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In this paper, we measured B cell function in elderly healthy individuals (EH) and in elderly patients with Type-2 Diabetes Mellitus (T2DM, ET2DM), which are treatment-naive, as compared to healthy young (YH) individuals. Results show a higher serum inflammatory status of elderly versus young individuals, and especially of ET2DM versus EH. This status is associated with a reduced response to the seasonal influenza vaccine and with increased frequencies of the circulating pro-inflammatory B cell subset called Double Negative (DN) B cells. B cells from ET2DM patients are not only more inflammatory but also hyper-metabolic as compared to those from EH controls. The results herein are to our knowledge the first to show that T2DM superimposed on aging further increases systemic and B cell intrinsic inflammation, as well as dysfunctional humoral immunity. Our findings confirm and extend our previously published findings showing that inflammatory B cells are metabolically supported. [ABSTRACT FROM AUTHOR]

Backgrounds: Freezing of gait (FoG) is a common and debilitating symptom of Parkinson's disease (PD) that can lead to falls and reduced quality of life. Wearable sensors have been used to detect FoG, but current methods have limitations in accuracy and practicality. In this paper, we aimed to develop a deep learning model using pressure sensor data from wearable insoles to accurately detect FoG in PD patients. Methods: We recruited 14 PD patients and collected data frommultiple trials of a standardized walking test using the Pedar insole system. We proposed temporal convolutional neural network (TCNN) and applied rigorous data filtering and selective participant inclusion criteria to ensure the integrity of the dataset. We mapped the sensor data to a structured matrix and normalized it for input into our TCNN. We used a train-test split to evaluate the performance of the model. Results: We found that TCNN model achieved the highest accuracy, precision, sensitivity, specificity, and F1 score for FoG detection compared to othermodels. The TCNN model also showed good performance in detecting FoG episodes, even in various types of sensor noise situations. Conclusions: We demonstrated the potential of using wearable pressure sensors andmachine learningmodels for FoG detection in PD patients. The TCNNmodel showed promising results and could be used in future studies to develop a real-time FoG detection system to improve PD patients' safety and quality of life. Additionally, our noise impact analysis identifies critical sensor locations, suggesting potential for reducing sensor numbers. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer’s disease (AD) and Type 2 diabetes (T2D) are both ageassociated diseases. Identification of shared genes could help develop early diagnosis and preventive strategies. Although genetic background plays a crucial role in these diseases, we noticed an underrepresentation tendency of North African populations in omics studies. Materials and methods: First, we conducted a comprehensive review of genes and pathways shared between T2D and AD through PubMed. Then, the function of the identified genes and variants was investigated using annotation tools including PolyPhen2, RegulomeDB, and miRdSNP. Pathways enrichment analyses were performed with g:Profiler and EnrichmentMap. Next, we analyzed variant distributions in 16 worldwide populations using PLINK2, R, and STRUCTURE software. Finally, we performed an inter-ethnic comparison based on the minor allele frequency of T2D-AD common variants. Results: A total of 59 eligible papers were included in our study. We found 231 variants and 363 genes shared between T2D and AD. Variant annotation revealed six single nucleotide polymorphisms (SNP) with a high pathogenic score, three SNPs with regulatory effects on the brain, and six SNPs with potential effects on miRNA-binding sites. The miRNAs affected were implicated in T2D, insulin signaling pathways, and AD. Moreover, replicated genes were significantly enriched in pathways related to plasma protein binding, positive regulation of amyloid fibril deposition, microglia activation, and cholesterol metabolism. Multidimensional screening performed based on the 363 shared genes showed that main North African populations are clustered together and are divergent from other worldwide populations. Interestingly, our results showed that 49 SNP associated with T2D and AD were present in North African populations. Among them, 11 variants located in DNM3, CFH, PPARG, ROHA, AGER, CLU, BDNF1, CST9, and PLCG1 genes display significant differences in risk allele frequencies between North African and other populations. Conclusion: Our study highlighted the complexity and the unique molecular architecture of North African populations regarding T2D-AD shared genes. In conclusion, we emphasize the importance of T2D-AD shared genes and ethnicity-specific investigation studies for a better understanding of the link behind these diseases and to develop accurate diagnoses using personalized genetic biomarkers. [ABSTRACT FROM AUTHOR]

Monitoring early changes in cognitive performance is useful for studying cognitive aging as well as for detecting early markers of neurodegenerative diseases. Repeated evaluation of cognition via a measurement burst design can accomplish this goal. In such design participants complete brief evaluations of cognition, multiple times per day for several days, and ideally, repeat the process once or twice a year. However, long-term cognitive change in such repeated assessments can be masked by short-term within-person variability and retest learning (practice) effects. In this paper, we show how a Bayesian double exponential model can account for retest gains across measurement bursts, as well as warm-up effects within a burst, while quantifying change across bursts in peak performance. We also highlight how this approach allows for the inclusion of person-level predictors and draw intuitive inferences on cognitive change with Bayesian posterior probabilities. We use older adults' performance on cognitive tasks of processing speed and spatial working memory to demonstrate how individual differences in peak performance and change can be related to predictors of aging such as biological age and mild cognitive impairment status. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of Alzheimer’s disease (AD) and other dementias is increasing; therefore, identifying individuals at risk for dementia is crucial. Traditional neuropsychological assessments are expensive and time-consuming; however, computerized cognitive testing is becoming popular in clinical and research settings, particularly during the COVID-19 pandemic. This study aimed to investigate the correlation between the computerized cognitive test, Inbrain cognitive screening test (CST), and the traditional neuropsychological battery, the consortium to establish a registry for Alzheimer’s disease assessment packet (CERAD-K). Methods: We enrolled 166 participants from five districts in Republic of Korea, including cognitively unimpaired individuals and those with mild cognitive impairment (MCI) diagnosed by experienced neurologists. We used the Inbrain CST and CERAD-K to evaluate the cognitive function of the participants, and the scores of each subtest of the Inbrain CST and CERAD-K were compared. Results: A significant correlation was found between the Inbrain CST and CERADK subtests. Furthermore, multivariate analysis revealed a significant correlation between the Inbrain CST and the CERAD-K test pairs after adjusting for age, educational level, and sex. Discussion: In conclusion, this study demonstrates that the Inbrain CST is a reliable tool for detecting cognitive impairment in cognitively unimpaired individuals and patients with MCI, because it has a high correlation and agreement with CERAD-K. Therefore, the Inbrain CST can be a useful, time-efficient, and cost-effective computer-based cognitive test for individuals at risk for cognitive impairment. [ABSTRACT FROM AUTHOR]

Postoperative cognitive dysfunction (POCD) poses a significant threat to patients undergoing anesthesia and surgery, particularly elderly patients. It is characterized by diminished cognitive functions post surgery, such as impaired memory and decreased concentration. The potential risk factors for POCD include age, surgical trauma, anesthetic type, and overall health condition; however, the precise mechanisms underlying POCD remain elusive. Recent studies suggest that neuroinflammation might be a primary pathogenic factor. NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasomes are implicated in exacerbating POCD by promoting the release of inflammatory factors and proteins that initiate pyroptosis, further influencing the disease process. The regulation of NLRP3 inflammasome activity, including its activation and degradation, is tightly controlled through multiple pathways and mechanisms. In addition, autophagy, a protective mechanism, regulates the NLRP3 inflammasome to control the progression of POCD. This review reviews recent findings on the role of the NLRP3 inflammasome in POCD pathogenesis and discusses therapeutic strategies aimed at reducing NLRP3 sources, inhibiting cellular pyroptosis, and enhancing autophagy. [ABSTRACT FROM AUTHOR]

Overweight, defined by a body mass index (BMI) between 25 and 30, has been associated with enhanced survival among older adults in some studies. However, whether being overweight is causally linked to longevity remains unclear. To investigate this, we conducted a Mendelian randomization (MR) study of lifespan 85+ years, using overweight as an exposure variable and data from the Health and Retirement Study and the Long Life Family Study. An essential aspect of MR involves selecting appropriate single nucleotide polymorphisms (SNPs) as instrumental variables (IVs). This is challenging due to the limited number of SNP candidates within biologically relevant genes that can satisfy all necessary assumptions and criteria. To address this challenge, we employed a novel strategy of creating additional IVs by pairing SNPs between candidate genes. This strategy allowed us to expand the pool of IV candidates with new "composite" SNPs derived from eight candidate obesity genes. Our study found that being overweight between ages 75 and 85, compared to having a normal weight (BMI 18.5-24.9), significantly contributes to improved survival beyond age 85. Results of this MR study thus support a causal relationship between overweight and longevity in older adults. [ABSTRACT FROM AUTHOR]

Background: Limbic structures have recently garnered increased attention in Parkinson's disease (PD) research. This study aims to explore changes at the whole-brain level in the structural network, specifically the white matter fibres connecting the thalamus and limbic system, and their correlation with the clinical characteristics of patients with PD. Methods: Between December 2020 and November 2021, we prospectively enrolled 42 patients with PD and healthy controls at the movement disorder centre. All participants underwent diffusion tensor imaging (DTI), 3D T1- weighted imaging (3D-T1WI), and routine brain magnetic resonance imaging on a 3.0 T MR scanner. We employed the tract-based spatial statistical (TBSS) analytic approach, examined structural network properties, and conducted probabilistic fibre tractography to identify alterations in white matter pathways and the topological organisation associated with PD. Results: In patients with PD, significant changes were observed in the fibrous tracts of the prefrontal lobe, corpus callosum, and thalamus. Notably, the fibrous tracts in the prefrontal lobe and corpus callosum showed a moderate negative correlation with the Freezing of Gait Questionnaire (FOG-Q) scores (r = -0.423, p = 0.011). The hippocampus and orbitofrontal gyrus exhibited more fibre bundle parameter changes than other limbic structures. The mean streamline length between the thalamus and the orbitofrontal gyrus demonstrated a moderate negative correlation with Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III (r = -0.435, p = 0.006). Topological parameters, including characteristic path length (Lp), global efficiency (Eg), normalised shortest path length (λ) and nodal local efficiency (Nle), correlated moderately with the MDS-UPDRS, HAMA, MoCA, PDQ-39, and FOG-Q, respectively. Conclusion: DTI is a valuable tool for detecting changes in water molecule dispersion and the topological structure of the brain in patients with PD. The thalamus may play a significant role in the gait abnormalities observed in PD. [ABSTRACT FROM AUTHOR]

Background: Drawing on prospective data from the National Health and Nutrition Examination Survey (NHANES), our goal was to construct and validate a 5-year survival prediction model for individuals with cognitive impairment (CI). Methods: This study entailed a prospective cohort design utilizing information from the 2011-2014 NHANES dataset, encompassing individuals aged 40 years or older, with updated mortality status as of December 31, 2019. Predictive models within the derivation and validation cohorts were assessed using logistic proportional risk regression, column-line plots, and least absolute shrinkage and selection operator (LASSO) binomial regression models. Results: The study enrolled a total of 1,439 participants (677 men, mean age 69.75 ± 6.71 years), with the derivation and validation cohorts consisting of 1,007 (538 men) and 432 (239 men) individuals, respectively. The 5-year mortality rate stood at 16.12% (n = 232). We devised a 5-item column-line graphical model incorporating age, race, stroke, cardiovascular disease (CVD), and blood urea nitrogen (BUN). The model exhibited an area under the curve (AUC) of 0.772 with satisfactory calibration. Internal validation demonstrated that the column-line graph model displayed strong discrimination, yielding an AUC of 0.733, and exhibited good calibration. Conclusion: To sum up, our study successfully developed and internally validated a 5-item nomogram integrating age, race, stroke, cardiovascular disease, and blood urea nitrogen. This nomogram exhibited robust predictive performance for 5-year mortality in individuals with CI, offering a valuable tool for prognostic evaluation and personalized care planning. [ABSTRACT FROM AUTHOR]

Background: Patients with carotid atherosclerotic stenosis (CAS) often have varying degrees of cognitive decline. However, there is little evidence regarding how brain morphological and functional abnormalities impact the cognitive decline in CAS patients. This study aimed to determine how the brain morphological and functional changes affected the cognitive decline in patients with CAS. Methods: The brain morphological differences were analyzed using surface and voxel-based morphometry, and the seed-based whole-brain functional connectivity (FC) abnormalities were analyzed using resting-state functional magnetic resonance imaging. Further, mediation analyses were performed to determine whether and how morphological and FC changes affect cognition in CAS patients. Results: The CAS-MCI (CAS patients with mild cognitive impairment) group performed worse in working memory, verbal fluency, and executive time. Cortical thickness (CT) of the left postcentral and superiorparietal were significantly reduced in CAS-MCI patients. The gray matter volume (GMV) of the right olfactory, left temporal pole (superior temporal gyrus) (TPOsup.L), left middle temporal gyrus (MTG.L), and left insula (INS.L) were decreased in the CAS-MCI group. Besides, decreased seed-based FC between TPOsup.L and left precuneus, between MTG.L and TPOsup.L, and between INS.L and MTG.L, left middle frontal gyrus, as well as Superior frontal gyrus, were found in CAS-MCI patients. Mediation analyses demonstrated that morphological and functional abnormalities fully mediated the association between the maximum degree of carotid stenosis and cognitive function. Conclusion: Multiple brain regions have decreased GMV and CT in CAS-MCI patients, along with disrupted seed-based FC. These morphological and functional changes play a crucial role in the cognitive impairment in CAS patients. [ABSTRACT FROM AUTHOR]

Background: Recent evidence suggests that anosognosia or unawareness of cognitive impairment in Alzheimer's Disease (AD) may be explained by a disconnection between brain regions involved in accessing and monitoring information regarding self and others. It has been demonstrated that AD patients with anosognosia have reduced connectivity within the default mode network (DMN) and that anosognosia in people with prodromal AD is positively associated with bilateral anterior cingulate cortex (ACC), suggesting a possible role of this region in mechanisms of awareness in the early phase of disease. We hypothesized that anosognosia in AD is associated with an imbalance between the activity of large-scale resting-state functional magnetic resonance imaging (fMRI) networks, in particular the DMN, the salience network (SN), and the frontoparietal network (FPN). Methods: Sixty patients with MCI and AD dementia underwent fMRI and neuropsychological assessment including the Anosognosia Questionnaire Dementia (AQ-D), a measure of anosognosia based on a discrepancy score between patient's and carer's judgments. After having applied Independent Component Analysis (ICA) to resting fMRI data we performed: (i) correlations between the AQ-D score and functional connectivity in the DMN, SN, and FPN, and (ii) comparisons between aware and unaware patients of the DMN, SN, and FPN functional connectivity. Results: We found that anosognosia was associated with (i) weak functional connectivity within the DMN, in posterior and middle cingulate cortex particularly, (ii) strong functional connectivity within the SN in ACC, and between the SN and basal ganglia, and (iii) a heterogenous effect concerning the functional connectivity of the FPN, with a weak connectivity between the FPN and PCC, and a strong connectivity between the FPN and ACC. The observed effects were controlled for differences in severity of cognitive impairment and age. Conclusion: Anosognosia in the AD continuum is associated with a dysregulation of the functional connectivity of three large-scale networks, namely the DMN, SN, and FPN. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the present study was to identify predictors of severe white matter hyperintensity (WMH) with obesity (SWO), and to build a prediction model for screening obese people with severe WMH without Nuclear Magnetic Resonance Imaging (MRI) examination. Patients subjects and methods: From September 2020 to October 2021, 650 patients with WMH were recruited consecutively. The subjects were divided into two groups, SWO group and non-SWO group. Univariate and Logistic regression analysis were was applied to explore the potential predictors of SWO. The Youden index method was adopted to determine the best cut-off value in the establishment of the prediction model of SWO. Each parameter had two options, low and high. The score table of the prediction model and nomogram based on the logistic regression were constructed. Of the 650 subjects, 487 subjects (75%) were randomly assigned to the training group and 163 subjects (25%) to the validation group. By resampling the area under the curve (AUC) of the subject's operating characteristics and calibration curves 1,000 times, nomogram performance was verified. A decision curve analysis (DCA) was used to evaluate the nomogram's clinical usefulness. By resampling the area under the curve (AUC) of the subject's operating characteristics and calibration curves 1,000 times, nomogram performance was verified. A decision curve analysis (DCA) was used to evaluate the nomogram's clinical usefulness. Results: Logistic regression demonstrated that hypertension, uric acid (UA), complement 3 (C3) and Interleukin 8 (IL-8) were independent risk factors for SWO. Hypertension, UA, C3, IL-8, folic acid (FA), fasting C-peptide (FCP) and eosinophil could be used to predict the occurrence of SWO in the prediction models, with a good diagnostic performance, Areas Under Curves (AUC) of Total score was 0.823 (95% CI: 0.760--0.885, p < 0.001), sensitivity of 60.0%, specificity of 91.4%. In the development group, the nomogram's AUC (C statistic) was 0.829 (95% CI: 0.760--0.899), while in the validation group, it was 0.835 (95% CI: 0.696, 0.975). In both the development and validation groups, the calibration curves following 1,000 bootstraps showed a satisfactory fit between the observed and predicted probabilities. DCA showed that the nomogram had great clinical utility. Conclusion: Hypertension, UA, C3, IL-8, FA, FCP and eosinophil models had the potential to predict the incidence of SWO. When the total score of the model exceeded 9 points, the risk of SWO would increase significantly, and the nomogram enabled visualization of the patient's WMH risk. The application prospect of our models mainly lied in the convenient screening of SWO without MRI examination in order to detect SWO and control the WMH hazards early. [ABSTRACT FROM AUTHOR]

Background: Family caregivers are family members or friends of care recipients who assist with activities of daily living, medication management, transportation, and help with finances among other activities. As a result of their caregiving, family caregivers are often considered a population at risk of experiencing increased stress, isolation, and loneliness. During the COVID-19 pandemic in the US, social isolation and decrease in social activities were a top concern among older adults and their family caregivers. Using secondary analysis of survey data as part of a multi-site implementation trial of a caregiver skills training program, we describe differences in caregiver experiences of loneliness before and during the COVID-19 pandemic. Methods: Health and wellbeing surveys of family caregivers were collected on 422 family caregivers of veterans before and during COVID-19. Logistic regression modeling examined whether the loneliness differed between caregiver groups pre vs during COVID-19, using the UCLA 3-item loneliness measure. Rapid directed qualitative content analysis of open-ended survey questions was used to explore the context of how survey responses were affected by the COVID-19 pandemic. Results: There were no significant differences in loneliness between caregivers pre vs during COVID-19. In open-ended responses regarding effects of COVID-19, caregivers described experiencing loneliness and social isolation; why they were unaffected by the pandemic; and how caregiving equipped them with coping strategies to manage negative pandemic-related effects. Conclusion: Loneliness did not differ significantly between pre vs during COVID-19 caregivers. Future research could assess what specific characteristics are associated with caregivers who have resiliency, and identify caregivers who are more susceptible to experiencing loneliness. Understanding caregiver loneliness could assist other healthcare systems in developing and implementing caregiver support interventions. [ABSTRACT FROM AUTHOR]

Background: Age-related decline in cognitive function is often linked to changed prefrontal cortex (PFC) activity and heart rate variability (HRV). Mild cognitive impairment (MCI), a transitional stage between normal aging and dementia, might have further degeneration beyond aging. This study aimed to investigate the differences between young and older adults with or without MCI in cognitive functions, task-induced PFC activation and HRV changes. Methods: Thirty-one healthy young adults (YA), 44 older adults (OA), and 28 older adults with MCI (OA-MCI) were enrolled and compared in this crosssectional study. Each participant received a one-time assessment including cognitive and executive functions, as well as the simultaneous recording of PFC activity and HRV during a cognitive task paradigm. Results: We observed age-related decrease in global cognitive functions, executive functions, HRV, and increase in PFC activity. The MCI further deteriorated the global cognitive and executive performances, but not the HRV or the prefrontal activation. Conclusion: Older people showed lower performances in general cognitive function and executive function, compensatory increase of PFC activity, and reduced HRV. Older people with MCI had further deterioration in cognitive performance, but not in PFC activation and HRV. [ABSTRACT FROM AUTHOR]

Age-related motor impairments often cause caregiver dependency or even hospitalization. However, comprehensive investigations of the different motor abilities and the changes thereof across the adult lifespan remain sparse. We, therefore, extensively assessed essential basic and complex motor functions in 444 healthy adults covering a wide age range (range 21 to 88 years). Basic motor functions, here defined as simple isolated single or repetitive movements in one direction, were assessed by means of maximum grip strength (GS) and maximum finger-tapping frequency (FTF). Complex motor functions, comprising composite sequential movements involving both proximal and distal joints/muscle groups, were evaluated with the Action Research Arm Test (ARAT), the Jebsen-Taylor Hand Function Test (JTT), and the Purdue Pegboard Test. Men achieved higher scores than women concerning GS and FTF, whereas women stacked more pins per time than men during the Purdue Pegboard Test. There was no significant sex effect regarding JTT. We observed a significant but task- specific reduction of basic and complex motor performance scores across the adult lifespan. Linear regression analyses significantly predicted the participants' ages based on motor performance scores (R² = 0.502). Of note, the ratio between the left- and right-hand performance remained stable across ages for all tests. Principal Component Analysis (PCA) revealed three motor components across all tests that represented dexterity, force, and speed. These components were consistently present in young (21-40 years), middle-aged (41-60 years), and older (61-88 years) adults, as well as in women and men. Based on the three motor components, K-means clustering analysis differentiated high- and low-performing participants across the adult life span. The rich motor data set of 444 healthy participants revealed age- and sex-dependent changes in essential basic and complex motor functions. Notably, the comprehensive assessment allowed for generating robust motor components across the adult lifespan. Our data may serve as a reference for future studies of healthy subjects and patients with motor deficits. Moreover, these findings emphasize the importance of comprehensively assessing different motor functions, including dexterity, force, and speed, to characterize human motor abilities and their age-related decline. [ABSTRACT FROM AUTHOR]

Background: A water extract (CAW) of the Ayurvedic plant Centella asiatica administered in drinking water has been shown to improve cognitive deficits in mouse models of aging and neurodegenerative diseases. Here the effects of CAW administered in drinking water or the diet on cognition, measures of anxiety and depression-like behavior in healthy aged mice are compared. Methods: Three- and eighteen-month-old male and female C57BL6 mice were administered rodent AIN-93M diet containing CAW (0, 0.2, 0.5 or 1% w/w) to provide 0, 200 mg/kg/d, 500 mg/kg/d or 1,000 mg/kg/d CAW for a total of 5 weeks. An additional group of eighteen-month-old mice were treated with CAW (10 mg/mL) in their drinking water CAW for a total of 5 weeks to deliver the same exposure of CAW as the highest dietary dose (1,000 mg/kg/d). CAW doses delivered were calculated based on food and water consumption measured in previous experiments. In the fourth and fifth weeks, mice underwent behavioral testing of cognition, anxiety and depression (n = 12 of each sex per treatment group in each test). Results: Aged mice of both sexes showed cognitive deficits relative to young mice while only female aged mice showed increased anxiety compared to the young female mice and no differences in depression were observed between the different ages. CAW (1,000 mg/kg/d) in the drinking water improved deficits in aged mice in learning, executive function and recognition memory in both sexes and attenuated the increased measures of anxiety observed in the aged female mice. However, CAW in the diet only improved executive function in aged mice at the highest dose (1,000 mg/kg/d) in both sexes and did so less robustly than when given in the water. There were no effects of CAW on depression-like behavior in aged animals regardless of whether it was administered in the diet or the water. Conclusions: These results suggest that CAW can ameliorate age-related changes in measures of anxiety and cognition and that the mode of administration is important for the effects of CAW on resilience to these age-related changes. [ABSTRACT FROM AUTHOR]

Introduction: The deterioration of white matter pathways is one of the hallmarks of the ageing brain. In theory, this decrease in structural integrity leads to disconnection between regions of brain networks and thus to altered functional connectivity and a decrease in cognitive abilities. However, in many studies, associations between structural and functional connectivity are rather weak or not observed at all. System segregation, defined as the extent of partitioning between different resting state networks has increasingly gained attention in recent years as a new metric for functional changes in the aging brain. Yet there is a shortage of previous reports describing the association of structural integrity and functional segregation. Methods: Therefore, we used a large a large sample of 2,657 participants from the Hamburg City Health Study, a prospective population-based study including participants aged 46-78 years from the metropolitan region Hamburg, Germany. We reconstructed structural and functional connectomes to analyze whether there is an association between age-related differences in structural connectivity and functional segregation, and whether this association is stronger than between structural connectivity and functional connectivity. In a second step, we investigated the relationship between functional segregation and executive cognitive function and tested whether this association is stronger than that between functional connectivity and executive cognitive function. Results: We found a significant age-independent association between decreasing structural connectivity and decreasing functional segregation across the brain. In addition, decreasing functional segregation showed an association with decreasing executive cognitive function. On the contrary, no such association was observed between functional connectivity and structural connectivity or executive function. Discussion: These results indicate that the segregation metric is a more sensitive biomarker of cognitive ageing than functional connectivity at the global level and offers a unique and more complementary network-based explanation. [ABSTRACT FROM AUTHOR]

Background: Changes in cognitive control are considered potential factors affecting voluntary motor movements during gait initiation (GI). Simulating environments with higher cognitive resource demands have an effect on the stability of GI task performance, which is of significant importance for assessing fall risk in the older adults and devising fall risk management measures in multiple environments. This study aims to reveal the influence of complex cognitive competitive environment with increased cognitive demands on the dynamic stability during GI in the older women. Methods: Twenty-three older females and twenty-three younger females performed walking tests under three conditions: voluntary initiation (SI), visual light reaction time task (LRT), and cognitive interference + visual light reaction time task (C + LRT). Eight cameras (Qualisys, Sweden, model: Oqus 600) and three force plates (Kistler, Switzerland, model: 9287C) are used to obtain kinematic and kinetic data. To recorde the trajectory of center of pressure (CoP) and the position of the foot placement, and compute the anterior--posterior (AP) and medio-lateral (M-L) dynamic stability at the onset and end moments of the single-leg support by means of center of mass (CoM) and gait spatiotemporal parameters. Results: Older women responded to the effect of complex environments involving cognitive competition on body stability by prolonging the lateral displacement time of the CoP during the anticipatory postural adjustments (APAs) phase, reducing step length and velocity, and increasing step width and foot inclination angle. Conclusion: Complex initiation environments lead to competition for cognitive resources in the brain, resulting in decreased stability of GI motor control in older adults. The higher the complexity of the cognitive resource demands environment, the lower the stability of GI in older adults, and the greater the effect on their M-L stability at the onset of stepping. [ABSTRACT FROM AUTHOR]

Background: Controllability is a measure of the brain's ability to orchestrate neural activity which can be quantified in terms of properties of the brain's network connectivity. Evidence from the literature suggests that aging can exert a general effect on whole-brain controllability. Mounting evidence, on the other hand, suggests that parenthood and motherhood in particular lead to longlasting changes in brain architecture that effectively slow down brain aging. We hypothesize that parenthood might preserve brain controllability properties from aging. Methods: In a sample of 814 healthy individuals (aged 33.9 ± 12.7 years, 522 females), we estimate whole-brain controllability and compare the aging effects in subjects with vs. those without children. We use diffusion tensor imaging (DTI) to estimate the brain structural connectome. The level of brain control is then calculated from the connectomic properties of the brain structure. Specifically, we measure the network control over many low-energy state transitions (average controllability) and the network control over difficult-to-reach states (modal controllability). Results and conclusion: In nulliparous females, whole-brain average controllability increases, and modal controllability decreases with age, a trend that we do not observe in parous females. Statistical comparison of the controllability metrics shows that modal controllability is higher and average controllability is lower in parous females compared to nulliparous females. In men, we observed the same trend, but the difference between nulliparous and parous males do not reach statistical significance. Our results provide strong evidence that parenthood contradicts aging effects on brain controllability and the effect is stronger in mothers. [ABSTRACT FROM AUTHOR]

The menopausal transition has been proposed to put women at risk for undesirable neurological symptoms, including cognitive decline. Previous studies suggest that alterations in the hormonal milieu modulate brain structures associated with cognitive function. This structured review provides an overview of the relevant studies that have utilized MRI to report volumetric differences in the brain following menopause, and its correlations with the evaluated cognitive functions. We performed an electronic literature search using Medline (Ovid) and Scopus to identify studies that assessed the influence of menopause on brain structure with MRI. Fourteen studies met the inclusion criteria. Brain volumetric differences have been reported most frequently in the frontal and temporal cortices as well as the hippocampus. These regions are important for higher cognitive tasks and memory. Additionally, the deficit in verbal and visuospatial memory in postmenopausal women has been associated with smaller regional brain volumes. Nevertheless, the limited number of eligible studies and cross-sectional study designs warrant further research to draw more robust conclusions. [ABSTRACT FROM AUTHOR]

Introduction: Healthy aging affects several domains of cognitive and motor performance and is further associated with multiple structural and functional neural reorganization patterns. However, gap of knowledge exists, referring to the impact of these age-related alterations on the neural basis of tool use- an important, complex action involved in everyday life throughout the entire lifespan. The current fMRI study aims to investigate age-related changes of neural correlates involved in planning and executing a complex object manipulation task, further providing a better understanding of impaired tool use performance in apraxia patients. Methods: A balanced number of sixteen older and younger healthy adults repeatedly manipulated everyday tools in an event-related Go-No-Go fMRI paradigm. Results: Our data indicates that the left-lateralized network, including widely distributed frontal, temporal, parietal and occipital regions, involved in tool use performance is not subjected to age-related functional reorganization processes. However, age-related changes regarding the applied strategical procedure can be detected, indicating stronger investment into the planning, preparatory phase of such an action in older participants. [ABSTRACT FROM AUTHOR]

The ability to predict the weight of objects is important for skilled and dexterous manipulation during activities of daily living. The observation of other people moving objects might represent an important source of information on object features and help to plan the correct motor interaction with it. In aging, an impaired ability to evaluate the object weight might have negative drawbacks in term of the safety of the person. The aim of this study was to investigate the role of aging in the ability to discriminate the object weight during action observation. Twenty older adults (Old) and twenty young subjects (Young) performed a twointerval forced-choice task consisting in the observation of a couple of videos showing an actor moving a box of different weights. The observer had to evaluate which video showed the heavier box. Handgrip strength was acquired from all subjects. Sensitivity analysis was performed and psychometric curves were built on participants' responses. The results showed a diminished sensitivity in the object weight discrimination in Old than in Young group. The analysis of the psychometric curves revealed that this impairment pertained both the light and heavy boxes and the minimum difference to discriminate different weights was greater in Old than in Young. At last, the sensitivity and the discrimination ability significantly correlated with individuals' handgrip strength. These findings allow us to deeply characterize the impairments older adults have in discriminating the weight of an object moved by another individual. [ABSTRACT FROM AUTHOR]

Background: An optimized anesthesia monitoring using electroencephalographic (EEG) information in the elderly could help to reduce the incidence of postoperative complications. Processed EEG information that is available to the anesthesiologist is affected by the age-induced changes of the raw EEG. While most of these methods indicate a "more awake" patient with age, the permutation entropy (PeEn) has been proposed as an age-independent measure. In this article, we show that PeEn is also influenced by age, independent of parameter settings. Methods: We retrospectively analyzed the EEG of more than 300 patients, recorded during steady state anesthesia without stimulation, and calculated the PeEn for different embedding dimensionsmthat was applied to the EEG filtered to a wide variety of frequency ranges. We constructed linear models to evaluate the relationship between age and PeEn. To compare our results to published studies, we also performed a stepwise dichotomization and used non-parametric tests and effect sizes for pairwise comparisons. Results: We found a significant influence of age on PeEn for all settings except for narrow band EEG activity. The analysis of the dichotomized data also revealed significant differences between old and young patients for the PeEn settings used in published studies. Conclusion: Based on our findings, we could show the influence of age on PeEn. This result was independent of parameter, sample rate, and filter settings. Hence, age should be taken into consideration when using PeEn to monitor patient EEG. [ABSTRACT FROM AUTHOR]

Introduction: Geometry-inspired notions of discrete Ricci curvature have been successfully used as markers of disrupted brain connectivity in neuropsychiatric disorders, but their ability to characterize age-related changes in functional connectivity is unexplored. Methods: We apply Forman-Ricci curvature and Ollivier-Ricci curvature to compare functional connectivity networks of healthy young and older subjects from the Max Planck Institute Leipzig Study for Mind-Body-Emotion Interactions (MPI-LEMON) dataset (N = 225). Results: We found that both Forman-Ricci curvature and Ollivier-Ricci curvature can capture whole-brain and region-level age-related differences in functional connectivity. Meta-analysis decoding demonstrated that those brain regions with age-related curvature differences were associated with cognitive domains known to manifest age-related changes--movement, affective processing, and somatosensory processing. Moreover, the curvature values of some brain regions showing age-related differences exhibited correlations with behavioral scores of affective processing. Finally, we found an overlap between brain regions showing age-related curvature differences and those brain regions whose non-invasive stimulation resulted in improved movement performance in older adults. Discussion: Our results suggest that both Forman-Ricci curvature and Ollivier-Ricci curvature correctly identify brain regions that are known to be functionally or clinically relevant. Our results add to a growing body of evidence demonstrating the sensitivity of discrete Ricci curvature measures to changes in the organization of functional connectivity networks, both in health and disease. [ABSTRACT FROM AUTHOR]

Introduction: Aging negatively impacts the ability to rapidly and successfully switch between two or more tasks that have different rules or objectives. However, previous work has shown that the context impacts the extent of this age-related impairment: while there is relative age-related invariance when participants must rapidly switch back and forth between two simple tasks (often called "switch costs"), age-related differences emerge when the contexts changes from one in which only one task must be performed to one in which multiple tasks must be performed, but a trial-level switch is not required (e.g., task repeat trials within dual task blocks, often called "mixing costs"). Here, we explored these two kinds of costs behaviorally, and also investigated the neural correlates of these effects. Methods: Seventy-one younger adults and 175 older adults completed a taskswitching experiment while they underwent fMRI brain imaging. We investigated the impact of age on behavioral performance and neural activity considering two types of potential costs: switch costs (dual-task switch trials minus dual-task nonswitch trials), and mixing costs (dual-task non-switch minus single-task trials). Results: We replicated previous behavioral findings, with greater age associated with mixing, but not switch costs. Neurally, we found age-related compensatory activations for switch costs in the dorsal lateral prefrontal cortex, pars opercularis, superior temporal gyrus, and the posterior and anterior cingulate, but agerelated under recruitment for mixing costs in fronto-parietal areas including the supramarginal gyrus and pre and supplemental motor areas. Discussion: These results suggest an age-based dissociation between executive components that contribute to task switching. [ABSTRACT FROM AUTHOR]

Introduction: Despite the relevance of advance care planning (ACP) for people with dementia, its uptake in this population is particularly low. Several challenges for ACP in dementia have been identified from physicians' perspectives. However, the literature available mainly includes general practitioners and focuses exclusively on the context of late-onset dementia. This is the first study to inquire physicians from four highly relevant specialisms in dementia care, with a focus toward potential specificities based on patients' age. The research question of this study is: "What are physicians' experiences with and perspectives on discussing ACP with people with young- and/or late-onset dementia?". Methods: Five online focus groups were conducted with 21 physicians (general practitioners, psychiatrists, neurologists and geriatricians) in Flanders, Belgium. Verbatim transcripts were analyzed through the qualitative method of constant comparative analysis. Results: Physicians believed that the societal stigma related to dementia influences people's reaction to their diagnosis, at times characterized by catastrophic expectations for the future. In this regard, they explained that the topic of euthanasia is sometimes addressed by patients very early in the disease trajectory. Respondents paid ample attention to actual end-of-life decisions, including DNR directives, when discussing ACP in dementia. Physicians felt responsible for providing accurate information on both dementia as a condition, and the legal framework of end-of-life decisions. Most participants felt that patients' and caregivers' wish for ACP was more driven by who their personality than by their age. Nonetheless, physicians identified specificities for a younger dementia population in terms of ACP: they believed that ACP covered more domains of life than for older persons. A high consistency regarding the viewpoints of physicians from differing specialisms was noted. Discussion: Physicians acknowledge the added value of ACP for people with dementia and especially their caregivers. However, they face several challenges for engaging in the process. Attending to specific needs in young-onset, in comparison to late-onset dementia, requires ACP to entail more than solely medical domains. However, a medicalized view on ACP still appears to be dominant in practice as opposed to its broader conceptualization in academia. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer’s disease (AD) and Lewy body disease (LBD) are the two most common neurodegenerative dementias and can occur in combination (AD+LBD). Due to overlapping biomarkers and symptoms, clinical differentiation of these subtypes could be difficult. However, it is unclear how the magnitude of diagnostic uncertainty varies across dementia spectra and demographic variables. We aimed to compare clinical diagnosis and post-mortem autopsy-confirmed pathological results to assess the clinical subtype diagnosis quality across these factors. Methods: We studied data of 1,920 participants recorded by the National Alzheimer’s Coordinating Center from 2005 to 2019. Selection criteria included autopsy-based neuropathological assessments for AD and LBD, and the initial visit with Clinical Dementia Rating (CDR) stage of normal, mild cognitive impairment, or mild dementia. Longitudinally, we analyzed the first visit at each subsequent CDR stage. This analysis included positive predictive values, specificity, sensitivity and false negative rates of clinical diagnosis, as well as disparities by sex, race, age, and education. If autopsy-confirmed AD and/or LBD was missed in the clinic, the alternative clinical diagnosis was analyzed. Findings: In our findings, clinical diagnosis of AD+LBD had poor sensitivities. Over 61% of participants with autopsy-confirmed AD+LBD were diagnosed clinically as AD. Clinical diagnosis of AD had a low sensitivity at the early dementia stage and low specificities at all stages. Among participants diagnosed as AD in the clinic, over 32% had concurrent LBD neuropathology at autopsy. Among participants diagnosed as LBD, 32% to 54% revealed concurrent autopsy-confirmed AD pathology. When three subtypes were missed by clinicians, “No cognitive impairment” and “primary progressive aphasia or behavioral variant frontotemporal dementia” were the leading primary etiologic clinical diagnoses. With increasing dementia stages, the clinical diagnosis accuracy of black participants became significantly worse than other races, and diagnosis quality significantly improved for males but not females. Discussion: These findings demonstrate that clinical diagnosis of AD, LBD, and AD+LBD are inaccurate and suffer from significant disparities on race and sex. They provide important implications for clinical management, anticipatory guidance, trial enrollment and applicability of potential therapies for AD, and promote research into better biomarker-based assessment of LBD pathology. [ABSTRACT FROM AUTHOR]

Background: Mobility impairments, in terms of gait and balance, are common in persons with dementia. To explore this relationship further, we examined the associations between mobility and cerebrospinal fluid (CSF) core biomarkers for Alzheimer's disease (AD). Methods: In this cross-sectional study, we included 64 participants [two with subjective cognitive decline (SCD), 13 with mild cognitive impairment (MCI) and 49 with dementia] from a memory clinic. Mobility was examined using gait speed, Mini-Balance Evaluation Systems test (Mini-BESTest), Timed Up and Go (TUG), and TUG dual-task cost (TUG DTC). The CSF biomarkers included were amyloid-β 42 (Aβ42), total-tau (t-tau), and phospho tau (p-tau181). Associations between mobility and biomarkers were analyzed through correlations and multiple linear regression analyses adjusted for (1) age, sex, and comorbidity, and (2) SCD/MCI vs. dementia. Results: Aβ42 was significantly correlated with each of the mobility outcomes. In the adjusted multiple regression analyses, Aβ42 was significantly associated with Mini-BESTest and TUG in the fully adjusted model and with TUG DTC in step 1 of the adjusted model (adjusting for age, sex, and comorbidity). T-tau was only associated with TUG DTC in step 1 of the adjusted model. P-tau181 was not associated with any of the mobility outcomes in any of the analyses. Conclusion: Better performance on mobility outcomes were associated with higher levels of CSF Aβ42. The association was strongest between Aβ42 and Mini-BESTest, suggesting that dynamic balance might be closely related with AD-specific pathology. [ABSTRACT FROM AUTHOR]

Introduction: Central anosmia is a potential marker of the prodrome and progression of Parkinson's disease (PD). Resting-state functional magnetic resonance imaging studies have shown that olfactory dysfunction is related to abnormal changes in central olfactory-related structures in patients with early PD. Methods: This study, which was conducted at Guanyun People's Hospital, analyzed the resting-state functional magnetic resonance data using the functional covariance connection strength method to decode the functional connectivity between the white-gray matter in a Chinese population comprising 14 patients with PD and 13 controls. Results: The following correlations were observed in patients with PD: specific gray matter areas related to smell (i.e., the brainstem, right cerebellum, right temporal fusiform cortex, bilateral superior temporal gyrus, right Insula, left frontal pole and right superior parietal lobule) had abnormal connections with white matter fiber bundles (i.e., the left posterior thalamic radiation, bilateral posterior corona radiata, bilateral superior corona radiata and right superior longitudinal fasciculus); the connection between the brainstem [region of interest (ROI) 1] and right cerebellum (ROI2) showed a strong correlation. Right posterior corona radiation (ROI") showed a strong correlation with part 2 of the Unified Parkinson's Disease Rating Scale, and right superior longitudinal fasciculus (ROI14) showed a strong correlation with parts 1, 2, and 3 of the Unified Parkinson's Disease Rating Scale and Hoehn and Yahr Scale. Discussion: The characteristics of olfactory-related brain networks can be potentially used as neuroimaging biomarkers for characterizing PD states. In the future, dynamic testing of olfactory function may help improve the accuracy and specificity of olfactory dysfunction in the diagnosis of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the presence and patterns of age-related differences in TMS-based measures of lateralization and distinctiveness of the cortical motor representations of two different hand muscles. In a sample of seventy-three right-handed healthy participants over the adult lifespan, the first dorsal interosseus (FDI) and abductor digiti minimi (ADM) cortical motor representations of both hemispheres were acquired using transcranial magnetic stimulation (TMS). In addition, dexterity and maximum force levels were measured. Lateralization quotients were calculated for homolog behavioral and TMS measures, whereas the distinctiveness between the FDI and ADM representation within one hemisphere was quantified by the center of gravity (CoG) distance and cosine similarity. The presence and patterns of age-related changes were examined using linear, polynomial, and piecewise linear regression. No age-related differences could be identified for the lateralization quotient of behavior or cortical motor representations of both intrinsic hand muscles. Furthermore, no evidence for a change in the distinctiveness of the FDI and ADM representation with advancing age was found. In conclusion this work showed that lateralization and distinctiveness of cortical motor representations, as determined by means of TMS-based measures, remain stable over the adult lifespan. [ABSTRACT FROM AUTHOR]

Increasing evidence links Alzheimer's disease (AD) to various sleep disorders, including obstructive sleep apnea (OSA). The core AD cerebrospinal fluid (CSF) biomarkers, including amyloid-b 42 (Ab42), total tau (t-tau), and phosphorylated tau (p-tau), can reflect key elements of AD pathophysiology before the emergence of symptoms. Besides, the amyloid-b (Ab) and tau burden can also be tested by positron emission tomography (PET) scans. Electronic databases (PubMed, Embase, Web of Science, and The Cochrane Library) were searched until August 2022 to assess the AD-related biomarkers measured by PET scans and CSF in OSA patients. The overall analysis showed significant differences in Ab42 levels (SMD = -0.93, 95% CI:-1.57 to -0.29, P < 0.001) and total tau (t-tau) levels (SMD = 0.24, 95% CI: 0.01-0.48, P = 0.308) of CSF, and Ab burden (SMD = 0.37, 95% CI = 0.13-0.61, P = 0.69) tested by PET scans between the OSA and controls. Furthermore, CSF Ab42 levels showed significant differences in patients with moderate/severe OSA compared with healthy control, and levels of CSF Ab42 showed differences in OSA patients with normal cognition as well. Besides, age and BMI have influences on heterogeneity. Our meta-analysis indicated abnormal ADrelated biomarkers (CSF and PET scans) in patients with OSA, supporting the current hypothesis that OSA, especially moderate/severe OSA, may start the AD neuropathological process. [ABSTRACT FROM AUTHOR]

Objective: Although multiple step saccades (MSS) is occasionally observed in healthy subjects, it is more pronounced in patients with aging-related neurodegenerative diseases, particularly Parkinson's disease (PD). Thus, MSS has been treated as a complementary biomarker for diagnosing PD. Despite the aforementioned knowledge, several questions remain unexplored: (1) How does aging affect MSS? (2) Is there a sex difference in MSS? (3) Are there differences in MSS between vertical and horizontal saccades? (4) Are MSS and corrective saccade (CS) the same behavior? (5) How do age and sex affect CS? The objectives of the present study are to address these questions. Method: Four hundred eighty healthy participants were recruited to perform a visually guided reactive saccade task. Participants were divided into six groups according to their ages. Each group consisted of 40 male and 40 female participants. Eye movements were recorded with infrared eye trackers. Results: The incidence of MSS increased as a function of age, whereas the incidence of CS first increased with age 20-49 and then decreased with age 50-79. The incidences of both MSS and CS did not show sex differences. The incidence of MSS in vertical saccades was significantly higher than that in horizontal saccades, and their difference increased with increasing age, whereas the incidence of CS showed a reversed pattern. Conclusion: Age and saccadic direction affect the occurrences of MSS and CS differently, indicating that MSS and CS are different saccadic behaviors. In addition, measuring saccades could reliably reflect the function of human's brain which is affected by aging. [ABSTRACT FROM AUTHOR]

When listening to musical rhythm, humans can perceive and move to beat-like metrical pulses. Recently, it has been hypothesized that meter perception is related to brain activity responding to the acoustic fluctuation of the rhythmic input, with selective enhancement of the brain response elicited at meter-related frequencies. In the current study, electroencephalography (EEG) was recorded while younger (<35) and older (>60) adults listened to rhythmic patterns presented at two different tempi while intermittently performing a tapping task. Despite significant hearing loss compared to younger adults, older adults showed preserved brain activity to the rhythms. However, age effects were observed in the distribution of amplitude across frequencies. Specifically, in contrast with younger adults, older adults showed relatively larger amplitude at the frequency corresponding to the rate of individual events making up the rhythms as compared to lower meter-related frequencies. This difference is compatible with larger N1-P2 potentials as generally observed in older adults in response to acoustic onsets, irrespective of meter perception. These larger low-level responses to sounds have been linked to processes by which age-related hearing loss would be compensated by cortical sensory mechanisms. Importantly, this low-level effect would be associated here with relatively reduced neural activity at lower frequencies corresponding to higher-level metrical grouping of the acoustic events, as compared to younger adults. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to examine the activation and functional connectivity of the prefrontal and temporal lobe in young and elder people during the Stroop test using functional near-infrared spectroscopy (fNIRS). Methods: A total of 33 healthy volunteers (20 young people, mean age: 23.7 ± 3.9 years; 13 elder people, mean age: 63.9 ± 4.0 years) participated in the study. All subjects were asked to finish the Stroop Color Word Test. The oxygenated hemoglobin concentration (Delta [HbO2]) signals and the deoxygenated hemoglobin (Delta [HbR]) signals were recorded fromtemporopolar area (TA), pars triangularis Broca's area (Broca), dorsolateral prefrontal cortex (DLPFC), and frontopolar area (FA) by fNIRS. The coherence between the left and right frontotemporal lobe delta [HbO2] oscillations in four frequency intervals (I, 0.6-2 Hz; II, 0.145-0.6 Hz; III, 0.052-0.145 Hz; and IV, 0.021-0.052 Hz) was analyzed using wavelet coherence analysis and wavelet phase coherent. Results: In the Stroop test, the young group was significantly better than the elder group at the responses time, whether at congruent tasks or at incongruent tasks (congruent: F = 250.295, p < 0.001; incongruent: p < 0.001). The accuracy of the two groups differed significantly when performing incongruent tasks but not when performing congruent tasks (incongruent: F = 9.498, p = 0.001; congruent: p = 0.254). Besides, only elders show significant activation in DLPFC, Broca, FA, and TA (p < 0.05) during the Stroop test, but young people did not show significant differences. In the functional connectivity of task states, younger people had stronger connections between different brain regions in both the left and right brain compared with the elderly (p < 0.05). In particular, the left and right DLPFC showed stronger connection strength in most of the brain areas. The result suggested that younger people had stronger functional connectivity of brain areas than older people when completing the task. Conclusion: According to these results, although the cortical activation in the elder people was higher than the young people, the young showed stronger connectivity in most of the brain areas than the elders. Both sides of DLPFC and right Broca area were the most significant cortical activation in Stroop test. It was suggested that the decrease in functional connectivity in the elder people resulted in the atrophy of white matter, to which we should pay more attention. [ABSTRACT FROM AUTHOR]

Ovarian hormones, particularly 17b-estradiol, are involved in numerous neurophysiological and neurochemical processes, including those subserving cognitive function. Estradiol plays a key role in the neurobiology of aging, in part due to extensive interconnectivity of the neural and endocrine system. This aspect of aging is fundamental for women's brains as all women experience a drop in circulating estradiol levels in midlife, after menopause. Given the importance of estradiol for brain function, it is not surprising that up to 80% of peri-menopausal and post-menopausal women report neurological symptoms including changes in thermoregulation (vasomotor symptoms), mood, sleep, and cognitive performance. Preclinical evidence for neuroprotective effects of 17b-estradiol also indicate associations between menopause, cognitive aging, and Alzheimer's disease (AD), the most common cause of dementia affecting nearly twice more women than men. Brain imaging studies demonstrated that middle-aged women exhibit increased indicators of AD endophenotype as compared to men of the same age, with onset in perimenopause. Herein, we take a translational approach to illustrate the contribution of ovarian hormones in maintaining cognition in women, with evidence implicating menopause-related declines in 17b-estradiol in cognitive aging and AD risk. We will review research focused on the role of endogenous and exogenous estrogen exposure as a key underlying mechanism to neuropathological aging in women, with a focus on whether brain structure, function and neurochemistry respond to hormone treatment. While still in development, this research area offers a new sexbased perspective on brain aging and risk of AD, while also highlighting an urgent need for better integration between neurology, psychiatry, and women's health practices. [ABSTRACT FROM AUTHOR]

Background: The aging of the world population poses a major health challenge, and brain-computer interface (BCI) technology has the potential to provide assistance and rehabilitation for the elderly. Objectives: This study aimed to investigate the electroencephalogram (EEG) characteristics during motor imagery by comparing young and elderly, and study Convolutional Neural Networks (CNNs) classification for the elderly population in terms of fatigue analysis in both frontal and parietal regions. Methods: A total of 20 healthy individuals participated in the study, including 10 young and 10 older adults. All participants completed the left- and right-hand motor imagery experiment. The energy changes in the motor imagery process were analyzed using time-frequency graphs and quantified event-related desynchronization (ERD) values. The fatigue level of the motor imagery was assessed by two indicators: (α)/β and β, and fatigue-sensitive channels were distinguished from the parietal region of the brain. Then, rhythm entropy was introduced to analyze the complexity of the cognitive activity. The phase-lock values related to the parietal and frontal lobes were calculated, and their temporal synchronization was discussed. Finally, the motor imagery EEG data was classified by CNNs, and the accuracy was discussed based on the analysis results. Result: For the young and elderly, ERD was observed in C3 and C4 channels, and their fatigue-sensitive channels in the parietal region were slightly different. During the experiment, the rhythm entropy of the frontal lobe showed a decreasing trend with time for most of the young subjects, while there was an increasing trend for most of the older ones. Using the CNN classification method, the elderly achieved around 70% of the average classification accuracy, which is almost the same for the young adults. Conclusion: Compared with the young adults, the elderly are less affected by the level of cognitive fatigue during motor imagery, but the classification accuracy of motor imagery data in the elderly may be slightly lower than that in young persons. At the same time, the deep learning method also provides a potentially feasible option for the application of motor-imagery BCI (MI-BCI) in the elderly by considering the ERD and fatigue phenomenon together. [ABSTRACT FROM AUTHOR]

Introduction: Population aging is likely to increase the number of people with dementia living in urban areas. The Trail Making Test (TMT) is widely used as a cognitive task to measure attention and executive function among older adults. Normative data from a sample of community-dwelling older adults are required to evaluate the executive function of this population. The purpose of this study was to examine the Trail Making Test completion rate and completion time among urban community-dwelling older adults in Japan. Methods: A survey was conducted at a local venue or during a home visit (n = 1,966). Cognitive tests were conducted as a part of the survey, and TMT Parts A (TMT-A) and B (TMT-B) were completed after the completion of the Japanese version of the Mini-Mental State Examination (MMSE-J). Testers recorded TMT completion status, completion time, and the number of errors observed. Results: In the TMT-A, 1,913 (99.5%) participants understood the instructions, and 1,904 (99.1%) participants completed the task within the time limit of 240 s. In the TMT-B, 1,839 (95.9%) participants understood the instructions, and 1,584 (82.6%) participants completed the task within the time limit of 300 s. The completion rate of TMT-B was 90.2 and 41.8% for participants with an MMSE-J score of >23 points and ≦23 points, respectively. Results of multiple regression analyses showed that age, education, and the MMSE-J score were associated with completion time in both TMTs. Conclusion: In both TMTs, completion time was associated with age, education, and general cognitive function. However, not all participants completed the TMT-B, and the completion rate was relatively low among participants with low MMSE-J scores. These findings may help interpret future TMT assessments. [ABSTRACT FROM AUTHOR]

Sirtuins are protein factors that can delay aging and alleviate age-related diseases through multiple molecular pathways, mainly by promoting DNA damage repair, delaying telomere shortening, and mediating the longevity effect of caloric restriction. In the last decade, sirtuins have also been suggested to exert mitochondrial quality control by mediating mitophagy, which targets damaged mitochondria and delivers them to lysosomes for degradation. This is especially significant for age-related diseases because dysfunctional mitochondria accumulate in aging organisms. Accordingly, it has been suggested that sirtuins and mitophagy have many common and interactive aspects in the aging process. This article reviews the mechanisms and pathways of sirtuin family-mediated mitophagy and further discusses its role in aging and age-related diseases. [ABSTRACT FROM AUTHOR]

With advanced age, there is a loss of reaction speed that may contribute to an increased risk of tripping and falling. Avoiding falls and injuries requires awareness of the threat, followed by selection and execution of the appropriate motor response. Using event-related potentials (ERPs) and a simple visual reaction task (RT), the goal of our study was to distinguish sensory and motor processing in the upper- and lower-limbs while attempting to uncover the main cause of age-related behavioral slowing. Strength (amplitudes) as well as timing and speed (latencies) of various stages of stimulus- and motor-related processing were analyzed in 48 healthy individuals (young adults, n = 24, mean age = 34 years; older adults, n = 24, mean age = 67 years). The behavioral results showed a significant age-related slowing, where the younger compared to older adults exhibited shorter RTs for the upper- (222 vs. 255 ms; p = 0.006, respectively) and the lower limb (257 vs. 274 ms; p = 0.048, respectively) as well as lower variability in both modalities (p = 0.001). Using ERP indices, age-related slowing of visual stimulus processing was characterized by overall larger amplitudes with delayed latencies of endogenous potentials in older compared with younger adults. While no differences were found in the P1 component, the later components of recorded potentials for visual stimuli processing were most affected by age. This was characterized by increased N1 and P2 amplitudes and delayed P2 latencies in both upper and lower extremities. The analysis of motor-related cortical potentials (MR) revealed stronger MRCP amplitude for upper- and a non-significant trend for lower limbs in older adults. The MRCP amplitude was smaller and peaked closer to the actual motor response for the upper- than for the lower limb in both age groups. There were longer MRCP onset latencies for lower- compared to upper-limb in younger adults, and a non-significant trend was seen in older adults. Multiple regression analyses showed that the onset of the MRCP peak consistently predicted reaction time across both age groups and limbs tested. However, MRCP rise time and P2 latency were also significant predictors of simple reaction time, but only in older adults and only for the upper limbs. Our study suggests that motor cortical processes contribute most strongly to the slowing of simple reaction time in advanced age. However, late-stage cortical processing related to sensory stimuli also appears to play a role in upper limb responses in the elderly. This process most likely reflects less efficient recruitment of neuronal resources required for the upper and lower extremity response task in older adults. [ABSTRACT FROM AUTHOR]

Cognitive aging, especially cognitive control, and processing speed aging have been well-documented in the literature. Most of the evidence was reported based on cross-sectional data, in which inter-individual age effects were shown. However, there have been some studies pointing out the possibility of overlooking intra-individual changes in cognitive aging. To systematically examine whether age-related differences and age-related changes might yield distinctive patterns, this study directly compared cognitive control function and processing speed between different cohorts versus follow-up changes across the adult lifespan. Moreover, considering that cognitive aging has been attributed to brain disconnection in white matter (WM) integrity, this study focused on WM integrity via acquiring diffusion-weighted imaging data with an MRI instrument that are further fitted to a diffusion tensor model (i.e., DTI) to detect water diffusion directionality (i.e., fractional anisotropy, FA; mean diffusivity, MD; radial diffusivity, RD; axial diffusivity, AxD). Following data preprocessing, 114 participants remained for further analyses in which they completed the two follow-up sessions (with a range of 1–2 years) containing a series of neuropsychology instruments and computerized cognitive control tasks. The results show that many significant correlations between age and cognitive control functions originally shown on cross-sectional data no longer exist on the longitudinal data. The current longitudinal data show that MD, RD, and AxD (especially in the association fibers of anterior thalamic radiation) are more strongly correlated to follow-up aging processes, suggesting that axonal/myelin damage is a more robust phenomenon for observing intra-individual aging processes. Moreover, processing speed appears to be the most prominent cognitive function to reflect DTI-related age (cross-sectional) and aging (longitudinal) effects. Finally, converging the results from regression analyses and mediation models, MD, RD, and AxD appear to be the representative DTI measures to reveal age-related changes in processing speed. To conclude, the current results provide new insights to which indicator of WM integrity and which type of cognitive changes are most representative (i.e., potentially to be neuroimaging biomarkers) to reflect intra-individual cognitive aging processes. [ABSTRACT FROM AUTHOR]

Brain health is an important research direction of neuroscience. In addition to the effects of diseases, we cannot ignore the negative effect of aging on brain health. There have been many studies on brain aging, but only a few have used dynamic models to analyze differences in micro brain characteristics in healthy people. In this article, we use the relaxed mean-field model (rMFM) to study the effects of normal aging. Two main parameters of this model are the recurrent connection strength and subcortical input strength. The sensitivity of the rMFM to the initial values of the parameters has not been fully discussed in previous research. We examine this issue through repeated numerical experiments and obtain a reasonable initial parameter range for this model. Differences in recurrent connection strength and subcortical input strength due to aging have also not been studied previously. We use statistical methods to find the regions of interest (ROIs) exhibiting significant differences between young and old groups. Further, we carry out a difference analysis on the process of change of these ROIs on a more detailed timescale. We find that even with the same final results, the trends of change in these ROIs are different. This shows that to develop possible methods to prevent or delay brain damage due to aging, more attention needs to be paid to the trends of change of different ROIs, not just the final results. [ABSTRACT FROM AUTHOR]

Episodic memory and executive function are two cognitive domains that have been studied extensively in older adults and have been shown to decline in normally-aging older individuals. However, one of the problems with characterizing cognitive changes in longitudinal studies has been separating effects attributable to normal aging from effects created by repeated testing or practice. In the present study, 166 people aged 65 and older were enrolled over several years and tested at least 3 times at variable intervals (M = 3.2 yrs). The cognitive measures were composite scores. Each composite was made up of five neuropsychological tests, previously identified through factor analysis. For one pair of composite scores, variance attributable to age was removed from each subtest through regression analyses before z -scores were computed, creating two age-corrected composites. A second pair of composites were not age-corrected. Using linear mixed-effects models, we first explored retest effects for each cognitive domain, independent of age, using the age-corrected composites. We then modeled aging effects using the age-uncorrected composites after subtracting out retest effects. Results indicated significant retest effects for memory but not for executive function, such that memory performance improved across the three testing sessions. When these practice effects were removed from the age-uncorrected data, effects of aging were evident for both executive and memory function with significant declines over time. We also explored several individual difference variables including sex, IQ, and age at the initial testing session and across time. Although sex and IQ affected performance on both cognitive factors at the initial test, neither was related to practice effects, although young-older adults tended to benefit from practice to a greater extent than old-older adults. In addition, people with higher IQs showed slower age-related declines in memory, but no advantages in executive function. These findings suggest that (a) aging affects both memory and executive function similarly, (b) higher IQ, possibly reflecting cognitive reserve, may slow age-related declines in memory, and (c) practice through repeated testing enhances performance in memory particularly in younger-older adults, and may therefore mask aging effects if not taken into account. [ABSTRACT FROM AUTHOR]

Background: Transcranial direct current stimulation (tDCS) has been employed to boost working memory training (WMT) effects. Nevertheless, there is limited evidence on the efficacy of this combination in older adults. The present study is aimed to assess the delayed transfer effects of tDCS coupled with WMT in older adults in a 15-day follow-up. We explored if general cognitive ability, age, and educational level predicted the effects. Methods: In this single-center, double-blind randomized sham-controlled experiment, 54 older adults were randomized into three groups: anodal-tDCS (atDCS)+WMT, sham-tDCS (stDCS)+WMT, and double-sham. Five sessions of tDCS (2 mA) were applied over the left dorsolateral prefrontal cortex (DLPFC). Far transfer was measured by Raven's Advanced Progressive Matrices (RAPM), while the near transfer effects were assessed through Digit Span. A frequentist linear mixed model (LMM) was complemented by a Bayesian approach in data analysis. Results: Working memory training improved dual n -back performance in both groups submitted to this intervention but only the group that received atDCS+WMT displayed a significant improvement from pretest to follow-up in transfer measures of reasoning (RAPM) and short-term memory (forward Digit Span). Near transfer improvements predicted gains in far transfer, demonstrating that the far transfer is due to an improvement in the trained construct of working memory. Age, formal education, and vocabulary score seem to predict the gains in reasoning. However, Bayesian results do not provide substantial evidence to support this claim. Conclusion: This study will help to consolidate the incipient but auspicious field of cognitive training coupled with tDCS in healthy older adults. Our findings demonstrated that atDCS may potentialize WMT by promoting transfer effects in short-term memory and reasoning in older adults, which are observed especially at follow-up. [ABSTRACT FROM AUTHOR]

Age-related deterioration of balance control is widely regarded as an important phenomenon influencing quality of life and longevity, such that a more comprehensive understanding of the neural mechanisms underlying this process is warranted. Specifically, previous studies have reported that older adults typically show higher neural activity during balancing as compared to younger counterparts, but the implications of this finding on balance performance remain largely unclear. Using functional near-infrared spectroscopy (fNIRS), differences in the cortical control of balance between healthy younger (n = 27) and older (n = 35) adults were explored. More specifically, the association between cortical functional activity and balance performance across and within age groups was investigated. To this end, we measured hemodynamic responses (i.e., changes in oxygenated and deoxygenated hemoglobin) while participants balanced on an unstable device. As criterion variables for brain-behavior-correlations, we also assessed postural sway while standing on a free-swinging platform and while balancing on wobble boards with different levels of difficulty. We found that older compared to younger participants had higher activity in prefrontal and lower activity in postcentral regions. Subsequent robust regression analyses revealed that lower prefrontal brain activity was related to improved balance performance across age groups, indicating that higher activity of the prefrontal cortex during balancing reflects neural inefficiency. We also present evidence supporting that age serves as a moderator in the relationship between brain activity and balance, i.e., cortical hemodynamics generally appears to be a more important predictor of balance performance in the older than in the younger. Strikingly, we found that age differences in balance performance are mediated by balancing-induced activation of the superior frontal gyrus, thus suggesting that differential activation of this region reflects a mechanism involved in the aging process of the neural control of balance. Our study suggests that differences in functional brain activity between age groups are not a mere by-product of aging, but instead of direct behavioral relevance for balance performance. Potential implications of these findings in terms of early detection of fall-prone individuals and intervention strategies targeting balance and healthy aging are discussed. [ABSTRACT FROM AUTHOR]

Almost 25% of all older adults experience difficulty walking. Mobility difficulties for older adults are more pronounced when they perform a simultaneous cognitive task while walking (i.e., dual task walking). Although it is known that aging results in widespread brain atrophy, few studies have integrated across more than one neuroimaging modality to comprehensively examine the structural neural correlates that may underlie dual task walking in older age. We collected spatiotemporal gait data during single and dual task walking for 37 young (18–34 years) and 23 older adults (66–86 years). We also collected T 1-weighted and diffusion-weighted MRI scans to determine how brain structure differs in older age and relates to dual task walking. We addressed two aims: (1) to characterize age differences in brain structure across a range of metrics including volumetric, surface, and white matter microstructure; and (2) to test for age group differences in the relationship between brain structure and the dual task cost (DTcost) of gait speed and variability. Key findings included widespread brain atrophy for the older adults, with the most pronounced age differences in brain regions related to sensorimotor processing. We also found multiple associations between regional brain atrophy and greater DTcost of gait speed and variability for the older adults. The older adults showed a relationship of both thinner temporal cortex and shallower sulcal depth in the frontal, sensorimotor, and parietal cortices with greater DTcost of gait. Additionally, the older adults showed a relationship of ventricular volume and superior longitudinal fasciculus free-water corrected axial and radial diffusivity with greater DTcost of gait. These relationships were not present for the young adults. Stepwise multiple regression found sulcal depth in the left precentral gyrus, axial diffusivity in the superior longitudinal fasciculus, and sex to best predict DTcost of gait speed, and cortical thickness in the superior temporal gyrus to best predict DTcost of gait variability for older adults. These results contribute to scientific understanding of how individual variations in brain structure are associated with mobility function in aging. This has implications for uncovering mechanisms of brain aging and for identifying target regions for mobility interventions for aging populations. [ABSTRACT FROM AUTHOR]

The ability to maintain relevant information on a daily basis is negatively impacted by aging. However, the neuronal mechanism manifesting memory persistence in young animals and memory decline in early aging is not fully understood. A novel event, when introduced around encoding of an everyday memory task, can facilitate memory persistence in young age but not in early aging. Here, we investigated in male rats how sub-regions of the hippocampus are involved in memory representation in behavioral tagging and how early aging affects such representation by combining behavioral training in appetitive delayed-matching-to-place tasks with the "cellular compartment analysis of temporal activity by fluorescence in situ hybridization" technique. We show that neuronal assemblies activated by memory encoding were also partially activated by novelty, particularly in the distal CA1 and proximal CA3 subregions in young male rats. In early aging, both encoding- and novelty-triggered neuronal populations were significantly reduced with a more profound effect in encoding neurons. Thus, memory persistence through novelty facilitation engages overlapping hippocampal assemblies as a key cellular signature, and cognitive aging is associated with underlying reduction in neuronal activation. [ABSTRACT FROM AUTHOR]

Background: The human brain structure undergoes considerable changes throughout life. Cognitive function can be affected either negatively or positively. It is challenging to segregate normal brain aging from the accelerated one. Objective: To work out a descriptive model of brain structural and functional changes in normal aging. Materials and Methods: By using voxel-based morphometry and lesion segmentation along with linear statistics and machine learning (ML), we analyzed the structural changes in the major brain compartments and modeled the dynamics of neurofunctional performance throughout life. We studied sex differences in lifelong dynamics of brain volumetric data with Mann-Whitney U -test. We tested the hypothesis that performance in some cognitive domains might decline as a linear function of age while other domains might have a non-linear dependence on it. We compared the volumetric changes in the major brain compartments with the dynamics of psychophysiological performance in 4 age groups. Then, we tested linear models of structural and functional decline for significant differences between the slopes in age groups with the T -test. Results: White matter hyperintensities (WMH) are not the major structural determinant of the brain normal aging. They should be viewed as signs of a disease. There is a sex difference in the speed and/or in the onset of the gray matter atrophy. It either starts earlier or goes faster in males. Marked sex difference in the proportion of total cerebrospinal fluid (CSF) and intraventricular CSF (iCSF) justifies that elderly men are more prone to age-related brain atrophy than women of the same age. Conclusion: The article gives an overview and description of the conceptual structural changes in the brain compartments. The obtained data justify distinct patterns of age-related changes in the cognitive functions. Cross-life slowing of decision-making may follow the linear tendency of enlargement of the interhemispheric fissure because the center of task switching and inhibitory control is allocated within the medial wall of the frontal cortex, and its atrophy accounts for the expansion of the fissure. Free online tool at https://med-predict.com illustrates the tests and study results. [ABSTRACT FROM AUTHOR]