sessions per week of HIIT or CT over 8 weeks. HIIT performed ten 1-min cycle-ergometry intervals at > 85% HRmax, separated by ten 1-min intervals of active recovery. The CT group performed up to 40-min of CT at 60–80% HRmax. CRF was measured using maximum oxygen uptake (dot{V}{text{O}}_{2hbox{max} }), ventilatory anaerobic threshold (dot{V}{text{O}}_{2} at VAT) and maximum oxygen pulse (dot{V}{text{O}}_{2}/HR).Resultsdot{V}{text{O}}_{2hbox{max} } increased by 12% following HIIT (mean difference 3.9 ml kg−1 min−1; 95% CI: 2.8–4.9; P < 0.001), and 3% in CT (mean difference 1.0 ml kg−1 min−1; 95% CI: − 0.4 to 2.0; P = 0.060). dot{V}{text{O}}_{2} at VAT increased by 16% following HIIT (mean difference 2.4 ml kg−1 min−1; 95% CI: 1.6–3.1; P < 0.001) and 4% in CT (mean difference 0.7 ml kg−1 min−1; 95% CI: − 0.1 to 1.4; P = 0.085). dot{V}{text{O}}_{2}/HR increased by 11% following HIIT (mean difference 1.4 ml beat−1; 95% CI: 0.9–2.0; P < 0.001) and 1% after CT (mean difference 0.3 ml beat−1; 95% CI: − 0.3 to 0.8; P = 0.318).ConclusionOur study demonstrated that HIIT led to greater improvements in CRF when compared to CT.Clinical trial registrationClinicalTrials.gov Identifier: NCT03700671.

Plasma kidney injury molecule-1 (p-KIM-1) levels and deterioration of kidney function over 16 years.

BackgroundThe kidney injury molecule-1 (KIM-1) has previously been associated with kidney function in rodents and humans. Yet its role as a predictive marker for future decline in kidney function has remained less clear.MethodsAt baseline (1991–1994), fasting plasma KIM-1 (p-KIM-1) was measured in 4739 participants of the population-based Malmö Diet and Cancer Study. Creatinine and cystatin C were used to calculate estimated glomerular filtration rate (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Collaboration 2012 creatinine–cystatin C equation at baseline and follow-up examination (2007–2012). Incident CKD was defined as an eGFR <60 mL/min/1.73 m2 at follow-up.ResultsDuring a mean follow-up time of 16.6 years, high p-KIM-1 levels were associated with a greater decline in eGFR (quartile 1 −1.36 versus quartile 4 −1.54 mL/min/1.73 m2; P < 0.001). In multivariate analyses, the risk for incident CKD at the follow-up examination was higher among participants with baseline p-KIM-1 levels in the highest quartile {odds ratio [OR] 1.45 [95% confidence interval (CI) 1.10–1.92]} compared with those within the lowest quartile. The relative impact of baseline p-KIM-1 on incidence of CKD [OR 1.20 (95% CI 1.08–1.33) per 1 standard deviation (SD) increase in p-KIM-1] was comparable to those of age and systolic blood pressure (SBP) [OR 1.55 (95% CI 1.38–1.74) and OR 1.21 (95% CI 1.09–1.35) per 1 SD increase, respectively]. Adding p-KIM-1 to a conventional risk model resulted in significantly improved C-statistics (P = 0.04) and reclassified 9% of the individuals into the correct risk direction (continuous net reclassification improvement P = 0.02). Furthermore, the risk for hospitalization due to impaired renal function increased with increasing baseline p-KIM-1 [hazard ratio per 1 SD 1.43; (95% CI 1.18–1.74)] during a mean follow-up time of 19.2 years.ConclusionOur results show that p-KIM-1 predicts the future decline of eGFR and risk of CKD in healthy middle-aged participants. Whether p-KIM-1 can be used to prioritize preventive action that needs to be further investigated.

Interactive effect of age and APOE-ε4 allele load on white matter myelin content in cognitively normal middle-aged subjects.

The apolipoprotein E gene (APOE) ε4 allele has a strong and manifold impact on cognition and neuroimaging phenotypes in cognitively normal subjects, including alterations in the white matter (WM) microstructure. Such alterations have often been regarded as a reflection of potential thinning of the myelin sheath along axons, rather than pure axonal degeneration. Considering the main role of APOE in brain lipid transport, characterizing the impact of APOE on the myelin coating is therefore of crucial interest, especially in healthy APOE-ε4 homozygous individuals, who are exposed to a twelve-fold higher risk of developing Alzheimer's disease (AD), compared to the rest of the population.We examined T1w/T2w ratio maps in 515 cognitively healthy middle-aged participants from the ALFA study (ALzheimer and FAmilies) cohort, a single-site population-based study enriched for AD risk (68 APOE-ε4 homozygotes, 197 heterozygotes, and 250 non-carriers). Using tract-based spatial statistics, we assessed the impact of age and APOE genotype on this ratio taken as an indirect descriptor of myelin content.Healthy APOE-ε4 carriers display decreased T1w/T2w ratios in extensive regions in a dose-dependent manner. These differences were found to interact with age, suggesting faster changes in individuals with more ε4 alleles.These results obtained with T1w/T2w ratios, confirm the increased vulnerability of WM tracts in APOE-ε4 healthy carriers. Early alterations of myelin content could be the result of the impaired function of the ε4 isoform of the APOE protein in cholesterol transport. These findings help to clarify the possible interactions between the APOE-dependent non-pathological burden and age-related changes potentially at the source of the AD pathological cascade.